Heart rate-lowering drugs and outcomes in hypertension and/or cardiovascular disease: a meta-analysis
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Published on: May 17, 2024
Elias Sanidas1, Michael Böhm2, Ilektra Oikonomopoulou1
1Department of Cardiology, Laiko General Hospital of Athens, 17, Agiou Thoma str., Athens 11527, Greece.
Insights
Heart rate lowering drugs reduce cardiovascular mortality and heart failure in hypertensive patients with existing cardiovascular disease. However, benefits are context-dependent, with no significant improvements in hypertension alone.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The clinical benefits of using heart rate (HR)-lowering medications in patients with hypertension are debated.
- Evaluating the impact of HR reduction on cardiovascular outcomes, mortality, and adverse events is crucial for this population.
Purpose of the Study:
- To systematically evaluate the effects of HR-lowering drug treatment on cardiovascular outcomes, mortality, and adverse events in patients with hypertension and/or cardiovascular disease.
- To assess the context-dependent benefits and risks associated with HR reduction strategies.
Main Methods:
- A comprehensive literature search was conducted across PubMed, Embase, and Cochrane Library for randomized trials.
- Meta-analysis using a random-effects model calculated risk ratios and confidence intervals for eight key outcomes.
- Subgroup analyses explored HR reduction effects across different HR groups and age strata.
Main Results:
- Analysis of 74 trials (157,764 patients) showed an average HR reduction of 8.2 bpm over 2.7 years.
- HR lowering significantly reduced coronary heart disease (16%), heart failure (9%), cardiovascular mortality (14%), and all-cause mortality (13%).
- Benefits were significant in post-MI and heart failure patients, but not in hypertension without CV disease; adverse event discontinuations increased by 25%.
Conclusions:
- The benefits of HR reduction are highly context-dependent, varying with baseline cardiovascular status.
- Targeting an HR of 65-70 bpm for individuals with HR above 70 bpm appears reasonable to optimize outcomes while managing risks.
Background And Aims:
The benefits of heart rate (HR)-lowering drug treatment in hypertension remain controversial. The effects of HR lowering on cardiovascular (CV) outcomes, mortality, and adverse events in patients with hypertension and/or CV disease were evaluated.
Methods:
PubMed, the Embase, and the Cochrane Library were searched for randomized trials comparing HR-lowering drugs with placebo or less intensive treatment. Risk ratios and 95% confidence intervals for eight outcomes were calculated (random-effects model). Subgroup analyses for a standard HR reduction were used to compare risk estimates in different HR groups or age strata (PROSPERO CRD42024540924).
Results:
The database included 74 HR-lowering treatment trials (n = 157 764 patients). The average HR reduction over 2.7 years was 8.2 b.p.m. (baseline/attained HR: 76.2/65.6 b.p.m.). HR-lowering reduced coronary heart disease by 16%, heart failure by 9%, CV mortality by 14%, and all-cause mortality by 13% but increased adverse event-driven discontinuations by 25%. Significant mortality reductions were noted in post-acute myocardial infarction and heart failure. No significant outcome changes were observed with HR reduction in hypertension without CV disease, while the entire hypertensive population experienced increased stroke and mortality. Threshold analysis revealed that the effect on outcomes was not different across cutoffs (from ≥80 b.p.m. to almost 70 b.p.m.), except for heart failure. Treatment outcome effects were not different across progressively lower targets (from ≥70 b.p.m. to <65 b.p.m.), except for permanent discontinuations, which showed an incremental trend.
Conclusions:
The HR reduction benefits are context-dependent. Optimising outcomes while considering potential risks, targeting 65-70 b.p.m. for all HR thresholds above 70 b.p.m. seems reasonable.
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