Clinical outcomes in >10,000 Asian vs >61,000 Non-Asian race patients with AF randomized to Warfarin vs DOACs: a patient-level meta-analyses from COMBINE AF

Abstract Background Randomized data comparing clinical outcomes of atrial fibrillation (AF) patients with Asian vs non-Asian races are limited. Methods Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48), we performed an individual patient-level meta-analysis to investigate and compare clinical outcomes of AF patients with self-defined Asian and non-Asian races adjusted for baseline characteristics. Standard-dose direct oral anticoagulants (SD DOAC) were defined as dabigatran 150mg bid; rivaroxaban 20mg (15mg) QD, apixaban 5 mg (2.5 mg) bid, or edoxaban 60 mg (30 mg) QD. Low-dose DOACs (DOACs [LD]) were defined as dabigatran 110 mg bid or edoxaban 30 mg (15mg) QD. Results There were 10,212 pts of Asian race and 61,471 non-Asian races in the COMBINE AF database. Compared with non-Asians, Asians were on average 3.2 yrs younger, 20 kg lighter, had worse renal function (mean CrCl 64.9 vs. 77.3 mL/min), and higher rates of prior stroke/transient ischemic attack (37.2% vs 26.6%), P<0.001 for each. The median value of time in therapeutic range of patients randomized to warfarin was lower in Asians than non-Asians (57.7% vs. 66.2%, P<0.001). In the warfarin arm, Asians had a higher adjusted risk of stroke/systemic embolic events (SEE), major bleeding (MB), ICH, GI bleeding (GIB), and net clinical outcome (NCO: stroke/SEE, MB, or death)(Figure; Upper panel). Compared to warfarin, SD DOACs significantly reduced the risks of stroke/SEE, MB, and NCO to a greater degree in Asians than non-Asians (HR stroke/SEE: Asians 0.65 vs Non-Asians 0.86; HR MB: Asians 0.62 vs Non-Asians 0.91; HR NCO: Asians 0.76 vs non-Asians 0.94; Pint <0.02 for each), while SD DOACs increased GIB only in non-Asians (Asian HR 0.92 [0.69-1.23] vs Non-Asians HR 1.41 [1.25-1.58], Pint 0.009; Figure Lower panel). Conclusions The adjusted risks of stroke/SEE and major bleeding with warfarin were higher in Asians compared to non-Asians. The benefits of DOACs over warfarin in preventing stroke/SEE, MB, and net clinical outcomes were significantly greater in Asians than non-Asians.