ESC®️ 2025 – Recent Trials in Heart Failure: New Perspectives and Challenges

Three major studies presented at ESC®️ 2025 (DAPA ACT HF-TIMI 68, VICTOR, and ODYSSEY-HCM) explore different dimensions of heart failure, ranging from acute phase management to therapeutic options in specific conditions.

DAPA ACT HF-TIMI 68: Dapagliflozin in Heart Failure Hospitalization

The DAPA ACT HF-TIMI 68 trial evaluated the early initiation of dapagliflozin in patients hospitalized for heart failure. Although no significant reduction was observed in the primary composite endpoint of cardiovascular death or worsening heart failure at two months, pooled analyses with other SGLT2 inhibitor trials suggest a potential benefit in early mortality, supporting the strategy of initiating this treatment during hospitalization.

VICTOR: Vericiguat in Heart Failure with Preserved Ejection Fraction (HFpEF)

Published in The Lancet, the VICTOR trial investigated vericiguat in patients with HFpEF. Despite expectations regarding modulation of the cGMP pathway, the drug did not demonstrate superiority over placebo in improving functional capacity (measured by peak VO₂) or quality of life. These findings confirm that HFpEF remains a major therapeutic challenge with limited treatment options.

ODYSSEY-HCM: Mavacamten in Nonobstructive Hypertrophic Cardiomyopathy

The phase 3 ODYSSEY-HCM trial, published in The New England Journal of Medicine, analyzed mavacamten in patients with symptomatic nonobstructive hypertrophic cardiomyopathy. After 48 weeks, the drug did not show significant improvements in functional capacity (peak VO₂) or symptoms compared to placebo, although it did reduce cardiac stress biomarkers. Additionally, the risk of reduced ejection fraction was noted, raising concerns regarding its clinical use.

Perspectives

Taken together, these three trials reflect both the advances and current limitations in heart failure management:

SGLT2i in hospitalization: Growing evidence supporting early initiation.

HFpEF and vericiguat: Lack of clear clinical efficacy.

Mavacamten in nonobstructive HCM: Negative results in functional endpoints, with safety concerns regarding contractility.

These findings underscore the heterogeneity of heart failure and the need to explore new pathophysiological targets and personalized treatment strategies.

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References

Berg DD, Patel SM, Haller PM, et al. Dapagliflozin in Patients Hospitalized for Heart Failure: Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial. Circulation. 2025. doi:10.1161/CIRCULATIONAHA.125.076575.

Armstrong PW, Lam CSP, Anker SD, et al. Vericiguat for heart failure with preserved ejection fraction (VICTOR). Lancet. 2025. doi:10.1016/S0140-6736(25)01665-4.

Desai MY, Owens AT, Abraham T, et al. Mavacamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy. N Engl J Med. 2025. doi:10.1056/NEJMoa2505927.