What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Cancer therapy-related cardiac dysfunction (n=410). Intervention: Sacubitril/valsartan vs. Control/Standard care. Primary outcome: Cancer therapy-related cardiac dysfunction (CTRCD) (RR 0.66, 95% CI 0.53 to 0.82, p=< 0.001).

What question did this study set out to answer?

This analysis aims to evaluate sacubitril/valsartan's effectiveness and safety in preventing cardiac dysfunction induced by cancer therapies.

April 24, 2026Open Access

Sacubitril/valsartan for the prevention of cancer therapy–related cardiac dysfunction: a systematic review and meta-analysis

Q: What are the key findings of this study?

Sacubitril/valsartan reduced the risk of cancer therapy-related cardiac dysfunction compared with control (RR 0.66).

Q: What question did this study set out to answer?

This analysis aims to evaluate sacubitril/valsartan's effectiveness and safety in preventing cardiac dysfunction induced by cancer therapies.

Key Result

Sacubitril/valsartan reduced the risk of cancer therapy-related cardiac dysfunction compared with control (RR 0.66).

Key Points

This analysis aims to evaluate sacubitril/valsartan's effectiveness and safety in preventing cardiac dysfunction induced by cancer therapies.
Conducted a systematic review and meta-analysis of randomized controlled trials.
Included studies compared sacubitril/valsartan with control groups during oncologic therapy.
Synthesis of treatment effects used risk ratio, mean differences, or standardized mean differences.
Sacubitril/valsartan significantly reduced the absolute risk of cardiac dysfunction (RR 0.66).
It improved left ventricular ejection fraction and global longitudinal strain compared to control.
Increased risk of hypotension was noted, but no significant differences for left ventricular volume or NT-proBNP were found.

Study Design

Type

Meta-Analysis (n=410)

Structured PICO

Does sacubitril/valsartan reduce cancer therapy-related cardiac dysfunction in patients with preserved baseline cardiac function receiving oncologic therapy?

Population

410 participants from 4 RCTs with preserved baseline cardiac function receiving oncologic therapy (mostly breast cancer or hematologic malignancies). Mean age ranged from 46.7 to 54.1 years, 88.5% female. Excluded patients with baseline heart failure. Baseline cardiovascular risk was generally low to moderate.

Intervention

Sacubitril/valsartan (doses ranging from 24.5/25.5 mg twice daily to up-titrated 97/103 mg twice daily or maximally tolerated dose) for 6 to 18 months.

Comparator

Control (standard care or placebo, with varying use of baseline renin-angiotensin system inhibitors).

Outcome

Cancer therapy-related cardiac dysfunction (CTRCD), defined according to 2022 ESC cardio-oncology guidelines or original trial criteria (incorporating LVEF decline or GLS decline).surrogate

Sacubitril/valsartan may modestly reduce the risk of cancer therapy-related cardiac dysfunction and attenuate LVEF/GLS decline, but current evidence is insufficient to change clinical practice.

Main Result

Effect estimate: RR 0.66 (95% CI 0.53 to 0.82)

p-value: p=< 0.001

Limitations

Trial sequential analysis indicated that the current evidence remains insufficient to draw firm conclusions
Two included studies were not double-blinded during the randomization process, raising some concerns regarding risk of bias
Modest magnitude of effect requiring confirmation in larger randomized trials

Abstract

Sacubitril/valsartan is being investigated for cardiac protection during cancer therapy. However, evidence regarding its preventive effect on cancer therapy–related cardiac dysfunction (CTRCD) remains inconsistent. To evaluate the efficacy and safety of sacubitril/valsartan for the prevention of CTRCD during oncologic therapy. We searched PubMed, EMBASE, and Web of Science for randomized controlled trials (RCTs) comparing sacubitril/valsartan with control for the prevention of CTRCD during oncologic therapy, with treatment effects synthesized using risk ratio (RR), mean differences (MD), or standardized mean differences (SMD) with 95% confidence intervals. Four RCTs involving 410 participants were included. Sacubitril/valsartan reduced the absolute risk of CTRCD compared with control (RR 0.66, 95% CI 0.53 to 0.82, p < 0.001). Sacubitril/valsartan was associated with a significant improvement in left ventricular ejection fraction (MD 1.19%, 95% CI 0.05 to 2.33, p = 0.045), global longitudinal strain (SMD 0.43, 95% CI 0.10 to 0.75, p = 0.026), and a reduction in troponin (log-MD − 0.43, 95% CI − 0.59 to − 0.26, p < 0.001), compared with the control group. Sacubitril/valsartan increased the risk of hypotension (RR 4.75, 95% CI 1.78 to 12.63, p = 0.002). No significant differences were observed in left ventricular volume, work indices, or NT-proBNP levels. Trial sequential analysis indicated that the current evidence remains insufficient to draw firm conclusions regarding the effect of cardioprotection on CTRCD. Sacubitril/valsartan may be associated with modest reductions in CTRCD risk and attenuation of LVEF and GLS decline in patients with preserved baseline cardiac function receiving chemotherapy. However, the clinical relevance remains inconclusive when considering the trial sequential analysis and the modest magnitude of effect. These findings are primarily hypothesis-generating rather than practice-changing, and require confirmation in larger randomized trials, particularly in higher-risk populations.

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Cite This Study

Wu et al. (Wed,) conducted a meta-analysis in Cancer therapy-related cardiac dysfunction (n=410). Sacubitril/valsartan vs. Control/Standard care was evaluated on Cancer therapy-related cardiac dysfunction (CTRCD) (RR 0.66, 95% CI 0.53 to 0.82, p=< 0.001). Sacubitril/valsartan reduced the risk of cancer therapy-related cardiac dysfunction compared with control (RR 0.66).

synapsesocial.com/papers/69eb0803553a5433e34b342f https://doi.org/https://doi.org/10.1186/s40959-026-00494-y

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