Dapagliflozin Reduces Risk for HF Events in Patients With HFmrEF or HFpEF

Use of dapagliflozin decreases the risk of total heart failure (HF) events and cardiovascular death by 23% among patients with HF with mildly reduced ejection fraction (HFmrEF) or HF with preserved EF (HFpEF), according to a study in JAMA Cardiology.

Researchers presented findings from a prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure; ClinicalTrials.gov Identifier: NCT03619213) trial. DELIVER enrolled patients aged 40 years or older with HFmrEF or HFpEF, defined as HF with New York Heart Association (NYHA) functional class II to IV and an EF greater than 40%, who were randomly assigned to dapagliflozin 10 mg once daily or matching placebo.

The primary outcome was the composite of worsening HF or cardiovascular death, whichever occurred first, and the analyses assessed the predefined secondary outcomes of total worsening episodes of HF and cardiovascular deaths.

The cohort included 6263 patients (43.9% women; mean age, 71.7 [SD, 9.6] years). During a median follow-up of 2.3 (IQR, 1.7-2.8) years, 1380 nonfatal worsening HF events (urgent visits or hospital admissions) occurred in 822 patients. The patients who had 2 or more HF events had increased heart rates, body mass index, and N-terminal pro-B-type natriuretic peptide and hemoglobin A_1c levels.

The rate for total HF events and cardiovascular death was 15.3 per 100 patient-years in patients who received placebo and 11.8 per 100 patient-years in those who received dapagliflozin. The rate ratio (RR) from the Lin, Wei, Yang, and Ying (LWYY) model for total HF events and cardiovascular death was 0.77 (95% CI, 0.67-0.89; P <.001) vs a hazard ratio (HR) of 0.82 (95% CI, 0.73-0.92; P <.001) for the traditional time to first event composite of worsening HF event or cardiovascular death.

In analysis of the components of the total worsening HF events and cardiovascular deaths composite outcome, a decrease was observed in total HF events, with an RR of 0.73 (95% CI, 0.62-0.87; P <.001), but not for cardiovascular death (HR, 0.88; 95% CI, 0.74-1.05; P =.17). The joint frailty model yielded an RR of 0.72 (95% CI, 0.65-0.81; P <.001) for HF events and 0.87 (95% CI, 0.72-1.05; P =.14) for cardiovascular death.

In a post hoc analysis, the HR of subsequent death was 1.67 (95% CI, 0.90-3.12) in patients whose first event was an urgent HF visit and 5.70 (95% CI, 4.95-6.56) in those whose first event was an HF hospitalization, compared with patients with no HF event.

Dapagliflozin’s effect on total HF events and cardiovascular deaths was not different among any of the predefined subgroups. Treatment heterogeneity was not found in patients with and without an improved EF or based on whether they were randomized within 30 days of hospitalization.

Study limitations include a limited follow-up, and the findings may not apply to all patients with HFmrEF or HFpEF in the broader population. Also, hospitalization rates vary widely, and the participants were enrolled in 20 countries.

“HF events are common and preventable, and the efficacy of dapagliflozin in reducing the number of these events is consistent across a broad range of subgroups and across the spectrum of EF,” wrote the investigators.

Disclosure: The DELIVER trial was funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.