Comparative risk of major bleeding with rivaroxaban and warfarin: Population‐based cohort study of unprovoked venous thromboembolism

Abstract

Objectives To assess the association between rivaroxaban and warfarin and major bleeding risk in unprovoked venous thromboembolism (VTE) patients. Methods Using US MarketScan claims from 1/2012‐12/2016, we identified patients who had ≥1 primary hospitalization/emergency department visit diagnosis code for an unprovoked VTE, newly initiated on rivaroxaban or warfarin within 30 days after the VTE and ≥12 months of insurance coverage prior to the VTE. Differences in baseline covariates were adjusted using inverse‐probability‐of‐treatment weights based on propensity scores (residual absolute standardized differences <0.1 achieved for all covariates). Endpoints included any major, gastrointestinal, genitourinary, intracranial, and other bleeds. Patients were followed for up to 12 months or until endpoint occurrence, index oral anticoagulant discontinuation/switch, insurance disenrollment or end of follow‐up. Results We identified 10 489 rivaroxaban and 26 364 warfarin patients with an unprovoked VTE. Upon Cox regression, rivaroxaban reduced patients’ hazard of major bleeding by 27% (95% confidence interval [CI] = 8%‐42%), gastrointestinal bleeding by 38% (95% CI = 14%‐55%), and intracranial hemorrhage by 81% (95% CI = 41%‐99%) vs warfarin. No subtype of major bleeding occurred statistically more often in rivaroxaban vs warfarin‐treated patients. Conclusions Rivaroxaban was associated with a reduced risk of overall, gastrointestinal, and intracranial major bleeding vs warfarin in unprovoked VTE. No bleeding subtype was significantly more frequent in rivaroxaban patients.

Effectiveness and Safety of Direct Oral Anticoagulants vs. Warfarin and Recurrence After Discontinuation in Patients With Acute Venous Thromboembolism in the Real World

“…Some reports suggested that there was no difference in bleeding in clinical practice, 24, 25 whereas others reported that the DOACs group had reduced bleeding. 26, 27 The target PT-INR in the present study was 1.5-2.5, which may be one of the reasons for the lack of difference in bleeding incidence between the groups. DOACs have been reported to improve quality of life 28 and shorten the length of hospital stay; 29 this therapy also does not require frequent dose adjustments like warfarin.…”

Rivaroxaban for treatment of livedoid vasculopathy: A systematic review

“…No evidence of visceral organ hemorrhage has been observed in LV patients treated with rivaroxaban. Comparison of the bleeding risks of rivaroxaban and warfarin showed that rivaroxaban had reduced risks of overall, gastrointestinal, and intracranial major bleeding in patients with unprovoked venous thromboembolism 22 . A few cases of rivaroxaban‐induced hepatotoxicity have been documented.…”

“…Comparison of the bleeding risks of rivaroxaban and warfarin showed that rivaroxaban had reduced risks of overall, gastrointestinal, and intracranial major bleeding in patients with unprovoked venous thromboembolism. 22 A few cases of rivaroxaban-induced hepatotoxicity have been documented. Liver damage was classified as hepatocellular, cholestatic, or mixed; hepatocellular was the major type.…”

Compared to randomized studies, observational studies may overestimate the effectiveness of DOACs: a metaepidemiological approach

“…As the second publication concerned a subgroup of 5004 patients with unprovoked venous thromboembolism within the study reported in the first publication (including 12,318 patients), only this larger study was retained [18]. Five studies conducted on the same American database (US Truven Market scan) were found [20][21][22][23][24]. Three studies [20][21][22] were excluded because they evaluated the same patients as two other larger studies [23,24], and more than half of their enrollment periods overlapped with those of the other studies.…”

“…Five studies conducted on the same American database (US Truven Market scan) were found [20][21][22][23][24]. Three studies [20][21][22] were excluded because they evaluated the same patients as two other larger studies [23,24], and more than half of their enrollment periods overlapped with those of the other studies. Finally, 26 studies (totalling 276,092 patients) were included : 6 RCTs [25-30], 4 prospective cohort studies [31][32][33][34], 12 studies using living databases (2 using living clinical databases [35][36] and 10 using living health administrative databases [18,23,24,[37][38][39][40][41][42][43]), and 4 retrospective cohort studies [44][45][46][47].…”