Research highlights the need to consider mental health impacts when prescribing beta-blockers to MI patients with preserved heart function.

Study: Short- and long-term effects of beta-blockers on symptoms of anxiety and depression in patients with myocardial infarction and preserved left ventricular function: a pre-specified quality of life sub-study from the REDUCE-AMI trial. Image Credit: Shidlovski/Shutterstock.com

In a recent study published in the European Heart Journal. Acute Cardiovascular Care, a group of researchers assessed the effects of beta-blockers on anxiety and depression symptoms in myocardial infarction (MI) (heart attack) patients with preserved left ventricular function.

Background

Beta-blockers have long been integral in preventing adverse outcomes following MI, initially proven effective in studies conducted before the widespread use of modern interventions like percutaneous coronary intervention and antithrombotic therapy.

They work by reducing myocardial oxygen demand and preventing cardiac remodeling and arrhythmias, yet they also have notable side effects, including bradycardia, hypotension, fatigue, exercise intolerance, and possible impacts on mental well-being, such as depression and anxiety.

Recent trials have yielded mixed findings on beta-blockers cardiovascular benefits in MI patients with preserved left ventricular function, highlighting a need for further research on their psychological effects.

About the study

The Randomized Evaluation of Decreased Usage of beta-bloCkErs (REDUCE-AMI) trial, conducted across 45 centers in Estonia, Sweden, and New Zealand, was a prospective, open-label, parallel-group, registry-based randomized clinical trial (RCT) assessing the effects of beta-blockers on MI patients with preserved left ventricular function.

This sub-study collected data on self-reported levels of anxiety and depression at three points: baseline, 6-10 weeks, and 12-14 months post-MI.

Eligible REDUCE-Quality of Life (RQoL) participants met criteria such as being aged ≥18, having confirmed obstructive coronary artery disease, preserved left ventricular ejection fraction (LVEF ≥50%), and providing informed consent.

Exclusion criteria included contraindications for beta-blockers or other non-study-related indications for their use. Additional eligibility for the RQoL sub-study included Swedish language proficiency.

Participants were assessed through self-reported questionnaires administered online or by mail, focusing on factors like psychological well-being, physical activity, and adherence.

Data analysis used linear mixed models adjusted for various baseline covariates, and multiple sensitivity analyses were conducted. The Hospital Anxiety and Depression Scale (HADS) measured primary outcomes.

Study results

Recruitment for the RQoL sub-study took place from August 2018 to June 2022, with follow-up concluding in June 2023. Out of 1,617 participants in the REDUCE-AMI main trial, 806 joined the RQoL sub-study.

These participants, predominantly male (77%) with a mean age of 64.7 years, were younger and more frequently smokers than non-participants in RQoL but showed no significant differences in baseline anxiety or depression scores.

Of the 806 RQoL participants, 682 (85%) completed follow-up 1 (6–10 weeks post-MI), and 657 (82%) completed follow-up 2 (12–14 months post-MI).

Participants who missed follow-ups tended to be younger, more often had diabetes, had lower education levels, smoked, used psychotropic medication, were non-Swedish-born, were less physically active, and reported higher anxiety and depression levels at baseline. Four participants died between the two follow-ups.

Adherence to the beta-blocker or non-beta-blocker allocation was tracked, revealing that 73 participants were non-adherent by follow-up 1, and 107 were non-adherent by follow-up 2, with some adherence data missing.

In the primary intention-to-treat analysis, the beta-blocker group displayed higher levels of depressive symptoms at both follow-ups, but there was no significant impact on anxiety scores.

Stratified analysis based on previous beta-blocker use showed different effects over time. Among participants not previously on beta-blockers, those randomized to beta-blocker treatment exhibited higher depression levels at follow-up 1, though this effect diminished by follow-up 2.

For participants already on beta-blockers at baseline, a significant increase in depressive symptoms was observed at follow-up 2.

Sensitivity analyses were conducted to assess the findings. Analyses using only complete cases yielded results consistent with the imputed analysis. Limiting the analysis to adherent participants showed similar results, with a slight reduction in the effect size for depressive symptoms at follow-up 1, which was no longer statistically significant.

When baseline values were excluded from adjustments, the difference between the beta-blocker and non-beta-blocker groups in depressive and anxiety symptoms was not significant.

Conclusions

To summarize, in the study, MI patients with preserved LVEF assigned to beta-blockers showed slightly higher depressive symptoms at 6–10 weeks and 12–14 months post-MI. However, effects remained below clinically significant thresholds.

No impact was observed on anxiety. Beta-blockers may induce depressive symptoms through neurotransmitter interactions and reduced engagement in enjoyable activities. Effects were more notable in patients already on beta-blockers, suggesting a potential cumulative impact.