Evaluation of Dual Versus Triple Therapy by Landmark Analysis in the RE-DUAL PCI Trial.

ABSTRACT

OBJECTIVES: The aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial. BACKGROUND: Patients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events. METHODS: A total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y12 inhibitor (and no aspirin), or warfarin plus a P2Y12 inhibitor plus aspirin. Landmark analysis was performed at 30 and 90 days. RESULTS: There was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg hazard ratio [HR] 0.45; 95% confidence interval [CI] 0.31 to 0.66; p < 0.0001; 150 mg HR 0.46; 95% CI 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg HR 0.65; 95% CI 0.47 to 0.88; p = 0.0062; 150 mg HR 0.54; 95% CI 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin. CONCLUSIONS: In RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events.