Sacubitril/Valsartan for Prevention of Cancer Therapy-Related Cardiac Dysfunction: A Systematic Review and...

Cancer therapy-related cardiac dysfunction (CTRCD) is a significant complication of anthracycline-based regimens and anti-HER2 agents. Global longitudinal strain (GLS) detects subclinical dysfunction before ejection fraction decline and is recommended by the 2022 ESC guidelines for surveillance. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has shown cardioprotective potential in recent trials. Following PRISMA 2020 guidelines, we searched PubMed, EMBASE, and Cochrane CENTRAL through February 2026. Three RCTs met eligibility criteria (n= 350; PROSPERO: CRD420261383124): Hsu 2025 (n = 100, 12 months), PRADA II 2025 (n = 138, 18 months), and SARAH 2025 (n = 112, 6 months). Random-effects meta-analysis used REML with Hartung-Knapp-Sidik-Jonkman adjustment. The pooled mean difference in final GLS significantly favored sacubitril/valsartan (MD -0.95%; 95% CI -1.40 to -0.50; p = 0.012; I² = 0%). Final LVEF showed a consistent trend (MD +1.53%; 95% CI -0.47 to 3.52; p = 0.082; I² = 0%). Hypotension was numerically more frequent with sacubitril/valsartan (OR 5.10; 95% CI 0.52-49.50; p = 0.091). Sacubitril/valsartan initiated during anthracycline therapy was associated with significant GLS preservation. However, GLS is a surrogate imaging marker and hard clinical events were rare or absent, so the modest effect magnitude and limited number of trials warrant cautious interpretation; the clinical benefit remains uncertain and requires confirmation in adequately powered trials with hard clinical endpoints.