Sacubitril/Valsartan and Prevention of Chemotherapy-Induced Cardiac Dysfunction: Meta-analysis of Randomized Trials
Clinical Snapshot
PICO Framework
| P — Population | Patients undergoing cardiotoxic chemotherapy |
| I — Intervention | Sacubitril/Valsartan (ARNI therapy) |
| C — Comparator | Control (placebo or standard care) |
| O — Outcomes | Chemotherapy-related cardiac dysfunction (CTRCD), left ventricular ejection fraction, global longitudinal strain, mortality, adverse events |
Bottom Line
This meta-analysis of four small randomized trials (412 patients) suggests Sacubitril/Valsartan may preserve cardiac function parameters during chemotherapy, improving LVEF by 1.47% and attenuating GLS deterioration. However, the evidence is insufficient to recommend routine use for cardioprotection. The intervention did not significantly reduce clinically meaningful endpoints including chemotherapy-related cardiac dysfunction (RR 0.40, 95% CI 0.08-1.97) or mortality. Hypotension emerged as a safety concern. The small sample size, wide confidence intervals, and lack of demonstrated clinical benefit limit practice-changing implications. Current evidence supports continued cardiac monitoring and established cardioprotective strategies. Larger trials with longer follow-up are needed before considering ARNI therapy for primary cardioprotection in cancer patients. Clinicians should focus on proven interventions like ACE inhibitors and beta-blockers for high-risk patients.
Key Findings
P Value: Not explicitly reported
Effect Size: LVEF improvement: MD 1.47% (95% CI 0.59-2.34); GLS preservation: MD -0.93% (95% CI -1.49 to -0.38)
Primary Outcome: Preservation of left ventricular systolic function and global longitudinal strain
Nnt Or Sensitivity: CTRCD prevention: RR 0.40 (95% CI 0.08-1.97, not significant); Mortality: RR 0.63 (95% CI 0.08-5.01, not significant)
Confidence Interval: Statistically significant for surrogate endpoints but not clinical outcomes
Clinical Application
Limited by hypotension risk and lack of demonstrated clinical benefit on hard endpoints Sacubitril/Valsartan available on PBS for heart failure; cardio-oncology services expanding in major centres; CSANZ guidelines emphasize cardiac monitoring during chemotherapy Cancer patients receiving cardiotoxic chemotherapy, particularly anthracyclines and HER2-targeted agents
Abstract
Chemotherapy-related cardiac dysfunction (CTRCD) is a major limitation of cardiotoxic cancer therapies. Although global longitudinal strain (GLS) allows early detection of myocardial injury, preventive strategies remain scarce. Angiotensin receptor-neprilysin inhibitors (ARNIs) may offer cardioprotection, but current evidence is limited. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating Sacubitril/Valsartan versus control in patients undergoing chemotherapy. PubMed, Embase, and Cochrane databases were searched. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were computed for binary and continuous outcomes. Four randomized controlled trials comprising 412 participants were included; 42.7% received ARNI therapy, with follow-up ranging from 6 to 18 months. Compared with control, ARNI significantly preserved left ventricular systolic function (MD 1.47%, 95% CI 0.59-2.34) and attenuated GLS deterioration (MD -0.93%, 95% CI -1.49 to -0.38). However, ARNI did not significantly reduce the incidence of CTRCD (RR 0.40, 95% CI 0.08-1.97) or all-cause mortality (RR 0.63, 95% CI 0.08-5.01). ARNI increased the risk of hypotension but had no significant effects on NT-proBNP or dyspnea. In conclusion, ARNI therapy improves GLS and left ventricular ejection fraction during chemotherapy but has not yet demonstrated reductions in CTRCD or mortality. Hypotension remains a key safety consideration.
References
- 1.Huntermann, R., Molinari, M. E., Batista, P. G., de Oliveira, J. P., Muniz, J., de Lucena, L. A., Sato, M. Y., Melo, E. S., Giorgi, J., & Bacca, C. de O. F. (2026). Sacubitril/Valsartan and Prevention of Chemotherapy-Induced Cardiac Dysfunction: Meta-analysis of Randomized Trials. American Journal of Cardiology. https://doi.org/10.1016/j.amjcard.2026.03.068
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