What question did this study set out to answer?

To comprehensively evaluate the clinical efficacy and safety of beta-blockers across multiple contemporary cardiovascular indications.

May 5, 2020BMC MedicineOpen Access

Beta-blocker efficacy across different cardiovascular indications: an umbrella review and meta-analytic assessment

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Why the study?

Beta-blockers are widely used for many cardiovascular conditions, but their efficacy in contemporary clinical practice remains uncertain.

Do beta-blockers reduce mortality, MI, incident HF, or stroke across different cardiovascular indications including CAD, HF, surgery, and hypertension?

Key Points

To comprehensively evaluate the clinical efficacy and safety of beta-blockers across multiple contemporary cardiovascular indications.
Conducted a prospectively registered umbrella review (PROSPERO CRD42016038375) searching MEDLINE, EMBASE, and Cochrane Library through December 2018.
Analyzed 98 meta-analyses comprising 284 unique randomized controlled trials and 1,617,523 patient-years of follow-up for outcomes including all-cause mortality, myocardial infarction, incident heart failure, and stroke.
In heart failure with reduced ejection fraction (66 RCTs, N=35,383), beta-blockers reduced all-cause mortality and heart failure hospitalization in sinus rhythm, but conferred no benefit in patients with atrial fibrillation.
In coronary artery disease (93 RCTs, N=103,481), beta-blockers reduced mortality prior to routine reperfusion but showed no mortality reduction in modern cohorts with ≥50% reperfusion, lowering myocardial infarction at the cost of higher incident heart failure.
In hypertension (36 RCTs, N=260,549) and non-cardiac surgery (89 RCTs, N=19,211), beta-blockers demonstrated inferiority to other antihypertensives for mortality and stroke, and increased risks of perioperative stroke and all-cause mortality.

Structured PICO

Do beta-blockers reduce mortality, MI, incident HF, or stroke across different cardiovascular indications including CAD, HF, surgery, and hypertension?

Population

Patients with coronary artery disease (CAD), heart failure (HF), undergoing surgery, or hypertension (98 meta-analyses including 284 unique RCTs)

Intervention

Beta-blockers

Comparator

Control (placebo or other active agents)

Outcome

All-cause mortality, myocardial infarction (MI), incident HF, or strokehard clinical

While beta-blockers provide substantial mortality benefit in HFrEF patients in sinus rhythm, their routine use in contemporary CAD, non-cardiac surgery, and hypertension may lack benefit or pose risks.

Implication

Supports selective use in HFrEF with sinus rhythm; challenges routine application in contemporary CAD, non-cardiac surgery, and hypertension.

Abstract

BACKGROUND: Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain. METHODS: We performed a prospectively designed, umbrella review of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence. RESULTS: We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke. CONCLUSIONS: Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.