Key result
SGLT2 inhibitors warrant guideline use in symptomatic anthracycline cardiotoxicity, but prophylactic use remains investigational.
Why the study?
Do SGLT2 inhibitors improve clinical, imaging, or biomarker outcomes across specific clinical states (State A, B, and C) of anthracycline-related cardiac dysfunction?
Do SGLT2 inhibitors improve clinical, imaging, or biomarker outcomes across specific clinical states (State A, B, and C) of anthracycline-related cardiac dysfunction?
Answers are grounded in this paper and cite their sources.
Current human evidence for SGLT2 inhibitors in anthracycline-related cardiac dysfunction is predominantly retrospective and lacks randomized efficacy data, supporting guideline-based SGLT2i use only when conventionally indicated in symptomatic or moderate/severe dysfunction (State C), while initiation in pre-exposure or mild asymptomatic stages (States A and B) remains investigational.
Purpose Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiorenal outcomes, but their role in anthracycline-related cardiac dysfunction (ARCD) beyond established indications is uncertain. We appraised mechanistic and clinical evidence across pre-exposure prophylaxis (State A); an isolated surveillance abnormality or mild asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), both with preserved left ventricular ejection fraction (State B); and symptomatic CTRCD/heart failure irrespective of ejection fraction or asymptomatic moderate/severe CTRCD (State C). Methods This critical narrative review used structured searches of PubMed/MEDLINE, Europe PMC, Web of Science Core Collection, and ClinicalTrials.gov, supplemented by an Embase search during revision. Peer-reviewed literature through 15 August 2026 and registry status through 22 August 2026 were assessed by clinical state, evidentiary directness, endpoint relevance, and validity threats. Results Human evidence was predominantly retrospective, and SGLT2i use usually reflected conventional indications. Small prospective nonrandomized studies focused on imaging or biomarkers. Favorable associations remain vulnerable to residual confounding, treatment selection, competing cancer mortality, exposure-timing bias, and source-cohort overlap. No peer-reviewed randomized between-group efficacy report was available by the literature cutoff. Experimental studies support biological plausibility but not direct myocardial target engagement, a uniform class effect, preserved anticancer activity, or clinical benefit. Conclusion State C warrants phenotype-appropriate guideline-based care, including SGLT2i when indicated; an incremental ARCD-specific benefit remains unproven. Without another indication, initiation in States A and B remains investigational. HFA-ICOS may guide surveillance and trial enrichment but is not a prescribing trigger.
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Wang et al. (2026) conducted a review in Anthracycline-related cardiac dysfunction (ARCD) across clinical states A (pre-exposure prophylaxis), B (isolated surveillance abnormality or mild asymptomatic CTRCD with preserved LVEF), and C (symptomatic CTRCD/HF or asymptomatic moderate/severe CTRCD). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) was evaluated. Sodium-glucose cotransporter 2 inhibitors warrant guideline-based use in symptomatic anthracycline-related cardiac dysfunction, whereas prophylactic initiation without a conventional indication remains investigational.
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