J&J’s Xarelto Shows Reduced Risk of Bleeding and Adverse Events in Analysis of PIONEER AF-PCI Data

April 12, 2024—Johnson & Johnson (J&J) recently announced findings from a new analysis of the PIONEER AF-PCI clinical trial data.

The international, multicenter, randomized, open-label clinical trial evaluated the safety of the company’s Xarelto (rivaroxaban) compared to warfarin for the treatment of patients aged ≥ 18 years of age with paroxysmal, persistent, or permanent nonvalvular atrial fibrillation (AF) who had undergone percutaneous coronary intervention (PCI) with stent placement.

According to J&J, the analysis demonstrated that Xarelto was associated with a reduced risk of clinically significant bleeding (CSB) and net adverse clinical events (NACE; a composite of CSB or major adverse cardiovascular event) or rehospitalization compared to warfarin among both elderly (aged ≥ 75 years) and nonelderly (aged < 75 years) patients with nonvalvular AF undergoing PCI.

These data were highlighted in an oral presentation (abstract #906-04 by Gerald Chi, MD, et al) at ACC.24, the American College of Cardiology Annual Scientific Session held April 6-8 in Atlanta, Georgia.

As summarized by J&J, the PIONEER AF-PCI exploratory trial enrolled 2,124 patients with nonvalvular AF undergoing PCI, of whom 729 (34.3%) were elderly. Patients were randomized to either rivaroxaban- or warfarin-based antithrombotic regimens.

The analysis showed that treatment with Xarelto versus warfarin was associated with the following:

• A lower rate of CSB at 12 months in both elderly patients (21.3% vs 31.4%; hazard ratio [HR], 0.64; 95% CI, 0.46-0.88; P = .005; number needed to treat [NNT]=10) and nonelderly patients (15.3% vs 24.6%; HR, 0.58; 95% CI, 0.45-0.75; P < .001; NNT = 11; interaction P = .676).
• A lower risk of NACE or rehospitalization in both elderly patients (HR, 0.77; 95% CI, 0.62-0.96) and nonelderly patients (HR, 0.69; 95% CI, 0.58-0.82; interaction P = .435), primarily driven by a lower risk of CSB.
• Lower rates of major bleeding in both elderly patients (3.7% vs 5.2%; HR, 0.71; 95% CI, 0.33-1.55) and nonelderly patients (1.1% vs 2.5%; HR, 0.45; 95% CI, 0.18-1.10).
• Lower rates of minor bleeding in both elderly patients (1.4% vs 3.8%; HR, 0.36; 95% CI, 0.12-1.07) and nonelderly patients (1.0% vs 1.4%; HR, 0.67; 95% CI, 0.23-1.92).

C. Michael Gibson, MD, is Senior Investigator of the PIONEER AF-PCI analysis. Dr. Gibson is CEO of the nonprofit Baim Institute and Professor of Medicine at Harvard Medical School in Boston, Massachusetts.

“Despite advances in cardiovascular care, patients with nonvalvular AF continue to be at risk of potentially life-threatening cardiovascular events, especially older patients considered difficult to treat due to multiple factors, including age and comorbidities,” commented Dr. Gibson in the company’s press release.

Dr. Gibson continued, “A significant challenge in managing nonvalvular AF in older individuals undergoing PCI is determining a treatment that balances the prevention of stroke with the risk for bleeding. Results from the PIONEER AF-PCI trial reinforce the need to continue to research this complex and fragile elderly patient population.”

Rivaroxaban is being developed by J&J’s pharmaceutical segment, Janssen (which is being renamed Johnson & Johnson Innovative Medicine) together with Bayer AG.

In November 2016, Janssen and Bayer separately announced the presentation of the phase 3b PIONEER AF-PCI study results at the American Heart Association annual scientific sessions in New Orleans, Louisiana.

Those findings were simultaneously published by Dr. Gibson et al in The New England Journal of Medicine (2016;375:2423-2434). The study met its primary endpoint and showed that rivaroxaban significantly reduced the risk of bleeding.

PIONEER AF-PCI, randomized the 2,124 patients in a 1:1:1 ratio as follows:

• Low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1).
• Low-dose rivaroxaban (2.5 mg twice daily) plus dual-antiplatelet therapy for 1, 6, or 12 months (group 2).
• Standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus dual-antiplatelet therapy for 1, 6, or 12 months (group 3).

The primary safety endpoint was the occurrence of clinically significant bleeding, a composite of major bleeding or minor bleeding according to thrombolysis in myocardial infarction criteria or bleeding requiring medical attention during the treatment period. The treatment period was defined as the time from the first administration of a trial drug to 2 days after the trial drugs were discontinued, through 12 months of therapy.

Secondary endpoints included the incidence of each component of the primary safety endpoint, as well as the following efficacy endpoints: the occurrence of a major adverse cardiovascular event (a composite of death from cardiovascular causes, myocardial infarction, or stroke), each component of the major adverse cardiovascular event endpoint, and stent thrombosis.