Abstract
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of heart failure cases and is associated with high morbidity and mortality. Beta-blockers (BB) and calcium channel blockers (CCB) are commonly used for symptom control and comorbidity management, but their comparative effectiveness and safety remain unclear. AIM: To compare the effectiveness and safety of BB vs CCB in patients with HFpEF using simulated real-world data and propensity score-matched analyses. METHODS: Simulated data for 4000 HFpEF patients (2000 BB, 2000 CCB) were generated based on distributions extracted from electronic medical records spanning 2014-2023. Inclusion criteria included adults with left ventricular ejection fraction ≥ 50% and initiation of BB or CCB. Effectiveness outcomes encompassed mortality, heart failure hospitalizations, and changes in clinical parameters. Safety outcomes included bradycardia, hypotension, and drug discontinuation. Statistical analyses used t-tests, χ (2) tests, Cox proportional hazards models for hazard ratios (HR), and incidence rate ratios (IRR) in R software. Propensity score matching (PSM) was performed to balance baseline characteristics, with outcomes reassessed in the matched cohort. RESULTS: Baseline characteristics were largely balanced, with minor differences in sex, chronic kidney disease, systolic blood pressure, and left atrial volume index. BB demonstrated lower all-cause mortality (crude HR 0.78, 95%CI: 0.70-0.87, P = 0.003), heart failure hospitalization (crude HR 0.86, 95%CI: 0.77-0.96, P = 0.031), and composite endpoint (crude HR 0.85, 95%CI: 0.79-0.91, P < 0.001) rates compared to CCB. IRR for heart failure hospitalizations and emergency visits favored BB. Safety profiles showed higher symptomatic bradycardia (9.2% vs 4.9%, P < 0.001) and drug discontinuation (11.3% vs 9.3%, P = 0.043) with BB, and higher hypotension (7.2% vs 11.5%, P < 0.001) with CCB. Matched analyses showed all-cause mortality rates of 0.0622 per person-year for BB vs 0.0649 for CCB (HR 0.96, 95%CI: 0.85-1.08), heart failure hospitalization rates of 0.0751 vs 0.0888 (HR 0.84, 95%CI: 0.75-0.94), and IRR for number of heart failure hospitalizations of 1.65 for CCB vs BB (95%CI: 1.51-1.80, P < 0.001). CONCLUSION: BB may offer potential advantages in reducing mortality and hospitalizations in HFpEF compared to CCB, with distinct safety considerations. PSM confirmed these trends with reduced confounding. Personalized therapy is recommended, warranting prospective trials for validation.