Cardioprotective role of antihypertensive treatment in chemotherapy-induced cardiotoxicity: umbrella review of meta-analyses of randomised controlled trials

Abstract

Background: Chemotherapy-induced cardiotoxicity is a major contributor to long-term cardiovascular morbidity among cancer survivors. ACE inhibitors (ACEIs), angiotensin receptor blockers and beta blockers have been proposed as prophylactic therapies; however, the robustness of existing evidence is unclear. We aimed to evaluate the strength, consistency and certainty of evidence from meta-analyses of randomised controlled trials (RCTs) assessing antihypertensive agents for preventing chemotherapy-related cardiac dysfunction. Methods: We conducted an umbrella review of meta-analyses of RCTs following Preferred Reporting Items for Overviews of Reviews guidelines. Systematic searches were performed in PubMed, Embase and Cochrane Database through May 2025. Data were extracted and reanalysed using random-effects models (DerSimonian-Laird if ≥10 studies; Hartung-Knapp-Sidik-Jonkman if <10). Certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Primary outcomes included measures of cardiac function and structure; secondary outcomes were clinical and adverse events. Results: 35 meta-analyses comprising 108 associations were included. Preservation of left ventricular (LV) ejection fraction was observed with ACEIs (mean difference, MD, 4.22%, 95% CI 1.56% to 6.88%; GRADE: very low) and beta blockers (MD 2.77%, 95% CI 1.40% to 4.14%; low). Beta blockers reduced ratio of the early (E-wave) to late (A-wave) velocity decline (MD 0.07, 95% CI 0.01 to 0.13; moderate). No significant effect was noted on LV dimensions or biomarkers. Beta blockers reduced incidence of heart failure (relative risk, RR, 0.29, 95% CI 0.26 to 0.34) and cardiotoxicity (RR 0.44, 95% CI 0.26 to 0.75), while ACEIs reduced arrhythmias (RR 0.17, 95% CI 0.03 to 0.91); certainty was low. No significant impact was detected on all-cause mortality or hypotension. Conclusions: ACEIs and beta blockers appear to confer modest cardioprotective effects during chemotherapy, particularly regarding systolic function and heart failure incidence, although with predominantly low-certainty evidence. Larger, robust RCTs with standardised endpoints are required before routine prophylactic use is recommended. PROSPERO registration number: CRD420251046471.