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DAPT with rivaroxaban or aspirin regimen confers similar outcomes in ACS
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WASHINGTON — Among patients with ACS, substituting rivaroxaban for aspirin in dual antiplatelet therapy with a P2Y12 inhibitor did not lead to increased bleeding risk, but did not confer superior outcomes in the phase 2 GEMINI-ACS-1 trial.
“Aspirin in [DAPT] has been the primary therapy for [ACS] for some time,” E. Magnus Ohman, MB, from Duke Clinical Research Institute, said during a presentation at the American College of Cardiology Scientific Session. “But nearly 10% of patients suffer from major CV events on follow-up.”
Early-stage studies suggested rivaroxaban (Xarelto, Janssen) plus a P2Y12 inhibitor had similar efficacy to traditional DAPT but with lower risk for bleeding, he said.
For the GEMINI-ACS-1 trial, researchers randomly assigned 3,037 patients with ACS and positive cardiac biomarkers and ischemic changes on ECG or an atherosclerotic culprit lesion found during angiography to receive aspirin 100 mg once daily or rivaroxaban 2.5 mg twice daily in addition to background P2Y12 therapy, which was clopidogrel (44%) or ticagrelor (Brilinta, AstraZeneca; 56%) for a minimum of 180 days.
The primary endpoint was Thrombolysis in Myocardial Infarction (TIMI) clinically significant bleeding not related to CABG at 390 days. Median duration of DAPT was 291 days (interquartile range, 239-354).
The primary outcome occurred in 5% of both the aspirin and rivaroxaban groups (HR = 1.09; 95% CI, 0.8-1.5).
Ohman said there were no differences between the groups in TIMI major bleeding; TIMI minor bleeding; GUSTO life threatening or severe bleeding; GUSTO life threatening, severe or moderate bleeding; or BARC 3a or higher bleeding.
ISTH major bleeding was higher in the rivaroxaban group (2% vs. 1.1%; HR = 1.83; 95% CI, 1.01-3.31), Ohman said.
There was no difference between the groups in the ischemic composite endpoint of CV death, MI, stroke or definite stent thrombosis (HR = 1.06; 95% CI, 0.77-1.46), nor was there difference in individual ischemic endpoints, but the study was not powered to determine ischemic endpoints, Ohman said.
In a subgroup analysis, patients were compared by choice of P2Y12 inhibitor. There was no difference by P2Y12 inhibitor observed in the primary bleeding endpoint (P = .5889) or the composite ischemic endpoint (P = .3889).
“Defining the best antithrombotic therapy in patients transitioning from the acute thrombotic early phase to the more chronic prevention deserves more research in this field,” Ohman said. – by Erik Swain
Reference:
Ohman EM, et al. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 17-19, 2017; Washington, D.C.
Ohman EM, et al. Lancet. 2017;doi:10.1016/S0140-6736(17)30751-1.
Disclosure : The study was funded by Bayer and Janssen Research & Development. Ohman reports receiving institutional research grants from Daiichi Sankyo, Gilead Sciences and Janssen Research & Development; consultant fees from Abbott Vascular, Abiomed, AstraZeneca, Bayer, Biotie, Boehringer Ingelheim, Daiichi Sankyo, Medscape, Merck, St. Jude Medical, Stealth Peptides and The Medicines Company.
Perspective
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Sandra J. Lewis, MD, PC, FACC
To make a leap from a phase 2 trial, which is provocative and hypothesis-generating, into clinical practice is a step I’m not ready to take. One of the biggest challenges we face is the patient with ACS and atrial fibrillation. We worry so much about high bleeding risk with triple therapy of oral anticoagulation, a P2Y12 inhibitor and aspirin. In many cases we have been stopping the aspirin. But we don’t have a definitive trial about what to do with this population. It is a huge opportunity for an event-driven trial.
Perspective
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Geoffrey A. Rose, MD, FACC, FASE
GEMINI-ACS was a negative trial. The question studied: Can we do better than aspirin and P2Y12 inhibitors in the ACS population? There has been enthusiasm that moving into Factor Xa inhibition might bring a sea change for post-ACS care. This was a well-designed and well-executed trial with robust numbers. There was really no benefit, and perhaps potential for harm, in terms of increased bleeding with rivaroxaban.
As a result, we will probably move away from this concept for the time being and stick with aspirin and P2Y12 inhibitors. These results may also highlight the differences among the P2Y12 inhibitors. I look forward to the follow-up that will come out with more information about those who took clopidogrel vs. those who took ticagrelor. That message will be distilled further as the researchers look at the dataset.
For ACS, we’re wrestling with duration of therapy. Aspirin for life has been our standard in patients who receive stents. We are still trying to determine who should stay on DAPT, and whether we can do better for those who are now treated with aspirin alone. The optimal long-term antiplatelet strategy for these patients is still an open question.
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