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. 2025 Aug 31:pvaf051.
doi: 10.1093/ehjcvp/pvaf051. Online ahead of print.

Long-term effectiveness of ACE inhibitors or angiotensin receptor blockers in myocardial infarction with preserved left ventricular ejection fraction

Anna B C Humphreys  1 , Bertil Lindahl  2 , Anita Berglund  1 , Vanessa Voelskow  3 , Si Fang  4 , Ole Fröbert  5   6   7   8 , Robin Hofmann  9 , Tomas Jernberg  10 , Miguel A Hernán  1   11   12 , Anthony A Matthews  1
Affiliations

Long-term effectiveness of ACE inhibitors or angiotensin receptor blockers in myocardial infarction with preserved left ventricular ejection fraction

Anna B C Humphreys et al. Eur Heart J Cardiovasc Pharmacother. .

Abstract

Aims: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are effective in the long-term treatment of myocardial infarction with reduced left ventricular ejection fraction (LVEF). However, it is unknown whether there is a benefit in myocardial infarction with preserved LVEF (≥50%).

Methods and results: We used Swedish healthcare registries to emulate a target trial of ACEi/ARBs vs. no ACEi/ARBs for the prevention of a composite outcome (death, myocardial infarction, or heart failure) and its individual components among individuals under 75 years with myocardial infarction and LVEF ≥ 50% between September 2010 and June 2021. We estimated observational analogues of the intention-to-treat effect and the per-protocol effect with confounding adjustment via inverse probability weighting. The 10 697 individuals in the ACEi/ARB group were on average older (median 61 vs. 60 years) and more likely to be male (80.2% vs. 75.3% male) than the 4730 individuals in the no ACEi/ARB group. The estimated 5-year risk of the composite outcome was 7.8% (95% confidence interval 7.1%, 8.5%) in the ACEi/ARB group and 8.1% (7.0%, 9.3%) in the no ACEi/ARB group; risk difference -0.3% (-1.6%, 1.0%). After adjustment for adherence, the risk of the composite outcome was 6.5% (5.9%, 7.2%) in the ACEi/ARB group and 6.7% (5.6%, 8.1%) in the no ACEi/ARB group; risk difference -0.2% (-1.7%, 1.0%).

Conclusion: The estimated risk of a composite of death, myocardial infarction or heart failure was similar in recipients and non-recipients of ACEi/ARB. Our estimates suggest ACEi/ARB treatment in myocardial infarction with preserved LVEF does not confer a benefit.

Keywords: Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitor; Myocardial infarction; Observational study; Preserved left ventricular ejection fraction; Target trial emulation.

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Conflict of interest statement

Conflict of interest: R.H. reports lecture and consulting fees to institution from AstraZeneca, Pfizer and BMS. O.F. reports consulting fees from GSK and speaker’s fees from Sanofi Pasteur and Pfizer. M.A.H. is a consultant to ProPublica and Adigens Health, a company of which he owns equity, and a member of ADIALab’s Advisory Board. His interests were declared, reviewed, and approved by Harvard University in accordance with its institutional compliance policies. A.B.C.H. is a shareholder in Eli Lilly, Johnson & Johnson and Procter and Gamble.

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