Outcomes After Use of Standard- and Low-Dose Non–Vitamin K Oral Anticoagulants in Asian Patients With Atrial Fibrillation

Abstract

Background and Purpose— Limited data are available describing the relative effectiveness, safety, and optimal dosing of non–vitamin K antagonist oral anticoagulants (NOACs) for treatment of nonvalvular atrial fibrillation in East Asian patients. We tried to compare effectiveness and safety outcomes of standard- and low-dose NOACs and warfarin in this population. Methods— Using nationwide administrative claims-based datasets from the Korean National Health Insurance Service Database (July 1, 2015, to December 31, 2016), this study comprised 56 504 anticoagulation-naive nonvalvular atrial fibrillation patients with high thromboembolic risk (CHA 2 DS 2 -VASc score, ≥2) treated with oral anticoagulants. Main study outcomes included thromboembolic events (ischemic stroke or systemic embolism), major bleeding, and mortality. Results— Among the study patients, 10 409 (18.4%) received warfarin and 46 095 (81.6%) were treated with NOACs: dabigatran (n=12 593; 22.3%), rivaroxaban (n=21 000; 37.2%), and apixaban (n=12 502; 22.1%). Low-dose NOAC (75.1% dabigatran, 59.7% rivaroxaban, and 62.7% apixaban) was more frequently used than standard-dose NOAC. During median follow-up of 15.0 months, each NOAC was associated with significantly lower risk of thromboembolic events (hazard ratio [HR], 0.76; 95% CI, 0.75–0.81 for dabigatran; HR, 0.74; 95% CI, 0.65–0.83 for rivaroxaban; and HR, 0.68; 95% CI, 0.59–0.78 for apixaban). Regarding safety outcomes, dabigatran (HR, 0.81; CI, 0.69–0.95) and apixaban (HR, 0.67; CI, 0.56–0.79) were associated with lower risk of major bleeding but not with rivaroxaban (HR, 0.96; CI, 0.84–1.11). Among adults <75 years of age without chronic kidney disease, use of low-dose apixaban did not demonstrate clinical benefit over warfarin with respect to thromboembolic events (HR, 0.99; CI, 0.76–1.28) and mortality (HR, 0.85; CI, 0.62–1.16). Conclusions— In this cohort of East Asian patients with nonvalvular atrial fibrillation, NOACs were associated with better effectiveness and safety outcomes versus warfarin. Lower NOAC doses were more often used, but an unjustified underdosing of apixaban seems to result in lower clinical benefit.

Efficacy and safety of non-vitamin K-antagonist oral anticoagulants for retinal vascular diseases in patients with atrial fibrillation: Korean cohort study

“…In terms of retinal vascular occlusion, female patients showed a higher risk of retinal vascular occlusion with NOACs than male patients. Our study did not investigate the dosage by sex, while more female patients are known to be prescribed lower dose of NOACs in Korea 30 . This may result in a higher risk of retinal vascular occlusion with lower efficacy.…”

“…Finally, the exact doses for anticoagulants were not investigated in this study. There is a tendency in Asian countries to use the lower doses of NOACs in clinical practice 2,29,30 , which may have affected the results of this study.…”

Effectiveness and Safety of Direct Oral Anticoagulant for Secondary Prevention in Asians with Atrial Fibrillation

“…A recent meta-analysis of four major clinical trials reported that compared to warfarin, DOACs showed a significantly lower risk of stroke or systemic embolism in patients with AF and a history of stroke [22]. Several studies using population-based claims databases have investigated the effectiveness and safety of different types of DOACs compared with that of warfarin in patients with AF and a history of stroke [9,[23][24][25]. A Danish nationwide cohort study reported that the risks of ischemic stroke or systemic embolism associated with apixaban, dabigatran, and rivaroxaban were comparable to those associated with warfarin [23].…”

Dose Selection of Non-Vitamin K Antagonist Oral Anticoagulants in Korean Patients with Non-Valvular Atrial Fibrillation

“…The use of reduced dose apixaban in non-eligible patients (those aged under 75 years and without chronic kidney disease) attenuated the benefit observed in the comparison between a standard dose apixaban and warfarin. 29) In patients with AF and those who were underweight (≤60 kg), on-label dosing of NOACs showed the best net clinical benefit. 26) In patients who were eligible (CrCl ≥50 mL/min), both on-label rivaroxaban 20 mg once daily and off-label underdosed rivaroxaban 15 mg once daily, showed better effectiveness and safety than warfarin.…”

“…20) In the Asian population, reduced doses of NOACs were mainly prescribed to patients with AF, and the use of such doses was considerably more common in the Asian population than in the non-Asian population ( Table 2). [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] There are several potential reasons for the more frequent use of reduced dose NOACs in Asian patients with AF. First, Asians generally have a lower body weight and smaller body size than non-Asians, who were represented to a greater degree in the pivotal RCTs.…”