Comparative Stroke, Bleeding, and Mortality

ARTICLE IN PRESS APPENDIX Methods description of post hoc analyses that were performed: To assess whether exclusion of warfarin users during the pro- pensity score-matching step affected the generalizability of hazard ratio estimates for the warfarin vs NOAC compari- sons, we performed unweighted multivariable Cox propor- tional hazards regression for each study outcome based on all eligible warfarin and NOAC users. We also conducted post hoc sensitivity analyses of our outcome definitions by restricting the definition of intracranial hemorrhage to vali- dated International Classification of Diseases, Ninth Revi- sion codes only , 18-20 and by expanding the definition of extracranial bleeding to include all hospitalized extracranial bleeding events. Supplementary Table 1 Number of Patients Meeting Study Eligibility Criteria at Various Steps in the Cohort Development Process Warfarin Dabigatran (300 mg/d) Rivaroxaban (20 mg/d) Apixaban (10 mg/d) Received oral anticoagulant fill between Oct 19, 2010 and Sept 30, 2015 4,805,044 254,242 339,721 179,205 Age ≥ 65 y and enrolled in Medicare Parts A, B, & D for ≥ 6 months 2,582,587 152,425 194,390 106,579 No oral anticoagulant use in 6 months prior to cohort-defining (index) fill, only in one cohort on the index date, and no missing dosage 1,439,770 108,210 156,494 96,057 Not in nursing home, skilled nursing, or hospice on index, or hospital- ized beyond index 1,213,948 103,368 144,989 90,936 Atrial fibrillation/flutter diagnosis during 6 months prior to index 714,421 96,684 122,981 83,792 No diagnoses of DVT/PE, valvular heart disease, joint replacement, dial- ysis, kidney transplant in 6 months prior to index 523,264 86,198 106,389 73,039 Propensity score matching of warfarin to pooled NOACs users with replacement 183,318 86,198 106,389 73,039 DVT = deep vein thrombosis; NOAC = nonvitamin K antagonist oral anticoagulant; PE = pulmonary embolism. Supplementary Table 2 International Classification of Disease, Ninth Edition, Clinical Modification (ICD-9-CM) Codes Used to Define Study Outcomes Outcome ICD-9 Codes Position Setting Ischemic stroke 433.x1, 434.x (except subcode: x0), 436 1st IP only Intracranial hemorrhage 430, 431, 432, + (852.0, 852.2, 852.4, 853.0) y 1st IP only Extracranial bleeding events A bleeding event is defined as a definite bleeding code, or a possible bleeding code (primary) supported by a definite bleeding code (secondary); without a corresponding trauma code (as defined in Cunningham et a l 21 ) Definite bleeding: 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, 535.01, 535.11, 535.21, 535.31, 535.41, 535.51, 535.61, 537.83, 456.0, 456.20, 530.7,530.82, 578.0, 455.2, 455.5, 455.8, 562.02, 562.03, 562.12, 562.13, 568.81, 569.3, 569.85, 578.1, 578.9, 593.81, 599.7, 623.8, 626.2, 626.6, 423.0, 459.0, 719.1x, 784.7, 784.8, 786.3 Possible bleeding: 531.1, 531.3, 531.5, 531.7, 531.9, 532.1, 532.3, 532.5, 532.7, 532.9, 533.1, 533.3, 533.5, 533.7, 533.9, 534.1, 534.3, 534.5, 534.7, 534.9, 535.00, 535.10, 535.20, 535.30, 535.40, 535.50, 535.60, 455.x, 562.00, 562.01, 562.10, 562.11, 530.1, 280.0, 285.1, 285.9, 790.92 1st IP only Major bleeding events Major bleeding is defined as a hospitalized bleeding event with (i) a critical site code, (ii) a transfusion, or (iii) death. Critical site: Intracranial: 430, 431, 432, 852.0, 852.2, 852.4, 853.0; Extracranial: 423.0, 568.81, 719.1x Transfusions: a) ICD-9 PRC: 9903, 9904, 9905, 9906, 9907, 9909, b) HCPC: P9010, P9011, P9016, P9017, P9019, P9020, P9021, P9022, P9023, P9031-P9040, P9044, P9051 - P9060, c) Revenue Center Codes: 0380-0392, 0399, d) Additional Value Codes: 37, 38, 39 N/A IP only Major GI bleeding events Major GI bleeding is defined as a major bleeding event at a GI site N/A IP only GI = gastrointestinal; IP = inpatient. y Intracranial hemorrhage was defined using codes for atraumatic hemorrhage (430-432), with a PPV of 89%-97% , 18-20 and codes for hemorrhage with closed head trauma (852-853), which have not been validated. We included these latter codes to capture situations where a bleeding event preceded by a fall may have been coded as trauma related. 9.e1 The American Journal of Medicine, Vol 000, No 000, && 2019