Sacubitril/Valsartan in Anthracycline-Treated Patients: A Systematic Review and Meta-Analysis of Available Evidence
A partir d'une revue systématique de la littérature (3 études, 352 patients), cette méta-analyse évalue l'intérêt d'une utilisation de sacubitril/valsartan pour prévenir le risque de dysfonctionnement cardiaque chez des patients atteints d'un cancer traité par chimiothérapie à base d'anthracyclines
Anthracyclines represent a cornerstone of systemic anticancer therapy1; however, their use is limited by their well-recognized cardiotoxic potential, which may manifest as cancer therapy–related cardiac dysfunction (CTRCD).1 Contemporary cardio-oncology practice emphasizes the early identification of subclinical myocardial injury, although robust evidence guiding pharmacologic cardioprotection remains limited.1 Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor, has demonstrated consistent benefits in heart failure populations, but its role in patients exposed to anthracyclines has not been systematically evaluated.
We performed a systematic review and meta-analysis of randomized trials testing sacubitril/valsartan in patients receiving anthracycline-based chemotherapy (CRD420261278068). PubMed, Embase, Scopus, and the Cochrane Library were searched from inception to January 2026. Eligible studies enrolled adults exposed to anthracyclines (with or without trastuzumab) and compared sacubitril/valsartan with placebo or standard care for the prevention of CTRCD. Two reviewers independently screened studies.
The primary endpoint was CTRCD according to the 2022 European Society of Cardiology cardio-oncology guidelines.2 Secondary outcomes included changes in left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and symptomatic hypotension. Risk ratios and mean differences (MDs) with 95% CIs were pooled using random-effects models. For continuous outcomes, between-group changes from baseline were preferentially extracted; however, if these were not available, post-treatment differences were calculated using the summary data. Heterogeneity was assessed using Q and I2 statistics. Risk for bias was evaluated with the Cochrane Risk of Bias 2 tool.
Our literature search identified 753 records. Sixteen underwent full-text review, with 3 studies included in the final analysis;3, 4, 5 13 were excluded because of nonrandomized design, use of the drug outside the preventive setting, or nonanthracycline regimens. A total of 352 patients were analyzed (mean age 52 ± 9 years, 94% with breast cancer). CTRCD outcomes were heterogeneously defined across studies; thus, no summary statistic was derived. In Hsu et al,3 CTRCD (the primary endpoint) was defined as either a relative ≥15% decline in GLS or a reduction in LVEF ≥10% to a value <50%. No patient in the sacubitril/valsartan group developed CTRCD, whereas 26.3% of patients in the standard care group did; all events were captured exclusively by the GLS criterion, with none meeting the LVEF threshold. In PRADA II (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy),4 the primary endpoint was LVEF change by cardiac magnetic resonance; echocardiography-based CTRCD per European Society of Cardiology criteria was a prespecified secondary outcome. Moderate or severe CTRCD was uncommon (2 placebo-treated patients, none with sacubitril/valsartan), whereas mild CTRCD (ie, asymptomatic patients with LVEFs ≥50% and new GLS declines >15% and/or biomarker elevations) occurred in 83% of placebo vs 71% of sacubitril/valsartan patients. In the SARAH (Sacubitril-Valsartan for the Prevention of Anthracycline Cardiotoxicity in Patients With Elevated hs-cTnI Concentrations During Chemotherapy) trial5, deterioration in GLS >15% from baseline occurred in 4 patients (7.1%) with sacubitril/valsartan and in 14 (25.0%) with placebo, whereas LVEF reductions >10% to <53% occurred in 4 patients in both groups.
JACC: CardioOncology , résumé, 2026