Comparative Safety and Effectiveness of Oral Anticoagulants in Nonvalvular Atrial Fibrillation

Abstract

Background and Purpose: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. Methods: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. Results: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS–matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40–0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63–0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81–1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56–0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97–1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78–1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. Conclusions: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.

Trends in Incidence of Intracerebral Hemorrhage and Association With Antithrombotic Drug Use in Denmark, 2005-2018

“…These results are in line with the only previous study 2 of ICH risk in association with OAC use in the wider population. In addition, these findings are similar to those reported in some studies 15 , 23 , 25 , 31 of the risk of intracranial hemorrhage with OAC use, including 2 recent large observational studies 24 , 50 of DOAC safety and effectiveness; however, most of these studies 24 , 25 , 31 , 50 found that all DOACs, including rivaroxaban, had lower risk estimates than warfarin.…”

Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation

“…[4][5][6] In the real world, approximately half of patients with AF starting on oral anticoagulants (OACs) are 75 years or older, and approximately half of these are women. 7 No RCT has investigated the efficacy and safety of NOACs specifically in elderly patients, but subgroup analyses of the RCTs, [8][9][10][11] and observational studies, 12 13 indicate that the benefits of NOACs over VKAs are maintained in the elderly population. More insight into the comparative abilities of anticoagulants to reduce the risk of stroke while keeping bleeding risk low in elderly patients is needed.…”

Cost-Effectiveness of Apixaban versus Other Direct Oral Anticoagulants and Warfarin in the Prevention of Thromboembolic Complications Among Finnish Patients with Non-Valvular Atrial Fibrillation

“…In our analysis, we applied the relative risk estimates for the primary efficacy and safety outcomes from the NAXOS study (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation). 7 NAXOS was a French real-world study including altogether 321,501 patients initiating VKA (35.0%), apixaban (27.2%), rivaroxaban (31.1%) or dabigatran (6.6%) with the aim to compare the safety, effectiveness, and mortality of the alternative anticoagulants in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. Even though the NAXOS study was conducted in France we chose it for the current analyses, since it had a highly representative sample of AF patients in France and it is one of the largest real-world studies ever conducted in Europe.…”

“…In the current assessment apixaban was compared to rivaroxaban, dabigatran and warfarin based on the relative effectiveness data available from the real-world NAXOS study (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation), 7 and representative Finnish input data for event risks, mortality, resource use, costs, and quality of life. NAXOS-study was chosen to provide relative effectiveness estimates for the comparison, because it is one of the largest real-world studies conducted on DOACs and thus far the largest in Europe.…”

“…NAXOS-study was chosen to provide relative effectiveness estimates for the comparison, because it is one of the largest real-world studies conducted on DOACs and thus far the largest in Europe. Because the NAXOS-study compared apixaban separately to each of the comparators using propensity score matching, 7 the relative cost-effectiveness was likewise assessed pair-wise as apixaban versus comparator, and comparisons between the other three anticoagulants could not be assessed in this setting. As NAXOS did not include comparison between apixaban and edoxaban (due to lack of reimbursement for the latter), edoxaban was excluded from the current analysis.…”