Janssen Announces XARELTO Phase 3b Met Primary Endpoint in NVAF Patients

November 14, 2016 11:46 AM EST

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New Phase 3b results from the PIONEER AF-PCI study met its primary endpoint and showed that both XARELTO (rivaroxaban) groups had significantly reduced risk of bleeding compared to the warfarin arm in people with non-valvular atrial fibrillation (NVAF) receiving antiplatelet therapy following angioplasty with stenting. The findings of this exploratory, open-label, randomized study were announced today by Janssen Pharmaceuticals, Inc. during a Late-Breaking Clinical Trial session at the American Heart Association (AHA) Scientific Sessions 2016 and simultaneously published in The New England Journal of Medicine. A sub-analysis, also published today in Circulation, showed people in both XARELTO® groups had a significantly reduced risk of being re-hospitalized compared to those in the warfarin arm.

Among people undergoing percutaneous coronary intervention (PCI), also known as angioplasty, a procedure to open clogged heart arteries, five to eight percent have concomitant NVAFi,ii,iii. Management of people with NVAF following 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 following PCI, guidelines recommend "triple therapy", which is a combination of dual antiplatelet therapy (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.

"For the first time in this population, a treatment regimen resulted in less bleeding than the current standard of care," said lead investigator C. Michael Gibson, MS, MD, Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA. "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 dual antiplatelet therapy."

In PIONEER AF-PCI, researchers examined the safety of XARELTO® compared to warfarin in 2,124 people with NVAF who received background antiplatelet therapy following PCI with stenting. The primary endpoint was clinically significant bleeding (composite of 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.

"Janssen is continuing to uncover the full potential of the safety and efficacy of XARELTO® in areas of critical medical need," said Paul Burton, MD, PhD, FACC, Vice President, Medical Affairs, Janssen. "PIONEER AF-PCI is an example of that commitment as it is the first study to evaluate a non-vitamin K antagonist oral anticoagulant (NOAC) in people with NVAF following PCI."

Patients were randomized in a 1:1:1 ratio, with one group receiving XARELTO® 15 mg once daily plus single antiplatelet therapy (clopidogrel or another thienopyridine) for 12 months, another group receiving XARELTO® 2.5 mg twice daily with dual antiplatelet therapy (clopidogrel or another thienopyridine plus aspirin), and a third receiving standard "triple therapy," warfarin with dual antiplatelet therapy. Prior to randomization, the duration of dual antiplatelet therapy (one, six or 12 months) was pre-specified for the two relevant groups and the intended thienopyridine (clopidogrel, prasugrel or ticagrelor). At one year:

  • 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 percent (Hazard Ratio [HR]=0.59; 95% CI, 0.47 to 0.76; p<0.001; absolute rate 16.8 percent), and the XARELTO® 2.5 mg group by 37 percent (HR=0.63; 95% CI, 0.50 to 0.80; p<0.001; absolute rate 18 percent) compared to the warfarin group (absolute rate 26.7 percent).
    • 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.
  • Although the study was not powered to make conclusions on efficacy, both XARELTO® groups showed similar rates of major adverse cardiovascular events compared to the group taking warfarin. Specifically, 6.5 percent of people in the XARELTO® 15 mg group and 5.6 percent in the XARELTO® 2.5 mg group experienced a major adverse cardiovascular event compared to 6.0 percent in the warfarin group.

XARELTO® Also Led to Fewer Re-HospitalizationsA separate sub-analysis of PIONEER AF-PCI showed a reduction in the risk of re-hospitalization or all-cause mortality (due to an adverse event, including bleeding, a cardiovascular cause or other cause) in both XARELTO® groups compared to the warfarin group. Specifically, all-cause mortality or re-hospitalization was observed in 34.9 percent of the XARELTO® 15 mg group (p=0.008) and 31.9 percent of the XARELTO® 2.5 mg group (p=0.002) compared to 41.9 percent of the warfarin group. When looking specifically at re-hospitalization, both XARELTO® groups had significantly fewer re-hospitalizations, with 34.1 percent of the XARELTO® 15 mg group (p=0.005) and 31.2 percent of the XARELTO® 2.5 mg group (p=0.001) being re-hospitalized due to an adverse event compared to 41.5 percent of the warfarin group.

"The costs associated with re-hospitalizations following PCI due to adverse events are substantial and can be burdensome to healthcare delivery systems," said Dr. Burton. "Results from the PIONEER AF-PCI sub-analysis provide important insights into ways to reduce this cost burden associated with readmissions."

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