ACEi/ARB treatment in patients with myocardial infarction and preserved left ventricular ejection fraction does not confer a benefit: a target trial emulation

Abstract Background Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are effective in the long-term treatment of individuals with myocardial infarction (MI) and reduced left ventricular ejection fraction. However, there is a lack of randomised trials assessing these agents in those with preserved ejection fraction (≥50%). One approach is to use observational data to emulate a hypothetical pragmatic trial ("target trial") that one would conduct. Methods We emulated a target trial of ACEis/ARBs versus no ACEis/ARBs in individuals under the age of 75 years with MI and left ventricular ejection fraction ≥50% between September 2010 and June 2021 for the prevention of a composite outcome (death, myocardial infarction, or heart failure) and its individual components. We used the Sweden-wide SWEDEHEART quality registry with linkage to other national registers, enabling complete coverage of hospital care and dispensed drugs. We estimated observational analogues of the intention-to-treat effect and the per-protocol effect with confounding adjustment via inverse probability weighting. Results The 10,697 individuals in the ACEi/ARB group were on average older (median 61 vs 60 years), more likely to be male (80.2% vs 75.3% male) and more likely to present with STEMI (45.4% vs 27.9%) compared with the 4,730 individuals in the no ACEi/ARB group. In an intention-to-treat analysis, the estimated five-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 non-ACEi/ARB group; risk difference -0.3% (-1.6%, 1.0%) (Figure 1). In a per protocol analysis, 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%) (Figure 2). Conclusions 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 that ACEi/ARB treatment in patients with myocardial infarction and preserved left ventricular ejection fraction does not confer a benefit.Table and forest plot of ITT effect Table forest plot of perprotocol effect