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Effects of Dapagliflozin According to the Heart Failure Collaboratory Medical Therapy Score: Insights From DAPA-HF
Jawad H Butt1, Pooja Dewan2, Ersilia M DeFilippis3
1British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Insights
Dapagliflozin effectively treated heart failure with reduced ejection fraction, regardless of guideline-directed medical therapy intensity. The modified Heart Failure Collaboratory (HFC) score helps assess new treatments in patients receiving comprehensive care.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The Heart Failure Collaboratory (HFC) developed a score to quantify guideline-directed medical therapy (GDMT) in heart failure (HF) patients.
- This score aids in evaluating new treatments' benefits in patients already on comprehensive GDMT.
Purpose of the Study:
- To investigate the efficacy of dapagliflozin in the DAPA-HF trial using a modified HFC score.
- To determine if dapagliflozin provides benefits across different levels of GDMT intensity.
Main Methods:
- The DAPA-HF trial randomized 4,744 patients with HF and reduced ejection fraction to dapagliflozin or placebo.
- A modified HFC score, incorporating race and ECG parameters, was used to assess treatment intensity.
- The primary outcome was a composite of worsening HF or cardiovascular death.
Main Results:
- Higher modified HFC scores were associated with a lower risk of worsening HF or cardiovascular death.
- Dapagliflozin consistently reduced the risk of worsening HF or cardiovascular death across all tertiles of the HFC score (HRs ranging from 0.71 to 0.76).
- Benefits of dapagliflozin were observed for HF hospitalization, cardiovascular death, all-cause mortality, and symptom improvement (KCCQ-TTS).
Conclusions:
- Dapagliflozin demonstrated consistent efficacy in improving HF outcomes compared to placebo, irrespective of the modified HFC score.
- The modified HFC score is a practical tool for clinical trials to evaluate incremental treatment effects in HF.
Background:
The Heart Failure Collaboratory (HFC) has developed a score integrating classes and doses of guideline-directed medical therapies prescribed for patients with heart failure (HF) and reduced ejection fraction. One potential use of this score is to test whether new treatments demonstrate incremental benefits, even in patients receiving comprehensive guideline-directed medical therapy.
Objectives:
The authors investigated the efficacy of dapagliflozin according to a modified HFC score in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial.
Methods:
In DAPA-HF, 4,744 patients with HF and reduced ejection fraction were randomized to dapagliflozin or placebo. The modified HFC score accounted for race and electrocardiogram rhythm and rate, with a maximum possible score of 100%. The primary outcome was the composite of worsening HF or cardiovascular death.
Results:
The median modified HFC score was 50% (IQR: 27.5%-62.5%; range 0%-100%). Compared with the lowest tertile, the highest tertile of the treatment score was associated with a lower risk of worsening HF or cardiovascular death (tertile 1, reference; tertile 2, HR: 0.97 [95% CI: 0.82-1.14]; tertile 3, HR: 0.83 [95% CI: 0.70-0.99]). Dapagliflozin reduced the risk of worsening HF or cardiovascular death, irrespective of treatment score (the HRs for dapagliflozin vs placebo from tertile 1 to 3 were: 0.76 [95% CI: 0.61-0.94], 0.76 [95% CI: 0.60-0.97], and 0.71 [95% CI: 0.55-0.90]), respectively; Pinteraction = 0.89). Consistent benefits were observed for HF hospitalization, cardiovascular death, all-cause mortality, and improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TTS).
Conclusions:
Dapagliflozin, compared with placebo, improved all outcomes examined, regardless of the modified HFC score. This score can be easily calculated in clinical trials and used to evaluate the incremental effects of new treatments. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
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