Early Tirzepatide After AMI/Ischemic Stroke: Real-World Propensity-Matched Findings

A recent American Journal of Cardiology analysis evaluated early initiation of tirzepatide within 14 days after acute myocardial infarction (AMI) or ischemic stroke in adults without diabetes and with BMI ≥27 kg/m². Using the TriNetX Research Network, investigators compared patients who started tirzepatide soon after the index event with otherwise similar patients who did not receive tirzepatide, and reported outcome associations between groups. Outcomes were tracked over 2 years after the qualifying AMI or ischemic stroke.

Data were drawn from the TriNetX Research Network, described in the as including 110 healthcare organizations, and the study window spanned June 2022 through November 2025. Eligible patients were adults aged ≥18 years with BMI ≥27 kg/m² and without diabetes who had AMI or ischemic stroke during that period; exposure was defined as tirzepatide initiated within 14 days of the event. To address measured confounding, investigators applied 1:1 propensity score matching across 28 covariates covering demographics, comorbidities, medications, and laboratory values, yielding 833 patients in each cohort. Cox proportional hazards models were used to estimate hazard ratios. The study specifies outcomes including all-cause ER visit or hospitalization, AKI, ischemic stroke, heart-failure hospitalization, and MACE.

Over 2 years of follow-up, the analysis reports hazard ratios comparing early tirzepatide use with no tirzepatide in the matched cohorts. For all-cause emergency department visit or hospitalization, the reported hazard ratio was 0.64 (95% CI 0.548–0.741). For acute kidney injury, the reported hazard ratio was 0.65 (95% CI 0.441–0.962). For ischemic stroke as an outcome, the reported hazard ratio was 0.82 (95% CI 0.703–0.947), and for heart-failure hospitalization the reported hazard ratio was 0.24 (95% CI 0.0001–0.383). Major adverse cardiovascular events (MACE) did not differ significantly between groups (HR 0.91, 95% CI 0.814–1.021).

In the conclusion, the authors state that early tirzepatide initiation after AMI or ischemic stroke in patients without diabetes was associated with fewer hospitalizations and reduced renal, heart-failure, and stroke events, and they add that these observations support prospective trials of tirzepatide for secondary cardiovascular prevention in non-diabetic patients. As presented, this highlights the need for prospective evaluation to further assess these associations in this post-event, non-diabetic population.

Key Takeaways:

• The abstract reports a TriNetX-based, retrospective matched comparison of tirzepatide started within 14 days after AMI or ischemic stroke versus no tirzepatide in adults without diabetes and BMI ≥27 kg/m², with outcomes assessed over 2 years.
• Lower hazards were reported for several individual outcomes (including all-cause ER visit or hospitalization, acute kidney injury, ischemic stroke, and heart-failure hospitalization), while MACE was reported as not significantly different.
• The authors conclude that these observational findings support prospective trials of tirzepatide for secondary cardiovascular prevention in non-diabetic patients.