Dapagliflozin Fails to Reduce Early HF Event Risk in Hospitalized Patients

DAPA ACT HF-TIMI 68 evaluates dapagliflozin's effect in acute heart failure, finding no short-term risk reduction.

dapagliflozinSGLT2 inhibitorsheart failurerandomized controlled trialhospitalization Cardiology / Anticoagulation

Authors: Berg DD, Patel SM, Haller PM, Cange AL, Palazzolo MG, Bellavia A, Kuder JF, Desai AS, Inzucchi SE, McMurray JJV, O'Meara E, Verma S, Bělohlávek J, Drożdż J, Merkely B, Ogunniyi MO, Drasnar T, Izzo JL, Sarman B, McGinty JE, Ramanathan K, Mulkay AJ, Przybylski A, Ruff CT, O'Donoghue ML, Murphy SA, Sabatine MS, Wiviott SD, DAPA ACT HF-TIMI 68 Trial Committees and Investigators

Citation: 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 and Meta-Analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Patients Hospitalized for Heart Failure. Circulation. 2025;152(20):1411-1422. doi:10.1161/CIRCULATIONAHA.125.076575

Article Links: PubMed · Journal / DOI · Free Full Text (PMC)

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Inconclusive Impact 2/5

The primary endpoint was not met, and better-defined benefits are needed for practice-changing implications.

Evidence Grade: Low

Due to the short follow-up and insufficient power to demonstrate a significant primary outcome effect.

Study Design

Randomized, double-blind, placebo-controlled, 2-months, registered (NCT04363697), funded by AstraZeneca.

Population

2401 patients, hospitalized for HF, median age 69, 33.9% women, 18.7% Black, 71.5% LVEF ≤40%, multinational.

Primary Endpoint

Composite of cardiovascular death or worsening HF event, HR 0.86, 95% CI 0.68–1.08, p=0.20, not met.

Key Results

No significant reduction in primary outcome: dapagliflozin 10.9% vs placebo 12.7%, HR 0.86, 95% CI 0.68–1.08. All-cause death was lower with dapagliflozin (3.0% vs 4.5%, HR 0.66, 95% CI 0.43–1.00). Meta-analysis showed SGLT2i reduced cardiovascular death/worsening HF (HR 0.71, 95% CI 0.54–0.93).

Safety & Tolerability

Higher symptomatic hypotension with dapagliflozin (3.6% vs 2.2%). Worsening kidney function events were 5.9% for dapagliflozin vs 4.7% for placebo. No diabetic ketoacidosis reported.

Limitations

Underpowered for primary outcome, short follow-up period, limited by in-hospital initiation model.

Clinical Interpretation

DAPA ACT HF-TIMI 68 did not show a significant reduction in cardiovascular death or HF worsening at 2 months. However, broader data suggest a potential benefit of SGLT2 inhibitors for mortality reduction.

Pharmacist Implications

Consider continuing SGLT2 inhibitors for potential mortality benefit based on broader evidence.
Monitor for hypotension when initiating SGLT2 inhibitors in vulnerable patients.
Educate patients on recognizing signs of kidney impairment during treatment.

Guideline Context

Results align with the current trend of favoring SGLT2i in HF but pose questions about timing and setting of initiation. References 2023 ESC and 2022 AHA/ACC guidelines.

Monitoring Guidance

Monitor blood pressure and renal function closely, especially in patients with eGFR <60 ml/min/1.73m².

Nuanced Considerations

Potential differential outcomes based on HF phenotype and presence of type 2 diabetes.

Controversies & Gaps

Unclear benefit of SGLT2i when initiated in-hospital. Need for larger studies with longer follow-up.

Cost & Logistics

Not discussed

Editor's Note

Full text analysis available. Abstract-only caveat is not applicable. Ensure blinding and analysis consistency.

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