Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation.

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 .).

• Authors: Christopher P Cannon, Deepak L Bhatt, Jonas Oldgren, Gregory Y H Lip, Stephen G Ellis, Takeshi Kimura, Michael Maeng, Bela Merkely, Uwe Zeymer, Savion Gropper, Matias Nordaby, Eva Kleine, Ruth Harper, Jenny Manassie, James L Januzzi, Jurrien M Ten Berg, P Gabriel Steg, Stefan H Hohnloser, RE-DUAL PCI Steering Committee and Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 377 Issue 16 Pg. 1513-1524 (10 19 2017) ISSN: 1533-4406 [Electronic] United States
• PMID: 28844193 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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