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RE-DUAL PCI: Dabigatran plus P2Y12 inhibitor lowers bleeding risk vs. triple therapy
For patients with atrial fibrillation undergoing PCI, bleeding risk was lower in those assigned dabigatran plus a P2Y12 inhibitor compared with those assigned warfarin plus a P2Y12 inhibitor plus aspirin, according to results published in The New England Journal of Medicine.
Researchers from the RE-DUAL PCI trial assigned 2,725 patients with AF who underwent PCI to either triple therapy of warfarin plus clopidogrel or ticagrelor (Brilinta, AstraZeneca) plus aspirin for 1 to 3 months or to dual therapy of dabigatran (Pradaxa, Boehringer Ingelheim) 110 mg or 150 mg twice daily plus clopidogrel or ticagrelor. Only elderly patients outside the U.S. received the 110-mg dose of dabigatran.
“As many as 30% of people with [AF] have [CAD] that may require [PCI] with stenting. Before now, there has been limited research on the use of novel oral anticoagulants in this setting,” Christopher P. Cannon, MD, cardiologist at Brigham and Women’s Hospital, executive director of cardiometabolic trials at Harvard Clinical Research Institute, professor of medicine at Harvard Medical School, said in a press release issued by Boehringer Ingelheim. “Because a rising number of these patients are already on [novel oral anticoagulant] treatment, we believe these results will provide important new insights for health care providers performing this procedure.”
The primary endpoint was major or clinically relevant bleeding. Mean follow-up was 14 months.
The researchers also assessed noninferiority for dual therapy vs. triple therapy for a composite endpoint of thromboembolic events (MI/stroke/systemic embolism), death or unplanned revascularization.
The primary endpoint occurred in 15.4% of the 110-mg dual-therapy group and in 26.9% of the triple-therapy group (HR = 0.52; 95% CI, 0.42-0.63), and in 20.2% of the 150-mg dual therapy group and 25.7% of the triple-therapy group minus elderly patients outside the U.S. (HR = 0.72; 95% CI, 0.58-0.88), the researchers reported.
The dual-therapy regimen met the threshold for noninferiority for the composite efficacy endpoint (dual therapy, 13.7%; triple therapy, 13.4%; HR = 1.04; 95% CI, 0.84-1.29; P for noninferiority = .005), according to the researchers.
Serious adverse events did not differ among the groups.
“In the dual-therapy regimens, each of the two doses of dabigatran led to a balance between the risk of bleeding and the prevention of thromboembolic events, which offers clinicians two additional options for the treatment of patients with varying risks of thromboembolic events and bleeding,” Cannon and colleagues wrote.
The results were also presented at the European Society of Cardiology Congress. – by Erik Swain
Disclosure: The study was funded by Boehringer Ingelheim. Cannon reports he receives grant support and/or personal fees from Alnylam, Amarin, Amgen, Arisaph Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, GlaxoSmithKline, Janssen, Kowa, Lipimedix, Merck, Pfizer, Regeneron, Sanofi and Takeda. Please see the full study for a list of the other authors’ relevant financial disclosures.
Perspective
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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.
Perspective
Back to TopIn 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.