The ATHENA-HF trial, published in JAMA Cardiology in 2017, evaluated the efficacy and safety of high-dose spironolactone in patients with acute heart failure (AHF). This was a double-blind, placebo-controlled randomized clinical trial, aiming to assess whether high-dose spironolactone could significantly reduce N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared to usual care.
Study Design and Methods
- Population: 360 patients with acute heart failure.
- Inclusion criteria:
- Adults aged ≥21 years with AHF.
- At least one symptom (e.g., dyspnea, orthopnea, fatigue) and one clinical sign (e.g., rales, edema, ascites, congestion).
- eGFR ≥30 mL/min/1.73m² and potassium levels ≤5.0 mmol/L.
- NT-proBNP ≥1000 pg/mL or BNP ≥250 pg/mL.
- Patients not on mineralocorticoid receptor antagonists (MRAs) or on low-dose spironolactone.
- Inclusion criteria:
- Intervention:
- High-dose spironolactone (100 mg daily) versus placebo or low-dose spironolactone (25 mg daily as part of usual care).
- Duration: 96 hours.
Primary Outcome
The primary outcome was the reduction in log NT-proBNP levels after 96 hours of treatment. NT-proBNP is a critical biomarker used to assess heart failure severity and guide treatment.
Results
- Log NT-proBNP Reduction:
- High-dose spironolactone: -0.55 (95% CI: -0.92 to -0.18).
- Usual care: -0.49 (95% CI: -0.98 to -0.14).
- Statistical Analysis:
- The difference in NT-proBNP reduction between the two groups was not statistically significant (P = 0.57).
- Safety and Tolerability:
- High-dose spironolactone was well tolerated in patients with AHF.
Conclusion
The ATHENA-HF trial concluded that adding high-dose spironolactone to usual care for 96 hours in acute heart failure was safe and well-tolerated but did not lead to a significant improvement in NT-proBNP levels or other efficacy endpoints.
This trial highlights the ongoing need for effective therapies in acute heart failure and demonstrates the importance of rigorous randomized trials in evaluating potential treatments.
Clinical Implications
For clinicians, the ATHENA-HF trial underscores the following:
- High-dose spironolactone may be safely used in AHF settings but should not be expected to provide additional benefit over usual care in reducing NT-proBNP levels.
- NT-proBNP remains a critical biomarker for evaluating heart failure, and future research should explore other interventions targeting its reduction.
Reference
Butler J et al. JAMA Cardiol. 2017 Sep 1;2(9):950-958.