4065Moderate to severe renal insufficiency and risk for cardiovascular and limb outcomes in patients with symptomatic peripheral artery disease: the EUCLID trial

Abstract

Background: In patients with symptomatic peripheral artery disease (PAD), the impact of concomitant moderate-severe renal insufficiency on the occurrence of major adverse cardiovascular events has not been well evaluated. Purpose: To assess rates of major adverse cardiovascular events in patients with PAD and moderate-severe renal insufficiency as compared with those with PAD and mild-no renal insufficiency. Methods: The Examining Use of tiCagreLor In paD (EUCLID) trial randomized 13,885 patients with PAD to monotherapy with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal anklebrachial index (ABI) <0.80 or a prior lower extremity revascularization. This post hoc analysis classified patients based on estimated glomerular filtration rate (eGFR) at randomization and compared the incidence of the primary composite endpoint (cardiovascular death, myocardial infarction, or ischemic stroke) among patients with moderate-severe renal insufficiency (eGFR <60 mL/min/1.73 m2) with those with mild-no renal insufficiency (eGFR ≥60 mL/min/1.73 m2). Secondary outcomes included all-cause mortality and hospitalization for acute limb ischemia. The primary safety endpoint was Thrombolysis In Myocardial Infarction (TIMI) major bleeding. Results: A total of 13,483 patients were included. Of these, 3332 patients had moderate-severe renal insufficiency. The median duration of follow-up was approximately 30 months. Patients with renal insufficiency had a higher degree of cardiovascular risk factors and more polyvascular disease compared with those with mild-no renal insufficiency. After accounting for these and other baseline differences, patients with moderate-severe renal insufficiency had an increased rate of the primary composite outcome compared with those with mild-no renal insufficiency (6.75 vs. 3.72 events/100 pt-years) (adjusted HR 1.45, 95% CI 1.30- 1.63). All-cause mortality was similarly increased in the moderate-severe renal insufficiency group (5.41 vs. 3.02 events/100pt years) (adjusted HR 1.40, 95% CI 1.24-1.59). Renal insufficiency was not associated with increased risk of hospitalization for acute limb ischemia (adjusted HR 0.96, 95% CI 0.69-1.34) or major amputation (adjusted HR 0.92, 95% CI 0.66-1.28). Similarly, moderate-severe renal insufficiency was not associated with increased risk of major bleeding. Conclusions: Patients with moderate-severe renal insufficiency and PAD had higher rates of the composite endpoint (cardiovascular death, myocardial infarction, and stroke) and all-cause mortality but similar rates of acute limb ischemia, major amputation, and TIMI major bleeding when compared with patients with mild-no renal insufficiency.