Figure 1A. Efficacy Outcomes Stratified by Baseline LDL-C



Clinical Efficacy and Safety of Evolocumab in Patients with Baseline LDL-C<70 mg/dL and non-HDL-C > 100 mg/dL, and in Patients Already onMaximal Statin: An Analysis from FOURIER4Robert P. Giugliano, Anthony C. Keech, Sabina A. Murphy, Kurt Huber, S. Lale Tokgozoglu,Basil S. Lewis, Jorge Ferreira, Armando Lira, Ransi Somaratne, Peter S. Sever, Terje RPedersen, and Marc S. Sabatine89Author Affiliations: Cardiovascular Division, Brigham and Women’s Hospital, Harvard MedicalSchool, Boston, Massachusetts (Giugliano, Sabatine, Murphy), Sydney Medical School,NHMRC Clinical Trials Centre, University of Sydney, Australia (Keech), 3rd Department ofMedicine, Cardiology, and Intensive Care Medicine and Sigmund Freud University, MedicalSchool, Vienna, Austria (Huber), Hacettepe University Faculty of Medicine, Department ofCardiology, Güven Sokak No: 9, Kavaklidere 06540, Ankara, Turkey (Tokgozoglu), Lady DavisCarmel Medical Center, Haifa, Israel (Lewis), Hospital de Santa Cruz, Lisbon, Portugal(Ferreira), International Centre for Circulatory Health, National Heart and Lung Institute,Imperial College London, United Kingdom (Sever), Amgen, Thousand Oaks, California (Lira,Somaratne), and Oslo University Hospital, Ullev?l and Medical Faculty, University of Oslo,Norway (Pedersen)20Corresponding Author: Robert P. Giugliano, MD, SM, TIMI Study Office, 60 Fenwood Road,Suite 7122, Boston, MA 02115 (rgiugliano@bwh.harvard.edu).23Text word count: 1522References: 15KEY POINTS27Question. Do patients with stable atherosclerotic cardiovascular disease treated with statin whohave an LDL-C <70 mg/dL and a non-HDL-C > 100 benefit from the addition of evolocumab?Would patients already on maximal potency statin benefit from evolocumab?Findings. Evolocumab safely reduced cardiovascular events compared to placebo whetherpatients were starting with an LDL-C <70 mg/dL or not, and whether they were treated withmaximal potency statin or a less potent statin regimen.Meaning. In high-risk patients with stable atherosclerotic cardiovascular disease treated with astatin, even patients who have a low LDL-C and patients on maximal statin experience furtherreduction of cardiovascular events with the addition of evolocumab.3738ABSTRACTIMPORTANCE. Current guidelines focus on high-intensity statins and targeting or using athreshold an LDL-C <70 mg/dL for highest risk patients. Whether further LDL-C reductionbeyond these boundaries would be beneficial is unknown.OBJECTIVE. To compare outcomes with evolocumab vs. placebo in 2 subgroups of patientswith stable atherosclerotic cardiovascular disease: 1) Baseline LDL-C <70 and non-HDL-C >100mg/dL, 2) Background treatment with maximal potency statin.DESIGN. Comparison of randomized treatments in 2 subgroups from a large clinical trial.SETTING. Patients with stable atherosclerotic cardiovascular disease on statin enrolled in theFOURIER trial.PARTICIPANTS. Patients were classified by baseline LDL-C <70 or >70 mg/dL, and by statinintensity (maximal: atorvastatin 80 mg or rosuvastatin 40 mg daily, submaximal: all others).MAIN OUTOCMES AND MEASURES: The primary efficacy end point was the composite ofcardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, orcoronary revascularization. The key secondary efficacy end point was the composite ofcardiovascular death, myocardial infarction, or stroke. Safety outcomes included adverse eventsand special events of interest as identified in the FOURIER trial. Interaction testing was used toassess the consistency of results in patients who did vs. did not satisfy the above criteria.RESULTS. Of 2034 patients (7.4%) who had a baseline LDL-C <70 mg/dL and HDL-C >100mg/dL, evolocumab reduced the risk of the primary endpoint (hazard ratio [HR], 0.80; 95% CI0.60-1.07) to a similar degree as in the 25,529 patients who had a baseline LDL-C >70 mg/dL(HR 0.86; 95% CI 0.79-0.92; PINT=0.65). Of 7533 patients (27.3%) on maximal intensity statin,evolocumab significantly reduced the primary (hazard ratio [HR], 0.86; 95% CI 0.75-0.98) to asimilar degree as in the 20,031patients not on maximal intensity statin (HR for primary endpoint0.85; 95% CI 0.78-0.93; PINT=0.88). The key secondary endpoint was also reduced to a similardegree in both analyses. No major safety concerns were identified.Conclusions. Evolocumab was equally effective in reducing cardiovascular events in patientswith stable atherosclerotic cardiovascular disease regardless of whether the baseline LDL-C was<70 or >70 mg/dL, and whether the background statin was maximal intensity or not.6869Abstract word count: 3507071Several guidelines endorse a target LDL cholesterol (LDL-C) <70 mg/dL (to convert tomillimoles per liter, multiply by 0.0259) or a threshold for treatment ≥70 mg/dL in highest riskpatients for secondary prevention of cardiovascular events.1-4 Likewise, high-intensity statinregimens (i.e., atorvastatin ≥40 or rosuvastatin ≥20 mg/d) are recommended as foundationaltherapy. Whether even more intensive LDL-C lowering would benefit patients who already havean LDL-C <70 mg/dL or patients who are currently being treated not just with high, but withmaximal intensity statin therapy (highest doses possible), is unknown. We explored the efficacyand safety of evolocumab vs. placebo in such patients in the FOURIER trial.5,680MethodsStudy Design and TreatmentThe design of FOURIER has been reported.5,6 In brief, 27,564 patients with prior myocardialinfarction (MI), non-hemorrhagic stroke, or symptomatic peripheral artery disease, as well asadditional characteristics that placed them at higher cardiovascular risk (including one major andtwo minor criteria5), were randomized to the PCSK9 inhibitor evolocumab or placebo. Eligiblepatients had either an LDL-C >70 mg/dL or a non-HDL cholesterol >100 mg/dL at the end ofscreening while on a moderate or high intensity statin (defined as atorvastatin >20 mg/d orequivalent). LDL-C was calculated based on the Friedewald equation, unless the calculated valuewas <40 mg/dL or the measured triglycerides were >400 mg/dL, in which caseultracentrifugation was performed In the current analysis, we compared outcomes withevolocumab vs. placebo in 2 subgroups: (1) patients with a baseline LDL-C (the average of thevalues obtained at the final screening visit and the day of randomization) <70 vs. ≥70 mg/dL; (2)patients on maximal potency background statin (i.e., atorvastatin 80 mg or rosuvastatin 40 mgdaily) at randomization. Ethics Committee approvals for the FOURIER trial were obtained fromall relevant organizations and each patient provided written informed consent.Study OutcomesThe primary endpoint of FOURIER was the composite of cardiovascular death, MI, stroke,hospitalization for unstable angina, or coronary revascularization; the key secondary endpointwas the composite of cardiovascular death, MI or stroke.5,6 Safety endpoints included overalladverse events as well as adverse events of interest including allergic and injection site reactions;and adverse events related to muscle symptoms, elevations in creatine kinase or transaminases,cataracts, new-onset diabetes, and neurocognitive events.Statistical AnalysisBaseline categorical variables were compared using ?2 or Fisher exact tests and continuousvariables using Wilcoxon rank-sum test. Efficacy analyses were performed in the intention-to-treat population including all patients who underwent randomization and provided writteninformed consent. Hazard ratios and 95% confidence intervals of the time to the first efficacyevent were generated using a Cox proportional-hazards model, and P values for time-to-eventanalyses were calculated using log-rank tests. Safety evaluations included all the patients whounderwent randomization, received at least one dose of a study agent and for whom post-dosedata were available. Interaction testing was performed using Cox models for efficacy endpointsand logistic regression for safety endpoints.ResultsPatients with a baseline LDL-C <70 mg/dLA total of 2034 (7.4%) of patients had a baseline LDL-C <70 mg/dL and non-HDL-C >100mg/dL. Compared to patients with LDL-C >70 mg/dL at baseline, these patients tended to beyounger (62.1 vs. 62.5 years), heavier (88 vs. 85 kg), more likely male (80 vs. 75%) and to havehad a prior stroke (21 vs. 19%), hypertension (82 vs. 80%), diabetes (49 vs. 36%), and metabolicsyndrome (73 vs. 58%) (Table 1). The median baseline (IQR) LDL-C was 65.5 (61-68) mg/dL.At 48 weeks, the least-squares mean percentage reduction in LDL-C with evolocumab, ascompared with placebo, was 66%, for a mean absolute reduction of 42 mg/dL, to a median of 21[11.5-37] mg/dL. Evolocumab reduced the risk of the primary composite endpoint by 20% (HR0.80, 95% CI 0.60-1.07) in patients with a baseline LDL-C <70 mg/dL, and by 14% (HR 0.86,95% CI 0.79-0.92) in patients with an LDL-C >70 mg/dL, with no evidence of treatment effectmodification by baseline LDL-C (PINT 0.65, Figure 1). Likewise, evolocumab reduced the riskof the key secondary endpoint by 30% (HR 0.70, 95% CI 0.48-1.01) in patients with a baselineLDL-C <70 mg/dl, and by 19% (HR 0.81, 95% CI 0.73-0.89) in patients with an LDL-C >70mg/dL, with no evidence for treatment effect modification due to baseline LDL-C (PINT 0.44).There was no heterogeneity for any of the individual outcomes (Supplemental Table 2). Likewisethere was no heterogeneity in the safety profile of evolocumab as a function of baseline LDL-C(Table 1).Patients on maximal intensity statinA total of 7533 (27.3%) of patients were on a maximal intensity statin (baseline characteristics inSupplemental Table 3). The median baseline (IQR) LDL-C was 93 (80-111.5) mg/dL. At 48weeks, the least-squares mean percentage reduction in LDL-C levels with evolocumab, ascompared with placebo, was 58%, for a mean absolute reduction of 57 mg/dL, to a median of 32[20-49] mg/dL. Evolocumab reduced the risk of the primary composite endpoint by 14% (HR0.86, 95% CI 0.75-0.98) in patients on maximal intensity statin therapy, and by 15% (HR 0.85,95% CI 0.78-0.93) in patients treated with sub on maximal statin therapy, with no evidence oftreatment effect modification due to background statin intensity (PINT 0.88, Figure 2). Likewise,evolocumab reduced the risk of the key secondary endpoint by 22% (HR 0.78, 95% CI 0.66-0.92) in patients on maximal intensity statin therapy, and by 19% (HR 0.81, 95% CI 0.72-0.90)in patients on less potent statin regimens, with no evidence for treatment effect modification dueto intensity of background statin therapy (PINT 0.71). There was no heterogeneity for any of theindividual outcomes (Supplemental Table 4). Likewise there was no heterogeneity in the safetyprofile of evolocumab as a function of intensity of background statin therapy (Table 1)DiscussionThe principal findings of this analysis were that high-risk patients with stable atheroscleroticcardiovascular disease who were treated with statins derived similar clinical benefit with theaddition of evolocumab over 2.2 years median follow-up, regardless of whether the baselineLDL-C was below or above 70 mg/dL, and regardless of the intensity of background statin(maximal vs. submaximal). Given the FOURIER entry criteria, the patients enrolled with LDL-C<70 mg/dL were required to have a non-HDL-C >100 mg/dL, thus as expected, these patientswere more likely to have diabetes or metabolic syndrome and on average were younger withmore cardiovascular risk factors.These findings extend prior observations reported with other lipid-lowering therapies. Forstatins, the meta-analysis by the Cholesterol Treatment Trialists Collaboration7 noted consistentbenefit in patient starting with an LDL-C <2 mmol/L or 77 mg/dL, but given the range ofbaseline LDL-C in these trials, very few patients would have had an LDL-C <70 mg/dL. TheJUPITER trial did report consistent benefit of statin therapy in patients starting with an LDL-C≤60 mg/dL, but there were only 511 individuals in that subgroup and the comparator wasplacebo.8 We have recently shown that the addition of ezetimibe to background moderateintensity statin (simvastatin 40 mg) in the IMPROVE-IT trial reduced cardiovascular events by6.4% over an average of 6 years in patients post ACS, with consistent benefit even amongpatients in the lowest quartile of baseline LDL-C (<64 mg/dL)9, however the achieved LDL-C inthat subgroup with the combination of ezetimibe + simvastatin was 45 mg/dL.10 More recently,the HPS3/TIMI55-REVEAL Collaborative Group reported that patients with stableatherosclerotic disease with a mean LDL-C of 61 mg/dL who were randomized to the CETP-inhibitor anacetrapib, reduced LDL-C levels to a mean of 53 mg/dL and experienced an 11%reduction in major coronary events compared to placebo.11 In this analysis we now showconsistent benefit not only when starting with an LDL-C <70 mg/dL, but when it is lowered by66% to a median of 21 mg/dL, with 25% of patients having an LDL-C <11.5 mg/dL.The consistent clinical benefit seen with randomized allocation to lipid-lowering therapythat reduced LDL-C to unprecedented low levels <20 mg/dL supports and extends observationalanalyses that have shown that lower achieved levels of LDL-C were associated with lower ratesof major cardiovascular events, most recently down to this same range of <20 mg/dL.12-14Moreover, prior to FOURIER, no non-statin therapy had shown clinical benefit on a backgroundof maximal statin therapy. Lastly, and equally important, the safety profile of evolocumab wasconsistent regardless of baseline LDL-C or intensity of statin therapy. It is important to note thatall patients in FOURIER were at high-risk and those with an LDL-C <70 mg/dL were required tohave a non-HDL-C >100 mg/dL; whether patients at lower risk or with LDL-C <70 mg/dl andnon-HDL-C levels <100 mg/dL would have similar benefit requires additional studies.ConclusionsEvolocumab safely reduced cardiovascular events in patients with stable atheroscleroticcardiovascular disease to a similar degree whether the baseline LDL-C was above or below 70mg/dL, and regardless of whether the background statin was maximal intensity or not. Thesefindings support using evolocumab beyond what is recommended in current guidelines and,more broadly, the value of lowering LDL-C down to levels ~20 mg/dL15 even in those high-riskpatients starting below current guideline targets or thresholds for treatment.Funding/Support: This FOURIER trial was supported by a research grant from Amgen,Thousand Oaks, CA. No funding was provided for preparation of this manuscript.Role of the Funder/Sponsor: The FOURIER trial was designed, conducted, and managed in acollaborative effort between the FOURIER Executive and Steering Committees, the FOURIERInvestigators, and the sponsor, Amgen. The sponsor played no role in the analysis andinterpretation of the data; preparation, review, or approval of the manuscript; and decision tosubmit the manuscript for publication.Disclaimer: This work is solely the responsibility of the authors.Additional Contributions: We are indebted to all the patients who participated in the study, theFOURIER Trial investigators, and members of the Data Safety Monitoring, Lipid Monitoring,and Clinical Endpoint Committees. For a full list of the Trial Investigators, please see theSupplemental AppendixAccess to Data and Data Analysis: Drs Giugliano and Sabatine had full access to all the data inthe study and take responsibility for the integrity of the data and the accuracy of the dataanalysis.Data Analysis: The data analysis was conducted by Ms. Sabina Murphy of the TIMI StudyGroup, Brigham and Women’s Hospital, Boston, MA.2112121.2132142.2152162172182193.2202212224.2232242252265.2272282296.2302317.2322332348.2352362372389.23924010.24124224311.24424512.24624724813.24925025114.25225325415.255256ReferencesCatapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. European heart journal. 2016;37(39):2999-3058.Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. Journal of the American College of Cardiology.2016;68(1):92-125.Orringer CE, Jacobson TA, Saseen JJ, et al. Update on the use of PCSK9 inhibitors in adults: Recommendations from an Expert Panel of the National Lipid Association. Journal of clinical lipidology. 2017.Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1-45.Sabatine MS, Giugliano RP, Keech A, et al. Rationale and design of the Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk trial. American heart journal. 2016;173:94-101.Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. The New England journal of medicine. 2017;376(18):1713-1722.Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681.Hsia J, MacFadyen JG, Monyak J, Ridker PM. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol <50 mg/dl with rosuvastatin. The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). Journal of the American College of Cardiology. 2011;57(16):1666-1675.Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. The New England journal of medicine. 2015;372(25):2387-2397.Giugliano RP, Cannon CP, Blazing MA, et al. Baseline LDL-C and clinical outcomes with addition of ezetimibe to statin in 18,144 patients post ACS. Journal of the American College of Cardiology. 2015;65(10S):A4.Group HTRC. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. The New England journal of medicine. 2017.Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. Journal of the American College of Cardiology. 2014;64(5):485-494.Giugliano RP, Pedersen TR, Park JG, et al. Clinical efficacy and safety of achieving very low LDL- cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet. 2017.Giugliano RP, Wiviott SD, Blazing MA, et al. Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol : A Prespecified Analysis of the IMPROVE-IT Trial. JAMA Cardiol. 2017;2(5):547-555.Sabatine MS, Giugliano RP. Low-Density Lipoprotein Cholesterol Treatment in the Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Era: Getting Back on Target. JAMA Cardiol. 2017.Table 1: Patient Characteristics Stratified by Baseline LDL-Ca and Background Statin IntensityBaseline LDL-CBaseline Statin IntensityCharacteristics<70 mg/dLb(N=2034)> 70 mg/dL (N=25529)PMaximal (N=7533)Submaximal (N=20031)PAge, mean + SD – yr62.1 + 9.262.5 + 9.00.05161.1 + 8.963.0 +9.0<0.001Weight, mean + SD – kg88.2 + 18.285.0 + 17.2<0.00188.2 + 17.684.2 + 17.2<0.001Male1632 (80.2)19162 (75.1)<0.0015722 (76.0)15073 (75.2)0.22White racec1708 (84.0)21749 (85.2)0.147027 (93.3)16431 (82.0)<0.001Region<0.001<0.001North America348 (17.1)4223 (16.5)1877 (24.9)2694 (13.4)Europe1226 (60.3)16108 (63.1)4862 (64.5)12473 (62.3)Latin America178 (8.8)1645 (6.4)180 (2.4)1643 (8.2)Asia, Pacific, South Africa282 (13.9)3553 (13.9)614 (8.2)3221 (16.1)Type of atherosclerosisdMyocardial infarction1591 (78.2)20759 (81.3)<0.0016499 (86.3)15852 (79.1)<0.001Non-hemorrhagic stroke430 (21.1)4907 (19.2)0.0351182 (15.7)4155 (20.7)<0.001Peripheral artery disease276 (13.6)3366 (13.2)0.621012 (13.4)2630 (13.1)0.51Cardiovascular risk factorsHypertension1673 (82.3)20410 (80.0)0.0126019 (79.9)16065 (80.2)0.57Diabetes mellitus987 (48.5)9093 (35.6)<0.0012536 (33.7)7545 (37.7)<0.001Metabolic syndrome1481 (72.8)14869 (58.2)<0.0014501 (59.8)11850 (59.2)0.38Current cigarette use544 (26.7)7232 (28.3)0.132067 (27.4)5710 (28.5)0.079TIMI Risk Score for secondary prevention eMean + SD, points3.4 + 1.23.3 + 1.2<0.0013.3 + 1.33.3 + 1.20.002Statin intensity at baselinee0.023NAHigh1365 (67.1)17737 (69.5)7533 (100)11570 (57.8)Atorvastatin 80 or rosuvastatin 40 mg524 (25.8)7008 (27.5)0.107533 (100)0Moderate667 (32.8)7725 (30.3)08392 (41.9)Low, unknown, or no data2 (0.1)67 (0.3)069 (0.3)Ezetimibe83 (4.1)1357 (5.3)0.016672 (8.9)768 (3.8)<0.001Other cardiovascular medicationsAspirin, P2Y12 inhibitor, or both1875 (92.2)23556 (92.4)0.777122 (94.6)18310 (91.5)<0.001Beta-blocker1582 (77.8)19232 (75.4)0.0176056 (80.4)14759 (73.8)<0.001Renin-angiotensin-aldosterone inhibitor1626 (79.9)19906 (78.1)0.0476016 (79.9)15517 (77.5)<0.001Median [IQR] lipid measures, mg/dLLDL cholesterol65.5[61.0, 68.0]93.5[82.0. 110.5]NA93.0[80.0, 111.5]91.0[79.5, 107.5]<0.001Total cholesterol141.0[132.0, 152.0]170.0[153.5, 190.5]NA168.0[150.5, 190.5]167.0[151.0, 187.5]0.004HDL cholesterol38.5[32.5. 47.0]44.0[37.5, 52.5]NA43.0[36.5, 51.5]44.0[37.0, 53.0]<0.001Triglycerides181.0[115.0, 252.0]131.0[99.5, 177.0]NA133.0 [98.5,181.0]133.0[100.0, 182.0]0.19LDL C < 70 mg/dL at baseline2034 (100)0NA524 (7.0)1510 (7.5)0.10Baseline LDL-C data were not available for one patient.Maximal statin potency indicates either atorvastatin 80 mg or rosuvastatin 40 mg daily. All other statin regimens were consideredsubmaximal.Date shown are n (%) unless otherwise specifiedaThere were no nominally significant differences between the randomized treatments in either group stratified by baseline LDLcholesterol. There were no nominally significant differences between the randomized treatments in either group stratified by baselinemaximal statin potency except for baseline triglycerides and aspirin use in the submaximal subgroup (both p=0.05).bBy trial design, these patients were required to have a non-HDL-C > 100 mg/dLcRace was reported by the patientsdPatients could have more than one type of atherosclerosiseCalculated as described by Bohula E et al. Circulation 2016;134: 304-13.fStatin intensity was categorized in accordance with the guidelines of the American College of Cardiology and American HeartAssociation4HDL high-density lipoprotein, IQR interquartile range, LDL low-density lipoprotein, NA not applicable, and SD standard deviationSI conversion factors: to convert cholesterol (total, LDL, and HDL) to millimoles per liter, multiply by 0.0259; to convert triglyceridesto millimoles per liter, multiply by 0.0113.Table 2 – Safety Outcomes With Evolocumab vs. Placebo Stratified by Baseline LDL-C and Potency of Background StatinBaseline LDL-C <70 mg/dLa (N=2033)Baseline LDL-C >70 mg/dL (N=25491)OutcomeEvolocumab (N=1030)Placebo (N=1003)Evolocumab (N=12739)Placebo (N=12752)Serious adverse event268 (26.0)274 (27.3)3142 (24.7)3130 (24.5)Adverse event related to study drug and leading to drug discontinuation19 (1.8)19 (1.9)207 (1.6)182 (1.4)Injection site reaction30 (2.9)b16 (1.6)266 (2.1)a203 (1.6)Muscle-related event49 (4.8)60 (6.0)633 (5.0)596 (4.7)Cataract19 (1.8)16 (1.6)209 (1.6)226 (1.8)New onset diabetes, CEC adjudicatedc45/509 (8.8)53/475 (11.2)632/7828 (8.1)591/7864 (7.5)Neurocognitive event17 (1.7)12 (1.2)200 (1.6)190 (1.5)AST or ALT > 3 times normal27 (2.7)23 (2.3)213 (1.7)219 (1.7)Creatine kinase >5 times normal9 (0.9)9 (0.9)86 (0.7)90 (0.7)Maximal Potency Background Statin (N=7524)Submaximal Potency Background Statin (N=20001)Evolocumab (N=3754)Placebo (N=3770)Evolocumab (N=10015)Placebo (N=9986)Serious adverse event979 (26.1)1010 (26.8)2431 (24.3)2394 (24.0)Adverse event related to study drug and leading to drug discontinuation53 (1.4)53 (1.4)173 (3.7)148 (1.5)Injection site reaction84 (2.2)68 (1.8)212 (2.1)a151 (1.5)Muscle-related event207 (5.5)194 (5.1)475 (4.7)462 (4.6)Cataract53 (1.4)64 (1.7)175 (1.7)178 (1.8)New onset diabetes, CEC adjudicatedc214/2385 (9.0)a176/2383 (7.4)463/5952 (7.8)468/5956 (7.9)Neurocognitive event64 (1.7)63 (1.7)153 (1.5)139 (1.4)AST or ALT > 3 times normal84 (2.3)81 (2.2)156 (1.6)161 (1.6)Creatine kinase >5 times normal28 (0.8)33 (0.9)67 (0.7)66 (0.7)Baseline LDL-C is not available for one patient.39 patients who did not receive study drug are excluded.Data shown are n (%), unless otherwise indicated.a By trial design, these patients were required to have a non-HDL-C > 100 mg/dLb Nominal P value <0.05 vs. placeboc Patients with prevalent diabetes were excludedThere were no significant treatment – subgroup interactions for either LDL-C at baseline or potency of background statin.ALT, alanine aminotransferase; AST, aspartate aminotransferaseTo convert LDL-C values from mg/dL to millimoles per liter, multiply by 0.0259.Figure LegendFigure. Efficacy Outcomes Stratified by Baseline LDL-C (Panels A and B) and by statinintensity (Panels C and D). Panel A shows the hazard ratios and 95% confidence intervals at 3years are shown for the primary (cardiovascular death, myocardial infarction, stroke,hospitalization for unstable angina, and coronary revascularization) and the secondary(cardiovascular death, myocardial infarction, and stroke) efficacy composite endpoints in thetotal population and in patients with baseline LDL-cholesterol <70 mg/dL mad with non-HDL-C> 100 mg/dL versus LDL-cholesterol > 70 mg/dL. Evolocumab significantly reduced bothcomposite endpoints to a similar degree regardless of the baseline LDL-cholesterol. Panel Bshows the cumulative event rate of the key secondary endpoint with evolocumab compared withplacebo in patients with baseline LDL-cholesterol <70 mg/dL and non-HDL-C >100 mg/dL.Panel C shows the hazard ratios and 95% confidence intervals at 3 years are shown for theprimary (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina,and coronary revascularization) and the secondary (cardiovascular death, myocardial infarction,and stroke) efficacy composite endpoints in the total population and in patients on patient treatedwith maximal and submaximal background statin therapy. Maximal statin therapy representseither atorvastatin 80 mg or rosuvastatin 40 mg daily. Evolocumab significantly reduced bothcomposite endpoints to a similar degree regardless of the potency of background statin. Panel Dshows the cumulative event rate of the key secondary endpoint with evolocumab compared withplacebo in patients treated with maximal potency statin. To convert LDL-C values from mg/dLto millimoles per liter, multiply by 0.0259.Figure 1Figure 1A. Efficacy Outcomes Stratified by Baseline LDL-CPrimary Composite EndpointHR (95% CI)PinteractionAll Patients0.85 (0.79-0.92)Baseline LDL-C <70 mg/dL0.80 (0.60-1.07)Baseline LDL-C ≥70 mg/dL0.86 (0.79-0.92)0.650.41.02.5Secondary Composite EndpointAll Patients0.80 (0.73-0.88)Baseline LDL-C <70 mg/dL0.70 (0.48-1.01)Baseline LDL-C ≥70 mg/dL0.81 (0.73-0.89)0.440.41.02.5Evolocumab betterPlacebo betterFigure 1B. Cardiovascular Death, Myocardial Infarction, or Stroke in Patients with Baseline LDL Cholesterol <70 mg/dLN=2034Hazard ratio 0.70(95% CI, 0.48-1.01)PlaceboEvolocumab9%8%7.7%7%CV Death, MI, Stroke6%5%5.2%4%3%2%1%0%0612182430Months from RandomizationFigure 1C. Efficacy Outcomes Stratifiedby Potency of Background StatinPrimary Composite EndpointHR (95% CI)PinteractionAll Patients0.85 (0.79-0.92)On maximum intensity statin0.86 (0.75-0.98)On less intense statin0.85 (0.78-0.93)0.880.41.02.5Secondary Composite EndpointAll Patients0.80 (0.73-0.88)On maximum intensity statin0.78 (0.66-0.92)On less intense statin0.81 (0.72-0.90)0.710.41.02.5Evolocumab betterPlacebo betterFigure 1D. Cardiovascular Death, Myocardial Infarction, or Strokein Patients on Maximal Potency Background Statin10%9%8%CV Death, MI, Stroke7%6%8.9%N=7533Hazard ratio 0.78(95% CI, 0.66-0.92)PlaceboEvolocumab6.8%5%4%3%2%1%0%0612182430Months from RandomizationOn-Line Supplement – Table of ContentsList of InvestigatorsTable S1. Efficacy Outcomes With Evolocumab vs. Placebo Stratified by Baseline LDL-CTable S2. Efficacy Outcomes With Evolocumab vs. Placebo Stratified Potency ofBackground StatinList of FOURIER InvestigatorsSteering Committee and National Lead InvestigatorsJose Luis Accini Mendoza (Colombia), John Amerena (Australia), Jolita Badariene (Lithuania),Lesley Burgess (South Africa), Richard Ceska (Czech Republic), Min-Ji Charng (Taiwan),Donghoon Choi (South Korea), Jorge Leonardo Cobos (Chile), Gheorghe Andrei Dan(Romania), Gaetano M. De Ferrari (Italy), Prakash C. Deedwania and Vijay Kumar Chopra(India), Andrejs Erglis (Latvia), Marat Vladislavovich Ezhov (Russia), Jorge Ferreira (Portugal),Slavomíra Filipová (Slovakia), Zbigniew A. Gaciong (Poland), Borislav Georgiev Georgiev(Bulgaria), Robert P. Giugliano (United States), Guillermo Gonzalez-Galvez (Mexico), IoannaGouni-Berthold (Germany), Atsushi Hirayama (Japan), Kurt Huber (Austria), Henrik KjaerulfJensen (Denmark), Lixin Jiang (China), J. Wouter Jukema (Netherlands), Oleg Kraydashenko(Ukraine), Lawrence A. Leiter (Canada), Basil S. Lewis (Israel), José López-Miranda (Spain),Alberto J. Lorenzatti (Argentina), Fran?ois Mach (Switzerland), Brendan McAdam (Ireland),Lennart Nilsson (Sweden), Terje R. Pedersen (Norway), Loukianos Rallidis (Greece), GregorioG. Rogelio (Philippines), José Francisco Kerr Saraiva (Brazil), André Scheen (Belgium),Fran?ois Schiele (France), Peter S. Sever (United Kingdom), Chung-Wah Siu (Hong Kong),Leslie Tay (Singapore), Gudmundur Thorgeirsson (Iceland), Matti J. Tikkanen (Finland), S. LaleTokgozoglu (Turkey), Kalman Toth (Hungary), Margus Viigimaa (Estonia), Wan Azman WanAhmad (Malaysia)Site Investigators by CountryParticipating Enrolling Centers: Included below are representatives from the 1242 enrollingcenters in 49 participating countries. Countries are listed alphabetically. Within each countrycenters are listed in order of enrollment contribution.Argentina:I. Mackinnon, Instituto de Investigaciones Clinicas Mar del Plata, Mar del Plata; D. R. Vogel,Instituto de Investigaciones Clinicas Bahia Blanca, Bahia Blanca; R. Leon de la Fuente, CentroCardiovascular Salta, Salta; E. Perna, Instituto de Cardiologia de Corrientes Juana FranciscaCabral, Corrientes; M. Amuchastegui, Hospital Privado Centro Medico de Cordoba, Cordoba; F.Pacora, Centro Medico Colon, Cordoba; A. Hershson, Fundacion Favaloro, Ciudad Autonoma deBuenos Aires; A. Lorenzatti, Instituto Medico DAMIC - Fundacion Rusculleda, Córdoba; E.Blumberg, Centro de Medicina Integral e Investigacion Clinica Medeos, Ciudad Autonoma deBuenos Aires; J. A. Glenny, Center Clinical and Basic Research, Ciudad Autonoma de BuenosAires; H. Colombo, Clinica Privada Colombo, Cordoba; J. A. Cuadrado, Framingham CentroMedico, La Plata; L. Nicolosi, Hospital Espa?ol de Buenos Aires, Ciudad Autonoma de BuenosAires; C. G. Rojas, Center Clinical and Basic Research, San Miguel de Tucuman; M. R. Ulla,Instituto Latinoamericano de Investigaciones Medicas, Cordoba; E. G. Hasbani, InvestigacionesClinicas Tucuman, San Miguel de Tucuman; C. Cuneo, Cardiomed, Salta; R. G. Lopez Santi,Fundacion Ciclo, La Plata; H. D. Sanabria, Centro de Osteopatias Medicas, Ciudad Autonoma deBuenos Aires; A. Hrabar, Instituto de Investigaciones Clinicas Quilmes Sociedad deResponsabilidad Limitada, Quilmes; A. Lozada, Fundacion para la Lucha contra lasEnfermedades Neurologicas de la Infancia, Ciudad Autonoma de Buenos Aires.Australia:A. Begg, SA Heart, Ashford, SA; S. Lehman, Adelaide Medical Research, Ashford, SA; G.Wittert, Royal Adelaide Hospital, Adelaide, SA; C. Juergens, Liverpool Hospital, Liverpool,NSW; K. Kostner, Dr Heart Pty Ltd, Woolloongabba, QLD; J. Beltrame, The Queen ElizabethHospital, Woodville South, SA; J. Amerena, Barwon Health Geelong Hospital, Geelong, VIC; R.Simpson, C. Gilfillan, S. L. Goh, J. Y. Mah, Eastern Health, Box Hill Hospital, Box Hill, VIC;A. Sinhal, Heart and Vascular Institute, Fullarton, SA; M. Adams, Royal Prince Alfred Hospital,Camperdown, NSW; L. Kritharides, Concord Repatriation General Hospital, Concord, NSW; P.Roberts Thomson, Royal Hobart Hospital, Hobart, TAS; D. Cross, HeartCare Partners,Auchenflower, QLD; P. Thompson, Sir Charles Gairdner Hospital, Nedlands, WA; W. VanGaal, The Northern Hospital, Epping, VIC; N. Cox, Footscray Hospital, Footscray, VIC; A.Farshid, Canberra Hospital, Woden, ACT; C. Hammett, Royal Brisbane and Womens Hospital,Herston, QLD; P. Garrahy, Princess Alexandra Hospital, Woolloongabba, NSW; A. Prasan, StGeorge Hospital, Kogarah, NSW; M. Horrigan, Austin Health, Austin Hospital, Heidelberg,VIC.Austria:C. Ebenbichler, Medizinische Universitaet Innsbruck, Innsbruck; U. Hanusch, Zentrum fuerklinische Studien - Dr. Hanusch GmbH, Wien; R. Prager, Krankenhaus Hietzing mitNeurologischem Zentrum Rosenhuegel, Wien; G. Schernthaner, Medizinische UniversitaetWien, Wien; A. Luger, Medizinische Universitaet Wien, Wien; P. Siostrzonek, Krankenhaus derBarmherzigen Schwestern Linz, Linz; H. Toplak, Medizinische Universitaet Graz, Graz; J.Bergler-Klein, Medizinische Universitaet Wien, Wien; K. Huber, Wilhelminenspital der StadtWien, Wien; B. Paulweber, Landeskrankenhaus Salzburg, Salzburg; M. Rammer, KlinikumWels Grieskirchen GmbH, Wels; H. Sinzinger, Institut Athos, Wien.Belgium:I. Buysschaert, Algemeen Stedelijk Ziekenhuis Aalst, Aalst; J. Thoeng, Algemeen ZiekenhuisTurnhout, Turnhout; A. Scheen, Centre Hospitalier Universitaire de Liege - Sart Tilman, Liege;H. Vandekerckhove, Algemeen Ziekenhuis Sint Lucas, Gent; E. Catez, Centre HospitalierUniversitaire Brugmann, Brussels; S. Verheye, Ziekenhuis Netwerk Antwerpen Middelheim,Antwerpen; O. Descamps, Centres Hospitaliers Jolimont - Hopital de Jolimont, La Louvière; E.Hoffer, Centre Hospitalier Regional de la Citadelle, Liège; B. Wollaert, Ziekenhuis NetwerkAntwerpen Stuivenberg, Antwerpen; P. Chenu, Universite Catholique de Louvain CliniquesUniversitaires Saint Luc, Bruxelles; P. van de Borne, Cliniques universitaires de BruxellesHopital Erasme, Brussels; M. De Meulemeester, Medif sprl, Gozee; A. Friart, Centre HospitalierUniversitaire de Tivoli, La Louviere; F. Charlier, Imelda Ziekenhuis vzw, Bonheiden; H. DeRaedt, Onze Lieve Vrouw Ziekenhuis Aalst, Aalst; E. Rietzschel, Universitair Ziekenhuis Gent,Gent; R. Roelandt, Jan Yperman Ziekenhuis, Ieper; J. Lalmand, Centre Hospitalier Universitairede Charleroi - H?pital Civil Marie Curie, Lodelinsart.Brazil:L. A. Tavares Russo, Center for Clinical and Basic Research Brasil, Rio De Janeiro; J. F. K.Saraiva, Hospital e Maternidade Celso Pierro, Campinas; G. Reis, Cardresearch CardiologiaAssistencial de Pesquisa, Belo Horizonte; E. C. Duarte Barbosa, Associacao Hospitalar Moinhosde Vento, Porto Alegre; M. H. Vidotti, Centro Especializado em Cardiologia, Campinas; E. R.Fernandes Manenti, Hospital Mae de Deus, Porto Alegre; O. Dutra, Instituto de Cardiologia doRio Grande do Sul, Porto Alegre; P. E. Leaes, Irmandade da Santa Casa de Misericordia de PortoAlegre, Porto Alegre; R. L. Rech, Hospital Universitario Mae de Deus, Canoas; D. BertolimPrecoma, Sociedade Hospitalar Angelina Caron, Campina Grande do Sul; J. C. Nicolau, Institutodo Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo,S?o Paulo; R. Amoedo, Centro Paulista de Investigacoes Clinicas Cepic, S?o Paulo; F. G.Eliaschewitz, Centro de Pesquisas Clinicas Cpclin, Sao Paulo; A. Pereira, Hospital de Clinicasde Porto Alegre, Porto Alegre; H. R. Kurtz Lisboa, Hospital Sao Vicente de Paulo, Passo Fundo;L. Soares Piegas, Hospital do Coracao, Sao Paulo; J. L. Cunha Borges, Centro de PesquisaClinica do Brasil, Brasília; P. R. Ferreira Rossi, Nucleo de Pesquisa Clinica, Curitiba; P.Pimentel Filho, Hospital Nossa Senhora da Conceicao, Porto Alegre; L. C. Bodanese, HospitalSao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre; R. de SaCunha, Hospital Universitario Cassiano Antonio Moraes, Vitória; J. C. Moura Jorge, Irmandadeda Santa Casa de Misericordia de Curitiba, Curitiba; W. R. Ardito, Instituto de MolestiasCardiovasculares, Sao Jose do Rio Preto; W. K. Barroso de Souza, Via Medica Centro Clinico,Goiania; M. Hissa, Centro de Pesquisas em Diabetes e Doencas Endocrino Metabolicas,Fortaleza; M. C. Izar, Hospital Sao Paulo Universidade Federal de Sao Paulo, S?o Paulo.Bulgaria:A. Manolova, Multiprofile Hospital for Active Treatment - Haskovo AD, Haskovo; L. Kitova,University Multiprofile Hospital for Active Treatment Sveti Georgi Ltd, Plovdiv; E. Kinova,University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD, Sofia; M.Tzekova, University Multiprofile Hospital for Active Treatment Dr Georgi Stranski EAD,Pleven; B. Georgiev, Multiprofile Hospital for Active Treatment National Heart Hospital EAD,Sofia; V. Velchev, Diagnostic-Consultative Center Sveta Anna EOOD, Sofia; R. Tarnovska-Kadreva, University Multiprofile Hospital for Active Treatment Alexandrovska EAD, Sofia; D.Gotchev, Military Medical Academy - Multiprofile Hospital for Active Treatment Sofia, Sofia; I.Petrov, City Clinic University Multiprofile Hospital for Acute Care EOOD, Sofia; D. Raev,University Multiprofile Hospital for Active Treatment, Sveta Anna, Sofia; D. Trendafilova-Lazarova, University Multiprofile Hospital for Active Treatment Sveta Ekaterina EAD, Sofia; Y.Yotov, Multiprofile Hospital for Active Treatment Sveta Marina EAD, Varna; P. Lazov,Multiprofile Hospital for Active Treatment Pazardzhik JSK, Pazardzhik.Canada:S. Rahimi, Multiprofile Hospital for Active Treatment Dr Hristo Stambolski Ltd, Kazanlak; E. StAmour, Q and T Recherche Outaouais Incorporated, Gatineau, QC; C. Constance, CliniqueSante Cardio MC, Montreal, QC; Y. Pesant, St Jerome Medical Research Incorporated, St-Jér?me, QC; A. Hess, Newmarket Cardiology Research Group, Newmarket, ON; T. Anderson,University of Calgary Health Sciences Centre, Foothills Campus, Calgary, AB; B. Sussex,Health Sciences Centre-Eastern Health, St. Johns, NL; S. Henein, SKDS Research Incorporated,Newmarket, ON; G. Tsoukas, Applied Medical Informatics Research, Westmout, QC; A. S.Pandey, Cambridge Cardiac Care Centre, Cambridge, ON; J. Bergeron, Clinique des MaladiesLipidiques de Quebec Incorporated, Quebec, QC; R. Hart, White Hills Medical Clinic, St.John’s, NL; G. Gosselin, Centre Integre de Sante et de Services Sociaux de Lanaudiere - H?pitalPierre-Le Gardeur, Terrebonne, QC; R. Chehayeb, ViaCar Recherche Clinique Incorporated,Greenfield Park, QC; P. Hamet, Clinique de recherché Medpharmgene, Montreal, QC; M.Hartleib, Kawartha Cardiology Clinical Trials, Peterborough, ON; A. Mukherjee, ScarboroughCardiology Research, Scarborough, ON; F. Halperin, Medical Arts Health Research Group adivision of PCT Networks, Kelowna, BC; R. Petrella, Western Centre for Public Health andFamily Medicine - Western University, London, ON; R. Bhargava, Heart Care Canada, Oshawa,ON; E. Lonn, Hamilton Health Sciences Hamilton General Hospital, Hamilton, ON; E. Sabbah,Le Centre de Depistage et de Recherche Cardiovasculaire Rive-Sud, Longueuil, QC; I. Bata,Queen Elizabeth II Health Sciences Centre, Halifax Infirmary, Halifax, NS; J. Cha, Dr JamesCha, Oshawa, ON; D. Gaudet, Ecogene-21, Chicoutimi, QC; K. Chapman, Inspiration ResearchLimited, Toronto, ON; D. Murthy, Regina General Hospital Regina Qu Appelle Health Region,Regina, SK; F. Nigro, Thunder Bay Regional Research Institute, Thunder Bay, ON; D. Rupka,Fraser Clinical Trials, New Westminster, BC; D. Gossard, CardioVasc HR Incorporated, St Jeansur Richelieu, QC; M. Gupta, Brampton Research Associates, Brampton, ON; A. Dowell,Dynamik Research Incorporated, Pointe-Claire, QC; S. Mansour, Centre Hospitalier Universitede Montreal- Hotel Dieu, Montreal, QC; A. Baass, McGill University Health Center Glen Site,Montreal, QC; C. Geadah, Recherches Cliniques Theradev, Granby, QC; T. Huynh, McGillUniversity Health Centre - Montreal General Hospital, Montreal, QC; S. Peterson, SarniaInstitute of Clinical Research, Sarnia, ON; P. Poirier, Institut Universitaire de cardiologie et depneumologie de Quebec, Québec, QC; G. Sabe-Affaki, Medialpha Research Centre, Lachine,QC; G. Vertes, Scarborough General Hospital Cardiology Research Associates, Scarborough,ON; D. Crowley, DCTM Clinical Trials Group Limited, Strathroy, ON; L. Duchesne, Universityof Ottawa Heart Institute, Ottawa, ON.Chile:J. L. Cobos Segarra, Cardiocob, Santiago; C. P. Pincetti Jofre, Centro de Investigacion Clinicadel Sur, Temuco; S. Potthoff Cardenas, Corporacion de Beneficiencia Osorno Clinica Alemana,Osorno; C. Conejeros Kindel, Sociedad Medica Cardiologica El Llano, Santiago; V. A. SaavedraGajardo, Center for Clinical and Basic Research Chile, Santiago; F. Lanas Zanetti, Centro deEstudios Cardiovasculares, Temuco; P. A. Sepulveda Varela, Clinica Tabancura, Santiago; B. A.Stockins Fernandez, Centro de Investigacion Medica Stockins y Larenas, Temuco.China:W. Li, The First Affiliated Hospital of Harbin Medical University, Harbin; D. Li, The AffiliatedHospital of Xuzhou Medical College, Xuzhou; S. Zhao, The Central Hospital of Wuhan, Wuhan;Z. Li, The Peoples Hospital of Liaoning Province, Shenyang; J. Wang, Siping City CenterPeoples Hospital, Siping; Y. Yang, Chinese Medical Science Academy Fuwai Hospital, Beijing;L. Zhang, The First Affiliated Hospital of Harbin Medical University, Harbin; P. Yang, China-Japan Union Hospital of Jilin University, Changchun; X. Zhang, Jilin Province Peoples Hospital,Changchun; H. Huang, Xiangtan Central Hospital, Xiangtan; L. Xue, The General Hospital ofNingxia Medical University, Yinchuan; Z. Zheng, Chinese Medical Science Academy FuwaiHospital, Beijing; W. Huang, The First Affiliated Hospital of Wenzhou Medical University,Wenzhou; H. Dai, Changsha Central Hospital, Changsha; W. Li, Tai Yuan City centre hospital,Taiyuan; H. Su, Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine,Hohhot; X. Zeng, Wuhan Puai Hospital, Wuhan; Y. Zheng, The First Hospital of JilinUniversity, Changchun; Y. Tang, Chinese Medical Science Academy Fuwai Hospital, Beijing; Z.Yao, Tianjin Peoples Hospital, Tianjin; Y. Sun, Tianjin Medical University General Hospital,Tianjin; Y. Du, Jilin Province Peoples Hospital, Changchun; Z. Ge, Inner Mongolia BaogangHospital, Baotou; J. Yan, Zhejiang Hospital, Hangzhou; X. Chen, Tai Yuan City centre hospital,Taiyuan; F. Liu, Suzhou Kowloon Hospital,Shanghai Jiaotong University school of medicine,Suzhou; H. Pei, The Affiliated Hospital of Qingdao University, Qingdao; X. Yang, BeijingChao-Yang Hospital, Capital Medical University, Beijing; H. Cui, Ningbo First Hospital,Ningbo; Y. Gu, Wuhan Puai Hospital, Wuhan; Z. Yang, Wuxi Peoples Hospital, Wuxi; J. Li,Chinese Medical Science Academy Fuwai Hospital, Beijing; Y. Lian, The First AffiliatedHospital of Zhengzhou University, Zhengzhou; Y. Cui, The First Automobile Works Hospital,Changchun; Z. Li, Peking University Third Hospital, Beijing; D. Wang, Inner MongoliaBaogang Hospital, Baotou; J. Jiang, Taizhou Hospital of Zhejiang Province, Linhai; X. Li, TheSecond Hospital of Tianjin Medical University, Tianjin; J. Chen, Guangdong General Hospital,Guangzhou; Z. Mo, The Third Xiangya Hospital of Central South University, Changsha; P. Xu,The First Peoples Hospital of Changde, Changde; Y. He, Zhuzhou Central Hospital, Zhuzhou; C.Zhou, The Affiliated Hospital of Qingdao University, Qingdao; P. Qu, The Second Hospital ofDalian Medical University, Dalian; Y. Zhu, The Second Affiliated Hospital of Harbin MedicalUniversity, Harbin; Y. Liu, Xiangya Hospital Central South University, Changsha; X. Shen, TheAffiliated Hospital of Xuzhou Medical College, Xuzhou; Y. Yang, The First Affiliated Hospitalof Xinjiang Medical University, Urumqi; X. Gao, The People's Hospital Of Hunan Province,Changsha.Colombia:M. A. Terront Lozano, Center for Clinical and Basic Research Colombia, Bogota; M. A.Moncada Corredor, Center for Clinical and Basic Research Colombia, Medellin; E. HernandezTriana, Endocare, Bogota; J. L. Accini Mendoza, Instituicion Prestadora de Salud CentroCientifico Asistencial Jose Luis Accini SAS, Barranquilla; R. Botero Lopez, Rodrigo BoteroSAS, Medellin; J. A. Coronel Arroyo, Centro Medico Julian Coronel, Santiago de Cali; A. E.Quintero Baiz, Fundacion del Caribe para la Investigacion Biomedica, Barranquilla; G. SanchezVallejo, Fundacion Cardiomet Eje Cafetero Cequin, Armenia; C. Arana Londo?o, Centro deInvestigaciones Clinicas SAS, Santiago de Cali; D. I. Molina de Salazar, Asociacion InstituicionPrestadora de Salud Medicos Internistas de Caldas, Manizales; R. Castellanos Bueno, FundacionOftalmologica de Santander Foscal, Floridablanca; F. Manzur Jattin, Centro de DiagnosticoCardiologico, Cartagena; C. A. Cure Cure, Biomelab, Barranquilla; A. Sotomayor Herazo,Centro Cardiovascular Aristides Sotomayor Santa Lucia SAS, Cartagena.Czech Republic:J. Spinar, Fakultni nemocnice Brno, Brno; T. Hala, Center for Clinical and Basic ResearchPardubice, as, Pardubice; M. Machkova, CCBR Czech Prague sro, Praha 3; Z. Klimsa,Nemocnice Jihlava po, Jihlava; R. Polasek, Krajska nemocnice Liberec as, Liberec; O. Jerabek,Poliklinika Ravak Pribram, Pribram VIII; P. Kazdera, Nemocnice Znojmo, po, Znojmo; Z.Pozdisek, Pozdisek sro, Kardiologicka ambulance, Mohelnice; J. Vaclavik, Kardio Vaclavik sro,Interni a kardiologicka ambulance, Prerov; P. Frana, Centrum pro zdravi sro, Brno; L. Elbl, profMUDr Lubomir Elbl, CSc, Kardiologicka ambulance, Brno; D. Kucera, Kardiologicka aangiologicka ambulance, Ostrava - Zabreh; R. Kryza, Mestska nemocnice Ostrava, Ostrava; J.Malecha, Ordinace pro choroby srdce sro, Chomutov; P. Reichert, AeskuLab ks, Lipidovaporadna, Teplice; K. Sochor, Jessenia as, Nemocnice Beroun, Beroun; O. Ludka, MUDr KarelKamenik sro, Privatni kardiologicka ambulance, Brno; I. Kellnerova, Nemocnice Pardubickehokraje as, Svitavska nemocnice, Svitavy; R. Ceska, Vseobecna fakultni nemocnice v Praze, Praha2; K. Peterka, Nemocnice Havlickuv Brod, Havlickuv Brod; E. Zidkova, Interni a kardiologickaordinace, Praha 5; V. Cech, Clinical Trials Service sro, Uherske Hradiste; T. Brabec, Vojenskanemocnice Brno, Brno; N. Fiserova, Center for Clinical and Basic Research Czech Brno sro,Brno; J. Kvasnicka, Ordinace pro choroby srdce a cev, Praha 10; H. Rosolova, Fakultninemocnice Plzen, Plzen; E. Nemecek, Vseobecna fakultni nemocnice v Praze, Praha 2; V.Adamkova, Institut klinicke a experimentalni mediciny, Praha 4; M. Dunaj, NemocnicePardubickeho kraje as, Litomyslska nemocnice, Litomysl; S. Pojsl, Mestska nemocnice vLitomericich, Litomerice; M. Cepelak, Kardio Michal Cepelak sro, Klatovy IV; I. Podpera,Oblastni nemocnice Kladno as, Kladno; L. Kuchar, Vseobecna intermi ambulance sro, Milevsko;D. Rysava, Oblastni nemocnice Kolin as, nemocnice Stredoceskeho kraje, Nemocnice KutnaHora, Kutna Hora; H. Burianova, Interni a kardiologicka ambulance, Bilovec; L. Spinarova,Fakultni nemocnice u sv Anny v Brne, Brno; J. Skrobakova, Kardiologicke centrum MUDrJanky Skrobakove sro, Praha 5 - Smichov; J. Charvat, Fakultni nemocnice v Motole, Praha 5; M.Homza, Benedor sro - Kardiologicka, cevni a interni ambulance, Ostrava-Poruba; J. Zemanek,Poliklinika Moravske Budejovice sro, Moravske Budejovice; P. Koleckar, Policska nemocnicesro, Policka; I. Karen, MUDr Igor Karen, Benatky nad Jizerou; J. Krupicka, Medicus Servicessro, Brandys nad Labem; V. Blaha, MUDr Ladislava Harrerova, kardiologicka ordinace, HradecKralove; J. Matuska, Clinical Trial Center Hodonin sro, Hodonin; J. Brotanek, Thomayerovanemocnice, Praha 4; R. Cifkova, Thomayerova nemocnice, Praha 4; R. Kuchar, Innera sro,Benesov; Z. Vomacka, MUDr Zdenek Vomacka, kardiologie a interna sro, Olomouc; Z. Kosek,MUDr Zbynek Kosek, kardiologicka ambulance sro, Mlada Boleslav; V. Hulinsky, NemocniceNymburk sro, Nymburk; H. Krejcova, Kardiologicka ambulance, Prachatice; J. Kuchar,Kardiologie Cesky Krumlov, Cesky Krumlov; Z. Jelinek, Nemocnice Hranice as, Hranice naMorave; P. Jelinek, Kardio LPV ambulance sro, Ceske Budejovice.Denmark:L. Markdanner Lindgren, Centre for Clinical and Basic Research Ballerup, Ballerup; A. SaetreLihn, Center for Clinical and Basic Research Aalborg, Aalborg; K. Korsgaard Thomsen,Sydvestjysk Sygehus, Esbjerg; S. Wermuth, Center for Clinical and Basic Research Vejle, Vejle;H. Kjaerulf Jensen, Aarhus Universitetshospital, Skejby, Aarhus N; J. Bronnum-Schou, AmagerHospital, K?benhavn S; H. Nielsen, Bispebjerg Hospital, K?benhavn; T. Nielsen, SjaellandsUniversitetshospital Koge, K?ge; K. Egstrup, Svendborg Sygehus, Svendborg; I. C. Klausen,Regionshospitalet Viborg, Viborg; H. Mickley, Odense Universitetssygehus, Odense; J. Hove,Hvidovre Hospital, Hvidovre; J. Jeppesen, Glostrup Hospital, Glostrup; T. Melchior, SjaellandsUniversitetshospital, Roskilde, Roskilde; E. B. Schmidt, Aalborg Hospital, Aalborg.Estonia:I. Valter, Center for Clinical and Basic Research Tallinn, Tallinn; A. Rosenthal, Dr ArvoRosenthal LLC, Tallinn; J. Kaik, Fertilitas, Harjumaa; A. Kork, East Tallinn Central Hospital,Tallinn; I. Alt, Vee Perearstikeskus, Paide; M. Viigimaa, North Estonia Medical CentreFoundation, Tallinn.Finland:J. Strand, Terveystalo Oulu, Diapolis, Oulu; S. Nieminen, IteLasaretti, Kuopio; J. Kahri,Helsingin ja Uudenmaan sairaanhoitopiiri - HUS, Helsinki; J. Suomi, Terveystalo Pulssi, Turku;K. Nyman, Terveystalo Jyvaskyla, Jyv?skyl?; T. E. Strandberg, Geri-Med, Helsinki; T. Piippo,Tampereen L??k?rikeskus Oy, Tampere; M. Savolainen, Oulu University Hospital, Oulo; S.Vikman, Tampereen yliopistollinen sairaala, Tampere.France:F. Schiele, Centre Hospitalier Regional Universitaire de Besancon, Hopital Jean Minjoz, 604Besan?on Cedex; Y. Pucheu, Centre Hospitalier Universitaire de Bordeaux, Hopital Haut- 605Leveque, Pessac Cedex; B. Cariou, Centre Hospitalier Universitaire de Nantes - Hopital606 Guillaume et Rene Laennec, Nantes Cedex 1; P. Henry, Hopital Lariboisiere, Paris; E. Ferrari, 607 Center Hospitalier Universitaire de Nice - Hopital Pasteur, Nice; G. Montalescot, P. Sabouret, 608 Hopital Pitie-Salpetriere, Paris; J. Ferrieres, M. Elbaz, M. Galinier, Centre Hospitalier609 Universitaire de Toulouse - Hopital Rangueil, Toulouse Cedex 9; F. Roubille, Centre Hospitalier 610 Regional Universitaire de Montpellier - Hopital Arnaud de Villeneuve, Montpellier cedex 05; B. 611 Bonnet, Centre Hospitalier Intercommunal Haute Saone, Vesoul; D. Angoulvant, Centre612Hospitalier Régional Universitaire de Tours - H?pital Trousseau, Chambray les Tours; G. Range, 613Hopital Louis Pasteur, Le Coudray; A. Bammert, Nouvelles Cliniques Nantaises, Nantes Cedex 6142; N. Delarche, Centre Hospitalier de Pau - Hopital Francois Mitterrand, Pau; C. Mariat, Centre 615Hospitalier Universitaire Nord de Saint Etienne - Hopital Nord, Saint Priest en Jarez; G. Cayla, 616Centre Hospitalier Universitaire de Nimes, Nimes; V. Durlach, Centre Hospitalier Universitaire 617de Reims - Hopital Robert Debre, Reims cedex; D. Coisne, Centre Hospitalier Universitaire de 618Poitiers, Poitiers; F. Paillard, Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou, 619Rennes; R. Rouzier, Centre Cap, Montpellier cedex 5; M. Goralski, Centre Hospitalier Regional 620d'Orleans - Hopital de la Source, Orleans; P. Khanoyan, Hopital Saint-Joseph, Marseille Cedex 62108; Y. Cottin, Centre Hospitalier Universitaire de Dijon - Hopital du Bocage, Dijon cedex; O.622Ziegler, T. Delmas, Centre Hospitalier Universitaire de Nancy - H?pital de Brabois,623Vandoeuvre les Nancy; K. Khalife, Centre Hospitalier Regional Metz Thionville - Hopital de624Mercy, Metz cedex 03; P. Le Corvoisier, Hopital Henri Mondor, Créteil; P. Motreff, Hopital625Gabriel Montpied, Clermont Ferrand; C. Spaulding, H?pital Européen Georges Pompidou, Paris; 626E. VanBelle, Centre Hospitalier Regional Universitaire de Lille - Hopital Cardiologique, Lille 627Cedex.628629Germany:630H. Bourhaial, Sankt-Johannes-Hospital, Dortmund; C. Opitz, Deutsches Rotes Kreuz Kliniken 631Berlin K?penick, Berlin; G. Kahrmann, Forschungszentrum Ruhr, Witten; C. Contzen, Synexus 632Clinical Research GmbH, Frankfurt am Main; K. Appel, Studienzentrum Dr Appel, Kassel; I.633Schenkenberger, Klinische Forschung Berlin GbR, Berlin; A. Rinke, Synexus Clinical Research634GmbH, Bochum; D. Trenk, Universitaets-Herzzentrum Freiburg - Bad Krozingen, Bad635Krozingen; I. Gouni-Berthold, Universit?tsklinikum K?ln, K?ln; O. Maus, Synexus Clinical636Research GmbH, Leipzig; M. Karakas, Universit?tsklinikum Hamburg-Eppendorf, Hamburg; M. 637Hanefeld, Gesellschaft f Wissens u Technologietransfer der Tech Uni Dresden Studienzentrum 638Prof Hanefeld, Dresden; H. Darius, Vivantes Klinikum Neuk?lln, Berlin; T. G. Sch?ufele,639Robert Bosch Krankenhaus, Stuttgart; G. Hetzel, DaVita Clinical Research Deutschland,640Düsseldorf; T. Münzel, Johannes Gutenberg Universit?t Mainz, Mainz; J. W?hrle,641Universit?tsklinikum Ulm, Ulm; P. Stawowy, Deutsches Herzzentrum Berlin, Berlin; I. Marten,642Klinische Forschung Hannover-Mitte GmbH, Hannover; B. Isermann, Otto von Guericke 643Universit?t Magdeburg, Magdeburg; P. Kast, Asklepios Klinik Sankt Georg, Hamburg; M. 644Vorpahl, Helios Universit?tsklinikum Wuppertal, Wuppertal; P. Bosiljanoff, Herz-Gef??- 645Zentrum Nymphenburg am Klinikum Dritter Orden, München; C. Hengstenberg, Deutsches 646Herzzentrum München des Freistaates Bayern, München; U. Kassner, Charite647Universit?tsmedizin Berlin, Charité Campus Virchow-Klinikum, Berlin; P. Salbach, zero Praxen648GbR, Mannheim; M. Fischer, Universit?tsklinikum Regensburg, Regensburg; S. Steiner, Sankt649Vincenz-Krankenhaus, Limburg; S. Wagner, Georg-Haas-Dialysezentrum, Giessen; U. Kraatz, 650Praxis Dr Kraatz, Demmin; E. von Hodenberg, MediClin Herzzentrum Lahr-Baden, Lahr; K. 651Weyland, Praxis für Allgemeinmedizin Dr Klaus Weyland, Ingelheim.652Greece:I. Mantas, General Hospital of Chalkida, Chalkida; D. Tziakas, G. Chalikias, UniversityHospital of Alexandroupolis, Alexandroupoli; S. Bousboulas, S. Pappas, General Hospital ofNikaia Piraeus Agios Panteleimon, Nikaia, Piraeus; S. Patsilinakos, Konstantopoulio - Agia OlgaHospital of Nea Ionia, Athens; G. Mertzanos, D. Babalis, General Hospital of Attica KAT,Athens; C. Panagoulis, General Hospital of Athens Georgios Gennimatas, Athens; H. Bilianou,Tzaneio General Hospital, Piraeus; I. Skoumas, C. Pitsavos, General Hospital of AthensIppokrateio, Athens; M. Elisaf, E. Liberopoulos, University Hospital of Ioannina, Ioannina; A. 661Manolis, General Hospital Asklipieio Voulas, Athens; N. Moschos, General Hospital of Rhodes, 662Rhodes; L. Rallidis, Attikon Hospital, Athens; G. Kochiadakis, University Hospital of Heraklion, 663Heraklion; G. Ntaios, G. Dalekos, University Hospital of Larissa, Larissa; D. Richter, Athens 664Euroclinic, Athens; V. Athyros, Ippokrateio Hospital of Thessaloniki, Thessaloniki; G. Kolovou, 665Onassis Cardiac Surgery Center, Athens; P. Danias, Hygeia Hospital, Athens; A. Melidonis,666Tzaneio General Hospital, Piraeus.667668Hong Kong:669C. W. D. Siu, University of Hong Kong, Queen Mary Hospital, Hong Kong; K. Y. Y. Fan,670Grantham Hospital, Hong Kong; S. C. Siu, Tung Wah Eastern Hospital, Hong Kong.671Page 12 of 57672Hungary:A. Hornyik, CRU Hungary Kft, Miskolc; F. Lakatos, Dr Lakatos Ferenc Private CardiologyPractice, Bekescsaba; Z. Zilahi, Medifarma 98 Kft, Nyiregyhaza; K. Nagy, SynexusMagyarorszag Kft, Budapest; Z. Laszlo, Szent Janos Korhaz es Eszak-budai EgyesitettKorhazak, Budapest; E. Peterfai, Drug Research Center Kft, Balatonfured; G. Lupkovics, ZalaMegyei Szent Rafael Korhaz, Zalaegerszeg; P. Andreka, Gottsegen Gyorgy OrszagosKardiologiai Intezet, Budapest; B. Merkely, Semmelweis Egyetem, Budapest; B. Herczeg, Jasz- 680Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet, Szolnok; G. A. Piros, Szegedi 681Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont Altalanos Orvostudomanyi Kar, 682Szeged; C. Salamon, Clinfan Kft, Szekszard; L. Mark, Bekes Megyei Kozponti Korhaz Pandy 683Kalman Tagkorhaz, Gyula; A. Papp, Szent Rokus Korhaz es Intezmenyei, Budapest; I. Szakal, 684Selye Janos Korhaz, Komarom; K. Toth, Pecsi Tudomanyegyetem Klinikai Kozpont, Pecs; A. 685Papp, Grof Tisza Istvan Korhaz, Berettyoujfalu; I. Edes, Debreceni Egyetem Klinikai Kozpont, 686Debrecen; A. Mohacsi, Pharma4 Trial Kft, Gyongyos; J. Tomcsanyi, Betegapolo Irgalmas Rend 687- Budai Irgalmasrendi Korhaz, Budapest; E. Hajko, Toldy Ferenc Korhaz-Rendelointezet,688Cegled; A. Nagy, Bacs-Kiskun Megyei Korhaz, Kecskemet; E. Papp, Somogy Megyei Kaposi 689Mor Oktato Korhaz, Kaposvar; R. Kiss, Magyar Honvedseg Egeszsegugyi Kozpont, Budapest; I. 690Karadi, Semmelweis Egyetem, Budapest.691692Iceland:693G. Thorgeirsson, Landspitali National University Hospital, Reykjavik; A. Sigurdsson,694Hjartamidstodin, Kopavogur.695696India:697A. Jain, Shah Alloys Limited Hospital and Medical Institute, Ahmedabad; R. Pai, Oyster and 698Pearl Hospital, Pune; V. Kothiwale, Karnataka Lingayat Education Societys Dr Prabhakar Kore 699Hospital & Medical Research Centre, Belgaum; G. Kulkarni, Shree Hospital, Pune; A. Mahajan, 700Lokmanya Tilak Muncipal General Hospital, Mumbai; S. Aggarwal, Maulana Azad Medical 701College, New Delhi; V. Mehta, Govind Ballabh Pant Hospital, New Delhi; G. Rajadhyaksha, 702Topiwala National Medical College and B Y L Nair Charitable Hospital, Mumbai; V. Chopra, 703Medanta MediCity, Gurgaon; A. Joshi, Niramaya Hospital Private Limited, Pune; V. Khandait, 704Government Medical College and Hospital, Nagpur; M. Parmar, Shree Sayaji General Hospital 705and Baroda Medical College, Vadodara; S. Tyagi, AMC MET Medical College and Seth L G 706General Hospital, Ahmedabad; R. Airody Govinda, Mysore Mdical College and Research707Institute, Mysore; S. K. Dwivedi, King Georges Medical University, Lucknow; K. Parikh, Care708Institute Of Medical Sciences, Ahmedabad; R. B. Pothineni, Dr Ramesh Cardiac and709Multispeciality Hospital Private Limited, Vijayawada; B. Solanki, B J Medical College and Civil710Hospital, Ahmedabad.711712Ireland:713B. McAdam, Beaumont Hospital, Dublin; M. O’Donnell, National University of Ireland, 714Galway; P. Crean, St James Hospital, Dublin; J. Barton, Portiuncula Hospital, Galway. 715716Israel:717M. Shechter, Sheba Medical Center, Tel Hashomer; B. Lewis, The Lady Davis Carmel Medical 718Center, Haifa; A. Shotan, Hillel Yaffe Medical Center, Hadera; M. Klutstein, Shaare Zedek, 719Jerusalem; E. Chorin, Tel-Aviv Sourasky Medical Center, Tel Aviv; D. Gavish, Wolfson720Medical Center, Holon; O. Kracoff, Kaplan Medical Center, Rehovot; S. Atar, Western Galilee721Hospital, Nahariya; S. Rigler, Clalit Health Services, Netanya; Y. Hasin, Herzliya Medical722Center, Herzliya-on-sea; E. Schiff, Bnai-Zion Medical Center, Haifa.723724Italy:725G. M. De Ferrari, Fondazione IRCCS Policlinico San Matteo, Pavia; P. Merlini, Azienda Socio 726Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milano; C. Rapezzi, Azienda 727Ospedaliero Universitaria di Bologna Policlinico S. Orsola Malpighi, Bologna; M. Pirro,728 Ospedale Santa Maria della Misericordia Università degli Studi di Perugia, Perugia; S. Gonnelli, 729 Policlinico Santa Maria alle Scotte, Siena; A. M. Floresta, Azienda Ospedaliera Ospedali Riuniti 730 Villa Sofia Cervello Presidio Ospedaliero V. Cervello, Palermo; M. Mennuni, Ospedale731Leopoldo Parodi Delfino, Colleferro RM; D. Ardissino, Azienda Ospedaliera Universitaria di 732Parma, Parma; M. Senni, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo; 733G. Marenzi, Centro Cardiologico Monzino, Milano; R. Marcucci, Azienda Ospedaliera734Universitaria Careggi, Firenze; T. Sampietro, Fondazione Toscana Gabriele Monasterio,735Stabilimento Ospedaliero di Pisa, Pisa; F. Cosmi, Ospedale Santa Margherita, Cortona AR; P. 736Perrone Filardi, Azienda Ospedaliera Universitaria Federico II, Napoli; R. De Caterina, Ospedale 737Santissima Annunziata Università degli Studi G. D’Annunzio, Chieti; F. Fedele, Umberto I738Policlinico di Roma, Roma; L. Moretti, Ospedale Generale Provinciale C. G. Mazzoni, Ascoli 739Piceno; L. M. Biasucci, Policlinico Universitario Agostino Gemelli, Roma; C. Ferri, Presidio 740Ospedaliero San Salvatore, L Aquila.741742Japan:743Y. Go, Go Neurosurgical Clinic, Chikushi-gun; A. Kiyosue, Tokyo-Eki Center-building Clinic,744Chuo-ku; Y. Higashi, Himeji Central Hospitals Clinic, Himeji-shi; A. Hirayama, Nihon745University School of Medicine Itabashi Hospital, Itabashi-ku; T. Tokunaga, JA Toride Medical 746Center, Toride-shi; T. Kawasaki, Tenjinkai Shin-Koga Hospital, Kurume-shi; S. Sakagami, 747National Hospital Organization Kanazawa Medical Center, Kanazawa-shi; S. Namba, Japan 748Organization of Occupational Health and Safety Okayama Rosai Hospital, Okayama-shi; K.Saku, Fukuoka University Hospital, Fukuoka-shi; K. Oku, National Hospital OrganizationNagasaki Medical Center, Omura-shi; T. Arakawa, Social Medical Corporation Kojunkai DaidoHospital, Nagoya-shi; H. Iida, National Hospital Organization Hamada Medical Center,Hamada-shi; Y. Nakamura, Nakamura Cardiovascular Clinic, Itoshima-shi; K. Yamamoto, SagaMemorial Hospital, Saga-shi; Y. Hata, Minamino Cardiovascular Hospital, Hachioji-shi; Y.Katsuda, Fukuoka city Medical Association Adult Medical Centre, Fukuoka-shi; Y. Koga,Sagaken Medical Centre Koseikan, Saga-shi; M. Shimizu, National Hospital Organization Kobe 756 Medical Center, Kobe-shi; H. Uehara, Urasoe Sogo Hospital, Urasoe-shi; S. Kajiyama, Medical 757 Corporation Keisei-kai Kajiyama Clinic, Kyoto-shi; H. Okamoto, Meitetsu Hospital, Nagoyashi; 758 T. Shinozaki, National Hospital Organization Sendai Medical Center, Sendai-shi; Y. Fujino,759New Tokyo Heart Clinic, Matsudo-shi; T. Funazaki, Saiseikai Kawaguchi General Hospital, 760Kawaguchi-shi; N. Higa, Okinawa Tokushukai Medical Corporation Chubu Tokushukai 761Hospital, Nakagami-gun; K. Kaigawa, Daiyukai Clinic, Ichinomiya-shi; A. Koike, National 762Hospital Organization Fukuoka-Higashi Medical Center, Koga-shi; H. Nakane, National 763Hospital Organization Fukuoka-Higashi Medical Center, Koga-shi; K. Sato, Social Medical764Corporation Tokeidai Memorial Clinic, Sapporo-shi; Y. Satoh, National Hospital Organization 765Disaster Medical Center, Tachikawa-shi; K. Shirasawa, Osaka Hospital of Japan Seafarers relief 766Association, Osaka-shi; H. Sugino, National Hospital Organization Kure Medical Center and 767Chugoku Cancer Center, Kure-shi; J. Tanabe, National Hospital Organization Shizuoka Medical 768Center, Sunto-gun; O. Uemura, National Hospital Organization Murayama Medical Center,769Musashimurayama-shi; G. Yoshimichi, National Hospital Organization Oita Medical Center, 770Oita-shi; A. Akai, Tokai Memorial Hospital, Kasugai-shi; H. Himeno, Fujisawa City Hospital, 771Fujisawa-shi; T. Inage, Takagi Hospital, Okawa-shi; M. Inoko, Tazuke Kofukai Foundation 772Medical Research Institute Kitano Hospital, Osaka-shi; T. Kadokami, Saiseikai Futsukaichi 773Hospital, Chikushino-shi; Y. Noguchi, Tsukuba Medical Center Foundation Tsukuba Medical 774Center Hospital, Tsukuba-city; K. Yamashita, Nagoya Medical Center, Nagoya-shi; Y.775Yasumura, Osaka Police Hospital, Osaka-shi; M. Yuge, Odawara Municipal Hospital,776Odawarashi; S. Hosokawa, Tokushima Red Cross Hospital, Komatsushima-shi; K. Kawamitsu,777Okinawa Tokushukai Medical Corporation Nanbu Tokushukai Hospital, Shimajiri-gun; K.778Kozuma, Teikyo University Hospital, Itabashi-ku; H. Matsuo, National Hospital Organization 779Nagasaki Kawatana Medical Center, Higashisonogi-gun; E. Nakashima, Chubu Rosai Hospital, 780Nagoyashi; M. Okada, Yoshida Hospital, Asahikawa-shi; A. Wada, Kusatsu General Hospital, 781Kusatsushi; K. Yokoya, National Hospital Organization Toyohashi Medical Center, Toyohashi- 782shi; K.Iwade, National Hospital Organization Yokohama Medical Center, Yokohama-shi; K.Kawabata, University of Yamanashi Hospital, Chuo-shi; H. Tanno, National HospitalOrganization Chiba Medical Center, Chiba-shi; J. Ako, Kitasato University Hospital,Sagamihara-shi; H. Fujita, Murakami Memorial Hospital, Saijo-shi; Y. Izumiya, KumamotoUniversity Hospital, Kumamoto-shi; M. Kanno, Southern Tohoku Research Institute forNeurosciense Southern Tohoku Medical Clinic, Koriyama-shi; T. Nunohiro, Nagasaki HarborMedical Center City Hospital, Nagasaki-shi; H. Ohmura, Juntendo University Hospital, Bunkyo-ku; T. Ueno, Kurume University Hospital, Kurume-shi.Latvia:N. Kakurina, Daugavpils Regional Hospital, Daugavpils; A. Erglis, Pauls Stradins Clinical 793University Hospital, Riga; I. Jasinkevica, Inga Jasinkevica Cardiologist Practice, Ogre; I. 794Stukena, Riga First Hospital, Riga; I. Veze, Outpatient Clinic Veselibas Centrs 4, Riga; R.795Eglite, Rutas Eglites private practice, Kuldiga; D. Teterovska, Dace Teterovska Doctor Practice796in Endocrinology, Ogre; I. Sime, Regional Hospital of Liepaja, Liepaja.797798Lithuania:799J. Badariene, Vilnius University Hospital Santariskiu Clinic Public Institution, Vilnius; V.800Strazdiene, Center for Clinical and Basic Research, Vilnius; L. Venceviciene, Vilnius University801 Hospital Santariskiu Clinic Public Institution, Vilnius; O. Gustiene, Hospital of Lithuanian 802 University of Health Sciences Kaunas Clinics Public Institution, Kaunas; R. Radzeviciene- 803 Jurgute, Mano seimos gydytojas, Klaipeda; A. Kucinskiene, INMEDICA, Kaunas.804805Malaysia:806W. A. Wan Ahmad, University Malaya Medical Centre, Kuala Lumpur; O. Maskon, Universiti 807Kebangsaan Malaysia Medical Centre, Kuala Lumpur; C. Y. Lee, Hospital Sultanah Aminah, 808Johor Bahru; T. Erng, Hospital Melaka, Melaka; H. W. Gan, Gleneagles Medical Centre,809Penang; A. K. Mohamed Yusof, Institut Jantung Negara, Kuala Lumpur; G. L. Ramanathan,810Hospital Taiping, Taiping; H. Liew, Hospital Queen Elizabeth II, Kota Kinabalu.811812Mexico:813A. Lopez Alvarado, Hospital Pedro Loza S.A. de C.V., Guadalajara; L. A. Nevarez Ruiz,814Investigacion en Salud y Metabolismo SC, Chihuahua; M. O. De los Rios Ibarra, Centro para el 815Desarrollo de la Medicina y de Asistencia Medica Especializada SC, Culiacan; A. E. Bazzoni 816Ruiz, CIMAB SA de CV, Torreon; G. A. Ramos Lopez, Nuevo Hospital Civil de Guadalajara Dr 817Juan I Menchaca, Guadalajara; G. A. Llamas Esperon, Hospital Cardiologica Aguascalientes, 818Aguascalientes; G. D. J. De la Pe?a Topete, ICLE SC, Guadalajara; G. Gonzalez-Galvez,819Instituto Jalisciense de Investigacion en diabetes y obesidad SC, Guadalajara; R. M. Violante 820Ortiz, Centro de Estudios de Investigacion Metabolicos y Cardiovasculares SC, Tampico; J. J. 821Illescas Diaz, Unidad de Investigacion Clinica Cardiometabolica de Occidente SC, Guadalajara; 822S. Leon Gonzalez, Centro de Estudios Clinicos de Queretaro SC, Queretaro; C. J. Sanchez Diaz, 823Unidad de Investigacion Clinica en Medicina SC, Monterrey; G. F. Mendez Machado, Hospital 824Angeles Xalapa, Xalapa; L. A. Venegas Carrillo, Investigacion Clinica de Leon SC, Leon; J. A. 825Aldrete Velasco, Paracelsus SA de CV, Mexico; E. G. Cardona Mu?oz, Centro Universitario de 826Ciencias de la Salud, Guadalajara; J. L. Leiva Pons, Hospital Central Dr Ignacio Morones Prieto, 827San Luis Potosi; J. C. Perez Alva, U de Inv Clinica Inst Tec y de Estudios Sup de Monterrey828Campus Cd de Mex, Mexico.829Netherlands:C. van der Zwaan, Ziekenhuis Rivierenland, Tiel; A. Oomen, Antonius Ziekenhuis, Sneek; R.van de Wal, Ziekenhuis Bernhoven, Uden; M. Magro, Elisabeth-TweeSteden Ziekenhuis,Tilburg; D. Boswijk, Noordwest Ziekenhuisgroep, Den Helder; C. Janus, Vasculair OnderzoekCentrum Hoorn, Hoorn; R. Groutars, Sint Lucas Andreas Ziekenhuis, Locatie Sint Lucas,Amsterdam; W. Tonino, Catharina Ziekenhuis, Eindhoven; J. H. Cornel, NoordwestZiekenhuisgroep, Alkmaar; A. Oude Ophuis, Canisius-Wilhelmina Ziekenhuis, Nijmegen; R.Troquay, VieCuri Medisch Centrum, Venlo; A. Liem, Franciscus Gasthuis, Rotterdam; I. 838Westendorp, Rode Kruis Ziekenhuis, Beverwijk; M. Van Hessen, Groene Hart Ziekenhuis, 839Gouda; D. Lok, Deventer Ziekenhuis, Deventer; C. De Nooijer, Maxima Medisch Centrum, 840Veldhoven; F. Den Hartog, Ziekenhuis Gelderse Vallei, Ede; E. Van Beek, Sint Jansdal841Ziekenhuis, Harderwijk; P. Bendermacher, Elkerliek Ziekenhuis, Helmond; R. Jansen,842Slingeland Ziekenhuis, Doetinchem; T. R?mer, Alrijne Ziekenhuis, Leiden; B. Rensing, Sint843Antonius Ziekenhuis, locatie Nieuwegein, Nieuwegein; F. Hersbach, Maasstad Ziekenhuis,844Rotterdam; J. Herrman, Onze Lieve Vrouwe Gasthuis, Amsterdam; G. Ladyjanskaia, Ziekenhuis 845Amstelland, Amstelveen; I. Karalis, Leids Universitair Medisch Centrum, Leiden; G. Linssen, 846Ziekenhuisgroep Twente, Almelo; M. Bokern, Waterland Ziekenhuis, Purmerend; A. Visman, 847Beatrix Ziekenhuis, Gorinchem; A. Kooij, Bethesda Diabetes Research Center, Hoogeveen; H. 848Monajemi, Rijnstate, Arnhem; A. Lieverse, Maxima Medisch Centrum, Eindhoven.849850New Zealand:851R. Scott, Lipid and Diabetes Research Group, Christchurch; J. Baker, Middlemore Hospital,852Papatoetoe, Auckland; S. Tie, Tauranga Hospital, Tauranga.853854Norway:855K. Risberg, Skedsmo Medisinske Senter, Skedsmokorset; J. Hysing, Sykehuset Telemark, Skien;856T. Pedersen, Oslo universitetssykehus, Oslo; H. O. Hoivik, M3 Helse, Hamar; P. Norheim,857Forusakutten-Kolibri, Stavanger; L. Solnor, Heiaklinikken, Lierskogen; A. Hovland,858Nordlandssykehuset, Bod?; T. Kjaernli, Medi 3 Klinikk, ?lesund.859860Philippines:861G. Jocson, J. Sibal, Angeles University Foundation, Angeles; R. M. Coching, Davao Doctors 862Hospital, Davao City; E. Batalla, Davao Doctors Hospital, Davao City; A. Go, Baguio General 863Hospital, Baguio City; R. Habaluyas, Amang Rodriguez Memorial Medical Center, Marikiina; 864R. Barcinas, Alexian Brothers Health and Wellness Center, Davao City; R. A. Sy, Ospital ng865Makati, Makati City; R. A. Estepar, St Pauls Hospital Iloilo, Iloilo; G. Rogelio, St Lukes Medical866Center, Quezon City; A. Germar, Veterans Memorial Medical Center, Quezon City.867868Poland:869J. Trebacz, Centrum Medyczne Zdrowa, Krakow; K. Szymkowiak, Synexus Polska Spzoo,870Wroclaw; R. Wnetrzak-Michalska, Synexus Polska Spzoo, Katowice; J. Kopaczewski, 871Specjalistyczne Gabinety Lekarskie Medicor Plus - Jerzy Kopaczewski, Wloclawek; M. 872Przekwas-Jaruchowska, Synexus Polska Spzoo, Gdynia; G. Kania, Centrum Medyczne 873Ogrodowa, Skierniewice; M. Zabowka, Centrum Szybkiej Diagnostyki Kardiologicznej 874Kardiomed M Zabowka E Zabowka Spolka cywilna, Tarnow; E. Mirek-Bryniarska,875Specjalistyczny Gabinet Lekarski Ewa Mirek-Bryniarska, Krakow; M. Dabrowska, Synexus876Polska Spzoo, Warszawa; P. Napora, Centrum Badan Klinicznych Przychodnia Badan877Klinicznych, Wroclaw; M. Konieczny, KO-MED Marek Konieczny Centrum878Wielospecjalistycznej Opieki Ambulatoryjnej z AmbulatorOsrodkZabieg, Pulawy; J. Spyra, 879NZOZ Przychodnia Specjalistyczna Andrzej Wittek Henryk Rudzki spolka jawna, Ruda Slaska; 880R. Lysek, Lecznice Citomed Spzoo, Torun; Z. Pijanowski, NZOZ Twoja Przychodnia Spzoo,881Lublin; B. Grzegorzewski, Centrum Medyczne Clinport, Katowice; Z. Bednarkiewicz, 882Wojewodzki Specjalistyczny Szpital im dr Wl Bieganskiego w Lodzi, Lodz; Z. Gaciong, 883Samodzielny Publiczny Centralny Szpital Kliniczny, Warszawa; L. Kinasz, Polsko-884Amerykanskie Kliniki Serca, Bielsko-Biala; K. Antkowiak-Piatyszek, Synexus Polska Spzoo, 885Poznan; K. Stania, Nyskie Centrum Sercowo Naczyniowe Polsko-Amerykanskich Klinik Serca, 886Nysa; M. Szpajer, Poliklinika Evi-Med, Gdynia; P. Staneta, NZOZ Specjalistyczna Przychodnia 887Lekarska Medikard, Plock; G. Skonieczny, Wojewodzki Szpital Zespolony im Ludwika888Rydygiera w Toruniu, Torun; E. Ksiezycka-Majczynska, Instytut Kardiologii im Prymasa 889Tysiaclecia Stefana Kardynala Wyszynskiego, Warszawa; T. Blicharski, Lubelskie Centrum 890Diagnostyczne, Swidnik; M. Piepiorka, Gabinet Kardiologiczno-Internistyczny, Gdynia; B.891Wozakowska-Kaplon, NZOZ Centrum Us?ug Medycznych Promont-Med, Kielce; T. Zechowicz,892Zechowicz Medeusz-Plus Lekarska Spolka Partnerska, Olsztyn; J. Ilkowski, NZOZ Neuro-Kard,893Poznan; B. Lubiszewska, Instytut Kardiologii im Prymasa Tysiaclecia Stefana Kardynala 894Wyszynskiego, Warszawa; J. Hiczkiewicz, NZOZ Kardiologia Nowa Sol, Nowa Sol; K. 895Wierzbicka, Specjalistyczny Osrodek Medycyny Wieku Dojrzalego Spzoo, Warszawa; D. 896Kosior, Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych w Warszawie,897Warszawa; P. Garbocz, Medica Centrum Spzoo, Pszczyna; J. Kubica, Szpital Uniwersytecki nr 1898im dr Antoniego Jurasza w Bydgoszczy, Bydgoszcz; G. Raczak, Uniwersyteckie Centrum899Kliniczne, Gdansk; I. Wozniak, KO-MED Centra Kliniczne Staszow, Staszow; J. Cygler, NZOZ 900Medica, Gizycko; E. Kramarczuk, KO-MED Centra Kliniczne Zamosc, Zamosc; L. Bystryk, 901Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej, Jelenia Gora; J. Pentela-Nowicka,902Somed Lodzkie Centrum Osteoporozy, Lodz; M. Dabrowski, SPZOZ Szpital Bielanski im903Ksiedza Jerzego Popieluszki, Warszawa; P. Podolec, Krakowski Szpital Specjalistyczny im Jana904Paw?a II, Krakow; B. Zieba, Gdanskie Centrum Zdrowia, Gdansk; J. Mosiewicz, Centrum905Medyczne Luxmed Spzoo, Lublin; T. Pasierski, Miedzyleski Szpital Specjalistyczny w906 Warszawie, Warszawa; W. Dubaniewicz, Pomorskie Centra Kardiologiczne, Starogard Gdanski; 907 M. Banach, SPZOZ Uniwersytecki Szpital Kliniczny, Lodz; G. Tyszecka, Wromedica, Wroclaw; 908 T. Lepich, Indywidualna Specjalistyczna Praktyka Lekarska Roman Spyra, Katowice; A.909Rychlewska-Hanczewska, Ai Centrum Medyczne, Poznan; T. Guzik, Malopolskie Centrum910Alergii i Immunoterapii Allmedis Sp. z o.o, Krakow.911912Portugal:913P. Monteiro, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra; H. Pereira, Hospital 914Garcia de Orta, EPE, Almada; L. Oliveira, Centro Hospitalar Cova da Beira, EPE - Hospital Pero 915da Covilha, Covilha; P. Matos, Hospital Cuf Infante Santo, Lisboa; S. Soares Goncalves, Centro 916Hospitalar de Setubal EPE Hospital de Sao Bernardo, Setubal; A. Leitao, Centro Hospitalar de 917Lisboa Ocidental, EPE - Hospital Sao Francisco Xavier, Lisboa; J. Ferreira, Centro Hospitalar de 918Lisboa Ocidental, EPE - Hospital de Santa Cruz, Carnaxide; A. Vasco Salgado, Hospital919Professor Doutor Fernando Fonseca, EPE, Amadora; A. T. Timoteo, Centro Hospitalar de Lisboa920Central, E.P.E. - Hospital de Santa Marta, Lisboa.921922Romania:923 E. Pintilei, Consultmed SRL, Iasi; E. Badila, Policlinica Center for Clinical and Basic Research 924 SRL, Bucuresti; C. Militaru, Cardiomed SRL, Craiova; M. Tudoran, Spitalul Clinic Judetean de 925 Urgenta Timisoara, Timisoara; C. Arsenescu-Georgescu, Institutul de Boli Cardiovasculare Prof 926 Dr George I.M. Georgescu Iasi, Iasi; F. Mitu, Spitalul Clinic de Recuperare Iasi, Iasi; D.927Zdrenghea, Spitalul Clinic de Recuperare Cluj-Napoca, Cluj-Napoca; D. Lighezan, Spitalul928 Clinic Municipal de Urgenta Timisoara, Timisoara; I. Teodorescu, Spitalul Clinic de Urgenta Sf 929 Ioan Bucuresti, Bucuresti; A. G. Dan, Spitalul Clinic Colentina, Bucharest; M. I. Popescu, Spital 930 Clinic Judetean de Urgenta Oradea, Oradea; I. Coman, Alcor Med SRL, Bucuresti; M. M.931Vintila, Spitalul Clinic de Urgenta Sfantul Pantelimon, Bucuresti.932933Russia:934 A. Vishnevsky, Saint Petersburg State Budget Healthcare Institution Pokrovskaya City Hospital, 935 Saint-Petersburg; Y. Lukyanov, SBEI of HPE First Saint-Petersburg State Medical University na 936 Academic I P Pavlov of MoH of the RF, Saint-Petersburg; A. Blokhin, FSBI Outpatient Clinic 3 937 of Russian Federation Presidents Management Department, Moscow; V. Kostenko, Saint938Petersburg State Budget Healthcare Institution City Polyclinic 109, Saint-Petersburg; Y. Shvarts, 939Clinical Hospital named after S R Mirotvortsev, Saratov; V. Markov, FSBSI Research Institute 940for ical Hospi, Tomsk; I. Motylev, SBHI of Nizhniy Novgorod region City Clinical Hospital 33 941of city Nizhniy Novgorod Leninskyi region, Nizhniy Novgorod; D. Dronov, Budget Healthcare 942Institution of Omsk region Medical-sanitary unit 9, Omsk; A. Sherenkov, Spb SBHI Medical and 943sports dispensary of Krasnogvardeisky district of Saint Petersburg, Saint Petersburg; O.Barbarash, FSBI Heart and Vessels Diseases complex problems Scientific Research Institution,Kemerovo; E. Shutemova, Regional Budget Healthcare Institution Cardiology Dispensary,Ivanovo; O. Bolshakova, SBEI of HPE First Saint-Petersburg State Medical University naAcademic I P Pavlov of MoH of the RF, Saint Petersburg; Z. Kobalava, SBHI of Moscow Cityclinical hospital 64 of Moscow Healthcare department, Moscow; M. Ezhov, FSBI RussianCardiology Research and Production Complex, Moscow; M. Voevoda, FSBI SRI of Therapy of 950Siberian Branch of RAMS, Novosibirsk; T. Treshkur, FSBI V.A.Almazov Federal Center of 951heart, blood and endocrinology of Ministry of Health and SD of RF, Saint Petersburg; K.952Zrazhevskiy, Saint Petersburg SBHI City Hospital 38 named after N A Semashko, Saint-953Petersburg; L. Pimenov, BHI of Republic Udmurtiya City clinical hospital 9 of Ministry of954healthcare of Republic Udmurtiya, Izhevsk; O. Solovev, Kirov Regional State Budget Healthcare955Institution Kirov City Clinical Hospital 1, Kirov; N. Tarasov, FSHI Medical-sanitary unit of956Chief Administration of IA of Kemerovo region, Kemerovo; M. Arkhipov, State Budget Medical 957Institution Sverdlovsk Regional Clinical Hospital N1, Ekaterinburg; M. Freidlin, SBHI of SR 958SPC of specialized types of medical care Ural cardiology institute, Ekaterinburg; S. Shalaev,959State Autonomy Health care Institution of Tyumen region Scientific and Practical Medical960Center, Tyumen; P. Yakhontova, SBHI of Novosibirsk Region Novosibirsk regional clinical 961cardiology dispensary, Novosibirsk; S. Shustov, FSMEI of HPE Military Medical Academy n.a. 962S.M.Kirov of Ministry of Defense of RF, St. Petersburg; B. Goloshchekin, St Petersburg State 963Budget Institution of Public Health City Hospital 15, Saint Petersburg; A. Panov, FSBI964 V.A.Almazov Federal Center of heart, blood and endocrinology of Ministry of Health and SD of 965 RF, Saint-Petersburg; B. Bart, Diagnostic and Clinical Center No1 Moscow Health Department, 966 branch No2, Moscow; M. Bubnova, FSBI State Scientific Research Center for Preventive967 Medicine of MoH of RF, Moscow; I. Gordeev, Moscow SBHI City Clinical Hospital 15 n a O M 968 Filatov of Moscow Healthcare Department, Moscow; I. Osipova, NSHI Departmental Hospital at 969 the station Barnaul of OJSC Russian Railways, Barnaul; S. Tereshenko, FSBI Russian970Cardiology Research and Production Complex, Moscow; E. Solovieva, FSBI Russian971Cardiology Research and Production Complex, Moscow; A. Meshkov, FSBI State Scientific972Research Center for Preventive Medicine of MoH of RF, Moscow; D. Zateyshchikov, Moscow9739749759769779789799809819829839849859869879889899909919929939949959969979989991000100110021003100410051006100710081009101010111012101310141015101610171018State Budget Healthcare Institution City Clinical Hospital 51 of Moscow Healthcare Department, Moscow.Singapore:L. Tay, Changi General Hospital, Singapore; J. L. Tan, National Heart Centre Singapore, Singapore; T. Subramaniam, Khoo Teck Puat Hospital, Singapore.Slovakia:D. Pella, Cardio D and R sro Kosice, Kosice; P. Fulop, Interna SK sro, Svidnik; L. Antalik, Nemocnica s poliklinikou Brezno, no, Brezno; A. Dzupina, Alian sro, Bardejov; A. Banikova, KardioMed sro, Lucenec; D. Sosovec, Diab sro, Roznava; L. Urgeova, Kardiomed, NZ sro, Nove Zamky; J. Mazur, Kardio - Onkologia sro, Dolny Kubin; M. Hranai, Kardiocentrum Nitra s.r.o., Nitra; M. Banik, Medi M and M sro, Moldava nad Bodvou; D. Vinanska, Medispol sro, Presov; J. Lennerova, Medilex sro, Rimavska Sobota; F. Kovar, Univerzitna nemocnica Martin, Martin; E. Pastrnakova, Agto spol sro, Kosice; R. Uhliar, Nemocnica svateho Michala as, Bratislava; P. Blasko, MUDr Peter Blasko sro, Banovce nad Bebravou; S. Filipova, Narodny ustav srdcovych a cievnych chorob, a.s., Bratislava; J. Gonsorcik, NZZ - internistu, kardiologa, Kosice; J. Lukacova, Mediluk sro, Snina; R. Oriesek, CardiOr sro, Trencin; K. Hatalova, Cardioconsult sro, Bratislava.South Africa:M. du Toit, Synexus Clinical Research South Africa, Val de Grace; L. Burgess, Tygerberg Hospital, Parow; I. Ebrahim, Unitas Hospital, Centurion; G. Vawda, Inkosi Albert Luthuli Central Hospital, Durban; S. Lipschitz, Apollo Clinical Research Pty Ltd, Johannesburg; S. Blignaut, Paarl Research, Paarl; J. Engelbrecht, Doctor JM Engelbrecht, Somerset West; T. F. Coetzer, Clinresco Centres Suites, Kempton Park; M. Pretorius, Tiervlei Trial Centre, Cape Town; D. Urbach, Synexus Helderberg Clinical Research Centre, Somerset West; A. Badat, Wits Clinical Research, Soweto; S. Pillay, Seadoone Medical Centre, Amanzimtoti; L. Van Zyl, Clinical Projects Research South Africa, Worcester; M. Abelson, Vergelegen Mediclinic, Somerset West; E. van der Walt, Medicross Roodeport Research Centre, Johannesburg; R. Moodley, Umhlanga Hospital Netcare, Durban; A. Jacovides, Midrand Medical Centre, Midrand; W. M. Oosthuysen, Limaro Research, Bloemfontein; E. Klug, Sunninghill Hospital, Sunninghill; H. Lottering, SCION Clinical Research, Pretoria; J. Kok, Union Hospital, Alberton;J. Saaiman, Kuils River Hospital, Kuils River; S. Dawood, Vincent Pallotti Hospital, Cape Town; D. M. De Jong, Jongaie Research, Pretoria west; C. Kapp, Cardiology Clinical Research, Alberton; E. Makotoko, Universitas Hospital, Bloemfontein; J. Bayat, Durban Medical Centre, Durban; A. Badat, Wits Clinical Research, Soweto; M. Sarvan, Mediclinic Victoria, Tongaat; E. Klug, Sunward Park Hospital, Boksburg; T. Vally, Synexus SA - Stanza Bopape Clinical Research Centre, Pretoria; A. Stapelberg, Syzygy Clinical Research Services Pty Ltd, Pretoria.South Korea:M. Kim, Dong-A University Hospital, Busan, Seo-gu; J. Bae, Konyang University Hospital, Daejeon; Y. Cho, Seoul National University Bundang Hospital, Seongnam-si; S. Kim, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul; K. H. Han, Asan Medical Center, Seoul; S. Her, The Catholic University of Korea Daejeon St Marys Hospital, Daejeon; D. Choi, Yonsei University Health System Severance Hospital, Seoul; B.1019102010211022102310241025102610271028102910301031103210331034103510361037103810391040104110421043104410451046104710481049105010511052105310541055105610571058105910601061106210631064Kim, Kangbuk Samsung Hospital, Seoul; S. Lee, Ilsan-Paik Hospital, Goyang-si, Gyeonggi-do;B. Hong, Gangnam Severance Hospital, Seoul; W. Kim, Kyung Hee University Hospital, Seoul;S. Rha, Korea University Guro Hospital, Seoul; M. Jeong, Chonnam National University Hospital, Gwangju; G. J. Shin, Ewha Womans University Mokdong Hospital, Seoul.Spain:M. Vida Gutierrez, Hospital Virgen del Mar, Almeria; J. Lopez Miranda, Hospital Universitario Reina Sofia, Cordoba; M. Valdes Chavarri, Hospital Universitario Virgen de la Arrixaca, El Palmar; X. Pinto Sala, Hospital Universitari de Bellvitge, L Hospitalet de Llobregat; J. R. Gonzalez Juanatey, Hospital Clinico Universitario de Santiago, Santiago de Compostela; F. Civeira Murillo, Hospital Universitario Miguel Servet, Zaragoza; J. L. Zamorano Gomez, Hospital Universitario Ramon y Cajal, Madrid; I. Lekuona Goya, Hospital de Galdakao, Galdakao; A. I?iguez Romo, Hospital Alvaro Cunqueiro, Vigo; A. Cordero Fort, Hospital Universitario San Juan de Alicante, San Juan de Alicante; J. F. Ascaso Gimilio, Hospital Clinico Universitario de Valencia, Valencia; J. Millan Nu?ez-Cortes, Hospital General Universitario Gregorio Mara?on, Madrid.Sweden:C. Lindholm, Capio Citykliniken, Lund; L. Nilsson, University Hospital, Link?ping; ?. Olsson, A-plus Science AB, Stockholm; S. S?derberg, Norrlands Universitetssjukhus, Ume?; A. Suutari, H?glandssjukhuset Eksj?, Eksj?; S. Berglund, Falu Lasarett, Falun; T. Mooe, ?stersunds sjukhus, ?stersund; D. Kusiak, L?nssjukhuset Ryhov, J?nk?ping; S. Bandh, V?stmanland sjukhus V?ster?s, V?ster?s; G. Dahlén, V?rdcentralen Silentzv?gen, Uddevalla; S. Olsson, Helsingborgs lasarett, Helsingborg; N. Witt, S?dersjukhuset, Stockholm; P. Tydén, Sk?nes Universitetssjukhus, Lund; P. Johansson, Sunderby Sjukhus, Lule?; S. Cizinsky, Universitetssjukhuset ?rebro, ?rebro; G. Falck, Aleris Specialistv?rd Bolln?s, Bolln?s; S. I. Pettersson, M?larsjukhuset, Eskilstuna; G. Rasmanis, Karolinska Universitetssjukhuset Huddinge, Stockholm; J. ?stergren, Karolinska University Hospital, Stockholm.Switzerland:F. Mach, Hopitaux Universitaires de Geneve, Geneva 14; T. Moccetti, G. Ponti, Fondazione Cardiocentro Ticino, Lugano; H. J. Beer, K. Steden, Kantonsspital Baden, Baden; F. Eberli, C. Liedtke, Stadtspital Triemli, Zurich; S. Kr?henbühl, Universitaetsspital Basel, Basel; A. Linka,B. Brinkers, Kantonsspital Winterthur, Winterthur; D. Ackermann, M. Winter-Pauling, Inselspital Bern, Bern; P. Michel, Centre Hospitalier Universitaire Vaudois, Lausanne.Taiwan:H. Yeh, Mackay Memorial Hospital Tamsui Branch, New Taipei City; C. F. Tsai, K. Ueng, Chung Shan Medical University Hospital, Taichung City; M. Charng, Taipei Veterans General Hospital, Taipei; C. Wu, C. J. Chen, C. I. Cheng, C. H. Yang, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung; C. Hsia, Changhua Christian Hospital, Changhua; J. Juang, F. Chiang, National Taiwan University Hospital, Taipei; I. Hsieh, Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation, Taoyuan; W. Lai, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung; C. Huang, Cathay General Hospital, Taipei; Y. Hsieh, Chi Mei Medical Center, Tainan.1065106610671068106910701071107210731074107510761077107810791080108110821083108410851086108710881089109010911092109310941095109610971098109911001101110211031104110511061107110811091110Turkey:T. Sahin, Kocaeli Universitesi Tip Fakultesi, Kocaeli; M. Duzenli, Necmettin Erbakan Universitesi Meram Tip Fakultesi, Konya; Z. Yigit, Istanbul University Cardiology Institute, Istanbul; M. Demir, Cukurova Universitesi Tip Fakultesi, Adana; M. B. Yilmaz, Cumhuriyet Universitesi Tip Fakultesi, Sivas; I. H. Muderrisoglu, Baskent Universitesi Ankara Hastanesi, Ankara; C. Kirma, Kartal Kosuyolu Yuksek Ihtisas Egitim ve Arastirma Hastanesi, Istanbul; E. Ercan, Izmir Medicalpark Hastanesi, Izmir; L. Kayikcioglu, Ege Universitesi Tip Fakultesi, Izmir; Y. Balbay, Turkiye Yuksek Ihtisas Hastanesi, Ankara; S. Tokgozoglu, Hacettepe Universitesi Tip Fakultesi Hastanesi, Ankara.Ukraine:Kraydashenko, Communal Institution City Clinical Hospital No 6, Zaporizhzhia; I. Lymar, Communal Noncommercial Institution Consultative and Diagnostic Center of Desnianskyi District of Kyi, Kyiv; O. Kulynych, Communal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council, Zaporizhzhya; O. Prokhorov, Communal Healthcare Institution Kharkiv City Clinical Hospital No27, Kharkiv; O. Karpenko, Kyiv City ClinicalHospital 1, Kyiv; I. Kra?z, Railway Transport Kharkiv Clinical Hospital No1 of HealthcareCenter Branch of Public Joint Stock, Kharkiv; I. Vakaliuk, vano-Frankivsk Regional Clinical Cardiological Dispensary, Ivano-Frankivsk; M. Stanislavchuk, Vinnytsia M I Pyrogov Regional Clinical Hospital Vinnytsia M I Pyrogov National Medical University, Vinnytsia; O. Korzh, Medical and Sanitary Unit of Open Joint Stock Company Kharkiv S Ordzhonikidze Tractor Plant, Kharkiv; I. Rudyk, Government Institution L T Malaya Therapy National Institute of NAMS of Ukraine, Kharkiv; S. Zhurba, Cherkasy Region Cardiological Center, Cherkasy; Y. Svishchenko, State Institution National Scientific Center Acad Strazhesko Institute of Cardiology, Kyiv; V. Tseluyko, Communal Healthcare Institution Kharkiv City Clinical Hospital No8 Kharkiv Medical Academy of Post g, Kharkiv; O. Gyrina, Limited Liability Company Treatment and Diagnostic Center Adonis plus, Kyiv; D. Reshotko, Oleksandrivska Clinical Hospital of Kyiv, Kyiv; M. Kopytsya, Government Institution L T Malaya Therapy National Institute of NAMS of Ukraine, Kharkiv; V. Volkov, Government Institution L T Malaya Therapy National Institute of NAMS of Ukraine, Kharkiv; G. Myshanych, Synexus State Institution Road Clinical Hospital 2 of Kyiv Station, Kyiv; B. Rebrov, Luhansk Regional Clinical Hospital State Institution Luhansk State Medical University, Lugansk; M. Rishko, Transcarpathian Regional Clinical Cardiological Dispensary, Uzhgorod; L. Rudenko, Kyiv City Clinical Emergency Medical Care Hospital, Kyiv; V. Shatylo, State Institution D F Chebotariov Institute of Gerontology of NAMS of Ukraine, Kyiv; O. Parkhomenko, State Institution National Scientific Center Acad MD Strazhesko Institute of cardiology of NAMS Ukr, Kyiv; L. Yena, State Institution D F Chebotariov Institute of Gerontology of NAMS of Ukraine, Kyiv; O. Golovchenko, Medical Clinical Investigational Center of Medical Center Health Clinic LLC, Vinnytsia; I. Sorokina, Synexus Medical Center of Private Educational Institution Institute, Kyiv; Y. Malynovsky, Communal Inst regional Medical Centre of Cardiovascular Diseases of Zaporizhzhia Regional Council, Zaporizhzhia.United Kingdom:Ivan, Synexus Merseyside Clinical Research Centre, Liverpool; M. Blagden, Ashgate Medical Practice, Chesterfield; H. Dear, Synexus Scotland Clinical Research Centre, Glasgow; A. Mathew, Synexus Midlands Clinical Research Centre, Birmingham; S. Lagocki, Synexus1111111211131114111511161117111811191120112111221123112411251126112711281129113011311132113311341135113611371138113911401141114211431144114511461147114811491150115111521153115411551156Lancashire Clinical Research Centre, Chorley; V. Kondagunta, Synexus Thames Valley Clinical Research Centre, Reading; A. Ahsan, Nottingham City Hospital, Nottingham; C. McKinnon, Castlemilk Group Practice, Glasgow; F. Douglas, Synexus North East Clinical Research Centre, Hexham; S. Thom, Imperial College Healthcare NHS Trust, London; G. Fiore, Synexus Manchester Clinical Research Centre, Manchester; M. Caulfield, D. Collier, Barts Health NHS Trust, London; M. Lynch, Lister Hospital, Stevenage; H. Thomas, Synexus Wales Clinical Research Centre, Cardiff; S. Bain, Singleton Hospital, Swansea; A. Hall, Leeds General Infirmary, Leeds; D. McNally, Ormeau Health Centre, Belfast; M. Fisher, Royal Liverpool University Hospital, Liverpool; P. Keeling, Torbay Hospital, Torquay; A. Al-Bahrani, A. Baksi, St Marys Hospital, Newport; G. Lip, City Hospital, Birmingham; A. Ellery, Cape Cornwall Surgery, Penzance; J. Purohit, Brannel Surgery, St Austell; C. Travill, Luton and Dunstable NHS Foundation Trust Hospital, Luton; F. Cappuccio, University Hospital Coventry, Coventry; G. Davis, Aintree University Hospital, Liverpool; R. Gaunt, Rowden Surgery, Chippenham; D. Adlam, Glenfield Hospital, Leicester; N. Asamoah, P. Harvey, S. Maxwell, Crouch OakFamily Practice, Addlestone; F. Jaafar, R. Falk, South Axholme Practice, Haxey, Doncaster; T. McCormack, Whitby Group Practice, Whitby; B. Jupp, D. Jenkinson, Royal Bournemouth Hospital, Bournemouth; M. Pye, York Hospital, York; P. Ainsworth, Sherbourne Medical Centre, Leamington Spa; A. Chauhan, Blackpool Teaching Hospital, Blackpool; D. Connolly, Sandwell General Hospital, West Bromwich; N. Paul, Ashfield Primary Care Centre, Sandbach;H. Fairlie, Connor Downs Surgery, Hayle; C. Fox, Northampton General Hospital, Northampton;S. Muzulu, Rotherham General Hospital, Rotherham; J. Trevelyan, Worcestershire Royal Hospital, Worcester; R. Aggarwal, Basildon University Hospital, Basildon; B. Issa, Wythenshawe Hospital, Manchester; P. Saravanan, George Eliot Hospital, Nuneaton; K. Cruickshank, Guys and St Thomas NHS Foundation Trust, London; D. Gorog, Queen Elizabeth II Hospital, Welwyn Garden City; S. Heller, Northern General Hospital, Sheffield; D. Newby, Edinburgh Royal Infirmary, Edinburgh; A. Nicolson, West Suffolk Hospital, Bury St Edmunds;P. O Hare, Hospital of St Cross, Rugby; P. Donnelly, Ulster Hospital, Belfast; S. Rutherfurd, N. Armstrong, Morrab Surgery, Penzance; M. de Belder, James Cook University Hospital, Middlesbrough; J. Finlayson, Highlands Clinical Research Facility, Inverness; J. Harvey, Wrexham Maelor Hospital, Wrexham; A. Hoye, Castle Hill Hospital, Cottingham; D. Kingston,P. Cormie, Penalverne Surgery, Penzance; D. Sarkar, Derriford Hospital, Plymouth; A. Negahban, A. Ahmed, M. Al-Bazzaz, Barnsley Hospital, Barnsley; P. Saravanan, M. Banerjee, Arrowe Park Hospital, Wirral; J. Webster, Aberdeen Royal Infirmary, Aberdeen; N. Wyatt, The Bradford on Avon and Melsham Health Partnership, Wiltshire; S. Muir, Southern General Hospital, Glasgow; M. Cummings, Queen Alexandra Hospital, Portsmouth; I. Mackenzie, T. MacDonald, Ninewells Hospital and Medical School, Dundee; R. Senior, Northwick Park Hospital, Harrow; N. Capps, Princess Royal Hospital, Telford; K. Fotherby, New Cross Hospital, Wolverhampton; H. McIntyre, Conquest Hospital, St. Leonards-on-Sea; J. Aldegather, Portmill Surgery, Hitchin; L. Dixon, Royal Victoria Hospital, Belfast; R. Saksena, Colchester General Hospital, Colchester; R. Butler, University Hospital of North Staffordshire, Stoke-on-Trent.United States:D. Ramstad, Hampton Roads Center for Clinical Research, SUFFOLK, VA; B. Pierpont, Advance Medical Research, Saint Petersburg, FL; D. Levinson, Apex Medical Research Incorporate, Chicago, IL; A. Mohammed, Apex Medical Research, Inc, Springfield, OH; T. Haddad, Virginia Heart, Falls Church, VA; A. Goel, Kansas City Veterans Affairs Medical115711581159116011611162116311641165116611671168116911701171117211731174117511761177117811791180118111821183118411851186118711881189119011911192119311941195119611971198119912001201Center, Kansas City, MO; K. Dave, Heart Care Associates, Hopewell, VA; W. H. Haught, Heart Center Research LLC, Huntsville, AL; A. Desire, Andre P Desire MD PA, Wichita Falls, TX; K. Hershon, North Shore Diabetes and Endocrine Associates, New Hyde Park, NY; M. Napoli, Clinical Trials of America Inc, Monroe, LA; L. Tami, M. Abdurrahman, Research Physicians Network Alliance, Hollywood, FL; R. Rothschild, Cabrillo Cardiology Medical Group, Oxnard, CA; S. Khurana, Healthy Heart Cardiology, Grandville, MI; D. Gupta, Tennessee Center for Clinical Trials, Tullahoma, TN; D. Cheung, Long Beach Center for Clinical Research, Long Beach, CA; S. Hearne, Delmarva Heart Research Foundation Inc, Salisbury, MD; S. Grubb, Tabor City Family Medicine, Tabor City, NC; A. Miller, Alta Pharmaceutical Research Center Inc, Dunwoody, GA; I. Baird, Remington Davis Clinical Research Inc, Columbus, OH; A. Marcus, South Orange County Endocrinology, Laguna Hills, CA; S. Srivastava, Pentucket Medical Associates, Haverhill, MA; L. Forgosh, HealthEast Medical Research Institute, Saint Paul, MN; R. Fritz, Kootenai Heart Clinics, LLC, Coeur D'Alene, ID; M. Mays, Portland Preventive Cardiology, Portland, OR; B. Bertolet, Cardiology Associates Research LLC, Tupelo, MS; J. Reddy, Sierra Clinical Research, Roseville, CA; M. Khan, AngioCardiac Care of Texas, Houston, TX; S. Nakhle, Palm Research Center Inc, Las Vegas, NV; S. Dill, S Bar D Inc, Pryor, OK; G. Fishbein, Dayton Heart Center, Dayton, OH; B. Khan, Atlanta Clinical Research Centers LLC, Atlanta, GA; H. Marais, Beaver Medical Group, Banning, CA; M. Reschak, Medex Healthcare Research Inc- St Louis, Saint Louis, MO; M. Malone, Charlotte Heart Group Research Center, Port Charlotte, FL; V. Nadar, Capital Area Research LLC, Camp Hill, PA; R. Whitney, Bryan Heart, Lincoln, NE; A. Reichman, Clinical Trial Network, Houston, TX; H. Reyes, MediSphere Medical Research Center LLC, Evansville, IN; M. El Shahawy, Cardiovascular Center of Sarasota, Sarasota, FL; A. Rabinowitz, South Texas Cardiovascular Consultants, Kerrville, TX; D. Weinstein, Zasa Clinical Research, Boynton Beach, FL; N. Farhat, North Ohio Heart Center-Elyria, Elyria, OH; D. Onyema, Healthwise Medical Associates, NewYork, NY; R. Potu, Nature Coast Clinical Research LLC, Crystal River, FL; L. Runquist, Piedmont Medical Group Research of Charleston, Charleston, SC; O. Barnum, Keyser Avenue Medical Park Medical Research Inc, Natchitoches, LA; T. Crater, Hutchinson Clinic PA, Hutchinson, KS; J. Fialkow, Cardiovascular Research Center of South Florida, Miami, FL; A. Shah, Piedmont Research Partners, Indian Land, SC; C. Thompson, Craig S Thompson MD LLC, Marion, OH; A. Wiseman, Eastern Maine Medical Center, Bangor, ME; T. Doyle, Northeast Ohio Heart Associates, LLC, Willoughby, OH; D. Henderson, Cardiology Research Associates Daytona Beach, FL; W. Herzog, Johns Hopkins University, Columbia, MD; R. Schnitzler, Mercury Medical LLC, San Antonio, TX; K. Carr, Carr Cardiology, Oceanside, CA;M. Davis, Rochester Clinical Research Inc, Rochester, NY; N. Nagajothi, Aultman Cardiology Clinical Trials, Canton, OH; S. Olsen, Utah Cardiology PC, Layton, UT; W. Rogers, University of Alabama at Birmingham Medical Center, Birmingham, AL; J. Rubino, Piedmont Medical Group Research of Raleigh, Raleigh, NC; I. Singh, Mercy Medical Group, Sacramento, CA; G. Tarleton, Clinical Trials of America Inc, Winston-Salem, NC; R. Bhagwat, Cardiovascular Research of Northwest Indiana LLC, Munster, IN; D. Clardy, Sanford Heart Center, Fargo, ND;M. Jardula, Desert Medical Group, Palm Springs, CA; J. Robinson, The University of Iowa College of Public Health, Iowa City, IA; M. Torres, A Plus Research Inc, Miami, FL; N. Vijay, Aurora Denver Cardiology Associates PC, Denver, CO; N. Farris, The Research Group of Lexington LLC, Lexington, KY; J. Lillo, Elite Clinical Studies LLC, Phoenix, AZ; P. Moriarty, University of Kansas Medical Center, Kansas City, KS; C. Recknor, Chris Recknor MD PC,1202120312041205120612071208120912101211121212131214121512161217121812191220122112221223122412251226122712281229123012311232123312341235123612371238123912401241124212431244124512461247Gainesville GA; P. Berlacher, ProMedica Northwest Ohio Cardiology Consultants, Toledo, OH;T. Christensen, Calabash Medical Center, Calabash, NC; N. Gabra, Burke Internal Medicine and Research, Burke, VA; M. Issa, Clinical Research of Hollywood PA, Pembroke Pines, FL; M. Janik, Piedmont Medical Group Research of Wilmington, Wilmington, NC; A. Lawless, Biofortis Inc, Addison, IL; D. Molter, North Myrtle Beach Family Practice, North Myrtle Beach, SC; E. Stout, Crossroads Clinical Research Inc, Mooresville, NC; B. Brezina, Southeastern Clinical Research and Management LLC, Augusta, GA; E. Claxton, Maine Research Associates, Auburn, ME; R. Linsky, University of Colorado Memorial Health System, Colorado Springs, CO; J. Poock, Northeast Iowa Medical Education Foundation, Waterloo, IA; R. Remler, Fellows Research Alliance Inc, Savannah, GA; H. Roseman, Cardiology Wellness Center, Nashville, TN;E. Schramm, D. Schlager, St Johns Center for Clinical Research, Ponte Vedra, FL; T. Al-Joundi, Gateway Cardiovascular Research Center Inc, St Louis, MO; J. Amin, Clearwater Cardiovascular and Interventional Consultants Bardmoor, Largo, FL; J. Hitchcock, Belleville Family Medical Associates, Belleville, IL; S. Isserman, Clinical Trials of America Inc, Hickory, NC; J. Kirstein, Advanced Clinical Research, West Jordan, UT; J. Rider, Cardiology Associates of Bellin Health, Green Bay, WI; M. Shalek, Legacy Heart Center Plano, Plano, TX; H. Sherman, Southern Maine Health Care, Biddeford, ME; M. Bernstein, Louisiana Heart Center, Slidell, LA; L. Chandra, Chicago Medical Research LLC, Hazel Crest, IL; R. Hatharasinghe, Piedmont Healthcare, Statesville, NC; H. Ibrahim, North Ohio Heart Center-Sandusky, Sandusky, OH; B. Iteld, Louisiana Heart Center, Hammond, LA; K. Linzmeyer, St Lukes Idaho Cardiology Associates, Meridian, ID; B. Seaton, Research Institute of the Carolinas, Mooresville, NC; S. Zeig, Pines Clinical Research Inc, Hollywood, FL; E. Christofides, Endocrinology Associates Inc, Columbus, OH; R. Dunbar, Perelman Center for Advanced Medicine, Philadelphia, PA; S. Griffin, Head to Toe Research and Wellness LLC, Athens, GA;N. Kohli, Discovery Clinical Trials, Austin, TX; M. Koren, Jacksonville Center for Clinical Research, Jacksonville, FL; W Pharr, Medication Management LLC, Greensboro, NC; D. Purdy, Black Hills Cardiovascular Research, Rapid City, SD; R. Spencer, Cardiology Consultants, Pensacola, FL; G. Yeoman, Founders Research Corporation, Philadelphia, PA; S. Banerjee, Veterans Affairs North Texas Health Care System, Dallas, TX; H. B. Cheek, University of North Carolina Regional Physicians Carolina Cardiology, High Point, NC; E. Engel, Bayview Research Group LLC, Valley Village, CA; G. Hamroff, New York University Langone at Hudson Valley Cardiology, Cortlandt Manor NY; R. Huling, Olive Branch Family Medical Center, Olive Branch, MS; L. Kozlowski, Buffalo Medical Group, Buffalo, NY; P. Levin, Model Clinical Research Inc, Baltimore, MD; S. Makam, Mid Hudson Medical Research PLLC, New Windsor, NY; M. Meengs, Mercy Health Partners, Muskegon, MI; R. Bhushan, Metabolic Center of Louisiana Research Foundation, Baton Rouge, LA; B. Erickson, Saint Cloud Hospital, Saint Cloud, MN; L. Herman, Herman Clinical Research LLC, Suwanee, GA; E. Lo, Edgewater Medical Research, Edgewater, FL; E. McDowell, Ilumina Clinical Associates, Indiana, PA; F. McGrew, Stern Cardiovascular Foundation Inc, Germantown, TN; M. Miller, University of Maryland Medical Center, Baltimore, MD; J. Ord, Aurora Denver Cardiology Associates, Aurora, CO; R. Webel, University of Missouri Health System, Columbia, MO; G. Wilhoit, PMG Research of Charleston, Moncks Corner, SC; J. Wise, Crescent City Clinical Research, Metairie, LA; E. Yang, University of Washington, Seattle, WA; M. Budoff, Harbor University of California Medical Center, Torrance, CA; J. Collins, Saint Marys of Michigan, Saginaw, MI; I. Dauber, South Denver Cardiology Associates, Littleton, CO; L. Dobkin, Clinical Trials Research Services LLC, Pittsburgh, PA; A. Focil, Diverse Research Solutions, Oxnard, CA; W. Gandy,1248124912501251125212531254125512561257125812591260126112621263126412651266126712681269127012711272127312741275127612771278127912801281128212831284128512861287128812891290129112921293Ellipsis Group, Atlanta, GA; J. Pasquini, Novant Health Heart and Vascular Institute, Charlotte, NC; M. Ramos, Intercoastal Medical Group, Sarasota, FL; D. Rodriguez, Advanced Research Institute Inc, New Port Richey, FL; R. Rosenson, Mount Sinai Medical Center, New York, NY;Sanford, Project Management Institute of Health Inc, Atlanta, GA; A. Schlau, Palm Harbor Medical Associates, Palm Harbor, FL; B. Snyder, Southgate Medical Group, West Seneca, NY;Stonesifer, Larry D Stonesifer MD Inc PS, Federal Way, WA; A. Tang, Chambersburg Hospital, Chambersburg, PA; J. De Souza, Glacier View Research Institute Endocrinology, Kalispell, MT; M. Elam III, Memphis Veterans Affairs Medical Center, Memphis, TN; J. French, Cor Healthcare Medical Associates, San Pedro, CA; J. Guyton, Duke University Medical Center, Durham, NC; E. Hage Korban, Kore Cardiovascular Research, Jackson, TN; D. Kereiakes, The Christ Hospital, Cincinnati, OH; M. King, Clearwater Cardiovascular Consultants, Clearwater, FL; I. Loh, Westlake Medical Research, Thousand Oaks, CA; J. Navarro, Genesis Clinical Research Inc, Tampa, FL; R. Simons, Nanticoke Cardiology Associates, Seaford, DE; T. Tobin, Portland Preventive Cardiology, LLC, Longview, TX; L. Younis, Gateway Cardiology, PC, Jerseyville, IL; R. Aboufakher, Altru Health System, Grand Forks, ND; D. Baldari, Cardiology Partners Clinical Research Institute, Wellington, FL; C. Ballantyne, Baylor College of Medicine, Houston, TX; S. Banerjee, University of Texas Southwestern Medical Center, Dallas, TX; R. Broughton, CB Flock Research Corporation, Mobile, AL; C. Eaton, Memorial Hospital of Rhode Island, Pawtucket, RI; J. Johnston, Arrowhead Health Centers, Glendale, AZ; W. Simon, Professional Research Network Of Kansas, Wichita, KS; S. Thomson, Southern Arizona Veterans Administration Health Care System, Tuscon, AZ; K. Vora, Research Integrity LLC, Owensboro, KY; D. Youngman, Kansas Nephrology Research Institute LLC, Wichita, KS; O. Alzohaili, Alzohaili Medical Consultants, Dearborn, MI; E. Auerbach, Oklahoma Heart Institute, Tulsa, OK; C. Brown, Mobile Heart Specialists PC, Mobile, AL; B. Burrough, McFarland Clinic PC, Ames, IA; Y. Chen, Bendel Medical Research Center, Lafayette, LA; M. Gilpatrick, Neurocare Center for Research, Newton, MA; J. Landzberg, Westwood Cardiology Associates, Westwood, NJ; C. Mitchell, MedTrial, LLC, Columbia, SC; L. Rice, Clinical Study Center of Asheville, LLC, Asheville, NC; M. Rubenfire, University of Michigan Health System, Dominos Farms, Ann Arbor, MI; C.W. Sofley, Internal Medicine Associates of Anderson PA, Anderson, SC; D. Strobl, Sparrow Clinical Research Institute, Lansing, MI; K. Atassi, Porter Physician Services, Valparaiso, IN;W. Davila, Fleming Island Center for Clinical Research, Fleming Island, FL; J. Diogo, New England Center for Clinical Research/ Internal Medicine and Cardiology Associates, LLC, Fall River, MA; T. Fagan, Arizona Endocrine and Rheumatology Associates, Tucson, AZ; I. Joffe, Lourdes Cardiology Services, Voorhees, NJ; J. Krishna, UnityPoint Health Meriter Heart and Vascular Institute, Madison, WI; E. Osea, Innovative Clinical Research, Harbor City, CA; W. Penny, Veterans Affairs San Diego Healthcare System, San Diego, CA; W. Rowe, Great Falls Clinic LLP, Great Falls, MT; M. Shapiro, Oregon Health and Science University, Portland, OR;J. Welker, Anne Arundel Medical Center, Annapolis, MD; R. Benton, Capital Cardiology Associates, Troy, NY; D. Dobratz, College Park Family Care Center Physicians Group, Overland Park, KS; F. Fortuin, Mayo Clinic Hospital, Phoenix, AZ; J. Graham, Saint Francis Medical Group Indiana Heart Physicians, Indianapolis, IN; B. Henry, Therapeutic Research Institute of Orange County, Laguna Hills, CA; B. Kusnick, Cardiovascular Associates Research LLC, Covington, LA; M. Lutskiy, Beacon Clinical Research LLC, Quincy, MA; A. McRae, Centennial Heart Cardiovascular Consultants, LLC, Nashville, TN; K. Sanford, Health First Physicians Inc, Atlanta; W. Saway, Columbia Medical Practice, Columbia, MD; J. Scott,129412951296129712981299130013011302130313041305130613071308130913101311131213131314131513161317131813191320132113221323132413251326132713281329133013311332133313341335133613371338National Clinical Research Richmond Inc, Richmond, VA; M. Shah, Shah Associates, MD LLC, Charlotte Hall, MD; B. Weinberg, Community Hospital South, Indianapolis, IN; S. Zarich, Bridgeport Hospital, Bridgeport, CT; R. Acheatel, Escondido Cardiology Associates Incorporated, Escondido, CA; C. Case, Jefferson City Medical Group PC, Jefferson City, MO; J. Earl, Piedmont Medical Group Research of Hickory LLC, Hickory, NC; S. Fernandez, State University of New York- University at Buffalo, Buffalo, NY; G. Giugliano, Baystate Medical Practice, Springfield, MA; Y. Handelsman, Metabolic Institute of America, Tarzana, CA; P. Hermany, Grand View Lehigh Valley Health Services, Sellersville, PA; S. Holder, International Clinical Research LLC, Sanford, FL; M. Kashyap, Veterans Affairs Long Beach Healthcare System, Long Beach, CA; A. Khan, The Iowa Clinic, PC, Des Moines, IA; E. Lader, Mid Valley Cardiology, Kingston, NY; J. Peniston, Feasterville Family Health Care Center, Feasterville, PA;T. Raoof, TJoseph Raoof MD Inc Encino Research Center, Encino, CA; J. Sacco, Stratton Veterans Affairs Medical Center, Albany, NY; K. Shore, Kenneth A Shore, MD, Plano, TX; D. Spriggs, Clearwater Cardiovascular and Interventional Consultants Countryside, Safety Harbor, FL; S. Stringam, Saint Lukes Regional Medical Center, Nampa, ID; N. Tahirkheli, South Oklahoma Heart Research, Oklahoma City, OK; E. Delgado, Family Medical Center dba Discovery Clinical Trials, Orlando; W. Derian, Quincy Medical Group, Quincy, IL; J. Greenwald, Medex Healthcare Research Inc, New York, NY; M. Harris, Bend Memorial Clinic, Bend, OR; R. Jackson, Dominion Medical Associates Incorporated, Richmond, VA; G. Marhefka, Thomas Jefferson University Hospital, Philadelphia, PA; W. McElveen, Bradenton Research Center, Bradenton, FL; A. Mooss, Chi Health Alegent Creighton Clinic, Omaha, NE;P. Morris, Medical University of South Carolina, Charleston, SC; J. Murray, Meharry Medical College, Nashville, TN; P. Pearlstein, Pearl Clinical Research Inc, Norristown, PA; A. Raisinghani, University of California San Diego Medical Center, San Diego, CA; S. Rezkalla, Marshfield Clinic, Marshfield, WI; L. Sakhrani, Comprehensive Research Institute, Alhambra;D. Schreibman, Sarasota Memorial Hospital Clinical Research Center, Sarasota, FL; E. Shaoulian, Pacific Coast Cardiology and Research, Newport Beach, CA; J. Steinsapir, Metabolic Research Institute Inc, West Palm Beach, FL; A. Yataco, IRC Clinics Inc, Towson, MD; A. De La Cruz, Genesis Research Center LLC, Miami, FL; M. Fredrick, HealthCare Partners Department of Research, Huntington Beach, CA; E. Goldenberg, Christiana Care Health System, Christiana Hospital, Newark, DE; D. Lee, California Cardiac Institute Medical Group, Glendale, CA; K. McCullum, York Hospital, York, PA; B. McLellan, Saint Charles Heath Center, Bend, OR; L. Stephens, Palmetto Clinical Trial Services, LLC, Fountain Inn, SC; S. Wilson, Partners in Clinical Research, Cumberland, RI; A. Alfieri, Alfieri Cardiology Research Company Inc, Wilmington, DE; M. Mandviwala, Northwest Heart Center, Tomball, TX; D. ORourke, Veterans Affairs Medical Center, White River Junction, VT; A. Samal, Northwest Houston Cardiology, Houston, TX; K. Sanford, Blair Medical Associates, Atlanta, GA; J. Schmedtje, Roanoke Heart Institute, Roanoke, VA; F. Waxman, GSA Medical Research LLC, Hollywood; R. Carhart, State University of New York Upstate Medical University, Syracuse, NY; B. Clements, Intermountain Medical Center, Murray, UT; C. Dyke, Alaska Heart Institute, Anchorage, AK; J. Ghali, Mercer University School of Medicine, Macon, GA; L. Gruberg, Stony Brook University Medical Center, Stony Brook, NY; T. Hack, Primary Care Cardiology Research, Inc, Ayer; A. Jehle, International Heart Institute of Montana, Missoula, MT; B. Pogue, Selah Medical Center, Boise;C. Schooley, Centrura Health Research Center, Colorado Springs, CO; G. Shifrin, Cleveland Clinic Cardiology Associates, Atlantis.1339134013411342134313441345134613471348Table S1 – Efficacy Outcomes With Evolocumab vs. Placebo Stratified by Baseline LDL-CBaseline LDL-C <70 mg/dLa(N=2034)Baseline LDL-C >70 mg/dL (N=25529)OutcomeEvolocumab (N=1030)Placebo (N=1004)Hazard Ratio (95% CI)Evolocumab (N=12754)Placebo (N=12775)Hazard Ratio (95% CI)PINTPrimary endpointb86 (8.3)106 (10.6)0.80 (0.60-1.07)1258 (9.9)1457 (11.4)0.86 (0.79-0.92)0.65Key secondary endpointc48 (4.7)68 (6.8)0.70 (0.48-1.01)768 (6.0)945 (7.4)0.81 (0.73-0.89)0.44Other endpointsCardiovascular death14 (1.4)14 (1.4)0.97 (0.46-2.04)237 (1.9)226 (1.8)1.05 (0.87-1.26)0.88Myocardial infarction25 (2.4)43 (4.3)0.58 (0.35-0.94)443 (3.5)596 (4.7)0.74 (0.65-0.84)0.32Stroke17 (1.7)20 (2.0)0.85 (0.44-1.62)190 (1.5)242 (1.9)0.78 (0.65-0.95)0.84Hospitalized for unstable angina16 (1.6)19 (1.9)0.84 (0.43-1.64)220 (1.7)220 (1.7)1.00 (0.83-1.20)0.63Coronary revascularization51 (5.0)65 (6.5)0.78 (0.54-1.13)708 (5.6)900 (7.0)0.78 (0.71-0.86)0.97Baseline LDL-C data were not available for one patient randomized to placebo. To convert LDL-C to millimoles per liter, multiply by 0.0259.Data shown are n (%)a By trial design, these patients had non-HDL-C > 100 mg/dLb Cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularizationc Cardiovascular death, myocardial infarction, stroke1349Table S2: Patient Characteristics Stratified Potency of Background StatinaCharacteristicsMaximal (N=7533)Submaximal (N=20031)P-valueAge, mean + SD – yr61.1 + 8.963.0 +9.0<0.001Male5722 (76.0)15073 (75.2)0.22White raceb7027 (93.3)16431 (82.0)<0.001Region<0.001North America1877 (24.9)2694 (13.4)Europe4862 (64.5)12473 (62.3)Latin America180 (2.4)1643 (8.2)Asia, Pacific, South Africa614 (8.2)3221 (16.1)Type of atherosclerosiscMyocardial infarction6499 (86.3)15852 (79.1)<0.001Non-hemorrhagic stroke1182 (15.7)4155 (20.7)<0.001Peripheral artery disease1012 (13.4)2630 (13.1)0.51Cardiovascular risk factorsHypertension6019 (79.9)16065 (80.2)0.57Diabetes mellitus2536 (33.7)7545 (37.7)<0.001Current cigarette use2067 (27.4)5710 (28.5)0.079Statin intensity at baselinedNAHigh7533 (100)11570 (57.8)Moderate08392 (41.9)Low, unknown, or no data069 (0.3)Ezetimibe672 (8.9)768 (3.8)<0.001Other cardiovascular medicationsAspirin, P2Y12 inhibitor, or both7122 (94.6)18310 (91.5)<0.001Beta-blocker6056 (80.4)14759 (73.8)<0.001Renin-angiotensin-aldosterone inhibitor6016 (79.9)15517 (77.5)<0.001Median lipid measures in mg/dL [IQR]LDL cholesterol93.0 [80.0,111.5]91.0 [79.5, 107.5]<0.001Total cholesterol168.0 [150.5,190.5]167.0 [151.0, 187.5]0.004HDL cholesterol43.0 [36.5, 51.5]44.0 [37.0, 53.0]<0.001Triglycerides133.0 [98.5, 181.0]133.0 [100.0, 182.0]0.19LDL cholesterol < 70 mg/dL at baseline524 (7.0)1510 (7.5)0.10135013511352135313541355Table S2 – Efficacy Outcomes With Evolocumab vs. Placebo Stratified by Potency of Background StatinMaximal Potency Background StatinSubmaximal Potency Background StatinOutcomeEvolocumab (N=3758)Placebo (N=3775)Hazard Ratio (95% CI)Evolocumab (N=10026)Placebo (N=10005)Hazard Ratio (95% CI)PINTPrimary endpointa421 (11.2)489 (13.0)0.86 (0.75-0.98)923 (12.4)1074 (13.9)0.85 (0.78-0.93)0.88Key secondary endpointb246 (6.5)315 (8.3)0.78 (0.66-0.92)570 (7.9)698 (9.7)0.81 (0.72-0.90)0.71Other endpointsCardiovascular death74 (2.0)67 (1.8)1.11 (0.80-1.54)177 (2.6)173 (2.3)1.02 (0.83-1.26)0.67Myocardial infarction141 (3.8)222 (5.9)0.63 (0.51-0.78)327 (4.3)417 (5.8)0.78 (0.67-0.90)0.11Stroke60 (1.6)60 (1.6)1.00 (0.70-1.44)147 (2.3)202 (2.8)0.72 (0.58-0.89)0.11Hospitalized for unstable angina75 (2.0)90 (2.4)0.84 (0.62-1.14)161 (2.4)149 (1.9)1.08 (0.86-1.35)0.20Coronary revascularization248 (6.6)316 (8.4)0.78 (0.66-0.93)511(6.5)649 (8.8)0.78 (0.69-0.88)0.95Maximal potency statin = atorvastatin 80 mg or rosuvastatin 40 mg daily. Data shown are n (%).aCardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularizationbCardiovascular death, myocardial infarction, strokeFigure 1A. Efficacy Outcomes Stratified by Baseline LDL-CPrimary Composite EndpointAll Patients?Baseline LDL-C <70 mg/dLIBaseline LDL-C 2:70 mg/dl0IIHR (95°/o Cl} 0.85 (0.79-0.92)0.80 (0.60-1.07)0.86 (0.79-0.92)Pinteraction0.650.41.02.5Secondary Composite EndpointAll PatientsI?I0.80 (0.73-0.88)Baseline LDL-C <70 mg/dL Baseline LDL-C 2:70 mg/dl0.70 (0.48-1.01)-a-II0.81 (0.73-0.89)II0.44OA1D2.5Evolocumab betterPlacebo betterFigure 1B. Cardiovascular Death, Myocardial Infarction, or Stroke in Patients with Baseline LDL-C <70 mg/dLN=2034Hazard ratio o.70(95°/o C l, 0.48-1.01)--PlaceboEvolocumab9%8%7%4).......ll::06%u,7.7°/o-5%5.2°/oJ:.4%4)C>3%u2%1%0%0612182430MonthsfromRandomizationFigure 2A. Efficacy Outcomes Stratified by Potency of Background StatinPrimary Composite EndpointAll PatientsOn maximum intensity statinOn less intense statin0.4Secondary Composite EndpointAll PatientsOn maximum intensity statinOn less intense statin?I0II1.0?II---I I II-frIIHR (95°/o Cl)0.85 (0.79-0.92)0.86 (0.75-0.98)0.85 (0.78-0.93)2.50.80 (0.73-0.88)0.78 (0.66-0.92)0.81 (0.72-0.90)Pinteraction0.880.71OA1D2.5Evolocumab betterPlacebo betterFigure 28. Cardiovascular Death, Myocardial Infarction, or Stroke in Patients on Maximal Potency Background StatinN=7533Hazard ratio o.78(95°o/Cl, 0.66-0.92)PlaceboEvolocumab10%9626600-185579%8%4>.......ll::7%0-u,6%7112001194115%4%3%2%1%0%0612182430MonthsfromRandomization ................
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