Atrial fibrillation is a disease of old age and so is coronary artery disease.
Many patients of atrial fibrillation undergo coronary angioplasty and as per the guidelines require triple anti-thrombotic therapy involving warfarin plus two antiplatelet agents. This therapy is found to be on extreme risk with incidence of increased bleeding and is restricted for only one month in case of bare metal stent or three months in case of DES (drug-eluting stent).
The RE-DUAL PCI trial was conducted to compare the use of 2 regimens of dual antithrombotic therapy (that included dabigatran) with triple antithrombotic therapy (that included warfarin) among patients with AF who had undergone PCI.
RE-DUAL randomly assigned 2725 patients with AF who had recently undergone PCI to:
- triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin;
- dual therapy with dabigatran 110 mg twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor);
- dual therapy with dabigatran 150 mg twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor).
In the triple therapy arm, aspirin was discontinued after 1 month for those who received a bare-metal stent and after 3 months for those who received a drug-eluting stent. Outside the United States, elderly patients (≥80 years of age or ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group, but were not eligible for the high-dose dabigatran arm.
The primary endpoint was a major or clinically relevant nonmajor bleeding event according to International Society on Thrombosis and Hemostasis (ISTH) criteria.
After a mean follow-up of 14 months, the incidence of the primary endpoint was 15.4% in the 110-mg dual-therapy group, as compared with 26.9% in the triple-therapy group (hazard ratio [HR], 0.52; p<0.0001 for noninferiority; p<0.0001 for superiority). For the 150-mg dual-therapy group, the rate was 20.2%, as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the U.S. (HR, 0.72; p<0.001 for noninferiority; p=0.002 for superiority). Similar reductions were seen when the TIMI bleeding definition was used.
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 endpoint of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization. The incidence of this composite efficacy endpoint was 13.7% for the dual-therapy groups combined, as compared with 13.4% for triple-therapy (HR, 1.04; p=0.0047 for noninferiority).
The rate of serious adverse events did not differ significantly among the groups (42.7% for 110-mg dual-therapy group, 39.6% in the 150-mg dual-therapy group, and 41.8% in the triple-therapy group).
The researcher concluded that in patients with AF who have undergone PCI, dual therapy with dabigatran and a P2Y12 antagonist significantly reduced the risk of bleeding versus warfarin triple therapy (even with the short duration of prescribed aspirin), with non-inferiority for overall thromboembolic events.
- C Cannon, Presenter. ESC 2017 Late-Breaking Clinical Trial: RE-DUAL PCI: Dual antithrombotic therapy with dabigatran after percutaneous coronary intervention in patients with atrial fibrillation. ESC 2017. 27 AUG 2017.
- A Cannon, A Bhatt, A Oldgren, et al. : Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 27 Aug 2017. (Published online ahead of print.)