RE-DUAL PCI: Dabigatran plus P2Y12 inhibitor lowers bleeding risk vs. triple therapy

Chandan Devireddy, MD, FACC, FSCAI

Until recently, there was little guidance other than anecdotal experience and expert consensus in directing whether prolonged anticoagulation was safe in patients with AF needing antiplatelet therapy post-PCI. WOEST demonstrated that warfarin could be administered for low stent thrombosis rates but with high bleeding rates. With the advent of direct oral anticoagulants offering patients stroke reduction but without the hassle of monitoring and potential reduction in bleeding, questions have arisen of their potential value for patients post-PCI.

RE-DUAL PCI was a randomized study of patients with nonvalvular AF patients undergoing PCI between triple therapy with warfarin, and 2 different dosing arms of dual therapy —dabigatran (either 150mg or 110mg) and a P2Y12 inhibitor. Dual therapy post-PCI was found to reduce bleeding events while showing no significant increase in ischemic or thrombotic coronary events. Given the many studies that have demonstrated the long-term morbidity associated with bleeding, the convenience of this dual therapy regimen is very compelling and will likely greatly alter clinical practice for those patients who can afford to obtain direct oral anticoagulants.

Further studies will need to elucidate the optimal dosing strategy of dabigatran for balancing bleeding reduction with reduction of adverse cardiac events. The question also remains whether RE-DUAL PCI represents a class effect amongst all direct oral anticoagulants vs. warfarin or whether the benefits seen here are specific to dabigatran only. This is pertinent to the patients who are already being treated with an alternative direct oral anticoagulant. Future studies may also seek to show which patients, if any, stand to benefit from maintaining aspirin as part of the regimen to reduce ischemic events. For now, I do believe this is a study that will greatly alter clinical practice.

Andrew J. Klein, MD, FACC, FSCAI

In patients with AF who undergo PCI, there is a great debate on the optimal strategy of antiplatelet use and anticoagulation. Physicians must weigh reducing the risks for stent thrombosis/recurrent events with more therapy vs. the very real risk for bleeding that occurs when antiplatelet and anticoagulant therapies are combined. Though shorter DAPT durations are now considered acceptable with the newer stent generations, what to do when anticoagulants are required remains in question. RE-DUAL PCI is one of three trials to date examining: What combination of medications should our patients with AF receive after PCI and for how long?

Specifically, RE-DUAL PCI evaluated the use of double therapy (dabigatran plus clopidogrel or ticagrelor) vs. triple therapy (aspirin plus clopidogrel or ticagrelor plus dabigatran) in patients with AF undergoing PCI, 82% of whom received a DES. This study follows PIONEER AF-PCI, which examined rivaroxaban (Xarelto, Janssen Pharmaceuticals) plus clopidogrel, and the older WOEST study, which examined warfarin plus clopidogrel in patients who require anticoagulation and received a stent. Only 10% of patients received ticagrelor. RE-DUAL PCI differs in its use of dabigatran, a novel oral anticoagulant that is available in both a 110-mg dose (only outside the U.S.) and a 150-mg dose. This trial also differs in its inclusion of many patients with ACS (52%), a group for whom current guidelines recommend DAPT for 12 months. RE-DUAL PCI only mandated aspirin use for 3 months after DES placement.

RE-DUAL PCI revealed that dual therapy bested triple therapy for incidence of major or clinically relevant nonmajor bleeding events and was noninferior for thromboembolic events (MI/stroke/systemic embolism), death or unplanned revascularization.

There were also no significant differences between the groups in MI and stent thrombosis.

RE-DUAL PCI shows that we should consider treating our patients with AF who receive a stent with dual therapy (dabigatran plus clopidogrel or ticagrelor) over triple therapy given the reduction in bleeding.