What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Cancer therapy-related cardiomyopathy (CTRC) (n=1049). Intervention: ACEi or ARBs vs. Control (placebo or no treatment). Primary outcome: Occurrence of cancer therapy-related cardiomyopathy (CTRC) (RR 0.67, 95% CI 0.31, 1.45, p=0.31).

What does this research mean for the field?

ACE inhibitors and ARBs do not significantly reduce the occurrence of cancer therapy-related cardiomyopathy in patients receiving anthracyclines, although they are associated with favorable changes in left ventricular ejection fraction and remodeling. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 16, 2025Open Access

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

WHWissam HarmouchThe University of Texas Medical Branch at Galveston RTRavi ThakkerYale University ADAlexander DangThe University of Texas Health Science Center at Houston

Key Result

ACEi/ARBs therapy did not significantly reduce the occurrence of cancer therapy-related cardiomyopathy compared to control in patients receiving anthracyclines (16% vs 24%; RR 0.67).

Study Design

Type

Meta-Analysis (n=1,049)

Structured PICO

Does ACEi or ARB therapy prevent cancer therapy-related cardiomyopathy in patients receiving anthracyclines?

Population

1,049 patients (average age 43.2 years, 90% female) with cancer (mostly breast cancer and lymphomas) receiving anthracycline-based chemotherapy, followed for a weighted average of 16.8 months.

Intervention

Angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs)

Comparator

Control

Outcome

Occurrence of cancer therapy-related cardiomyopathy (CTRC)surrogate

ACEi/ARB therapy did not significantly reduce the occurrence of cancer therapy-related cardiomyopathy in patients receiving anthracyclines, though it was associated with favorable changes in LVEF and left ventricular remodeling.

Main Result

Relative Risk: 0.67 (95% CI 0.31–1.45)

Absolute Event Rate: 16% vs 24%

p-value: p=0.31

Limitations

Aggregate data from the RCTs lacked the power to detect a statistically significant difference in CTRC.
Differences in definitions of CTRC across included RCTs (e.g., different LVEF cutoffs).
Insufficient data to verify a dose-dependent preventive effect of ACEi/ARBs.
High heterogeneity in the primary outcome (I2 = 76%).

Abstract

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.

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