PIONEER AF-PCI Results Presented for Xarelto in NVAF Patients After PCI With Stenting

November 14, 2016—Janssen Pharmaceuticals, Inc. announced new phase 3b results from the PIONEER AF-PCI study of the company’s Xarelto (rivaroxaban) compared to warfarin in patients with nonvalvular atrial fibrillation (NVAF) receiving antiplatelet therapy after angioplasty (percutaneous coronary intervention [PCI]) with stenting. Bayer AG, which is the development partner with Janssen for Xarelto, also separately announced the data.

Xarelto met the study’s primary endpoint and showed that in both of the study’s dosage groups, Xarelto significantly reduced the risk of bleeding. The findings of this exploratory, open-label, randomized study were presented during a late-breaking clinical trial session at the American Heart Association scientific sessions 2016 in New Orleans, Louisiana. The findings were simultaneously published online ahead of print by lead investigator C. Michael Gibson, MD, et al in The New England Journal of Medicine. 

As part of the EXPLORER research program for Xarelto, the global PIONEER AF-PCI clinical study is assessing the safety of three treatment strategies in a broad group of PCI-plus-stenting patients from 26 countries. EXPLORER includes ongoing and completed studies, independent registries, and noninterventional studies. The EXPLORER program is a collaborative research effort of Janssen and Bayer and includes six additional indication-seeking programs underway beyond the currently approved six indications in the United States.

In Janssen Pharmaceutical’s announcement, the investigators noted that among patients undergoing PCI, 5% to 8% have concomitant NVAF. They stated that management of patients with NVAF after PCI with stenting is challenging, as the risks of NVAF-related stroke, stent-related blood clots (thrombosis) and bleeding from both oral anticoagulant and antiplatelet therapy must be considered. For people with NVAF after PCI, guidelines recommend "triple therapy," which is a combination of dual antiplatelet therapy (DAPT: clopidogrel or another thienopyridine plus aspirin) and anticoagulation therapy with a vitamin K antagonist (warfarin), but this regimen comes with recognized increased rates of major bleeding, including intracranial bleeding.  

Dr. Gibson commented in the company’s press release, “For the first time in this population, a treatment regimen resulted in less bleeding than the current standard of care. Pairing rivaroxaban with single or dual antiplatelet therapy has the potential to transform current practice, as demonstrated in this study with significantly less bleeding and numerically similar efficacy when compared to warfarin with DAPT.” Dr. Gibson is Professor of Medicine at Harvard Medical School, Beth Israel Deaconess Medical Center in Boston, Massachusetts.

As summarized by Janssen Pharmaceuticals, the PIONEER AF-PCI investigators examined the safety of Xarelto compared to warfarin in 2,124 people with NVAF who received  antiplatelet therapy after PCI with stenting. The primary endpoint was clinically significant bleeding (composite of Thrombolysis in Myocardial Infarction [TIMI] major bleeding, TIMI minor bleeding, or bleeding requiring medical attention). Secondary endpoints included the incidence of the components of TIMI clinically significant bleeding, the composite of major adverse cardiovascular events (cardiovascular death, heart attack, or stroke), individual components of the adverse cardiovascular event endpoint, and stent-related thrombosis.

At 1 year, the investigators found that both Xarelto groups had significantly lower rates of bleeding compared to the group taking warfarin. Specifically, the Xarelto 15-mg group reduced clinically significant bleeding by 41% (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.47 to 0.76; P < .001; absolute rate, 16.8%). The Xarelto 2.5-mg group reduced clinically significant bleeding by 37% (HR, .63; 95% CI, 0.5 to 0.8; P < .001; absolute rate, 18%) compared to the warfarin group (absolute rate, 26.7%). This reduction in bleeding for the two Xarelto groups was consistent across multiple subgroups; fatal bleeds were rare and numerically fewer in patients taking Xarelto compared to those taking warfarin.