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Prophylactic ACE Inhibition in Anthracycline-Induced Cardiotoxicity: Signal, Context, and Clinical Uncertainty.

Beatrice Simeone^1,2, Erica Rocco¹, Luigi Spadafora^2,3

¹Cardiology Division, ICOT Istituto "Marco Pasquali" University Hospital, Latina, Italy.

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|July 7, 2026

Summary

Angiotensin-converting enzyme inhibitors (ACEi) may reduce heart damage from cancer drugs, but benefits are modest and depend on patient risk. Universal prophylaxis is not recommended; targeted use in high-risk patients is suggested.

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Area of Science:

Cardio-oncology
Cardiovascular toxicology
Pharmacological prophylaxis

Background:

Anthracyclines are vital cancer drugs but can cause heart failure (HF).
The effectiveness of universal pharmacologic prophylaxis for anthracycline-induced cardiotoxicity is uncertain.
A meta-analysis synthesized randomized evidence on angiotensin-converting enzyme inhibitors (ACEi) for preventing cardiotoxicity.

Purpose of the Study:

To evaluate the role of ACEi in preventing anthracycline-related cardiotoxicity.
To synthesize current randomized evidence on ACEi prophylaxis.
To inform risk-adapted strategies for cardioprotection in cancer patients.

Main Methods:

Meta-analysis of randomized controlled trials.
Evaluation of ACEi for preventing left ventricular ejection fraction (LVEF) decline.
Analysis of context-dependent benefits in various risk settings.

Main Results:

ACEi prophylaxis significantly attenuated LVEF decline, but the effect size was modest.
Substantial heterogeneity was observed, with greater benefit in higher-risk settings (e.g., combined anthracycline/trastuzumab therapy, early myocardial injury markers).
No significant effects on clinical endpoints were observed, highlighting limitations of surrogate markers and trial design.

Conclusions:

ACEi prophylaxis may be beneficial in specific high-risk populations, not universally.
A risk-adapted approach integrating early detection (e.g., global longitudinal strain) and biomarker-guided intervention is recommended.
Future cardio-oncology studies need risk enrichment and clinically meaningful outcomes to define cardioprotective strategies.