Dapagliflozin in heart failure with improved ejection fraction: a prespecified analysis of the DELIVER trial.
Orly VardenyJames C FangAkshay S DesaiPardeep S JhundBrian ClaggettMuthiah VaduganathanRudolf A de BoerAdrian F HernandezCarolyn Su Ping LamSilvio E InzucchiFelipe A MartinezMikhail Naum KosiborodDavid DeMetsEileen O'MearaShelley ZierothJosep Comín ColetJarosław DrożdżChern-En ChiangMasafumi KitakazeMagnus PeterssonDaniel LindholmAnna Maria LangkildeJohn Joseph Valentine McMurrayScott D SolomonPublished in: Nature medicine (2022)
With modern treatments for heart failure with reduced ejection fraction (EF), indicative of impaired cardiac systolic function, patients may exhibit an increase in EF. Limited data are available regarding the clinical management of this growing population, categorized as heart failure with improved EF (HFimpEF), which has a high event rate and has been excluded from virtually all prior heart failure outcomes trials. In a prespecified analysis of the DELIVER trial ( NCT03619213 ), of a total of 6,263 participants with symptomatic heart failure and a left ventricular EF >40%, 1,151 (18%) had HFimpEF, defined as patients whose EF improved from ≤40% to >40%. Participants were randomized to 10 mg dapagliflozin or placebo daily and the primary outcome of the trial was a composite of cardiovascular death or worsening heart failure (heart failure hospitalization or an urgent heart failure visit). Participants with HFimpEF had similar event rates to those with an EF consistently >40%. In participants with HFimpEF, dapagliflozin reduced the primary composite outcome (hazard ratio (HR) = 0.74, 95% confidence interval (CI) = 0.56-0.97), first worsening heart failure events (HR = 0.78, 95% CI = 0.61-1.14), cardiovascular death (HR = 0.62, 95% CI = 0.41-0.96) and total worsening heart failure events (rate ratio = 0.68, 95% CI = 0.50-0.94) to a similar extent as for individuals with an EF consistently >40%. These data suggest that patients with HFimpEF who are symptomatic may benefit from the addition of a sodium/glucose cotransporter 2 inhibitor to previously instituted guideline-directed medical therapy to further reduce morbidity and mortality.
Keyphrases
- heart failure
- left ventricular
- ejection fraction
- cardiac resynchronization therapy
- acute heart failure
- phase iii
- atrial fibrillation
- end stage renal disease
- clinical trial
- newly diagnosed
- chronic kidney disease
- acute myocardial infarction
- phase ii
- open label
- physical activity
- bone marrow
- mitral valve
- metabolic syndrome
- machine learning
- stem cells
- type diabetes
- adipose tissue
- hypertrophic cardiomyopathy
- smoking cessation
- left atrial
- percutaneous coronary intervention