1. Beta-blocker therapy did not significantly reduce all-cause mortality or time-to-first cardiovascular hospital admission in patients with heart failure and atrial fibrillation, compared to placebo.
2. However, beta-blockers significantly reduced the all-cause mortality and time-to-first cardiovascular hospital admission in patients with heart failure and normal sinus rhythm, compared to placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Beta-blockers have been shown to decrease morbidity and mortality in patients with heart failure with reduced ejection fraction. However, questions concerning the use of beta-blockers still exist in certain patient groups with heart failure, including those with atrial fibrillation. Heart failure and atrial fibrillation are common illnesses associated with an increased morbidity and are expected to increase in incidence and prevalence in the near future. This meta-analysis assessed the safety and efficacy of beta-blockers for patients with heart failure and concomitant atrial fibrillation to patients with heart failure and normal sinus rhythm, using individual-patient data.
The results showed that patients with heart failure and atrial fibrillation who were given beta-blockers did not have a significant reduction in all-cause mortality, time-to-first cardiovascular hospital admission, or clinical outcomes when compared to placebo. However, beta-blockers were shown to significantly reduce mortality and hospital admission in patients with heart failure and normal sinus rhythm. Limitations of this study included being unable to characterize the type of atrial fibrillation seen in patients, as well as being unable to separate patients with both atrial fibrillation and atrial flutter. Strengths of this study included the use of individual-patient data from large, randomized controlled trials, as well as including post-publication data for mortality. The authors concluded that beta-blockers should not be used as standard therapy or over other medications for rate-control in patients with heart failure and atrial fibrillation.
This study was funded by Menarini Farmeceutica Internazionale.
In-Depth [meta-analysis]: Data from ten randomized controlled trials comparing beta-blockers to placebo for heart failure were used in the study with the primary outcome as all-cause mortality. The presence of sinus rhythm or atrial fibrillation was obtained from baseline electrocardiographs (ECG). 18,254 patients with heart failure were included in the study, composed of 13,946 (76%) with sinus rhythm, and 3,066 (17%) with atrial fibrillation. 1,124 (6%) patients had other rhythms and 118 (<1%) had a missing or uninterpretable ECG. The median duration of heart failure before enrollment in the studies was 3 years.
Beta-blockers significantly reduced all-cause mortality in patients with sinus rhythm vs. placebo (Hazard Ratio [HR] 0.73, 95% Confidence Interval [CI] 0.67-0.80, p<0.001), but did not significantly improve mortality in atrial fibrillation vs. placebo (HR 0.97, 95% CI 0.83-1.14, p=0.73), with a p-value comparing atrial fibrillation vs. sinus rhythm of p=0.002. Over a mean follow-up of 1.5 years (SD 1.1), the crude death rates were lower in patients with normal sinus rhythm (2,237 [16%] of 12,945) vs. atrial fibrillation (633 [21%] of 3,064), with the most common causes of death in both groups being sudden death and heart failure. Beta-blockers also significantly reduced the time-to-first cardiovascular hospital admission in patients with sinus rhythm (HR 0.78, 95% CI 0.73-0.83, p<0.001), but did not significantly reduce admissions in patients with atrial fibrillation (0.91, 0.79-1.04, p=0.15), with a p-value comparing atrial fibrillation to sinus rhythm of p=0.05. Additionally, beta-blockers reduced the incidence of atrial fibrillation (253 [4%] of 6,722 patients) compared to placebo (357 [6%] of 6362 patients).
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