Efficacy and Safety of Zalunfiban by Creatinine Clearance Among Patients with ST-Elevation Myocardial Infarction: Analysis from the CELEBRATE Trial

Renal impairment portends higher rates of clinical events and bleeding among patients with ST-segment elevation myocardial infarction (STEMI). Zalunfiban is a novel, subcutaneous glycoprotein IIb/IIIa inhibitor designed for pre-hospital administration. This post hoc analysis of the CELEBRATE trial evaluated the efficacy and safety of zalunfiban in STEMI patients across different levels of renal function. A total of 2,154 patients were categorized by baseline creatinine clearance (CrCl) levels. The primary efficacy endpoint was a 30-day major adverse composite clinical endpoint. The primary safety endpoint was GUSTO severe or life-threatening bleeding at 30 days. Among patients with CrCl ≥30 to <60 mL/min, treatment with zalunfiban was associated with lower odds of the composite outcome (adjusted OR 0.46; 95% CI 0.23-0.94; p=0.03). The treatment effect was not significantly modified by CrCl (p for interaction=0.25). In addition, there were no significant differences in severe or life-threatening bleeding across all CrCl categories. Zalunfiban was associated with higher rates of mild-to-moderate bleeding among patients with CrCl ≥90 mL/min and those with ≥60 to <90 mL/min. A single subcutaneous dose of zalunfiban administered at first medical contact was not associated with an increased risk of major bleeding across the spectrum of renal function. In conclusion, although a signal for greater clinical benefit was observed among STEMI patients with CrCl ≥30 to <60 mL/min, there was no significant interaction by renal function, and these findings should be considered exploratory. STUDY REGISTRATION: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (CELEBRATE); ClinicalTrials.gov identifier: NCT04825743.