Long-term outcomes of premature acute myocardial infarction: impact of multivessel disease

Background – Premature acute myocardial infarction (AMI) is increasingly prevalent yet underrepresented in trials. We aimed to evaluate the prognosis of premature AMI and the prognostic impact of multivessel coronary artery disease. Methods – We analyzed consecutive AMI patients undergoing percutaneous coronary intervention in the multicenter Cardiovascular Risk and Identification of Potential High-Risk Population in AMI registry between April 2001 and April 2015, with follow-up through October 2019. Patients with premature AMI (age ≤ 45 years) were analyzed, and those who experienced in-hospital death were excluded. The primary outcome was major adverse cardiovascular events (MACE, a composite of recurrent myocardial infarction (MI), stroke, or repeat revascularization). Risks of ischemic outcomes were evaluated using multivariable Fine-Gray subdistribution hazard models. Sensitivity analyses included cause-specific Cox regression and multiple-imputation Cox models, accounting for competing risks. Results – Of the 10 144 AMI patients, 907 (8.9%) had premature AMI (mean 40.4 years; 94.3% male). Compared with older patients, premature AMI was not associated with lower risk of MACE [adjusted subdistribution hazard ratio (sHR) 1.01, 95% confidence interval (CI): 0.84–1.21], recurrent MI (adjusted sHR 1.49, CI: 1.07–2.06), and repeat revascularization (adjusted sHR 1.16, 95% CI: 0.95–1.44), despite fewer comorbidities. Findings were consistent across sensitivity analyses. In premature AMI, 34.3% had multivessel disease, which independently predicted higher risks of MACE (sHR 2.46), recurrent MI (sHR 3.34), and repeat revascularization (sHR 2.46) compared with older patients (sHR 1.47, 1.22, 1.61, respectively) with significant age-by-multivessel interactions. Conclusion – Premature AMI exhibited sustained long-term ischemic risk despite favorable baseline profiles. Multivessel disease conferred a greater prognostic impact in younger patients, highlighting the need for intensified secondary prevention strategies. Given the extended inclusion period encompassing major therapeutic advances, these findings should be interpreted with caution and warrant validation in contemporary clinical practice. Registration: unique identifier: NCT02806102.