Rivaroxaban Plus Aspirin Significantly Reduces Total Ischemic Events in Patients With PAD After Lower Extremity Revascularization

Data from the phase 3 VOYAGER PAD study demonstrated that rivaroxaban (Xarelto, Janssen) at 2.5 mg twice daily in combination with aspirin at 100 mg once daily was able to reduce severe vascular events in patients with peripheral artery disease (PAD) following lower extremity revascularization (LER) compared to aspirin alone, regardless of the number of vascular events that had occurred prior.

Presented as a late-breaking presentation during the virtual American College of Cardiology’s 70th Annual Scientific Session, the results of the trial showed that rivaroxaban plus aspirin was able to reduce the occurrence of first events by 15% among patients with PAD after LER. Additionally, the analysis showed a significant burden of subsequent events and a consistent 14% reduction in both primary endpoint events and total vascular events over a median of 2.5 years.

Currently, approximately 8.5 million patients have been diagnosed with PAD; however, it is estimated that 20 million Americans are living with PAD but have not yet been diagnosed. Although PAD can frequently present as asymptomatic initially, symptoms can advance and require revascularization in order to avoid the potential need for amputation in the future.

“Even years after revascularization, patients with PAD continue to have a markedly high-risk for future thrombotic events due to excessive thrombin generation and platelet aggregation,” said Marc P. Bonaca, MD, Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, in a press release. “This analysis from VOYAGER PAD looked beyond the first event and found subsequent thrombotic event reduction with rivaroxaban plus aspirin, underscoring the importance of long-term prevention in these high-risk patients.”

During the study, the investigators evaluated the time to first event and the thrombotic events that occurred following that first event. From this evaluation, the data showed rivaroxaban plus aspirin was able to significantly reduce the total primary endpoint events—which included acute limb ischemia, major amputation for vascular causes, non-fatal myocardial infarction, non-fatal ischemic stroke, or death from vascular causes—compared to aspirin alone (hazard ratio (HR)=0.86, 95% confidence interval (CI) 0.75 to 0.98; p=0.02).

Furthermore, the regimen of rivaroxaban plus aspirin was shown to significantly reduce the total number of vascular events, including all primary endpoints and subsequent peripheral revascularizations of index and contralateral leg and venous thromboembolic events, compared to aspirin by itself (HR 0.86, 95% CI 0.79 to 0.95; p=0.003).

However, the investigators found no significant increase in thrombolysis in myocardial infarction major bleeding during the VOYAGER PAD study in patients treated with rivaroxaban plus aspirin compared to aspirin by itself (2.65% vs. 1.87% respectively; HR=1.43, 95% CI, 0.97–2.10; p=0.07).

“The VOYAGER PAD trial is the first and only study of antithrombotic therapy in the past 20 years to demonstrate a significant benefit in patients with peripheral artery disease after lower-extremity revascularization,” said James List, MD, PhD, global therapeutic area head, cardiovascular and metabolism, Janssen Research & Development, in a press release. “With these new data, we now have a full picture of evidence demonstrating the potential of [rivaroxaban] in treating patients through various stages of peripheral artery disease—chronic, symptomatic, those requiring revascularization and beyond.”

REFERENCE

Late-Breaking Data at ACC.21 Show XARELTO® (rivaroxaban) Plus Aspirin Significantly Reduced Total Ischemic Events in Peripheral Artery Disease (PAD) Patients After Lower-Extremity Revascularization. Raritan, NJ: Janssen Pharmaceutical Companies; May 16, 2021.