Abstract 4338221: EVOLocumab Very Early after Myocardial Infarction (EVOLVE-MI): A Pragmatic Randomized Multicenter International Trial - Design and Baseline Characteristics

Abstract

Introduction: Patients with myocardial infarction (MI) are at risk of recurrent coronary events. Studies have shown that PCSK9 inhibition can reduce LDL-C to very low levels decreasing the ischemic risk in stable patients with chronic atherosclerotic vascular disease. Hypothesis: Low levels of LDL-C can be beneficial in terms of plaque reduction. The magnitude of the benefit may be greater in patients with acute MI, suggesting that an early approach may reduce the adverse outcomes. A pragmatic effectiveness trial can efficiently evaluate this hypothesis. Aims: To evaluate the effectiveness of early administration of evolocumab, a PCSK9 inhibitor, combined with usual care in reducing recurrent MI. Methods: EVOLVE-MI is an international, pragmatic, randomized trial (Panel A) with streamlined activities including remote study visits, data collected directly from registries and electronic medical records, de-centralized adjudication, patient self-reporting, and drug distribution through pharmacy cards. A total of 114 sites across United States, Brazil, and Sweden enrolled patients within 10 days of MI. Patients were randomized 1:1 to evolocumab with usual care or usual care alone (high-intensity statins or moderate-intensity statins with ezetimibe). No qualifying LDL-C or background lipid modifying therapy was required. The primary efficacy outcome is the composite of total (first and recurrent) MI, ischemic stroke, arterial revascularization, or death with a planned number of total events of 1891. Enrollment was completed in May 2024. Results: The study randomized 6019 patients (Panel B). Patients have a mean age of 62 years, with 32% having diabetes mellitus, 66% having hypertension, and 55% being current or former smokers. In addition, 15% have prior MI, 37% have multivessel CAD, and 5% and 2% having known cerebrovascular disease or peripheral artery disease, respectively. The presenting syndrome was STEMI in 53% and NSTEMI in 47% of patients. Baseline ejection fraction was 55% and baseline LDL-C was 108 mg/dL. For the index event, 92% and 91% received aspirin and P2Y 12 inhibition, respectively. Statins were used 89% and ezetimibe in 9% of the enrolled patients. Conclusion: This pragmatic randomized trial is evaluating the hypothesis that early administration of potent LDL-C lowering with evolocumab in patients with MI improves outcomes. The trial is ongoing to obtain the planned number of events to determine if this strategy reduces cardiovascular events.