Rivaroxaban Improved CV, Limb Events After Lower Extremity Revascularization in PAD with CKD

Rivaroxaban reduced major cardiovascular (CV) events and limb events in patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) including the high-risk population of patients with chronic kidney disease (CKD).

Judith Hsia, MD, of CPC Clinical Research, University of Colorado, presented this subgroup analysis from VOYAGER-PAD at the American Heart Association Scientific Sessions 2020.

“Patients with recent PAR are at high risk for subsequent cardiovascular and limb events,” Dr. Hsia said. “Prior to VOYAGER-PAD no antithrombotic strategy had demonstrated efficacy for reducing these events.”

Previous results from VOYAGER PAD showed the efficacy of rivaroxaban in patients with PAD after LER on a composite of cardiovascular and limb ischemic events. Here, Dr. Hsia presented results for a prespecified subgroup analysis of patients with CKD.

The trial randomly assigned patients with recent LAR to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. The primary composite endpoint included acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke or CV death. The primary safety endpoint was TIMI major bleeding.

Of the patients in VOYAGER, 1,327 patients had a baseline estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m² (mostly CKD stage 3) and 4,992 were 60 mL/min/1.73 m² or greater. As a group, patients with CKD were older, more often women, and had higher prevalence of hypertension, diabetes, and hyperlipidemia.

Major CV events, but not acute limb ischemia or major amputation, were more frequent among patients with CKD compared with patients assigned to placebo.

Rivaroxaban reduced major cardiovascular and limb events compared with placebo in patients with CKD (HR=0.90; 95% CI, 0.71-1.15) and those without CKD (HR=0.85; 95% CI, 0.73-0.97; P for interaction 0.62). Among patients assigned rivaroxaban TIMI major bleeding was in 3.2% of patients with CKD and 1.5% without CKD.

Looking separately at CV events and limb events, MI, stroke and CV death were more frequent among patients with CKD compared with those without, but there was no heterogeneity by treatment group. Limb events occurred with similar frequency among patients with or without CKD, but rivaroxaban significantly improved outcomes for those with CKD (HR=0.55; 95% CI, 0.36-0.86) and without CKD (HR=0.77; 95% CI, 0.63-0.94; P for interaction 0.18).

“In PAD patients with recent revascularization, patients with CKD were at higher risk for major CV events but not for limb events,” Dr. Hsia concluded. “The efficacy and safety of rivaroxaban in patients with CKD were consistent with the overall [VOYAGER-PAD] cohort.”