Beta-blockers in the treatment of chronic heart failure: How did the analysis of the effects of 4 drugs in 26 studies turn out?
As a cornerstone of therapy for chronic heart failure with reduced ejection fraction (HFrEF), it is recommended to start treatment with a very low dose of beta-blockers (BB) and titrate it to the maximum tolerated dose. However, it remains unclear whether one BB is superior to others. For this reason, a comprehensive pooled analysis of the efficacy and safety of bisoprolol, carvedilol, nebivolol, and metoprolol in 26 studies, including 14 randomized controlled and 12 observational, was recently published.
Introduction
Bisoprolol, metoprolol, and nebivolol are selective β1-blockers, whereas carvedilol is a non-selective α1-blocker and beta-blocker with nearly balanced selectivity for β1 and β2 receptors. Carvedilol and nebivolol belong to the third generation of BBs, with half-lives of 7–10 and 12–19 hours, respectively. Bisoprolol, metoprolol succinate, and nebivolol can be administered once daily, significantly improving patient compliance. Although carvedilol needs to be administered twice daily, some studies have shown that it outperforms metoprolol in treating chronic heart failure (CHF), possibly due to the additional benefit from its ability to block the α1 receptor.
Results of the analysis
Bisoprolol vs. carvedilol
Using bisoprolol compared to carvedilol reduced all-cause mortality (odds ratio [OR] 1.25; 95% confidence interval [CI] 1.11–1.42; p = 0.0002), but it did not lead to a significant reduction in CHF-related readmissions. Furthermore, bisoprolol significantly increased left ventricular ejection fraction (LVEF) compared to carvedilol (pooled weighted mean difference [WMD] –4.98%; 95% CI –7.11 to –2.84%; p < 0.00001).
Both drugs had similar effects on slowing heart rate and length of hospital stay. No differences were observed in the overall incidence of adverse events related to the therapy, including worsening heart failure and hypotension, but carvedilol caused fewer bradycardias (OR 0.60; 95% CI 0.41–0.89; p = 0.01). Bisoprolol, compared to carvedilol, reduced all-cause mortality in patients with LVEF < 40% (OR 1.32; 95% CI 1.15–1.53; p = 0.0001), but this did not apply to those with LVEF ≥ 40% (OR 0.93; 95% CI 0.52–1.66; p = 0.69). For these reasons, it was concluded that bisoprolol had superior benefits in treating CHF compared to carvedilol with similar therapy safety.
Metoprolol vs. carvedilol
The comparison of results between the group treated with carvedilol and the group using metoprolol succinate showed no differences in all-cause mortality, repeated hospitalization, or LVEF. It was therefore evaluated that metoprolol succinate and carvedilol have similar evidence in treating CHF.
Compared to metoprolol tartrate, carvedilol reduced all-cause mortality (OR 0.77; 95% CI 0.69–0.86; p < 0.00001), but not CHF-related readmissions, increased LVEF(LVEF) (WMD 4.83%; 95% CI 2.43–7.22%; p < 0.0001), but did not affect the 6-minute walk test (6MWT), heart rate, or quality of life as measured by the Minnesota Living with Heart Failure Questionnaire. Carvedilol also performed better in mitigating worsening of heart failure (OR 0.41; 95% CI 0.18–0.98; p = 0.04). No differences were identified between the two groups in the overall incidence of adverse effects or therapy discontinuation. Therefore, carvedilol provides greater benefit than metoprolol tartrate in treating CHF with a similar safety profile.
Carvedilol vs. nebivolol
Evaluating the effects of carvedilol compared to nebivolol revealed no differences in all-cause mortality, heart failure-related readmissions, or adverse events related to the drug's use. Nebivolol was thus found to be as reliable as carvedilol for patients with CHF.
Bisoprolol vs. metoprolol succinate
Comparing the results of metoprolol succinate and bisoprolol in CHF showed that treatment with bisoprolol did not lead to a significant reduction in all-cause mortality, although it was associated with a lower rate of readmissions (OR 1.29; 95% CI 1.03–1.63; p = 0.03).
Conclusion
The authors conclude that carvedilol provides similar benefits to metoprolol succinate and nebivolol in patients with CHF. Bisoprolol appears to be more effective than other beta-blockers. However, the therapeutic effect of metoprolol tartrate is deemed worse than that of the other mentioned BBs. The incidence of adverse reactions to different BBs was similar. Direct comparison of their efficacy and safety would only be possible through randomized head-to-head studies.
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Source: Liu B., Zhang R., Zhang A. et al. Effectiveness and safety of four different beta-blockers in patients with chronic heart failure. MedComm (2020) 2023 Jan 6; 4(1): e199, doi: 10.1002/mco2.199.
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