Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation

N Engl J Med. 2017 Oct 19;377(16):1513-1524. doi: 10.1056/NEJMoa1708454. Epub 2017 Aug 27.

Abstract

Background: Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding.

Methods: In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (≥80 years of age; ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization.

Results: The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups.

Conclusions: Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y12 inhibitor than among those who received triple therapy with warfarin, a P2Y12 inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. (Funded by Boehringer Ingelheim; RE-DUAL PCI ClinicalTrials.gov number, NCT02164864 .).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / adverse effects
  • Adenosine / analogs & derivatives
  • Adenosine / therapeutic use
  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Aspirin / therapeutic use
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / therapy
  • Clopidogrel
  • Dabigatran / adverse effects
  • Dabigatran / therapeutic use*
  • Drug Therapy, Combination / adverse effects
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Risk
  • Ticagrelor
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Warfarin / adverse effects
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Warfarin
  • Clopidogrel
  • Ticagrelor
  • Dabigatran
  • Adenosine
  • Ticlopidine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT02164864
  • ClinicalTrials.gov/NCT02164864