Prevalence of high on-treatment (aspirin and clopidogrel) platelet reactivity in patients with critical limb ischemia

Abstract

The goal of this study is to establish the prevalence of high on-treatment platelet reactivity to aspirin (HPRA) and clopidogrel (HPRC) in patients with critical limb ischemia (CLI). CLI is associated with an increased risk of death and cardiovascular events. Unlike other patient populations with atherosclerotic cardiovascular disease, previous studies failed to demonstrate a benefit of antiplatelet therapy in patients with CLI. From June 2014 to November 2016, we performed platelet reactivity studies for P2Y12 and thromboxane A2 (TXA2) inhibition in 100 CLI patients receiving daily treatment with aspirin and clopidogrel. P2Y12 inhibition was measured by two assays: vasodilator-stimulated phosphoprotein (VASP) and VerifyNow P2Y12 assays. HPRC was defined as VerifyNow P2Y12 reactive units (PRU) >208 and VASP-platelet reactivity index (VASP-PRI) >50%. TXA2 inhibition was measured with the VerifyNow aspirin test and HPRA was defined as aspirin reaction units (ARU) >550. Mean age was 67±11 years, 50% were male, 80% had diabetes mellitus, and 26% had chronic renal insufficiency. Thirty-three percent of patients had a PRU >208 and 46% a VASP-PRI >50%. HPRC was present in 26% of patients based on the criteria of both a PRU >208 and VASP-PRI >50%. HPRA was present in 25% of patients. The overall prevalence of HPR to ASA or clopidogrel was 35% and HPR to both drugs was present in 8% of patients. Clinical characteristics were similar between groups. HPR to aspirin or clopidogrel is highly prevalent in patients with CLI. Nearly one in ten patients with CLI is a hyporesponder to both aspirin and clopidogrel.