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Dapagliflozin and Timing of Prior HF Hospitalization
Quick Takes
- In a pooled meta-analysis, the benefit of dapagliflozin in reducing worsening HF/CV death was noted independent of EF and HF hospitalization status.
- However, the absolute benefit was largest with the lowest number needed to treat in patients with their last HF hospitalization within 3 months prior to therapy initiation.
Study Questions:
How does efficacy of dapagliflozin correlate with recency of heart failure hospitalization (HFH) across the range of left ventricular ejection fraction (LVEF)?
Methods:
This was a pooled meta-analysis of two randomized controlled trials: DAPA-HF and DELIVER. DAPA-HF enrolled HF patients with LVEF ≤40% and DELIVER patients with EF >40%. Both trials captured the date of most recent HFH. This study pooled time from last HFH into categories of: within 3 months, 3-12 months, and >1 year. The primary outcomes were worsening HF or cardiovascular (CV) death.
Results:
This meta-analysis included 4,789 patients with HFH prior to enrollment in DAPA-HF or DELIVER trials. Patients with more recent HFH were older, women, and White with higher B-type natriuretic peptide, lower glomerular filtration rate, and higher comorbidity burden. A more recent HFH was associated with higher risk for worsening HF or CV death that persisted with multivariable adjustment and was independent of LVEF. Compared with placebo, dapagliflozin reduced the risk for worsening HF and CV death independent of time from last HFH. However, the greatest absolute benefit was largest for patients with hospitalization within 3 months prior. The number needed to treat (NNT) to prevent one worsening HF/CV death over a median of 22 months was 13 for patients with HFH within 3 months prior, 20 for 3-12 months, 23 for >1 year, and 28 for patients without any HFH.
Conclusions:
In a pooled meta-analysis, the benefit of dapagliflozin in reduced worsening HF/CV death was noted independent of EF and HFH status. However, absolute benefit was largest with lowest NNT in patients with their last HFH within 3 months prior to therapy initiation.
Perspective:
HFHs are associated with a high morbidity and mortality risk. This study demonstrates the efficacy of SGLT2 inhibitors in high-risk HF patients with recent hospitalizations. These patients often have labile renal functions and volume status, which often results in suboptimal use of guideline-directed therapy. Notable findings include that the benefit of dapagliflozin was independent of HFH status and timing. Furthermore, patients with the most recent HFH (within 3 months) had the largest benefit, highlighting the importance of aggressive medical management for these patients that should be initiated as soon as possible. The NNT to prevent one event in a patient with HFH within 3 months of therapy initiation was low at only 13. Notable limitations of this meta-analysis include heterogeneity in study design with DAPA-HF did not include patients hospitalized within 4 weeks prior.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure
Keywords: Heart Failure, Hospitalization
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