Janssen’s Xarelto Evaluated in VOYAGER PAD Analyses of High-Risk and Complex Patients

November 14, 2023—The Janssen Pharmaceutical Companies of Johnson & Johnson announced data from two new analyses from the phase 3 VOYAGER PAD clinical trial that reinforce the benefit of Xarelto (rivaroxaban; 2.5 mg twice daily plus aspirin 100 mg once daily) over standard of care (aspirin alone).

According to the company, the data from the two analyses demonstrate the role of Xarelto in treating both high-risk and fragile patients, as well as patients with and without comorbid coronary artery disease (CAD). Results were presented at AHA 2023, the American Heart Association’s scientific sessions held November 11-13 in Philadelphia, Pennsylvania.

Marc P. Bonaca, MD, with the Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus in Aurora, Colorado, is the lead study author of the two analyses from VOYAGER PAD: “Impact of Low-Dose Rivaroxaban plus Aspirin on Total Vascular Events in Fragile Patients with Peripheral Artery Disease: Insights from VOYAGER PAD” and “Impact of Low-Dose Rivaroxaban plus Aspirin on Myocardial Infarction in Patients with Peripheral Artery Disease with and without Concomitant Coronary Artery Disease: Insights from VOYAGER PAD.”

“These analyses reinforce the consistency of the favorable benefit-risk profile of Xarelto plus aspirin for patients with vascular disease, regardless of comorbidity,” commented Dr. Bonaca in the company’s press release. “For example, patients categorized as ‘fragile’ are often undertreated due to concerns about benefit-risk, particularly with antithrombotic treatments.”

Dr. Bonaca continued, “We hope the ongoing wealth of data coming from VOYAGER PAD presented at AHA offers clinicians the information they need to support shared decision-making in prescribing Xarelto plus aspirin as the standard of care for their peripheral artery disease [PAD] patients, including those who are high-risk or complex.”

In the analysis of total vascular events in fragile patients with PAD, patients were aged > 75 years, weight < 50 kg, or baseline estimated glomerular filtration rate < 50 mL/min/1.73. Fragile patients with PAD can be at a heightened risk for major adverse limb events (MALE), defined as a composite of acute limb ischemia and major amputation, noted the press release.

The analysis showed that Xarelto plus aspirin was effective in reducing the occurrence of MALE compared to aspirin alone in both fragile patients (6.2% vs 10.3%) and nonfragile patients (7.9% vs 9.7%).

Additionally, Xarelto plus aspirin compared to aspirin alone reduced the occurrence of total vascular events in fragile patients over 3 years (absolute rate of 82.1 events vs 99.3 events, per 100 patients). A similar benefit was seen in nonfragile patients (70.4 vs 81.6 events, per 100 patients).

Importantly, thrombolysis in myocardial infarction (TIMI) major bleeding was consistent in both the fragile and nonfragile treatment groups. Xarelto plus aspirin demonstrated a consistent, numerical increase in TIMI major bleeding for both fragile (hazard ratio [HR], 1.66; 95% CI, 0.87-3.19) and nonfragile (HR, 1.37; 95% CI, 0.83-2.24; P-interaction = .65) patients.

The press release next summarized the analysis of the role of Xarelto plus aspirin on myocardial infarction (MI) in patients with PAD with and without concomitant CAD after lower extremity revascularization (LER). The company noted that after LER, patients with PAD are four times more likely to experience acute limb ischemia or a rapid decrease in lower limb blood flow, which is often associated with long hospitalizations and high incidences of amputation, disability, and death unless appropriate treatment is given. Patients with PAD are also at a heightened risk of MACE, defined as MI, ischemic stroke, or cardiovascular death.

In patients treated with Xarelto plus aspirin versus aspirin alone, the rates of MACE were:

• 14.1% versus 17.6% in patients with PAD and CAD
• 11% versus 9.8% in patients with PAD only

Overall, Xarelto plus aspirin showed a consistent benefit in reducing MACE in patients with and without CAD.

In this analysis, patients with CAD (HR, 2.23; CI, 1.10-4.53) and patients without CAD (HR, 1.15; CI, 0.72-1.84) had higher rates of TIMI major bleeding with Xarelto plus aspirin compared to those treated with aspirin alone.

The rates of intracerebral hemorrhage and fatal bleeding were similar across both patient groups. Overall, the safety of Xarelto plus aspirin in patients with PAD was consistent regardless of CAD, with no significant interactions.

In August 2021, the company announced FDA approval of an expanded indication for Xarelto (2.5 mg twice daily plus aspirin 75-100 mg once daily) to include patients after recent LER caused by symptomatic PAD. Xarelto acts on a dual pathway inhibition approach to target clotting mechanisms, thrombin, and platelet activation, advised the Janssen Pharmaceutical Companies press release.