Direct oral anticoagulant and antiplatelet combination therapy: Hemorrhagic events in coronary artery stent recipients

Direct oral anticoagulant (DOAC) use is growing as monotherapy and combined with platelet inhibitors. The safety of such combination therapy, especially in comparison to regimens including warfarin, in real world populations remains uncertain. We investigated hemorrhage associated with DOAC and antiplatelet combination therapy in a cohort of elderly coronary artery stent recipients. We employed Medicare data 2010-2013 for a 40% random sample of beneficiaries enrolled in inpatient, outpatient and prescription benefits. We used Cox proportional hazards models to examine the association of the combination anticoagulant (DOAC or warfarin) plus antiplatelets with major hemorrhage events (upper gastrointestinal or intracranial) in the 12 months following stent placement. We identified 70,900 stent recipients. 14.4% had atrial fibrillation (AF) diagnosis preoperatively. Among the 24.5 million observation days, exposure distribution was: 73.8% antiplatelets only, 4.7% antiplatelets plus warfarin, 0.6% antiplatelets plus DOAC, 2.2% warfarin only, 0.3% DOAC only and 18.4% no observed antiplatelets or anticoagulant. Overall, 8,029 patients (11.3%) experienced major hemorrhage. Among AF patients, compared to antiplatelets only, DOAC plus antiplatelets was associated with increased hemorrhage risk (HR, 1.94; 95%CI, 1.48-2.54); warfarin plus antiplatelets conferred comparable bleed risk (HR, 1.69; 95%CI, 1.47-1.94). In the non-AF group, compared to antiplatelets alone, combination DOAC plus antiplatelets (HR, 3.09; 95%CI, 2.15-4.46), and warfarin plus antiplatelets (HR, 2.21; 95%CI, 1.97-2.48) conferred greater bleed risk. Among elderly coronary artery stent recipients with AF, the two drug combinations, DOAC plus antiplatelets and warfarin plus antiplatelets, were associated with similarly increased risk of major hemorrhage compared to antiplatelets alone.