Benefits of Dapagliflozin in HFmrEF/HFpEF Not Modified by AF at Baseline

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Researchers evaluated if atrial fibrillation affects dapagliflozin therapy in patients with heart failure with preserved ejection fraction.

The beneficial effects of treatment with dapagliflozin, compared with placebo, on clinical events and symptoms in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) is not modified by the presence of atrial fibrillation (AF). These findings were published in the Journal of the American College of Cardiology.

A secondary analysis of the randomized, controlled, double-blind Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure (DELIVER; Identifier: NCT03619213) trial was conducted. Investigators sought to evaluate the effects of the sodium-glucose cotransporter-2 inhibitor dapagliflozin, based on the presence or absence of AF, in patients with HFmrEF or HFpEF.

The primary study outcome was a composite of worsening HF (hospitalization for HF or urgent HF visit) or cardiovascular (CV) death. Secondary outcomes included the following:

  • total HF events (first and repeat hospitalizations for HF) and CV death
  • change from baseline to 8 months in the Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score (KCCQ-TSS)
  • death from CV causes
  • death from any cause

Worsening HF and HF hospitalization (as components of the primary composite outcome), sudden cardiac death, and death from pump failure were examined as well.

A total of 6263 patients with HF and who were New York Heart Association functional class II to IV with a left ventricular ejection fraction of more than 40%, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were included in the study. The patients were randomly assigned to treatment with dapagliflozin or placebo. Of these individuals, 2 were excluded because of lack of electrocardiogram data at baseline, leaving a total of 6261 participants for analysis. The study assessed clinical outcomes, along with the effect of dapagliflozin based on AF status.

Results of the study showed that 43.3% of patients had no AF, 18.0% exhibited paroxysmal AF, and 38.7% had persistent/permanent AF. Risk for occurrence of the primary endpoint was significantly higher among participants with AF, particularly those with paroxysmal AF, which was driven by a higher rate of hospitalization for HF. In patients without AF, HF hospitalization rate per 100 person-years was 4.5 (95% CI, 4.0-5.1). In patients with paroxysmal AF, HF hospitalization rate per 100 person-years was 7.5 (95% CI, 6.4-8.7). In patients with persistent/ permanent AF, HF hospitalization rate per 100 person-years was 6.4 (95% CI, 5.7-7.1; P <.001).

Additionally, the benefits of dapagliflozin on the primary outcome were consistent across all types of AF. In patients without AF, the hazard ratio [HR] was 0.89 (95% CI, 0.74-1.08). In patients with paroxysmal AF the HR was 0.75 (95% CI, 0.58-0.97). In patients with persistent AF the HR was 0.79 (95% CI, 0.66-0.95; Pinteraction =.49). There were consistent effects observed for HF hospitalization, CV death, all-cause mortality, and improvement in KCCQ-TSS.

Some limitations of the study include that although AF is considered a predefined subgroup analysis, the evaluation of secondary and exploratory outcomes according to AF status is performed post hoc. Further, because the prespecified inclusion and exclusion criteria in DELIVER precluded the enrollment of very high-risk patients, this may impact the generalizability of the results.

 “These findings provide further evidence for dapagliflozin as a new treatment option for patients with HFmrEF/HFpEF,” the researchers wrote.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Butt JH, Kondo T, Jhund PS, et al. Dapagliflozin, atrial fibrillation, and heart failure with mildly reduced or preserved ejection fraction in DELIVER. J Am Coll Cardiol. Published online August 27, 2022. doi:10.1016/j.jacc.2022.08.718