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Rivaroxaban in Fragile Patients After PAD Diagnosis
Quick Takes
- Dual pathway inhibition with rivaroxaban and aspirin is guideline recommended for patients with PAD undergoing lower extremity revascularization.
- Fragile patients, including those with older age, lower body weight, and chronic kidney disease, are at increased risk of thromboembolic complications following lower extremity revascularization.
- Use of dual pathway inhibition did not lead to an increase in bleeding among fragile vs. nonfragile patients undergoing lower extremity revascularization.
Study Questions:
What are the safety and efficacy outcomes of rivaroxaban 2.5 mg twice daily plus aspirin in fragile patients undergoing lower extremity revascularization?
Methods:
The authors analyzed the VOYAGER PAD study of patients with symptomatic peripheral artery disease (PAD) undergoing lower extremity revascularization. They identified patients with fragility, defined as age >75 years, weight ≤50 kg, or baseline estimated glomerular filtration rate <50 mL/min/1.73 m2. The primary efficacy outcome was the composite of acute limb ischemia, major amputation from a vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The primary safety outcome was TIMI major bleeding.
Results:
Among the 6,564 patients initially randomized in the VOYAGER PAD study, 1,674 (25.5%) were considered fragile at baseline. Fragile patients had an increased risk of the primary efficacy outcome (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.12-1.61) but not the primary safety outcome (HR, 1.57; 95% CI, 0.83-2.96) as compared to nonfragile patients in the placebo arm of the VOYAGER PAD study. The effect of rivaroxaban plus aspirin on the primary efficacy endpoint (p for interaction = 0.37) and the primary safety endpoint (p for interaction = 0.65) was not modified by fragility. Of note, the cumulative incidence of major adverse limb events (MALE) was numerically reduced to a greater degree in patients with baseline fragility than those without (absolute risk reduction, 4.2% vs. 1.6%; p for interaction = 0.13).
Conclusions:
The authors conclude that among patients with PAD undergoing lower extremity revascularization, those with baseline fragility are at increased risk of thromboembolic complications. Furthermore, the benefits of rivaroxaban plus aspirin were not modified based on baseline fragility.
Perspective:
Patients with PAD undergoing lower extremity revascularization are among the most high risk for major adverse cardiovascular events (MACE) and MALE. Use of dual pathway inhibition with rivaroxaban 2.5 mg twice daily plus low-dose aspirin has been shown to reduce both MACE and MALE, leading to a Class 1 recommendation in the most recent American College of Cardiology/American Heart Association (ACC/AHA) multisociety guideline for the management of lower extremity PAD (J Am Coll Cardiol 2024;83:2497-604).
This analysis provides additional information about the impact of baseline fragility on both the efficacy benefits and the bleeding risks associated with dual pathway inhibition. Reassuringly, there was no statistical interaction with either efficacy or safety and baseline fragility. However, it is notable that patients with baseline fragility experienced a numerically greater reduction in MALE events than nonfragile patients. This differential benefit was not statistically significant, however, perhaps limited by statistical power. Reassuringly, there was no difference in bleeding risk associated with dual pathway inhibition for patients with and without baseline fragility. This analysis supports the recent ACC/AHA guideline recommendation for use of dual pathway inhibition in patients with known PAD undergoing lower extremity revascularization, even if they have a baseline fragile state.
Clinical Topics: Cardiac Surgery, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Interventions and Vascular Medicine, Anticoagulation Management and Venothromboembolism
Keywords: Frail Elderly, Myocardial Revascularization, Peripheral Arterial Disease, Rivaroxaban
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