Key result
Dapagliflozin and sacubitril/valsartan show limited, mixed evidence in doxorubicin-induced cardiotoxicity.
Why the study?
Anthracycline-induced cardiotoxicity involves complex mechanisms and current cardioprotective strategies with dapagliflozin and sacubitril/valsartan have uncertain efficacy and safety profiles.
Do dapagliflozin and sacubitril/valsartan, alone or in combination, prevent doxorubicin-induced cardiotoxicity?
Do dapagliflozin and sacubitril/valsartan, alone or in combination, prevent doxorubicin-induced cardiotoxicity?
Despite promising mechanistic rationales, clinical evidence for sacubitril/valsartan in preventing doxorubicin-induced cardiotoxicity remains mixed, and randomized data for dapagliflozin or the combination are still needed.
Insufficient evidence precludes routine use in doxorubicin cardiotoxicity; leaves open need for powered RCTs.
Anthracyclines are still indispensable in oncology, yet cumulative myocardial injury can curtail treatment and leave survivors with late heart failure. Current work describes doxorubicin (DOX) cardiotoxicity as a convergent network in which mitochondrial redox stress, topoisomerase IIβ poisoning, ferroptosis, disrupted autophagy, and inflammasome-driven pyroptosis all contribute. Against that background, this critical narrative review appraises two heart-failure drugs with complementary biology: the sodium–glucose cotransporter 2 inhibitor dapagliflozin and the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan. Dapagliflozin has shown protective effects in experimental DOX models, and one small prospective observational study followed 60 women with diabetes receiving DOX. No randomized efficacy result was identified within the review search period. Evidence for sacubitril/valsartan is genuinely mixed. PRADA II missed its primary LVEF endpoint while SARAH reduced strain-defined cardiotoxicity, and meta-analyses find small gains in LVEF and global longitudinal strain alongside more hypotension and no statistically significant reduction in clinical cancer therapy-related cardiac dysfunction or mortality. Whether combined dapagliflozin and sacubitril/valsartan provides additional cardioprotection over either agent alone against doxorubicin-induced cardiotoxicity, while preserving antitumor efficacy, remains to be established in tumor-bearing animal models. Addressing this question requires exposure-informed, adequately powered comparisons of cardiac efficacy, tolerability, and tumor response.
No takes yet. Share an insight, caveat, or question.
Bilal et al. (2026) conducted a review in Doxorubicin-induced cardiotoxicity. Dapagliflozin and Sacubitril/Valsartan was evaluated. This critical review of dapagliflozin and sacubitril/valsartan for doxorubicin-induced cardiotoxicity found limited and mixed clinical evidence, requiring further adequately powered comparisons.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: