Marc Bonaca, MD, MPH: Benefit of Rivaroxaban for High-Risk Patients with PAD

New analyses from the VOYAGER-PAD trial support the beneficial effects of rivaroxaban plus aspirin across both high-risk and complex populations with peripheral artery disease (PAD).¹

The data, presented at the American Heart Association (AHA) Scientific Sessions 2023 in Philadelphia, Pennsylvania, showed consistent reductions in major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in complex patients with PAD treated with rivaroxaban plus aspirin.²

“These analyses reinforce the consistency of the favorable benefit-risk profile of [rivaroxaban] plus aspirin for patients with vascular disease, regardless of comorbidity,” said Marc P. Bonaca, MD, of the department of medicine, division of cardiovascular medicine, University of Colorado Anschutz Medical Campus, in a statement.³ “For example, patients categorized as ‘fragile’ are often undertreated due to concerns about benefit-risk, particularly with antithrombotic treatments.”

The first analysis evaluated the impact of rivaroxaban plus aspirin on total vascular events in fragile patients with PAD.¹ Fragile patients with PAD may be at a greater risk for MALE, a composite of acute limb ischemia and major amputation. Fragile patients were defined as >75 years or age, with weight <50 kg or baseline eGFR <50 mL/min/1.73.

Investigators found twice-daily rivaroxaban 2.5mg plus once-daily aspirin 100 mg was effective in reducing the occurrence of MALE in both fragile and non-fragile patients, compared to placebo (aspirin alone). Among fragile patients treated with rivaroxaban plus aspirin, 6.2% experienced a MALE, compared to 10.3% of patients treated with placebo. Among non-fragile patients, 7.9% treated with rivaroxaban plus aspirin and 9.7% treated with placebo experienced a MALE.

Moreover, rivaroxaban plus aspirin lowered the occurrence of total vascular events in fragile patients over time, with an absolute rate of 82.1 events per 100 patients at 3 years, compared to 99.3 events per 100 patients in the placebo group. There were similar benefits observed in non-fragile patients at 3 years, with an equivalent rate of 70.4 events and 81.6 events per 100 patients, respectively.

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

The second analysis assessed the role of rivaroxaban plus aspirin on myocardial infarction in patients with PAD with and without concomitant coronary artery disease (CAD) following lower extremity revascularization (LER).² Post-LER, patients with PAD have a 4-fold increased likelihood of experiencing acute limb ischemia, often associated with a high incidence of amputation, disability, or death without appropriate treatment. Patients with PAD are also at an increased risk of MACE, or myocardial infarction, ischemic stroke, or cardiovascular death.

​​Upon analysis, investigators found 14.1% of patients with PAD and CAD treated with rivaroxaban plus aspirin experienced a MACE, compared to 17.6% of patients treated with placebo. Among individuals with PAD only, 11% of patients treated with rivaroxaban plus aspirin experienced MACE, compared to 9.8% in the placebo group. Overall, the analysis indicated rivaroxaban plus aspirin showed consistent benefit in MACE reduction for patients with and without CAD.

Safety analyses revealed patients with CAD (HR, 2.23; 95% CI, 1.10 - 4.53) and those without CAD (HR, 1.15; 95% CI, 0.728 4) had higher rates of TIMI major bleeding with rivaroxaban plus aspirin, compared to placebo. Intracerebral hemorrhage and fatal bleeding were similar across patient groups. Overall, safety of rivaroxaban plus aspirin was considered consistent, regardless of CAD status, without significant interactions.

In discussion with HCPLive, Bonaca further described the benefit of rivaroxaban plus aspirin in fragile patients and how these results might inform differences in care strategies.

Watch the full interview with Bonaca in the video below.

References

1. _{Canonico ME. 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. Paper presented at: American Heart Association Scientific Sessions 2023; November 10 - 13; Philadelphia, PA.}
2. _{Canonico ME. Impact of Low-Dose Rivaroxaban Plus Aspirin on Total Vascular Events in Fragile Patients with Peripheral Artery Disease: Insights from VOYAGER PAD.}
3. _{New voyager pad analyses reinforce benefit of Xarelto® (RIVAROXABAN) plus aspirin across high-risk and complex patient populations with peripheral artery disease (PAD). Janssen. November 14, 2023. Accessed November 15, 2023. https://www.janssen.com/new-voyager-pad-analyses-reinforce-benefit-xareltor-rivaroxaban-plus-aspirin-across-high-risk-and.}