Background: Adverse events after acute myocardial infarction (AMI) are individually associated with poor outcomes, but the prognostic impact of the overlap of different event types occurring sequentially within the same patient remains uncertain.
Aims: Mortality associated with multiple events-defined as ≥ 2 different event types among spontaneous myocardial infarction (MI), ischemic stroke, and major bleeding-was compared with single events after AMI.
Methods: We analyzed 10,719 AMI patients in the multicenter Korean AMI registry. Patients contributed person-time to mutually exclusive, time-varying states: no event; MI only; stroke only; Bleeding Academic Research Consortium (BARC) type 3 bleeding only; and multiple events (≥ 2 different types). Mortality was modeled using multivariable Cox regression with stabilized inverse-probability weighting (IPW) and piecewise intervals for early (≤ 30 days), intermediate (30 days to 1 year), and late (>1 year) risk.
Results: Over a median 4.9 years, 2625 patients died. Multiple events occurred in 108 patients (1.0%): MI + bleeding (55%), stroke+bleeding (31%), and MI + stroke (15%). Mortality patterns were consistent across multiple-event combinations. Multiple events conferred the highest risk of death (5-year IPW-adjusted hazard ratio [HR]: 5.85, 95% confidence interval [CI]: 3.48-9.85), exceeding MI only (HR: 3.78), stroke only (HR: 2.72), or bleeding only (HR: 3.08). Mortality was most pronounced within 30 days, most markedly after multiple events (IPW-adjusted HR: 24.0, 95% CI: 12.9-44.7).
Conclusions: Multiple adverse events after AMI confer substantially higher mortality risk than single events, with the greatest impact in the first 30 days. These findings support the need for an immediate and tailored approach and sustained surveillance to prevent further ischemic or bleeding complications.
Keywords: acute myocardial infarction; bleeding; mortality; multiple events; stroke; time‐dependent analysis.
© 2026 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.