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SUPPLEMENTAL MATERIALCYP2C19 inhibitors: Ketoconazole, intraconazole, voriconazole, fluconazole, diltiazem, verapamil, omerpazole, esomeprazole, erythromycin, clarithromycin, atazanavir, ritonavir, cimetidine, etravirine, felbamate, ticlopidineInternational Classification of Diseases, 9th Revision (ICD-9) Diagnostic or Procedure Codes, or Current Procedure Terminology, 4th Revision (CPT-4) Codes used to identify outcomes of interest OutcomeAlgorithmMyocardial infarctioninpatient ICD-9 diagnosis code 410.xx, excluding 410.x2, as primary; minimum 3 day stay required (unless patient died) and maximum of 180 daysIschemic strokeinpatient ICD-9 diagnosis code 433.x1, 434.x1, or 436.xxStentICD-9 procedure code 36.06 or 36.07 or CPT-4 code 392980, 92981 (inpatient or outpatient)PTCA without stentingICD-9 procedure code 00.66, 36.01, 36.02, 36.05, 36.09 or CPT-4 code 92973, 92982, 92984, 92995, 92996 (inpatient or outpatient)CABGinpatient ICD-9 procedure code 36.1x or 36.2x or CPT-4 code 33510-33536, 33545, 33572 Hemorrhagic strokeinpatient ICD-9 diagnosis code 430.x or 431.x Severe upper GI bleeddefined by the occurrence of any one of the following:inpatient ICD-9 diagnosis code 531.0x, 531.2x, 531.4x, 531.6x, 532.0x, 532.2x, 532.4x, 532.6x, 533.0x, 533.2x, 533.4x, 533.6x, 534.0x, 534.2x, 534.4x, 534.6x, 578.0inpatient ICD-9 procedure code 44.43inpatient CPT code 43255CABG = coronary artery bypass grafting; GI = gastrointestinal; PTCA = percutaneous transluminal coronary angioplasty.Supplementary Table 1a. Baseline characteristics of study patients with standardized differences?SSRI Exposure groups?Before PS matchingAfter PS matchingPatient characteristicInhibitors(n = 9,284)Non Inhibitors(n = 45,073)Stand. Diff.Inhibitors(n = 9,281)Non Inhibitors(n = 9,281 out of 44,278?)Stand. Diff.Age (years), mean ± SD59.1 ± 12.261.7 ± 13.6-0.2059.1 ±12.159.2 ± 12.6-0.01Women6139 (66.1%)29139 (64.6%)0.036136 (66.1%)6166 (66.4%)-0.01Type of insurance Commercial 3120 (33.6%)14562 (32.3%)0.033119 (33.6%)3119 (33.6%)0.00 Medicaid4594 (49.5%)19661 (43.6%)0.124594 (49.5%)4594 (49.5%)0.00 Medicare1570 (16.9%)10850 (24.1%)-0.181568 (16.9%)1568 (16.9%)0.00Year of clopidogrel initiation 1998-20011464 (15.8%)5096 (11.3%)0.131462 (15.8%)1420 (15.3%)0.01 2002-20054434 (47.8%)21543 (47.8%)0.004433 (47.8%)4495 (48.4%)-0.01 2006-20092507 (27.0%)13902 (30.8%)-0.082507 (27.0%)2476 (26.7%)0.01 2009-2013879 (9.5%)4532 (10.1%)-0.02879 (9.5%)890 (9.6%)0.00Region Midwest2134 (23.0%)9496 (21.1%)0.052134 (23.0%)2147 (23.1%)0.00 Northeast2060 (22.2%)12226 (27.1%)-0.112058 (22.2%)2031 (21.9%)0.01 South3889 (41.9%)18503 (41.1%)0.023889 (41.9%)3892 (41.9%)0.00 West1135 (12.2%)4546 (10.1%)0.071135 (12.2%)1144 (12.3%)0.00Atrial fibrillation669 (7.2%)4482 (9.9%)-0.10668 (7.2%)631 (6.8%)0.02Atherosclerosis157 (1.7%)789 (1.8%)-0.01157 (1.7%)160 (1.7%)0.00Coronary artery disease5769 (62.1%)28261 (62.7%)-0.015767 (62.1%)5735 (61.8%)0.01Congestive heart failure1790 (19.3%)9736 (21.6%)-0.061789 (19.3%)1751 (18.9%)0.01Diabetes3642 (39.2%)17921 (39.8%)-0.013640 (39.2%)3641 (39.2%)0.00Prior hemorrhagic stroke39 (0.4%)228 (0.5%)-0.0139 (0.4%)35 (0.4%)0.00Hyperlipidemia4820 (51.9%)24145 (53.6%)-0.034819 (51.9%)4802 (51.7%)0.00Hypertension6585 (70.9%)33441 (74.2%)-0.076583 (70.9%)6595 (71.1%)0.00Prior MI1160 (12.5%)5576 (12.4%)-0.041160 (12.5%)1194 (12.9%)0.02Prior ischemic stroke1139 (12.3%)6143 (13.6%)0.011137 (12.3%)1094 (11.8%)-0.02Recent (within 2 prior weeks) MI 875 (9.4%)4051 (9.0%)0.01875 (9.4%)917 (9.9%)0.00Recent (within 2 prior weeks) CABG51 (0.5%)196 (0.4%)0.0551 (0.5%)49 (0.5%)0.00Recent (within 2 prior weeks) PCI2235 (24.1%)9821 (21.8%)-0.032234 (24.1%)2256 (24.3%)0.00Peptic ulcer disease2098 (22.6%)10831 (24.0%)-0.062098 (22.6%)2094 (22.6%)-0.01Peripheral vascular disease1021 (11.0%)5848 (13.0%)0.001020 (11.0%)1036 (11.2%)-0.01Prior TIA1250 (13.5%)6449 (14.3%)-0.021250 (13.5%)1245 (13.4%)0.00Unstable angina1463 (15.8%)6411 (14.2%)0.041463 (15.8%)1488 (16.0%)-0.01Prior upper GI bleeding94 (1.0%)502 (1.1%)-0.0194 (1.0%)87 (0.9%)0.01Venous thromboembolism253 (2.7%)1493 (3.3%)-0.04253 (2.7%)255 (2.7%)0.00Prior valve replacement*79 (0.2%)-0.03**0.00Combined comorbidity score, mean ±SD1.7 ± 2.21.9 ± 2.4-0.091.7 ± 2.21.7 ± 2.20.00ACE Inhibitor or ARB5256 (56.6%)26375 (58.5%)-0.045254 (56.6%)5199 (56.0%)0.01Beta blocker4976 (53.6%)25188 (55.9%)-0.054974 (53.6%)4986 (53.7%)0.00Calcium channel blocker2911 (31.4%)15097 (33.5%)-0.042910 (31.4%)2879 (31.0%)0.01Other antihypertensive agent4646 (50.0%)22360 (49.6%)0.014645 (50.0%)4644 (50.0%)0.00H2 receptor antagonists1270 (13.7%)5783 (12.8%)0.031270 (13.7%)1257 (13.5%)0.01Proton pump inhibitors 3866 (41.6%)18877 (41.9%)-0.013864 (41.6%)3849 (41.5%)0.00Other gastroprotective agent267 (2.9%)1341 (3.0%)-0.01267 (2.9%)255 (2.7%)0.01Statin5508 (59.3%)27096 (60.1%)-0.025507 (59.3%)5474 (59.0%)0.01Other lipid-lowering agent1509 (16.3%)7812 (17.3%)-0.031509 (16.3%)1529 (16.5%)-0.01Non-selective NSAID2256 (24.3%)10412 (23.1%)0.032255 (24.3%)2291 (24.7%)-0.01COX 2 inhibitor1510 (16.3%)6642 (14.7%)0.041509 (16.3%)1493 (16.1%)0.01Warfarin744 (8.0%)4019 (8.9%)-0.03742 (8.0%)745 (8.0%)0.00Other oral anticoagulant*43 (0.1)0.00**0.00Concomitant Inducer*34 (0.1)0.00**0.04Concomitant inhibitor1341 (14.4%)6737 (14.9%)-0.011340 (14.4%)1337 (14.4%)0.00Concomitant NSAID1760 (19.0%)7517 (16.7%)0.061758 (18.9%)1720 (18.5%)0.01Concomitant oral anticoagulant442 (4.8%)2482 (5.5%)-0.03440 (4.7%)449 (4.8%)0.00Health care utilization, mean ± SD??????Number of distinct prescription medications15.4 ± 7.515.3 ± 7.40.0115.4 ± 7.515.3 ± 7.50.01Number of hospitalizations0.9 ± 1.21.0 ± 1.2-0.080.9 ± 1.20.9 ± 1.10.00Number of outpatient physician visits9.3 ± 7.69.6 ± 7.9-0.049.3 ± 7.6 9.3 ± 7.70.00Number of days hospitalized5.2 ± 9.65.8 ± 10.8-0.065.2 ± 9.6 5.2 ± 9.50.00Number of days in a nursing home7.2 ± 32.88.6 ± 34.8-0.047.2 ± 32.87.6 ± 33.8-0.01?Since variable ratio propensity score matching produces covariate balance within a matched set, but not marginally, one non-inhibiting SSRI-exposed patient along with their corresponding inhibiting SSRI-exposed patient was randomly sampled from each matched set.*As per Centers for Medicare and Medicaid Services cell size suppression policy, cell sizes are too small for display (<11)ARB = angiotensin receptor blocker; ACE = angiotensin converting enzyme; CABG = coronary artery bypass grafting; COX = cyclooxygenase; GI = gastrointestinal; MI = myocardial infarction; NSAID = nonsteroidal anti-inflammatory drug; PCI = percutaneous coronary intervention; PS = propensity score; SD = standard deviation; SSRI = selective serotonin reuptake inhibitor; TIA = transient ischemic attack.Supplementary Table 1b. Characteristics of the patients at baseline, Optum database0000?Exposure groups?Before PS matchingAfter PS matchingCharacteristicNon InhibitorsInhibitorsNon InhibitorsInhibitors145513119Patients, N14562312031193119Age, mean(SD), y60.7(11.5)59.3(10.3)59.5(11.4)59.3(10.3)Women7389(50.7)1771(56.8)1779(57)1770(56.7)Year of clopidogrel initiation 20041118(7.7)272(8.7)282(9.0)271(8.7)20052191(15.0)518(16.6)564(18.1)518(16.6)20061838(12.6)414(13.3)403(12.9)414(13.3)20071555(10.7)382(12.2)390(12.5)382(12.2)20081754(12.0)343(11.0)339(10.9)343(11.0)20091574(10.8)312(10.0)280(9.0)312(10.0)20101297(8.9)252(8.1)285(9.1)252(8.1)20111200(8.2)223(7.1)211(6.8)223(7.1)20121051(7.2)211(6.8)198(6.3)211(6.8)2013984(6.8)193(6.2)167(5.4)193(6.2)Region MidWest4378(30.1)973(31.2)942(30.2)973(31.2)NorthEast1135(7.8)204(6.5)211(6.8)204(6.5)South7458(51.2)1565(50.2)1563(50.1)1565(50.2)West1471(10.1)340(10.9)402(12.9)376(12.1)Comorbidities????Atrial fibrillation1329(9.1)217(7.0)216(6.9)217(7.0)Atherosclerosis210(1.4)37(1.2)39(1.3)37(1.2)Coronary artery disease9921(68.1)2154(69)2121(68.0)2154(69.1)Congestive heart failure2130(14.6)433(13.9)432(13.9)433(13.9)Diabetes4909(33.7)1065(34.1)1028(33.0)1065(34.1)Prior hemorrhagic stroke91(0.6)17(0.5)14(0.4)17(0.5)Hyperlipidemia10051(69.0)2177(69.8)2163(69.3)2177(69.8)Hypertension11116(76.3)2330(74.7)2319(74.4)2330(74.7)Prior myocardial infarction2202(15.1)491(15.7)489(15.7)491(15.7)Prior ischemic stroke1632(11.2)322(10.3)337(10.8)321(10.3)Hospitalization for recent MI1598(11.0)389(12.5)389(12.5)389(12.5)Hospitalization for recent ACS25(0.2)4(0.1)4(0.1)4(0.1)Recent CABG68(0.5)15(0.5)13(0.4)15(0.5)Recent PCI4562(31.3)1079(34.6)1048(33.6)1079(34.6)Peptic ulcer disease3140(21.6)631(20.2)620(19.9)631(20.2)Peripheral vascular disease1595(11.0)309(9.9)291(9.3)309(9.9)Prior transient ischemic attack1968(13.5)379(12.1)393(12.6)379(12.2)Unstable angina2127(14.6)504(16.2)491(15.7)504(16.2)Prior upper GI bleeding114(0.8)20(0.6)20(0.6)20(0.6)Venous thromboembolism386(2.7)71(2.3)87(2.8)71(2.3)Prior valve replacement40(0.3)3(0.1)4(0.1)3(0.1)Combined comorbidity score, mean(SD)1.3(2.2)1.2(2.1)1.2(2.1)1.2(2.1)Medication use????ACE Inhibitor or ARB8473(58.2)1803(57.8)1764(56.6)1803(57.8)Beta blocker8640(59.3)1835(58.8)1775(56.9)1834(58.8)Calcium channel blocker3997(27.4)812(26)787(25.2)812(26)Other antihypertensive medication6187(42.5)1377(44.1)1331(42.7)1377(44.1)Statin10119(69.5)2132(68.3)2099(67.3)2132(68.4)Other lipid-lowering medication3436(23.6)692(22.2)691(22.2)692(22.2)H2 receptor antagonist367(2.5)104(3.3)94(3.0)104(3.3)Proton pump inhibitor4703(32.3)974(31.2)956(30.7)973(31.2)Misoprostol or sucralfate290(2.0)56(1.8)60(1.9)56(1.8)Cox 2 inhibitor764(5.2)205(6.6)217(7.0)205(6.6)Non selective NSAID2634(18.1)587(18.8)565(18.1)586(18.8)Warfarin1098(7.5)215(6.9)209(6.7)214(6.9)Other oral anticoagulant (dabigatran or rivaroxaban)43(0.3)6(0.2)6(0.2)6(0.2)Concomitant rifampin 6(0)1(0)2(0.1)1(0)Concomitant CYP2C19 Inhibitor 1633(11.2)345(11.1)360(11.5)345(11.1)Concomitant NSAID 1355(9.3)347(11.1)346(11.1)346(11.1)Concomitant oral anticoagulant 712(4.9)133(4.3)132(4.2)132(4.2)Health care utilization, mean(SD)????Number of distinct prescription medications12.4(5.7)12.4(5.5)12.3(5.7)12.4(5.5)Number of hospitalizations0.7(0.9)0.8(0.9)0.8(0.9)0.8(0.9)Number of outpatient physician visits10(7.4)9.5(7.0)9.4(7.0)9.5(7.0)Number of days hospitalized4(8.3)3.7(7.0)3.8(7.0)3.7(7.0)Number of days in a nursing home2.4(17.5)1.5(13.7)1.9(14.8)1.5(13.7)Since variable ratio propensity score matching produces covariate balance within a matched set, but not marginally, one non-inhibiting SSRI-exposed patient along with their corresponding inhibiting SSRI-exposed patient was randomly sampled from each matched set.ARB = angiotensin receptor blocker; ACE = angiotensin converting enzyme; CABG = coronary artery bypass grafting; COX = cyclooxygenase; GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug; PCI = percutaneous coronary intervention; PS = propensity score; SD = standard deviation; SSRI = selective serotonin reuptake inhibitor; TIA = transient ischemic attack.Supplementary Table 1c. Characteristics of the patients at baseline, MAX database ?Exposure groups?Before PS matchingAfter PS matchingCharacteristicNon InhibitorsInhibitorsNon InhibitorsInhibitors???196604594Patients, N19661459445944594Age, mean(SD), y53.3(7.9)53.1(7.9)53(8.1)53.1(7.9)Women13671(69.5)3250(70.7)3237(70.5)3250(70.7)Year of clopidogrel initiation 2000884(4.5)327(7.1)326(7.1)327(7.1)20012267(11.5)695(15.1)677(14.7)695(15.1)20022732(13.9)780(17.0)792(17.2)780(17.0)20034220(21.5)971(21.1)934(20.3)971(21.1)20044917(25.0)941(20.5)940(20.5)941(20.5)20052403(12.2)485(10.6)521(11.3)485(10.6)20062238(11.4)395(8.6)404(8.8)395(8.6)Race: White12846(65.3)3159(68.8)3182(69.3)3159(68.8)Black2946 (15.0)595(13.0)577(12.6)595(13.0)American Indian or Alaska Native152(0.8)34(0.7)40(0.9)34(0.7)Asian188 (1.0)40(0.9)44(1.0)40(0.9)Native Hawaiian or other Pacific Islander147(0.8)59(1.3)60(1.3)59(1.3)Unknown race3382(17.2)707(15.4)691(15.0)707(15.4)Region MidWest4263(21.7)1040(22.6)1025(22.3)1040(22.6)NorthEast3728(19.0)790(17.2)776(16.9)790(17.2)South9208(46.8)2075(45.2)2099(45.7)2075(45.2)West2187(11.1)629(13.7)634(13.8)629(13.7)Comorbidities????Atrial fibrillation832(4.2)178(3.9)185(4.0)178(3.9)Atherosclerosis225(1.1)64(1.4)57(1.2)64(1.4)Coronary artery disease11005(56.0)2565(55.8)2595(56.5)2565(55.8)Congestive heart failure3763(19.1)840(18.3)826(18)840(18.3)Diabetes8750(44.5)1982(43.1)1961(42.7)1982(43.1)Prior hemorrhagic stroke89(0.5)17(0.4)22(0.5)17(0.4)Hyperlipidemia7754(39.4)1744(38.0)1733(37.7)1744(38.0)Hypertension13165(67)2973(64.7)2960(64.4)2973(64.7)Prior myocardial infarction2094(10.7)499(10.9)496(10.8)499(10.9)Prior ischemic stroke2723(13.8)576(12.5)570(12.4)576(12.5)Hospitalization for recent MI1567(8.0)360(7.8)352(7.7)360(7.8)Hospitalization for recent ACS899(4.6)257(5.6)241(5.2)257(5.6)Recent CABG100(0.5)31(0.7)33(0.7)31(0.7)Recent PCI3717(18.9)904(19.7)910(19.8)904(19.7)Peptic ulcer disease4551(23.1)1036(22.6)1020(22.2)1036(22.6)Peripheral vascular disease1988(10.1)406(8.8)422(9.2)406(8.8)Prior transient ischemic attack2230(11.3)552(12.0)547(11.9)552(12)Unstable angina2936(14.9)741(16.1)738(16.1)741(16.1)Prior upper GI bleeding242(1.2)54(1.2)67(1.5)54(1.2)Venous thromboembolism661(3.4)128(2.8)125(2.7)128(2.8)Prior valve replacement13(0.1)***Combined comorbidity score, mean(SD)1.7(2.2)1.6(2)1.6(2.1)1.6(2)Medication use????ACE Inhibitor or ARB11476(58.4)2563(55.8)2524(54.9)2563(55.8)Beta blocker10179(51.8)2298(50)2303(50.1)2298(50.0)Calcium channel blocker6678(34.0)1470(32.0)1465(31.9)1470(32.0)Other antihypertensive medication10045(51.1)2370(51.6)2333(50.8)2370(51.6)Statin11036(56.1)2528(55)2522(54.9)2528(55.0)Other lipid-lowering medication2957(15.0)617(13.4)612(13.3)617(13.4)H2 receptor antagonist4000(20.3)949(20.7)922(20.1)949(20.7)Proton pump inhibitor9306(47.3)2201(47.9)2190(47.7)2201(47.9)Misoprostol or sucralfate703(3.6)156(3.4)156(3.4)156(3.4)Cox 2 inhibitor4302(21.9)1070(23.3)1056(23,0)1070(23.3)Non selective NSAID6207(31.6)1420(30.9)1409(30.7)1420(30.9)Warfarin1531(7.8)333(7.2)308(6.7)333(7.2)Other oral anticoagulant (dabigatran or rivaroxaban)0(0)0(0)0(0)0(0)Concomitant rifampin 23(0.1)***Concomitant CYP2C19 Inhibitor 3121(15.9)710(15.5)683(14.9)710(15.5)Concomitant NSAID 4619(23.5)1166(25.4)1141(24.8)1166(25.4)Concomitant oral anticoagulant 957(4.9)199(4.3)190(4.1)199(4.3)Health care utilization, mean(SD)????Number of distinct prescription medications18.3(8.2)18(7.9)18(8.0)18(7.9)Number of hospitalizations1.1(1.4)1(1.4)1(1.4)1(1.4)Number of outpatient physician visits9.1(8.3)9.1(7.9)9.1(8.2)9.1(7.9)Number of days hospitalized6.3(11.3)5.7(10.7)5.8(10.1)5.7(10.7)Number of days in a nursing home14(47.3)11.8(43.5)11.4(42.4)11.8(43.5)Since variable ratio propensity score matching produces covariate balance within a matched set, but not marginally, one non-inhibiting SSRI-exposed patient along with their corresponding inhibiting SSRI-exposed patient was randomly sampled from each matched set.*As per Centers for Medicare and Medicaid Services cell size suppression policy, cell sizes are too small for display (<11)ARB = angiotensin receptor blocker; ACE = angiotensin converting enzyme; CABG = coronary artery bypass grafting; COX = cyclooxygenase; GI = gastrointestinal; MAX = Medicaid Analytic Extract; NSAID = nonsteroidal anti-inflammatory drug; PCI = percutaneous coronary intervention; PS = propensity score; SD = standard deviation; SSRI = selective serotonin reuptake inhibitor; TIA = transient ischemic attack.Supplementary Table 1d. Characteristics of the patients at baseline, Caremark database ?Exposure groups?Before PS matchingAfter PS matchingCharacteristicNon InhibitorsInhibitorsNon InhibitorsInhibitors0000???4650661Patients, N4943661661661Age, mean(SD), y77.5(7.8)75.6(7.4)75.6(7.3)75.6(7.4)Women3256(65.9)414(62.6)417(63.1)414(62.6)Year of clopidogrel initiation: 2006929(18.8)117(17.7)110(16.6)117(17.7)20071553(31.4)206(31.2)199(30.1)206(31.2)20082461(49.8)338(51.1)352(53.3)338(51.1)Race: White4284(86.7)579(87.6)581(87.9)579(87.6) Black303(6.1)41(6.2)34(5.1)41(6.2)American Indian32(0.6)***Asian73(1.5)***Race Unknown251(5.1)28(4.2)29(4.4)28(4.2)Region: MidWest847(17.1)120(18.2)129(19.5)120(18.2)NorthEast1543(31.2)171(25.9)174(26.3)171(25.9)South1776(35.9)237(35.9)232(35.1)237(35.9)West756(15.3)129(19.5)124(18.8)129(19.5)Comorbidities????Atrial fibrillation977(19.8)106(16)97(14.7)106(16)Atherosclerosis128(2.6)18(2.7)10(1.5)18(2.7)Coronary artery disease3266(66.1)426(64.4)430(65.1)426(64.4)Congestive heart failure1546(31.3)193(29.2)206(31.2)193(29.2)Diabetes2151(43.5)277(41.9)276(41.8)277(41.9)Prior hemorrhagic stroke24(0.5)***Hyperlipidemia3230(65.3)426(64.4)430(65.1)426(64.4)Hypertension4230(85.6)542(82.0)541(81.8)542(82)Prior myocardial infarction556(11.2)66(10.0)75(11.3)66(10.0)Prior ischemic stroke679(13.7)77(11.6)71(10.7)77(11.6)Hospitalization for recent MI373(7.5)41(6.2)52(7.9)41(6.2)Hospitalization for recent ACS124(2.5)14(2.1)10(1.5)14(2.1)Recent CABG15(0.3)2(0.3)2(0.3)2(0.3)Recent PCI756(15.3)117(17.7)118(17.9)117(17.7)Peptic ulcer disease1440(29.1)179(27.1)199(30.1)179(27.1)Peripheral vascular disease945(19.1)114(17.2)110(16.6)114(17.2)Prior transient ischemic attack761(15.4)82(12.4)88(13.3)82(12.4)Unstable angina493(10)71(10.7)64(9.7)71(10.7)Prior upper GI bleeding45(0.9)5(0.8)8(1.2)5(0.8)Venous thromboembolism185(3.7)20(3.0)20(3.0)20(3.0)Prior valve replacement****Combined comorbidity score, mean(SD)2.9(3.0)2.6(2.8)2.6(2.7)2.6(2.8)Medication use????ACE Inhibitor or ARB3045(61.6)392(59.3)393(59.5)392(59.3)Beta blocker3050(61.7)379(57.3)385(58.2)379(57.3)Calcium channel blocker1839(37.2)238(36.0)247(37.4)238(36.0)Other antihypertensive medication2774(56.1)385(58.2)381(57.6)385(58.2)Statin3148(63.7)432(65.4)447(67.6)432(65.4)Other lipid-lowering medication961(19.4)139(21.0)154(23.3)139(21.0)H2 receptor antagonist514(10.4)72(10.9)60(9.1)72(10.9)Proton pump inhibitor2162(43.7)268(40.5)286(43.3)268(40.5)Misoprostol or sucralfate123(2.5)14(2.1)15(2.3)14(2.1)Cox 2 inhibitor248(5.0)35(5.3)36(5.4)35(5.3)Non selective NSAID811(16.4)115(17.4)119(18)115(17.4)Warfarin554(11.2)85(12.9)86(13)85(12.9)Other oral anticoagulant (dabigatran or rivaroxaban)0(0)0(0)0(0)0(0)Concomitant rifampin 0(0)0(0)0(0)0(0)Concomitant CYP2C19 Inhibitor 939(19.0)135(20.4)145(21.9)135(20.4)Concomitant NSAID 549(11.1)79(12.0)79(12.0)79(12.0)Concomitant oral anticoagulant 348(7.0)49(7.4)51(7.7)49(7.4)Health care utilization, mean(SD)????Number of distinct prescription medications13.6(6.1)13.3(8.8)13.4(6.4)13.3(8.8)Number of hospitalizations0.9(1.1)0.8(1.1)0.8(1)0.8(1.1)Number of outpatient physician visits8.7(8.0)8.2(7.2)8.6(7.8)8.2(7.2)Number of days hospitalized5.8(11.6)4.6(8.5)4.3(7.0)4.6(8.5)Number of days in a nursing home7.8(25.5)5.8(21.7)5.1(17.1)5.8(21.7)Since variable ratio propensity score matching produces covariate balance within a matched set, but not marginally, one non-inhibiting SSRI-exposed patient along with their corresponding inhibiting SSRI-exposed patient was randomly sampled from each matched set.*As per Centers for Medicare and Medicaid Services cell size suppression policy, cell sizes are too small for display (<11)ARB = angiotensin receptor blocker; ACE = angiotensin converting enzyme; CABG = coronary artery bypass grafting; COX = cyclooxygenase; GI = gastrointestinal; MAX = Medicaid Analytic Extract; NSAID = nonsteroidal anti-inflammatory drug; PCI = percutaneous coronary intervention; PS = propensity score; SD = standard deviation; SSRI = selective serotonin reuptake inhibitor; TIA = transient ischemic attack.Supplementary Table 1e. Characteristics of the patients at baseline, PACE database ?Exposure groups?Before PS matchingAfter PS matchingCharacteristicNon InhibitorsInhibitorsNon InhibitorsInhibitors0000???2989521Patients, N3192523521521Age, mean(SD), y80.6(7.0)79.1(7.1)79.4(6.5)79.1(7.1)Women2749(86.1)422(80.7)428(82.1)420(80.6)Year of clopidogrel initiation 1998145(4.5)46(8.8)39(7.5)46(8.8)1999311(9.7)71(13.6)79(15.2)71(13.6)2000283(8.9)77(14.7)78(15)76(14.6)2001407(12.8)76(14.5)75(14.4)75(14.4)2002444(13.9)79(15.1)84(16.1)79(15.2)2003503(15.8)58(11.1)59(11.3)58(11.1)2004546(17.1)66(12.6)64(12.3)66(12.7)2005553(17.3)50(9.6)43(8.3)50(9.6)White3096(97.0)503(96.2)502(96.4)503(96.5)Black77(2.4)14(2.7)15(2.9)14(2.7)Region: NorthEast3192(100)523(100)521(100)521(100)Comorbidities????Atrial fibrillation730(22.9)97(18.5)98(18.8)96(18.4)Atherosclerosis124(3.9)21(4)15(2.9)21(4.0)Coronary artery disease2182(68.4)363(69.4)365(70.1)361(69.3)Congestive heart failure1267(39.7)196(37.5)192(36.9)195(37.4)Diabetes1111(34.8)182(34.8)186(35.7)180(34.5)Prior hemorrhagic stroke12(0.4)2(0.4)3(0.6)2(0.4)Hyperlipidemia1576(49.4)254(48.6)266(51.1)253(48.6)Hypertension2638(82.6)414(79.2)423(81.2)412(79.1)Prior myocardial infarction429(13.4)57(10.9)58(11.1)57(10.9)Prior ischemic stroke622(19.5)109(20.8)115(22.1)108(20.7)Hospitalization for recent MI311(9.7)49(9.4)50(9.6)49(9.4)Hospitalization for recent ACS167(5.2)35(6.7)37(7.1)35(6.7)Recent CABG****Recent PCI424(13.3)72(13.8)72(13.8)71(13.6)Peptic ulcer disease961(30.1)142(27.2)144(27.6)142(27.3)Peripheral vascular disease786(24.6)108(20.7)107(20.5)107(20.5)Prior transient ischemic attack828(25.9)149(28.5)164(31.5)149(28.6)Unstable angina435(13.6)79(15.1)80(15.4)79(15.2)Prior upper GI bleeding56(1.8)***Venous thromboembolism107(3.4)14(2.7)12(2.3)14(2.7)Prior valve replacement**0(0)1(0.2)Combined comorbidity score, mean(SD)3(2.7)3(2.6)3(2.5)3(2.6)Medication use????ACE Inhibitor or ARB1785(55.9)291(55.6)287(55.1)289(55.5)Beta blocker1798(56.3)267(51.1)263(50.5)266(51.1)Calcium channel blocker1373(43.0)210(40.2)212(40.7)209(40.1)Other antihypertensive medication1781(55.8)291(55.6)280(53.7)290(55.7)Statin1389(43.5)221(42.3)229(44)220(42.2)Other lipid-lowering medication212(6.6)26(5.0)33(6.3)26(5.0)H2 receptor antagonist515(16.1)82(15.7)76(14.6)82(15.7)Proton pump inhibitor1412(44.2)229(43.8)209(40.1)228(43.8)Misoprostol or sucralfate105(3.3)19(3.6)17(3.3)19(3.6)Cox 2 inhibitor674(21.1)107(20.5)117(22.5)106(20.3)Non selective NSAID392(12.3)70(13.4)62(11.9)70(13.4)Warfarin463(14.5)65(12.4)70(13.4)64(12.3)Other oral anticoagulant (dabigatran or rivaroxaban)0(0)0(0)0(0)0(0) Concomitant rifampin *0(0)0(0)0(0)Concomitant CYP2C19 Inhibitor 540(16.9)88(16.8)81(15.5)87(16.7)Concomitant NSAID 540(16.9)97(18.5)101(19.4)96(18.4)Concomitant oral anticoagulant 255(8.0)38(7.3)39(7.5)37(7.1)Health care utilization, mean(SD)????Number of distinct prescription medications13.3(5.1)13.1(5.3)12.9(4.9)13.1(5.3)Number of hospitalizations1.2(1.2)1.2(1.2)1.2(1.2)1.2(1.2)Number of outpatient physician visits9.9(7.1)9.9(6.9)10(6.9)9.9(6.8)Number of days hospitalized8.8(12.1)8.8(10.8)8.6(11.7)8.8(10.8)Number of days in a nursing home6.2(17.3)4.3(13)3.6(12.2)4.3(13)Since variable ratio propensity score matching produces covariate balance within a matched set, but not marginally, one non-inhibiting SSRI-exposed patient along with their corresponding inhibiting SSRI-exposed patient was randomly sampled from each matched set.*As per Centers for Medicare and Medicaid Services cell size suppression policy, cell sizes are too small for display (<11).ARB = angiotensin receptor blocker; ACE = angiotensin converting enzyme; CABG = coronary artery bypass grafting; COX = cyclooxygenase; GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug; PACE = Pharmaceutical Assistance Contract for the Elderly; PCI = percutaneous coronary intervention; PS = propensity score; SD = standard deviation; SSRI = selective serotonin reuptake inhibitor; TIA = transient ischemic attack.Supplementary Table 1f. Characteristics of the patients at baseline, PAAD database ?Before PS matchingAfter PS matchingCharacteristicNon InhibitorsInhibitorsNon InhibitorsInhibitors0000???2428386Patients, N2715386386386Age, mean(SD), y77.5(10.0)74(10.8)74.6(10.7)74.2(10.7)Women2074(76.4)282(73.1)292(75.6)282(73.1)Year of clopidogrel initiation 199864(2.4)16(4.1)17(4.4)16(4.1)1999168(6.2)38(9.8)45(11.7)38(9.8)2000244(9.0)54(14.0)45(11.7)54(14.0)2001323(11.9)64(16.6)55(14.2)64(16.6)2002459(16.9)71(18.4)75(19.4)71(18.4)2003485(17.9)61(15.8)60(15.5)61(15.8)2004542(20.0)49(12.7)61(15.8)49(12.7)2005430(15.8)33(8.5)28(7.3)33(8.5)White2459(90.6)351(90.9)349(90.4)351(90.9)Black167(6.2)22(5.7)21(5.4)22(5.7)Region MidWest****NorthEast2628(96.8)372(96.4)369(95.6)372(96.4)South61(2.2)12(3.1)13(3.4)12(3.1)West15(0.6)***Comorbidities????Atrial fibrillation614(22.6)71(18.4)77(19.9)71(18.4)Atherosclerosis102(3.8)17(4.4)24(6.2)17(4.4)Coronary artery disease1887(69.5)261(67.6)265(68.7)261(67.6)Congestive heart failure1030(37.9)128(33.2)131(33.9)128(33.2)Diabetes1000(36.8)136(35.2)131(33.9)136(35.2)Prior hemorrhagic stroke12(0.4)0(0)0(0)0(0)Hyperlipidemia1534(56.5)219(56.7)209(54.1)219(56.7)Hypertension2292(84.4)326(84.5)331(85.8)326(84.5)Prior myocardial infarction295(10.9)47(12.2)37(9.6)47(12.2)Prior ischemic stroke487(17.9)55(14.2)76(19.7)55(14.2)Hospitalization for recent MI202(7.4)36(9.3)32(8.3)36(9.3)Hospitalization for recent ACS139(5.1)25(6.5)20(5.2)25(6.5)Recent CABG****Recent PCI362(13.3)63(16.3)54(14.0)63(16.3)Peptic ulcer disease739(27.2)110(28.5)114(29.5)110(28.5)Peripheral vascular disease534(19.7)84(21.8)89(23.1)84(21.8)Prior transient ischemic attack662(24.4)88(22.8)93(24.1)88(22.8)Unstable angina420(15.5)68(17.6)58(15.0)68(17.6)Prior upper GI bleeding45(1.7)6(1.6)7(1.8)6(1.6)Venous thromboembolism154(5.7)20(5.2)17(4.4)20(5.2)Prior valve replacement*0(0)0(0)0(0)Combined comorbidity score, mean(SD)3(2.8)2.8(2.6)3(2.7)2.8(2.6)Medication use????ACE Inhibitor or ARB1596(58.8)207(53.6)185(47.9)207(53.6)Beta blocker1521(56.0)197(51.0)184(47.7)197(51.0)Calcium channel blocker1210(44.6)181(46.9)182(47.2)181(46.9)Other antihypertensive medication1573(57.9)223(57.8)238(61.7)223(57.8)Statin1404(51.7)195(50.5)198(51.3)195(50.5)Other lipid-lowering medication246(9.1)35(9.1)37(9.6)35(9.1)H2 receptor antagonist387(14.3)63(16.3)72(18.7)63(16.3)Proton pump inhibitor1294(47.7)194(50.3)184(47.7)194(50.3)Misoprostol or sucralfate120(4.4)22(5.7)24(6.2)22(5.7)Cox 2 inhibitor654(24.1)93(24.1)77(19.9)93(24.1)Non selective NSAID368(13.6)64(16.6)71(18.4)64(16.6)Warfarin373(13.7)46(11.9)51(13.2)46(11.9)Other oral anticoagulant (dabigatran or rivaroxaban)0(0)0(0)0(0)0(0)Concomitant rifampin 0(0)0(0)0(0)0(0)Concomitant CYP2C19 Inhibitor 504(18.6)63(16.3)65(16.8)63(16.3)Concomitant NSAID 454(16.7)71(18.4)52(13.5)71(18.4)Concomitant oral anticoagulant 210(7.7)23(6.0)20(5.2)23(6.0)Health care utilization, mean(SD)????Number of distinct prescription medications14.5(6.0)15(6.2)14.8(6.1)15(6.2)Number of hospitalizations1.2(1.3)1.1(1.3)1.1(1.1)1.1(1.3)Number of outpatient physician visits11.7(8.4)12.7(8.8)12.9(8.9)12.7(8.8)Number of days hospitalized9.1(13.4)8.1(12.6)8.8(13.5)8.1(12.6)Number of days in a nursing home7.2(19.5)4.2(14.4)5.5(15.2)4.2(14.4)Since variable ratio propensity score matching produces covariate balance within a matched set, but not marginally, one non-inhibiting SSRI-exposed patient along with their corresponding inhibiting SSRI-exposed patient was randomly sampled from each matched set.*As per Centers for Medicare and Medicaid Services cell size suppression policy, cell sizes are too small for display (<11)ARB = angiotensin receptor blocker; ACE = angiotensin converting enzyme; CABG = coronary artery bypass grafting; COX = cyclooxygenase; GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug; PAAD = Pharmaceutical Assistance to the Aged and Disabled; PCI = percutaneous coronary intervention; PS = propensity score; SD = standard deviation; SSRI = selective serotonin reuptake inhibitor; TIA = transient ischemic attack.Supplementary Table 2. Effect of exposure to clopidogrel plus inhibiting SSRI versus clopidogrel plus non-inhibiting SSRI, intention-to-treat analysisInhibiting SSRI (N = 9 281)Non-inhibiting SSRI (N = 44 278)OutcomeEvents, No.Rate / 1000 PYsEvents, No.Rate / 1000 PYsHR (95% CI)Any Ischemic745192.313256178.671.08 (0.99-1.17) Myocardial infarction11227.5151727.11.05 (0.85-1.29) Ischemic stroke10425.5455028.850.98 (0.79-1.21) Stent448113.271866100.451.12 (1.01-1.24) PTCA398100.15165788.741.09 (0.98-1.22) CABG9022.0939020.441.03 (0.82-1.30)Any Bleeding6515.9233117.311.02 (0.78-1.33) Hemorrhagic stroke112.69904.690.64 (0.34-1.19) Upper GI bleeding5413.2224212.651.16 (0.86-1.56)Events and rates are from the variable ratio propensity score-matched cohort. HRs are adjusted for a database and matching ratio.CABG = coronary artery bypass grafting; CI = confidence intervals; GI = gastrointestinal; HR = hazard ratio; PTCA = percutaneous transluminal coronary angioplasty; PYs = person years; SSRI = selective serotonin reuptake inhibitor.Supplementary Table 3. Database-specific analysesDatabase AS TREATED ANALYSISITT ANALYSIS Inhibiting SSRINon-inhibiting SSRIInhibiting SSRINon-inhibiting SSRIPooledN = 9281N = 44278?N = 9281N = 44278OutcomeEventsRateEventsRateHR (95% CI)EventsRateEventsRateHR (95% CI)Any Ischemic450230.811965209.471.12 (1.01-1.24)745192.313256178.671.08 (0.99-1.17)Any Bleeding2512.2516917.310.76 (0.50-1.17)6515.9233117.311.02 (0.78-1.33)AMI5024.5626326.970.97 (0.71-1.32)11227.5151727.11.05 (0.85-1.29)Ischemic Stroke5225.5229530.260.94 (0.70-1.27)10425.5455028.850.98 (0.79-1.21)Hemorrhagic Stroke*2.45414.190.68 (0.27-1.74)112.69904.690.64 (0.34-1.19)Upper GI Bleeding209.7912813.110.79 (0.49-1.27)5413.2224212.651.16 (0.86-1.56)Stent305155.041237130.671.18 (1.04-1.34)448113.271866100.451.12 (1.01-1.24)PTCA250125.941018106.671.17 (1.01-1.34)398100.15165788.741.09 (0.98-1.22)CABG4019.618418.841.02 (0.72-1.44)9022.0939020.441.03 (0.82-1.30)Inhibiting SSRINon-inhibiting SSRIOPTUMN = 3119N = 14551OutcomeEventsRateEventsRateHR (95% CI)EventsRateEventsRateHR (95% CI)Any Ischemic182277.5734239.231.18 (1.00-1.38)264204.761082179.181.13 (0.99-1.30)Any Bleeding*2.874012.330.23 (0.06-0.97)*6.547111.110.60 (0.30-1.20)AMI*14.363711.411.37 (0.68-2.78)2719.667712.051.65 (1.06-2.57)Ischemic Stroke1420.095817.891.23 (0.68-2.22)2316.749815.361.15 (0.73-1.81)Hemorrhagic Stroke*2.87123.70.88 (0.19-3.98)*1.45182.810.56 (0.13-2.43)Upper GI Bleeding00288.63?*5.08538.29?Stent142214.83574185.681.15 (0.96-1.39)188143.35798130.371.08 (0.92-1.27)PTCA110164.23426135.861.17 (0.95-1.44)158119.3261398.941.15 (0.97-1.37)CABG1622.986219.131.26 (0.73-2.20)3424.8213320.891.22 (0.83-1.78)Inhibiting SSRINon-inhibiting SSRIMAXN = 4594N = 19660OutcomeEventsRateEventsRateHR (95% CI)EventsRateEventsRateHR (95% CI)Any Ischemic188212.84760211.821.08 (0.92-1.27)341175.891412173.591.02 (0.90-1.14)Any Bleeding1415.36517.50.94 (0.52-1.68)3617.7413916.341.19 (0.82-1.72)AMI2426.3310428.020.96 (0.62-1.51)5326.223427.60.93 (0.69-1.26)Ischemic Stroke2830.6213536.460.97 (0.64-1.46)5125.2325229.750.91 (0.67-1.23)Hemorrhagic Stroke*1.09174.570.26 (0.03-1.95)*2.46435.040.52 (0.21-1.32)Upper GI Bleeding1314.24812.921.18 (0.63-2.19)3115.279711.391.49 (0.99-2.24)Stent118132.34431118.851.20 (0.98-1.47)19397.4473488.31.12 (0.96-1.31)PTCA94104.49368100.761.12 (0.89-1.41)16884.4570083.971.00 (0.84-1.18)CABG1617.478623.150.79 (0.46-1.35)4220.7319222.630.86 (0.61-1.20)Inhibiting SSRINon-inhibiting SSRICaremarkN = 661N = 4650OutcomeEventsRateEventsRateHR (95% CI)EventsRateEventsRateHR (95% CI)Any Ischemic36246.47197198.241.28 (0.90-1.84)52204.27297168.411.22 (0.90-1.64)Any Bleeding*25.952625.361.19 (0.41-3.45)*26.444725.731.03 (0.46-2.28)AMI*38.934644.890.89 (0.38-2.12)*30.147340.050.75 (0.36-1.56)Ischemic Stroke*45.973635.131.46 (0.64-3.32)1245.246837.241.34 (0.72-2.48)Hemorrhagic Stroke00*1.95?*3.75*4.9?Upper GI Bleeding*25.952423.411.27 (0.43-3.70)*22.663820.81.09 (0.46-2.59)Stent22147.71112111.931.31 (0.83-2.08)31119.8815687.121.33 (0.90-1.95)PTCA20133.019695.191.41 (0.87-2.30)30116.0413876.821.46 (0.98-2.17)CABG*12.951514.60.97 (0.22-4.26)*15.042714.751.04 (0.36-2.98)Inhibiting SSRINon-inhibiting SSRIPACEN = 521N = 2989OutcomeEventsRateEventsRateHR (95% CI)EventsRateEventsRateHR (95% CI)Any Ischemic23125.16152133.230.83 (0.53-1.31)46206.7260208.410.96 (0.70-1.32)Any Bleeding*10.542723.070.41 (0.10-1.74)*34.194937.530.94 (0.44-2.01)AMI*36.955345.540.82 (0.37-1.82)1669.027860.031.15 (0.67-1.99)Ischemic Stroke*15.834538.50.39 (0.12-1.26)*47.418767.150.69 (0.37-1.31)Hemorrhagic Stroke*5.27*5.971.41 (0.17-1.72)*8.52139.890.95 (0.21-4.33)Upper GI Bleeding*5.272017.090.23 (0.03-1.75)*25.633627.540.94 (0.39-2.25)Stent*43.395245.130.79 (0.35-1.76)1356.198566.010.82 (0.45-1.49)PTCA*48.825346.010.85 (0.40-1.81)1565.149674.670.80 (0.46-1.39)CABG*26.371210.241.89 (0.65-5.45)*30.072317.551.51 (0.64-3.56)Inhibiting SSRINon-inhibiting SSRIPAADN = 386N = 2428OutcomeEventsRateEventsRateHR (95% CI)EventsRateEventsRateHR (95% CI)Any Ischemic21260.34122206.71.11 (0.69-1.77)42248.68205197.261.26 (0.90-1.77)Any Bleeding*35.4*17.992.38 (0.65-8.67)*27.952522.931.54 (0.58-4.07)AMI*35.382337.760.73 (0.21-2.50)*44.885550.750.86 (0.41-1.84)Ischemic Stroke002134.4?*38.984541.35?Hemorrhagic Stroke*11.79*4.92.53 (0.26-24.62)*5.55*6.391.20 (0.15-9.79)Upper GI Bleeding*23.56*13.082.30 (0.48-11.11)*22.341816.51.66 (0.55-4.99)Stent15184.4468114.111.46 (0.82-2.58)23133.099387.351.44 (0.91-2.30)PTCA17210.375126.131.41 (0.82-2.41)27157.33110103.811.40 (0.91-2.15)CABG*11.78*14.740.68 (0.09-5.47)*16.71513.731.22 (0.35-4.30)Rates are for 1000 person-years; HRs are adjusted for matching ratio and additionally for the database in the pooled analysis.*As per Centers for Medicare and Medicaid Services cell size suppression policy, cell sizes are too small for display (<11).AMI = acute myocardial infarction; CABG = coronary artery bypass grafting; CI = confidence intervals; GI = gastrointestinal; HR = hazard ratio; ITT = intention to treat; MAX = Medicaid Analytic Extract; PAAD = Pharmaceutical Assistance to the Aged and Disabled; PACE = Pharmaceutical Assistance Contract for the Elderly; PTCA = percutaneous transluminal coronary angioplasty; SSRI = selective serotonin reuptake inhibitor.Supplementary Table 4. Effect of exposure to clopidogrel plus inhibiting SSRI versus clopidogrel plus non-inhibiting SSRI, primary (as treated) analysis, stratified by age Patients ≥ 65 years of age Inhibiting SSRI (N = 2 250)Non-inhibiting SSRI (N = 14 241)OutcomeEvents, No.Rate / 1000 PYsEvents, No.Rate / 1000 PYsHR (95% CI)Any Ischemic123216.84642173.741.22 (1.00-1.48) Myocardial infarction1931.9313034.140.95 (0.58-1.54) Ischemic stroke1626.9612432.50.90 (0.53-1.52) Stent78136.4435294.511.39 (1.08-1.78) PTCA66114.1229277.931.38 (1.05-1.81) CABG1118.464912.821.31 (0.67-2.54)Any Bleeding*16.797920.70.84 (0.43-1.63) Hemorrhagic stroke*5.03153.921.89 (0.54-6.65) Upper GI bleeding*11.756416.760.67 (0.30-1.47)Mortality4272.11395103.290.78 (0.57 – 1.07)Patients < 65 years of ageInhibiting SSRI (N = 7 031)Non-inhibiting SSRI (N = 30 037)OutcomeEvents, No.Rate / 1000 PYsEvents, No.Rate / 1000 PYsHR (95% CI)Any Ischemic327236.541323232.681.08 (0.95-1.22) Myocardial infarction3121.5113322.380.99 (0.67-1.46) Ischemic stroke3624.9317128.820.98 (0.68-1.41) Stent227162.66885154.121.12 (0.96-1.29) PTCA184130.81726125.261.10 (0.93-1.29) CABG2920.0713522.710.93 (0.62-1.39)Any Bleeding1510.379015.130.72 (0.41-1.25) Hemorrhagic stroke*1.38264.370.33 (0.08-1.41) Upper GI bleeding138.996410.760.88 (0.48-1.60)Events and rates are from the variable ratio propensity score-matched cohort. HRs are adjusted for a database and matching ratio.*As per Centers for Medicare and Medicaid Services cell size suppression policy, cell sizes are too small for display (<11).CABG = coronary artery bypass grafting; CI = confidence intervals; GI = gastrointestinal; HR = hazard ratio; PTCA = percutaneous transluminal coronary angioplasty; PYs = person years; SSRI = selective serotonin reuptake inhibitor.Supplementary Table 5. Effect of exposure to clopidogrel plus inhibiting SSRI versus clopidogrel plus non-inhibiting SSRI, intention-to-treat analysis, stratified by age Patients ≥ 65 years of age Inhibiting SSRI (N = 2 250)Non-inhibiting SSRI (N = 14 241)OutcomeEvents, No.Rate / 1000 PYsEvents, No.Rate / 1000 PYsHR (95% CI)Any Ischemic192207.541002173.471.19 (1.02-1.39) Myocardial infarction3839.0722136.761.06 (0.75-1.51) Ischemic stroke3535.9623639.270.97 (0.68-1.39) Stent106111.9449483.881.31 (1.06-1.62) PTCA97102.144174.571.31 (1.05-1.64) CABG1818.459415.581.15 (0.69-1.91)Any Bleeding2323.5714223.561.05 (0.67-1.63) Hemorrhagic stroke*5.1335.451.05 (0.41-2.71) Upper GI bleeding1818.4310918.081.04 (0.63-1.73)Mortality141143.65998164.350.95 (0.79-1.13)Patients < 65 years of ageInhibiting SSRI (N = 7 031)Non-inhibiting SSRI (N = 30 037)OutcomeEvents, No.Rate / 1000 PYsEvents, No.Rate / 1000 PYsHR (95% CI)Any Ischemic553187.532254181.091.04 (0.95-1.14) Myocardial infarction7423.8829622.661.04 (0.80-1.34) Ischemic stroke6922.2631424.050.98 (0.75-1.27) Stent342113.691372108.141.06 (0.94-1.20) PTCA30199.54121695.311.03 (0.91-1.17) CABG7223.2429622.681.00 (0.77-1.29)Any Bleeding4213.5118914.441.00 (0.71-1.40) Hemorrhagic stroke*1.93574.340.47 (0.20-1.09) Upper GI bleeding3611.5813310.151.23 (0.85-1.78)Events and rates are from the variable ratio propensity score-matched cohort. HRs are adjusted for a database and matching ratio.*As per Centers for Medicare and Medicaid Services cell size suppression policy, cell sizes are too small for display (<11).CABG = coronary artery bypass grafting; CI = confidence intervals; GI = gastrointestinal; HR = hazard ratio; PTCA = percutaneous transluminal coronary angioplasty; PYs = person years; SSRI = selective serotonin reuptake inhibitor; ITT=intention-to-treatSupplementary Figure 1. Hazard ratios for study outcomes stratified by database, primary (as-treated) analysisCI = confidence intervals; HR = hazard ratio; MAX = Medicaid Analytic Extract; PAAD = Pharmaceutical Assistance to the Aged and Disabled; PACE = Pharmaceutical Assistance Contract for the Elderly.Supplementary Figure 2. Hazard ratios for study outcomes stratified by database, intention-to-treat analysisCI = confidence intervals; HR = hazard ratio; MAX = Medicaid Analytic Extract; PAAD = Pharmaceutical Assistance to the Aged and Disabled; PACE = Pharmaceutical Assistance Contract for the Elderly.Supplementary Figure 3. Hazard ratios for study outcomes stratified by age, intention-to-treat analysisAMI = acute myocardial infarction; CABG = coronary artery bypass grafting; CI = confidence intervals; GI = gastrointestinal; HR = hazard ratio; PTCA = percutaneous transluminal coronary angioplasty. ................
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