Heart rate-lowering drugs and outcomes in hypertension and/or cardiovascular disease: a meta-analysis

Abstract 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.