Efficacy and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Asians With Nonvalvular Atrial Fibrillation

Abstract

BackgroundWhether non–vitamin K antagonist oral anticoagulants (NOACs) are superior to warfarin among Asians with nonvalvular atrial fibrillation remains unclear.Methods and ResultsIn this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, there were 5843, 20 079, 27 777, and 19 375 nonvalvular atrial fibrillation patients taking apixaban, dabigatran, rivaroxaban and warfarin, respectively, from June 1, 2012 to December 31, 2016. Propensity‐score weighting was used to balance covariates across study groups. Patients were followed until the first occurrence of any efficacy or safety outcome or the end date of study. Hazard ratios (95% confidence intervals) comparing apixaban, dabigatran, and rivaroxaban with warfarin were: ischemic stroke/systemic embolism (IS/SE), 0.55 (0.43–0.69), 0.82 (0.68–0.98), and 0.81 (0.67–0.97); major bleeding, 0.41 (0.31–0.53), 0.65 (0.53–0.80), and 0.58 (0.46–0.72); and all‐cause mortality, 0.58 (0.51–0.66), 0.61 (0.54–0.68), and 0.57 (0.51–0.65). A total of 3623 (62%), 17 760 (88%), and 26 000 (94%) patients were taking low‐dose apixaban (2.5 mg twice daily), dabigatran (110 mg twice daily), and rivaroxaban (10–15 mg once daily), respectively. Similar to all‐dose NOACs, all low‐dose NOACs had lower risk of IS/SE, major bleeding, and mortality when compared with warfarin. In contrast to other standard‐dose NOACs, apixaban was associated with lower risks of IS/SE (0.45 [0.31–0.65]), major bleeding (0.29 [0.18–0.46]), and mortality (0.23 [0.17–0.31]) than warfarin.ConclusionsAll NOACs were associated with lower risk of IS/SE, major bleeding, and mortality compared with warfarin in the largest real‐world practice among Asians with nonvalvular atrial fibrillation. All low‐dose NOACs had lower risk of IS/SE, major bleeding, and mortality when compared with warfarin. Standard‐dose apixaban caused a lower risk of IS/SE, major bleeding, and mortality compared with warfarin.

Effectiveness and safety of 110 or 150 mg dabigatran vs. vitamin K antagonists in nonvalvular atrial fibrillation

“…warfarin. These results were reasonably similar to ours (HR < 1, but wide confidence intervals because of fewer patients and events), for both doses of dabigatran .…”

Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

“…Also, in ORBIT‐AF, DOAC overdosing was, in fact, associated with increased all‐cause mortality compared with recommended doses (adjusted HR: 1.91; 95% CI: 1.02 to 3.60; P = .04). Rates of adverse events were higher in underdosed and overdosed patients than in those receiving the recommended DOAC doses …”

“…However, these recommendations are not uniform worldwide, hampering the selection of the preferable posology and the identification of DOAC suboptimal use. Indeed, the approved doses and dose adjustment criteria defined by European Medicine Agency (EMA) and Food and Drugs Administration (FDA) are summarized in Table while the recommendations reported by Health Canada regulatory agency, European Society of Cardiology and Japanese guidelines, regarding DOAC dose adjustment in patients with AF, are presented in Table . Note that Japanese guidelines mention some differences in relation to EMA and FDA, particularly related to the smaller body size, different pharmacokinetic and genetic profiles of Asian populations when compared with European or American patients.…”

Safety and effectiveness of apixaban in Japanese patients with nonvalvular atrial fibrillation in clinical practice: A regulatory postmarketing surveillance, the STANDARD study

“…Apixaban received regulatory approval in Japan in 2012 for the prevention of ischemic stroke and SE in patients with NVAF. To date, the real‐world safety and effectiveness of apixaban in patients with NVAF have been assessed in retrospective claims database studies both outside of Japan and in Japan . However, data are still limited in Japanese NVAF patients.…”