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BARCELONA -- Atrial fibrillation (Afib) patients on triple therapy after percutaneous coronary intervention (PCI) can safely avoid aspirin by switching to dual antithrombotic therapy with dabigatran (Pradaxa) and a P2Y12 inhibitor, researchers of the RE-DUAL trial found.

A low dose, 110 mg, of the non-vitamin K antagonist oral anticoagulant (NOAC) with a P2Y12 inhibitor nearly halved major and clinically-relevant non-major bleeds over 14 months when compared with triple therapy of warfarin plus aspirin and a P2Y12 inhibitor (15.4% versus 26.9%, HR 0.52, 95% CI 0.42-0.63, P<0.001 for superiority).

Higher-dose dual therapy, with 150-mg dabigatran, was associated with fewer bleeds as well (20.2% versus 25.7% with corresponding triple-therapy group, HR 0.72, 95% CI 0.58-0.88, P<0.001 for noninferiority).

Christopher Cannon, MD, of Brigham and Women's Hospital in Boston, reported the findings here at the European Society of Cardiology meeting, with the simultaneously publishing the data online.

"These findings indicate a net clinical benefit of each of the two dual-therapy regimens, and clinicians could potentially select one of these two regimens on the basis of a patient's risk of bleeding and risk of thromboembolic events," Cannon's group wrote.

"In the group that received triple therapy with warfarin, the duration of aspirin therapy was just 1 to 3 months; we adopted this approach in accordance with evolutions in practice and guidelines. In effect, triple therapy shifted to dual therapy for most of the trial period," the investigators acknowledged.

In terms of combined thromboembolic events, death, or unplanned revascularization, dual therapy was not inferior for efficacy (13.7% for the two dual therapy groups combined versus 13.4% for triple therapy, HR 1.04, 95% CI 0.84-1.29, P=0.005 for noninferiority). Individual endpoints showed no statistical differences between groups; however, the lower-dose dabigatran group was numerically worse off for death, MI, stroke, and stent thrombosis when compared against triple therapy.

RE-DUAL "was not powered to allow for comparisons of individual components of this end point," the authors maintained. "We thus have to exercise caution in examining the nonsignificant small numerical excesses in some components of this end point."

Still, "these higher rates make me concerned that lower-dose dabigatran may not be fully protective against ischemic events against aspirin," commented Christopher Granger, MD, of Duke Clinical Research Institute in Durham, N.C., who was not involved in the trial.

Nonetheless, he told 番茄社区app, "the trial reinforces the message from PIONEER that it's reasonable to use one of the NOACs combined with clopidogrel, avoiding aspirin, as an alternative to traditional triple therapy."

Sites participating in RE-DUAL enrolled 2,725 patients who were randomized to triple therapy or one of two doses of dual therapy with dabigatran. Outside the U.S., people 80 years or older (70 and older in Japan) were randomized only to triple therapy or low-dose dual therapy.

Participants took their assigned anticoagulant for an average of 12.3 months. The proportion who stopped therapy prematurely was 13% in both dual therapy groups and 17% in the triple-therapy arm.

Importantly, Cannon and colleagues pointed out, "with respect to the results for both the bleeding and thromboembolic-event end points, we may only speculate on the relative contributions of the omission of aspirin and the type of oral anticoagulant in the dual-therapy groups and the triple-therapy group. A trial conducted with a formal 2-by-2 factorial design would be able to discern these contributions, and is ongoing."

Granger said that no single, better trial will come along to answer all the questions on its own. It will take several studies -- including the AUGUST trial slated for presentation next year -- to get a better sense of whether offer enough protection against stroke and other events in this setting.

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