ACEi and ARBs as Primary Prevention of Cancer Therapy-Related Cardiomyopathy in Patients Undergoing Chemotherapy with Anthracyclines: A Systematic Review and Meta-Analysis

INTRODUCTION: Anthracyclines treat a myriad of malignancies; however, they are known to lead to cancer therapy-related cardiomyopathy (CTRC). Randomized controlled trials (RCTs) evaluating the role of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in primary prevention of CTRC have yielded mixed results. METHODS: A systematic search of MEDLINE, Cochrane, and Scopus databases was performed to identify RCTs that evaluated outcomes in patients receiving anthracyclines and ACEi or ARBs versus control. The primary outcome was occurrence of CTRC. All data were pooled using a random-effects model. RESULTS: The final analysis included 10 RCTs, with 1049 patients assessed. The weighted follow-up period was 16.8 months. The average age was 43.2 years and 90% were female. Breast cancer (80%) and lymphomas (13%) were the most common malignancies. There was no statistically significant difference between the groups with regards to occurrence of CTRC (16% vs 24%; risk ratio (RR) 0.67, 95% confidence interval (CI) [0.31, 1.45]). Compared with control, ACEi/ARBs were associated with favorable absolute changes in left ventricular ejection fraction (LVEF) (standardized mean difference (SMD) + 1.20%, 95% CI [0.40, 2.00]), left ventricular end-diastolic volume (SMD - 0.36 mL, 95% CI [- 0.66, - 0.06]), and left ventricular end-systolic volume (SMD - 1.04 mL, 95% CI [- 1.79, - 0.29]). There was also a lower risk of arrhythmias in the ACEi/ARBs group compared to control (1.6% vs 8.0%; RR 0.30, 95% CI [0.10, 0.94]), but no difference in all-cause mortality (2.8% vs 3.2%; RR 0.82, 95% CI [0.26, 2.61]), or heart failure (1.2% vs 7.1%; RR 0.40, 95% CI [0.03, 4.54]). CONCLUSIONS: ACEi/ARBs therapy was not associated with a reduction in CTRC among patients with cancer receiving anthracyclines. However, there were favorable changes in LVEF and left ventricular remodeling with ACEi/ARBs therapy. Further large-scale studies are needed to better understand the potential role of ACEi/ARBs in preventing long-term cardiotoxicity.