Comparative Outcomes of Beta-Blockers vs Non-Dihydropyridine Calcium Channel Blockers in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Determining the most effective medication regimen to manage blood pressure and heart rate in patients with heart failure with preserved ejection fraction (HFpEF) continues to lack a clear clinical consensus. Although beta-blockers (BBs) are widely prescribed, their negative chronotropic effects may worsen exercise intolerance. Alternative agents like verapamil and diltiazem, which belong to the non-dihydropyridine calcium channel blocker (non-DHP CCB) class, offer a physiological alternative, yet comparative data are scarce. A systematic review and meta-analysis were conducted, comparing BBs vs non-DHP CCBs in adults with HFpEF (left ventricular ejection fraction ≥ 50%). A literature search across key databases was conducted up until May 2026. Primary outcomes included all-cause mortality and heart failure (HF) hospitalization. Pooled hazard ratios (HRs) with 95% CIs were calculated using a random-effects analytical framework incorporating the Hartung-Knapp-Sidik-Jonkman variance correction. Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Of the 576 retrieved records, two observational cohorts (106,848 patients) met the inclusion criteria. Only one of the two eligible cohorts analyzed real patient-level data; the other was generated. The two-study pooled estimates are reported as exploratory: all-cause mortality HR 0.88 (95% CI 0.34-2.26; p = 0.336) and HF hospitalization HR 0.91 (95% CI 0.34-2.42; p = 0.446), with I² > 80% for both outcomes. At k = 2, these dispersion statistics are themselves unstable, and the pooled intervals are not clinically interpretable. Restricted to the single real-world cohort, the estimates were HR 0.83 (95% CI 0.80-0.85) and HR 0.98 (95% CI 0.91-1.05), respectively, which are the figures of one observational study and carry no meta-analytic weight. Cardiovascular mortality, major adverse cardiovascular events, exercise capacity, and quality of life were prespecified but reported by neither study in poolable form. The confidence in these findings was rated as very low because the data stem from observational research and exhibit significant statistical variability alongside wide CIs. Current evidence does not demonstrate the prognostic superiority of either BBs or non-DHP CCBs in HFpEF. Given the very low certainty of the available data and high clinical heterogeneity, pharmacological selection should remain individualized. High-quality randomized controlled trials are needed to inform clinical guidelines.