Association of Beta Blocker Use Beyond 1 Year After MI With Cardiovascular Outcomes

While the benefits of beta-blocker therapy in patients with low LVEF (including after myocardial infarction [MI]) is solid, their clinical benefit in patients without reduced ejection fraction after MI is surprisingly unknown to date. The evidence showing the benefits of beta blockers in the general post-MI population (regardless of LVEF or heart failure [HF]) was generated in an era where the treatment for MI was very primitive (ie, patients with ST-segment elevation MI not reperfused, with no routine revascularization and no antithrombotic therapy in place).¹ Because of this historical perspective, the vast majority of patients after MI are discharged with beta-blocker prescription regardless of LVEF, but the evidence is lacking.

The present study is the most recent of an infinite list of observational studies trying to determine whether beta blockers are associated with any benefit in the population of patients without reduced LVEF after MI. In this specific case, investigators tried to evaluate whether beta blockers had any benefit beyond 1 year after MI. The authors interrogated the web-based SWEDEHEART registry. They identified more than 43,000 patients who were admitted for MI between 2005 and 2016 with an LVEF >50% who were alive and without any cardiovascular event during the 12 months following index MI hospitalization. Patients were divided into those on beta blockers (n = 34,253) or not (n = 9365) at 12 months after MI (date of initiation of the evaluation period). Baseline characteristics were remarkably unbalanced between the groups as evidenced by the prevalence of prior MI and PCI (before index event): 4.4% and 2.6%, respectively, in patients in the beta blocker arm versus 8.6% and 5.8%, respectively, in those without beta blockers among other variables. The (unadjusted) primary outcome (composite of death, MI, HF hospitalization, and unplanned revascularization) occurred significantly less frequent in the beta blocker group (3.8% vs 4.9%; HR, 0.76). All individual components of the composite outcome (except revascularization) occurred significantly less in the beta blocker arm. After inverse propensity score weighting and adjustment (for 15 variables), the incidence of the primary composite outcome was not different anymore between groups (HR, 0.99). The authors conclude that beta-blocker treatment beyond 1 year of MI for patients without HF or LVEF dysfunction was not associated with improved cardiovascular outcomes.

The study is a noble attempt to address the question, but the great limitations (shared by all observational studies in the matter) preclude any firm conclusion. This study tries to address whether beta blockers after 1 year are beneficial or not. However, the first premise (beta blockers are beneficial during the first year after MI) is still unresolved. In addition, we do not know whether some of the patients not on beta blockers at 1 year had withdrawn treatment at anytime in the previous year. This study has all the (great) limitations of the previous attempts to solve this clinically relevant question. The bottom line in all these studies is that there is always an important imbalance between groups (patients not prescribed beta blockers after MI are always much sicker, as is the case in this study). The second common feature of all these studies is that unadjusted analysis shows a remarkable difference in hard endpoints (always less in the beta blocker group), and most of the times, after propensity scoring and multivariable adjustment, these differences fade away. Despite elegant statistical methodologies to overcome these imbalances, the chances for residual confounders is huge. The only way of addressing this question is by random assignment of beta blockers to patients after MI. There are three large ongoing trials in Europe — REBOOT-CNIC (N = 8468),² REDUCE-SWEDEHEART (N = 5000), and BETAMI-DANBLOCK (N ≈ 5500) — randomizing patients immediately after MI to beta blockers or control. A fourth trial (AβYSS [N = 3700]) is randomizing patients >6 months after MI to withdraw beta blockers or continue on them. The results of these four trials will be made public within the next 2 years (enrollment in all will be finalized during 2023). Until then, there is no observational study that can inform the best art of prescribing beta blockers.¹

References

1. Desta L, Raposeiras-Roubin S, Ibáñez B. The Art of Prescribing β-Blockers After Myocardial Infarction. CircCardiovascInterv. 2021;14(4):e010720. https://www.ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.121.010720
2. Rossello X, Raposeiras-Roubin S, Latini R, et al. Rationale and Design of the Pragmatic Clinical Trial TREatment With Beta-Blockers After MyOcardial Infarction WithOut Reduced Ejection FracTion (REBOOT). Eur Heart J Cardiovasc Pharmacother. 2022;8(3):291-301. https://academic.oup.com/ehjcvp/article/8/3/291/6342142