Rivaroxaban eases ischaemic events, ups bleeding in frail patients after revascularization

The risks of ischaemic complications and bleeding are higher among patients with peripheral artery disease (PAD) who meet the frailty criteria after lower extremity revascularization in the VOYAGER PAD study. Regardless of frailty status, use of rivaroxaban lowers the ischaemic risk and increases bleeding.

“Major bleeding events were more frequent among fragile patients and were numerically increased with rivaroxaban,” the investigators said. “However, when considering benefit-risk, the regimen of low-dose rivaroxaban in combination with aspirin may represent a strategy to reduce cardiovascular (CV) and limb risk even in high CV risk patients who met fragile criteria in VOYAGER PAD.”

In this study, the investigators examined the efficacy and safety of low-dose rivaroxaban (2.5 mg) in fragile patients from VOYAGER PAD. Patients were deemed fragile based on prespecified criteria: age >75 years, weight ≤50 kg, or baseline estimated glomerular filtration rate <50 mL/min/1.73 m².

The composite of acute limb ischaemia, major amputation of a vascular aetiology, myocardial infarction, ischaemic stroke, or cardiovascular death served as the primary efficacy outcome. For safety, the principal outcome was major bleeding defined according to the TIMI classification. [N Engl J Med 2020;382:21:1994-2004]

A total of 6,564 patients were included, of whom 1,674 met the fragile criteria at baseline. Compared with nonfragile patients, those who were categorized as fragile in the placebo arm showed an increased risk of the primary outcome (hazard ratio [HR], 1.34, 95 percent confidence interval [CI], 1.12‒1.61) and TIMI major bleeding (HR, 1.57, 95 percent CI, 0.83‒2.96). [J Am Coll Cardiol 2024;84:801-811]

Frailty status did not influence the effect of rivaroxaban on the primary outcome (fragile HR, 0.93, 95 percent CI, 0.75‒1.15; nonfragile HR, 0.83, 95 percent CI, 0.72‒0.97; p=0.37 for interaction). Notably, rivaroxaban increased bleeding in fragile (HR, 1.54, 95 percent CI, 0.82‒2.91) and nonfragile patients (HR, 1.37, 95 percent CI, 0.84‒2.23; p=0.65 for interaction).

“It is important to recognize that patients categorized as fragile were at increased risk of bleeding,” the investigators said. “The American Geriatrics Society recently updated their Beers Criteria for potentially inappropriate medication use in older adults.”

Specifically, apixaban is preferrable over other oral anticoagulants in older patients affected by venous thromboembolic events or atrial fibrillation. However, recommendations for low-dose rivaroxaban in this high-risk population do not exist. [J Am Geriatr Soc 2023;71:7:2052-2081]

“Importantly, in our analysis, the presence of frailty did not increase the risk of major bleeding on rivaroxaban,” the investigators said. “TIMI major bleeding was numerically increased with rivaroxaban regardless of frailty status, with a 1-percent absolute increase in fragile patients with no increase in intracranial of fatal bleeding.”

The absolute benefit in ischaemic events, however, remained greater than the bleeding increases seen in the fragile patient population, according to the investigators.

“In fragile patients, the benefit of rivaroxaban in combination with aspirin in reducing major CV, limb, and total vascular events observed with rivaroxaban was consistent with the overall cohort and was driven mainly by limb outcomes,” they said.