Dove Medical Press
TOC \h \z \c "Supplemental table" Supplemental table 1: Definitions of CHA2DS2VASc and HAS-BLED scores PAGEREF _Toc44571325 \h 2Supplemental table 2: Other anticoagulants specified according to ATC codes PAGEREF _Toc44571326 \h 3Supplemental table 3: Definition of covariates according to International Classification of Diseases 10th version codes and the Anatomic Therapeutic Chemical classification system. PAGEREF _Toc44571327 \h 4Supplemental table 4: Definition of studied outcomes according to ICD 10 codes PAGEREF _Toc44571328 \h 5Supplemental table 5: Standardized difference as the differences in means between each pair of treatment groups divided by the standard deviation, before and after propensity score PAGEREF _Toc44571329 \h 7Supplemental table 6: Hazard ratios with 95% confidence intervals, for each outcome and comparison, by sex. All patients were 60 years of age or older and with a diagnosis of atrial fibrillation within 6 months before start of treatment with direct thrombin inhibitors, direct factor Xa inhibitors or with vitamin K antagonists PAGEREF _Toc44571330 \h 10Supplemental table 7: Hazard ratios with 95% confidence intervals, for each outcome and comparison, by age. All patients were 60 years of age or older and with a diagnosis of atrial fibrillation within 6 months before start of treatment with direct thrombin inhibitors, direct factor Xa inhibitors or with vitamin K antagonists PAGEREF _Toc44571331 \h 10Supplemental table 8: Hazard ratios with 95% confidence intervals, for each outcome and comparison, by user status. All patients were 60 years of age or older and with a diagnosis of atrial fibrillation within 6 months before start of treatment with direct thrombin inhibitors, direct factor Xa inhibitors or with vitamin K antagonists PAGEREF _Toc44571332 \h 11Supplemental table SEQ Supplemental_table \* ARABIC 1: Definitions of CHA2DS2VASc and HAS-BLED scoresRisk scorePoints if present*CHA2DS2VAScCongestive heart failure1Hypertension1Age ≥ 65 years1Age ≥ 75 years1Diabetes1Stroke (ischemic stroke Transient ischemic attack or systemic embolism)2Vascular disease 1Sex (female)1?HAS-BLEDHypertension1Abnormal renal function1Abnormal hepatic function1Stroke (ischemic stroke Transient ischemic attack)1Bleedings1Age ≥ 65 years1Medicines (aspirin, clopidogrel or non-steroidal anti-inflammatory)1Alcohol intake1Labile international normalized ratio (not available in our study)1*Reflects stroke risk in atrial fibrillation patients not in anticoagulant therapy, according to Lip et al 2010PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaXA8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 26Supplemental table SEQ Supplemental_table \* ARABIC 2: Other anticoagulants specified according to ATC codesDrug groupSpecific drugVitamin K-antagonistB01AA04 phenprocumonB01AA07 acenocoumarolHeparin groupB01AB01 heparinB01AB02 antithrombin IIIB01AB04 dalteparinB01AB05 enoxaparinB01AB09 danaparoidB01AB10 tinzaparinPlatelet aggregation inhibitors excl. heparinB01AC04 clopidogrelB01AC05 ticlopidineB01AC06 acetylsalicylic acidB01AC07 dipyridamoleB01AC09 epoprostenolB01AC11 iloprostB01AC21 treprostinilB01AC22 prasugrelB01AC24 ticagrelorB01AC30 combinationsEnzymesB01AD01 streptokinaseB01AD02 alteplaseB01AD10 drotrecogin alfaDirect thrombin inhibitorsB01AE02 lepirudinB01AE03 argatrobanB01AE05 ximelagatranOther antithrombotic agentsB01AX05 fondaparinuxSupplemental table SEQ Supplemental_table \* ARABIC 3: Definition of covariates according to International Classification of Diseases 10th version codes and the Anatomic Therapeutic Chemical classification system.CovariatesICD 10 / ATC codesCongestive heart failureI110, I130, I132, I420, I50 or ATC C03CVascular diseaseI21-I22, I700, I702-I709Ischemic stroke I63, I64EmbolismI26, I74Transient ischemic attack (TIA) G45Peripheral arterial disease I702-I709, I71, I739Myocardial infarctionI21-I23Abnormal renal function Hypertensive renal disease: I12, I13Glomerular diseases: N00-N05, N07 Renal tubulo-interstitial diseases N11, N14 Renal failure N17-N19Cystic kidney disease Q61Abnormal hepatic function Hepatitis with hepatic coma: B150, B160, B162, B190, Esophageal varices I85Hepatic failure K704, K72Portal hypertension K766Alcohol relatedE244, E529A, F10, G312, G621, G721, I426, K292, K70, K860, L278A, O354M, T51, Z714, Z721DiabetesE10-E14 or ATC: A10 HypertensionI10-I15 orcombination treatment with at least two of the following classes of antihypertensive drugs:I. Alpha adrenergic blockers (C02A, C02B, C02C)II. Non-loop diuretics (C02DA, C02L, C03A, C03B, C03D, C03E, C03X, C07C, C07D, C08G, C09BA, C09DA, C09XA52)III. Vasodilators (C02DB, C02DD, C02DG, C04, C05)IV. Beta blockers (C07)V. Calcium channel blockers (C07F, C08, C09BB, C09DB)VI. Renin-angiotensin system inhibitors (C09)Renal diseaseDiabetes mellitus with renal complications: E102, E112, E132, E142Hypertensive renal disease with renal failure: I120Systemic connective tissue disorders with renal involvement: M300, M313, M321BGlomerular diseases: N02-N08, Renal tubulo-interstitial diseases: N11-N12, N14, N158-N160, N162-N164, N168, Chronic kidney disease/failure/contraction: N18-N19, N26, Cystic kidney disease: Q612-Q613, Q615, Q619Anuria and oliguria R34 Dialysis/kidney transplant: Z49, Z940Procedure codes for dialysis: DR015-DR016, DR023-DR024, DR055-DR056Surgical code for kidney transplant: KASHepatic diseaseB15-B19, C22, D684C, I982B, K70-K77, R16, R17, Z944 Surgical code: JJCDisorders of thyroid glandE00-E07Low dose acetylsalicylic acidB01AC06ClopidogrelB01AC04AntidepressantsN06AB, N06AX21, N06AX16AntibioticsJ04AB02, J01FA09AntiarrhythmicsC01BD01, C01BD07, C08DA01Non-steroidal anti-inflammatoryM01AAntimycoticsD01AC08, J02AC02, J02AC04SteroidsH02ASupplemental table SEQ Supplemental_table \* ARABIC 4: Definition of studied outcomes according to ICD 10 codesOutcomesTextICD 10Other BleedingAcute posthaemorrhagic anaemiaD62 Haemorrhagic disorder due to circulating anticoagulantsD683Haemorrhagic condition, unspecifiedD699Conjunctival haemorrhageH113Choroidal haemorrhage and ruptureH313Retinal haemorrhageH356Vitreous haemorrhageH431Vitreous haemorrhage in diseases classified elsewhereH450OtorrhagiaH922Oesophageal varices with bleedingI850Oesophageal varices with bleeding in diseases classified elsewhereI983HaemothoraxJ942Gastro-oesophageal laceration-haemorrhage syndromeK226Other specified diseases of oesophagus (Haemorrhage of oesophagus NOS)K228Gastric ulcer Chronic or unspecified with haemorrhageK254Gastric ulcer Chronic or unspecified with both haemorrhage and perforationK256Duodenal ulcer Chronic or unspecified with haemorrhageK264Duodenal ulcer Chronic or unspecified with both haemorrhage and perforationK266Peptic ulcer, site unspecified Chronic or unspecified with haemorrhageK274Peptic ulcer, site unspecified Chronic or unspecified with both haemorrhage and perforationK276Gastrojejunal ulcer Chronic or unspecified with haemorrhageK284Gastrojejunal ulcer Chronic or unspecified with both haemorrhage and perforationK286Haemorrhage of anus and rectumK625HaemoperitoneumK661Recurrent and persistent haematuriaN02Vascular disorders of male genital organs (Haematocele NOS, Haemorrhage, Thrombosis)N501Haemorrhage from respiratory passagesR04Spontaneous ecchymosesR233Unspecified haematuriaR31Haemorrhage, not elsewhere classifieR58Other intracranial injuriesS068DeathAll-cause mortalityN/AGastro-intestinal bleedingGastric ulcer Acute with hemorrhageK250Gastric ulcer Acute with both hemorrhage and perforationK252Duodenal ulcer Acute with hemorrhageK260Duodenal ulcer Acute with both hemorrhage and perforationK262Peptic ulcer, site unspecified Acute with hemorrhageK270Peptic ulcer, site unspecified Acute with both hemorrhage and perforationK272Gastrojejunal ulcer Acute with hemorrhageK280Gastrojejunal ulcer Acute with both hemorrhage and perforationK282Acute hemorrhagic gastritisK290HematemesisK920MelaenaK921Gastrointestinal hemorrhage, unspecifiedK922Intracranial bleedingSubarachnoid haemorrhageI60Intracerebral haemorrhageI61Other nontraumatic intracranial haemorrhageI62Sequelae of subarachnoid haemorrhageI690Sequelae of intracerebral haemorrhageI691Sequelae of other nontraumatic intracranial haemorrhageI692Epidural haemorrhageS064Traumatic subdural haemorrhageS065Traumatic subarachnoid haemorrhageS066Supplemental table SEQ Supplemental_table \* ARABIC 5: Standardized difference as the differences in means between each pair of treatment groups divided by the standard deviation, before and after propensity scoreVariableDTI vs VKAXAB vs DTIXAB vs VKABeforeAfterBeforeAfterBeforeAfterAbnormal hepatic function0.19-0.01-0.100.020.09-0.01Abnormal renal function0.020.01-0.01-0.010.01-0.02Age <75-0.310.000.290.00-0.020.01Age 75-790.06-0.01-0.04-0.020.02-0.01Age 80-840.170.00-0.110.030.06-0.01Age 85 +0.220.01-0.27-0.01-0.060.00Alcohol related-0.050.010.050.00-0.01-0.01Antiarrhythmics0.090.01-0.04-0.010.050.02Antibiotics0.010.02-0.010.020.000.01Antidepressants0.020.01-0.04-0.01-0.02-0.01Antimycotics-0.02-0.030.010.03-0.01-0.03Bleeding0.030.00-0.06-0.01-0.040.00CHA2DS2VASc score >70.050.01-0.05-0.010.000.01CHA2DS2VASc score 0-1-0.230.000.170.01-0.050.01CHA2DS2VASc score 2-3-0.13-0.010.08-0.02-0.04-0.01CHA2DS2VASc score 4-70.290.01-0.210.010.080.00Clopidogrel0.07-0.01-0.06-0.010.010.00Congestive heart failure0.190.01-0.090.010.10-0.01County Blekinge0.09-0.01-0.100.000.00-0.02County Dalarna0.040.02-0.110.03-0.070.00County G?vleborg0.18-0.01-0.030.020.150.01County Gotland0.130.00-0.080.010.070.02County Halland-0.310.020.20-0.01-0.12-0.01County J?mtland0.13-0.01-0.090.010.040.00County J?nk?ping0.150.00-0.19-0.01-0.04-0.03County Kalmar0.130.01-0.100.010.030.00County Kronoberg0.180.00-0.200.01-0.030.02County Norrbotten0.180.00-0.100.010.09-0.02County ?rebro0.190.00-0.180.020.000.01County ?sterg?tland0.230.00-0.24-0.01-0.01-0.02County Sk?ne-0.19-0.020.19-0.04-0.010.02County S?dermanland0.04-0.010.00-0.010.040.01County Stockholm-0.340.000.33-0.01-0.010.02County Uppsala-0.030.010.000.02-0.030.00County V?rmland-0.310.020.220.04-0.10-0.02County V?sterbotten0.17-0.01-0.100.020.070.00County V?sternorrland0.21-0.01-0.08-0.020.130.01County V?stmanland-0.210.02-0.01-0.03-0.22-0.02County V?stra g?taland0.330.00-0.300.020.03-0.02Diabetes0.11-0.01-0.050.000.060.00Disorders of thyroid gland0.020.00-0.030.01-0.010.00Education 9-year compulsory school0.20-0.01-0.120.020.08-0.01Education High school0.020.02-0.01-0.010.01-0.02Education missing0.010.01-0.01-0.020.000.02Education Tertiary education-0.24-0.020.140.00-0.100.02Embolism0.030.02-0.010.010.01-0.01Female0.080.00-0.100.01-0.020.00Fenproc-0.02-0.030.010.00-0.010.00HAS-BLED score >50.030.00-0.030.010.00-0.01HAS-BLED score 0-0.110.000.09-0.01-0.020.00HAS-BLED score 1-3-0.050.000.040.01-0.020.01HAS-BLED score 4-50.120.00-0.090.000.03-0.01Hepatic disease0.010.000.000.000.01-0.02Home support0.07-0.02-0.160.01-0.090.00Home support hours/week >900.04-0.01-0.080.01-0.04-0.01Home support hours/week 0-0.070.020.16-0.010.090.00Home support hours/week 1-440.04-0.01-0.09-0.01-0.050.00Home support hours/week 45-890.05-0.01-0.100.02-0.060.01Hospitalization days >90.100.01-0.100.02-0.010.00Hospitalization days 0-0.17-0.020.090.01-0.080.01Hospitalization days 1-30.080.02-0.010.000.070.00Hospitalization days 4-90.130.01-0.09-0.030.04-0.01Hypertension0.160.01-0.090.020.070.01Ischemic stroke0.06-0.02-0.060.010.00-0.01Non-na?ve0.160.010.00-0.020.160.01Non-steroidal anti-inflammatory-0.05-0.010.040.01-0.010.00Number drugs <=5-0.220.000.17-0.03-0.050.00Number drugs >50.220.00-0.170.030.050.00Nursing home0.060.01-0.12-0.01-0.060.00Outpatient visits >9-0.010.010.080.010.070.00Outpatient visits 0-0.13-0.02-0.610.00-0.750.01Outpatient visits 1-30.130.020.500.000.65-0.01Outpatient visits 4-9-0.010.000.220.000.220.01Peripheral arterial disease0.090.01-0.05-0.030.030.00Platelet inhibitors0.110.010.040.000.150.00Private clinic-0.25-0.010.19-0.01-0.08-0.01Renal disease0.19-0.01-0.090.020.10-0.01Short-term housing0.040.03-0.09-0.01-0.050.00Steroids0.060.00-0.07-0.03-0.010.01Time period 2012 Q1 0.290.010.230.000.450.00Time period 2012 Q2 0.220.020.260.000.430.00Time period 2012 Q3 0.230.010.230.000.410.00Time period 2012 Q4 0.14-0.010.29-0.010.400.01Time period 2013 Q1 0.110.030.300.010.390.01Time period 2013 Q2 0.070.000.310.010.370.01Time period 2013 Q3 0.06-0.010.270.010.32-0.01Time period 2013 Q4 -0.02-0.010.290.000.27-0.01Time period 2014 Q1 0.010.010.17-0.020.180.01Time period 2014 Q2 -0.090.000.13-0.010.040.00Time period 2014 Q3 -0.14-0.010.130.02-0.01-0.02Time period 2014 Q4 -0.120.000.010.00-0.11-0.05Time period 2015 Q1 -0.100.00-0.11-0.03-0.200.01Time period 2015 Q2 -0.08-0.02-0.21-0.02-0.29-0.02Time period 2015 Q3 -0.010.00-0.290.01-0.290.00Time period 2015 Q4 -0.080.00-0.320.01-0.390.01Time period 2016 Q1 -0.210.00-0.190.01-0.390.00Time period 2016 Q2 -0.20-0.02-0.250.00-0.420.01Time period 2016 Q3 -0.220.00-0.240.01-0.430.03Time period 2016 Q4 -0.200.01-0.19-0.01-0.360.00Transient ischemic attack (TIA)0.060.00-0.050.010.010.01Urban city living0.100.000.450.010.55-0.03Vascular disease0.140.01-0.09-0.010.050.001: DTI = direct thrombin inhibitors, VKA = vitamin K antagonists, XAB = direct factor Xa inhibitorsSupplemental table SEQ Supplemental_table \* ARABIC 6: Hazard ratios with 95% confidence intervals, for each outcome and comparison, by sex. All patients were 60 years of age or older and with a diagnosis of atrial fibrillation within 6 months before start of treatment with direct thrombin inhibitors, direct factor Xa inhibitors or with vitamin K antagonistsComparison1MenWomenBleedingsDTI vs. VKA0.86?(0.65, 1.12)0.93?(0.66, 1.31)XAB vs. VKA0.95?(0.76, 1.19)1.21?(0.94, 1.56)XAB vs. DTI1.12?(0.84, 1.52)1.26?(0.89, 1.81)GastrointestinalDTI vs. VKA0.73?(0.40, 1.30)2.41?(1.31, 4.74) 2XAB vs. VKA0.78?(0.51, 1.20)1.38?(0.89, 2.17)XAB vs. DTI1.00?(0.55, 1.81)0.69?(0.39, 1.18)IntracranialDTI vs. VKA0.69?(0.33, 1.44)0.51?(0.19, 1.30)XAB vs. VKA0.67?(0.38, 1.16)0.88?(0.51, 1.54)XAB vs. DTI1.39?(0.55, 3.78)1.78?(0.64, 5.65)DeathDTI vs. VKA1.29?(0.79, 2.14)1.78?(0.98, 3.40)XAB vs. VKA1.66?(1.21, 2.30)21.60?(1.16, 2.25) 2XAB vs. DTI1.12?(0.71, 1.76)1.45?(0.90, 2.36)1: DTI = direct thrombin inhibitors, VKA = vitamin K antagonists, XAB = direct factor Xa inhibitors2: Statistically significant at the 5% significance levelSupplemental table SEQ Supplemental_table \* ARABIC 7: Hazard ratios with 95% confidence intervals, for each outcome and comparison, by age. All patients were 60 years of age or older and with a diagnosis of atrial fibrillation within 6 months before start of treatment with direct thrombin inhibitors, direct factor Xa inhibitors or with vitamin K antagonistsComparison160-7475-7980-8485+BleedingsDTI vs. VKA0.71 (0.53, 0.95)1.16 (0.76, 1.80)1.09 (0.59, 2.04)0.98 (0.49, 1.97)XAB vs. VKA0.83 (0.64, 1.09)1.15 (0.80, 1.65)1.99 (1.30, 3.14) 21.03 (0.72, 1.48)XAB vs. DTI1.05 (0.74, 1.49)1.18 (0.76, 1.86)1.39 (0.80, 2.47)1.62 (0.83, 3.29)GastrointestinalDTI vs. VKA1.14 (0.66, 2.00)1.22 (0.55, 2.83)1.70 (0.53, 6.41)0.89 (0.24, 3.40)XAB vs. VKA0.78 (0.45, 1.35)1.34 (0.66, 2.83)1.92 (0.88, 4.65)1.03 (0.57, 1.89)XAB vs. DTI0.61 (0.32, 1.13)1.16 (0.53, 2.56)0.61 (0.20, 1.77)1.86 (0.58, 7.03)IntracranialDTI vs. VKA0.45 (0.18, 1.05)0.70 (0.22, 2.15)0.54 (0.07, 3.28)1.10 (0.18, 8.43)XAB vs. VKA0.63 (0.33, 1.18)0.86 (0.38, 1.98)2.21 (0.84, 6.85)0.76 (0.33, 1.76)XAB vs. DTI1.49 (0.36, 7.27)0.91 (0.28, 3.02)2.34 (0.49, 17.17)0.53 (0.02, 5.60)DeathDTI vs. VKA2.66 (1.31, 5.99) 21.00 (0.49, 2.09)1.51 (0.52, 4.96)1.73 (0.79, 4.06)XAB vs. VKA1.48 (0.93, 2.42)1.30 (0.76, 2.30)1.52 (0.94, 2.52)1.89 (1.32, 2.75)XAB vs. DTI0.79 (0.43, 1.46)0.72 (0.32, 1.55)2.93 (1.33, 7.38) 21.65 (0.90, 3.18)1: DTI = direct thrombin inhibitors, VKA = vitamin K antagonists, XAB = direct factor Xa inhibitors2: Statistically significant at the 5% significance levelSupplemental table SEQ Supplemental_table \* ARABIC 8: Hazard ratios with 95% confidence intervals, for each outcome and comparison, by user status. All patients were 60 years of age or older and with a diagnosis of atrial fibrillation within 6 months before start of treatment with direct thrombin inhibitors, direct factor Xa inhibitors or with vitamin K antagonistsComparison1Na?veNon-na?veBleedingsDTI vs. VKA0.78 (0.56, 1.07)1.01 (0.75, 1.35)XAB vs. VKA0.97 (0.75, 1.27)1.12 (0.90, 1.40)XAB vs. DTI1.33 (0.94, 1.90)1.10 (0.81, 1.50)GastrointestinalDTI vs. VKA1.24 (0.67, 2.31)1.27 (0.75, 2.19)XAB vs. VKA1.05 (0.64, 1.74)1.28 (0.84, 1.96)XAB vs. DTI0.76 (0.41, 1.40)0.70 (0.39, 1.24)IntracranialDTI vs. VKA0.48 (0.20, 1.04)1.02 (0.35, 3.12)XAB vs. VKA0.55 (0.29, 1.00)1.09 (0.63, 1.91)XAB vs. DTI0.99 (0.35, 2.82)5.05 (1.69, 21.66)2DeathDTI vs. VKA1.90 (1.02, 3.70)21.28 (0.79, 2.10)XAB vs. VKA1.39 (0.96, 2.04)1.79 (1.35, 2.38)2XAB vs. DTI0.92 (0.55, 1.54)1.36 (0.87, 2.15)1: DTI = direct thrombin inhibitors, VKA = vitamin K antagonists, XAB = direct factor Xa inhibitors2: Statistically significant at the 5% significance level ................
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