Beta blockers and hypertrophic obstructive cardiomyopathy: a systematic review and meta-analysis

Abstract

Background: Since the 1960s, beta blockers have been used to treat hypertrophic obstructive cardiomyopathy (HOCM), a genetic disorder causing abnormal heart muscle thickening. This systematic review evaluates their efficacy across clinical outcomes.

Methods: Registered on PROSPERO (CRD42022344255), searches were performed in June 2022 and updated in September 2025 across MEDLINE, Embase, CINAHL and PubMed. Two reviewers independently screened studies. Meta-analysis was undertaken when ≥3 comparable datasets were available; otherwise, narrative synthesis was used.

Results: 21 studies including 775 adults met inclusion criteria. Beta blockers significantly reduced left ventricular outflow tract (LVOT) gradient (Standardised mean difference (SMD) -1.57; 95% CI -2.07 to -1.07) and heart rate (SMD -1.19; 95% CI -2.24 to -0.14). Sensitivity analyses confirmed the robustness of the LVOT effect, while heart rate effects remained heterogeneous. Improvements in New York Heart Association class, exercise tolerance and symptom burden were consistently reported, although data were subjective and small in scale. Mortality evidence was limited to two retrospective cohorts with divergent findings.

Conclusions: Beta blockers provide consistent haemodynamic and symptomatic benefits in HOCM, but most evidence derives from small, older studies with high risk of bias and limited survival data. Contemporary, adequately powered randomised controlled trials are required to define optimal agent selection, dosing and long-term outcomes.

Prospero registration number: CRD42022344255.

Keywords: Cardiomyopathy, Hypertrophic; Meta-Analysis; Pharmacology, Clinical; Systematic Reviews as Topic.

Figure 1. Risk of bias assessment for included studies. Assessment of included studies using the Cochrane ROB-1 tool (for RCTs) and ROBINS-I (for cohorts). ROB-1 domains (RCTs): random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; incomplete outcome data; selective reporting; other bias. ROBINS-I domains (cohorts): confounding; selection of participants; classification of interventions; deviations from intended interventions; missing data; measurement of outcomes; selection of the reported result. Colour coding (both tools): green=low risk; yellow=moderate/some concerns; red=high/serious risk; dark red/black=critical risk. Note: Of 6 RCTs, 2 (33%) were rated low risk and 4 (67%) high risk. Of 15 cohorts, 4 (27%) were moderate and 11 (73%) serious risk. RCT, randomised controlled trial; ROB-1, Risk of Bias 1. (ROBINS-I) Risk of bias in non randomised studies of interventions

Figure 2. PRISMA flow diagram for study selection. Flowchart showing identification, screening, eligibility assessment and inclusion of studies in accordance with PRISMA guidelines. 441 records identified through databases and 2 through registers. 93 duplicates removed → 348 records screened. 320 records excluded at title/abstract level. 28 full-text reports assessed; 3 not retrieved. 24 excluded (reasons: insufficient outcome data (n=9); non-English (n=7); graphical-only data (n=4); ineligible design (n=4)). 21 studies included: 19 from the original search, 1 on rescreening, 1 via citation searching. PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools. Source: Page et al BMJ 2021;372:n71. doi: 10.1136/bmj.n71.This work is licensed under CC BY 4.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 3. Forest plot of standardised mean differences in LVOT gradients before and after beta-blocker therapy. Meta-analysis of three studies reporting LVOT gradients (mm Hg) pre-beta-blocker and post-beta-blocker therapy. Each row=individual study (means, SD and sample size pre/post). Right column=SMD with 95% CI (random-effects model). Square size=study weight; horizontal lines=95% CI. Diamond=pooled effect estimate (SMD=1.57 (95% CI 1.07 to 2.07)), favouring post-treatment. Heterogeneity: I²=55% (moderate). Note: IV=inverse variance method; SMD>0 favours post-beta-blocker treatment. LVOT, left ventricular outflow tract. SMD, Standardised mean difference.

Figure 4. Forest plot of standardised mean differences in heart rate before and after beta-blocker therapy. Meta-analysis of three studies reporting heart rate (bpm) pre-beta-blocker and post-beta-blocker therapy. Each row=individual study (means, SD and sample size pre/post). Right column=SMD with 95% CI (random-effects model). Square size=study weight; horizontal lines=95% CI. Diamond=pooled effect estimate (SMD=1.19 (95% CI 0.14 to 2.24)), favouring post-treatment. Heterogeneity: I²=84% (high). Note: IV=inverse variance method; SMD>0 favours post-treatment reductions in heart rate. SMD, Standardised mean difference.