Beta blockers and renin-angiotensin-aldosterone system inhibitors after type 2 myocardial infarction, a target trial emulation study

Background

Type 2 myocardial infarction (MI) carries a high mortality risk, yet no randomized clinical trials exist to guide treatment (1). Standard secondary preventive therapies—such as beta blockers and renin–angiotensin–aldosterone system (RAAS) inhibitors—are frequently prescribed despite the lack of trial evidence (2). Target trial emulation provides a framework for estimating treatment effects using observational data when randomized studies are not feasible (3).

Purpose

To evaluate the prognostic effect of routinely initiating beta blockers and RAAS inhibitors after type 2 MI in patients without other clear indications for these therapies.

Methods

Two hypothetical target trials were specified and then emulated using Swedish registry data to estimate the intention-to-treat effects of initiating a beta blocker versus no initiation, and initiating a RAAS inhibitor versus no initiation, following type 2 MI. In both emulations, the primary endpoint was a composite of all-cause mortality, readmission for myocardial infarction, stroke, or heart failure. Confounding was addressed using inverse probability weighting.

Results

A total of 12,889 patients with a diagnosis of type 2 MI in the SWEDEHEART registry between September 2010, and June 2021, who were discharged alive, were included. After excluding patients with other indications or contraindications according to prespecified eligibility criteria, 4,213 and 4,242 patients were eligible for the beta blocker and RAAS inhibitor trial emulations, respectively (Figure 1).

Beta blockers were initiated in 2,341 patients and withheld in 1,872 with no significant difference in the primary endpoint between groups (adjusted hazard ratio 0.93; 95% confidence interval 0.84-1.03; P = 0.15). RAAS inhibitors were initiated in 1,506 patients and withheld in 2,736 with no significant difference in the primary endpoint (adjusted hazard ratio 0.94; 95% confidence interval 0.85-1.04; P = 0.21) (Figure 2).

Conclusion

Initiating beta blockers and RAAS inhibitors after type 2 MI does not seem to offer any prognostic benefit unless supported by other established clinical indications.Figure 1.Patient selectionFigure 2.Adjusted survival curves