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Sacubitril/Valsartan and Prevention of Chemotherapy-Induced Cardiac Dysfunction: Meta-analysis of Randomized Trials

Ramon Huntermann1, Maria Eduarda Molinari1, Pedro Gomes Batista2

  • 1University Center for the Development of Alto Vale, Rio do Sul, Brazil.

The American Journal of Cardiology
|April 3, 2026
PubMed

Insights

Angiotensin receptor-neprilysin inhibitors (ARNIs) improved cardiac function markers like global longitudinal strain (GLS) and ejection fraction during chemotherapy. However, ARNIs did not significantly reduce chemotherapy-related cardiac dysfunction (CTRCD) or mortality, with hypotension as a key concern.

Area of Science:

  • Cardiology
  • Oncology
  • Pharmacology

Background:

  • Chemotherapy-related cardiac dysfunction (CTRCD) poses a significant risk during cancer treatment.
  • Early detection of myocardial injury using global longitudinal strain (GLS) is possible, but preventive measures are limited.
  • Angiotensin receptor-neprilysin inhibitors (ARNIs) show potential for cardioprotection, yet evidence is scarce.

Purpose of the Study:

  • To systematically review and meta-analyze randomized controlled trials (RCTs) assessing the efficacy of sacubitril/valsartan (an ARNI) in preventing CTRCD.
  • To evaluate the impact of ARNI therapy on cardiac function parameters and clinical outcomes in patients undergoing chemotherapy.

Main Methods:

  • A systematic review and meta-analysis of four RCTs involving 412 participants was conducted.
  • Data from PubMed, Embase, and Cochrane databases were synthesized.
  • Risk ratios (RRs) and mean differences (MDs) with 95% CIs were calculated for various outcomes.

Main Results:

  • ARNI therapy significantly preserved left ventricular systolic function (MD 1.47%) and attenuated GLS deterioration (MD -0.93%).
  • No significant reduction in CTRCD incidence (RR 0.40) or all-cause mortality (RR 0.63) was observed with ARNI use.
  • Hypotension was a notable side effect, while NT-proBNP and dyspnea were not significantly affected.

Conclusions:

  • ARNI therapy demonstrates potential in improving cardiac function metrics during chemotherapy.
  • Current evidence does not support ARNI use for reducing CTRCD or mortality, highlighting the need for further research.
  • Hypotension is a critical safety consideration when using ARNIs in this patient population.
Keywords:
ARNISacubitril-Valsartancardio-oncologychemotherapy-related cardiac dysfunctionglobal longitudinal strain

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