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Data from an analysis of the DELIVER trial suggest the benefits of dapagliflozin in heart failure with preserved ejection fraction (HFpEF) were statistically significant for the trial’s primary endpoint in less than 2 weeks.
A prespecified secondary analysis of the trial, results indicate the time to first nominal statistical significance for the primary endpoint was 13 days and this significance was sustained from day 15 and beyond in the trial.
“These data from the DELIVER trial underscore the rapid clinical benefits observed with the SGLT-2 inhibitor dapagliflozin and highlight key opportunities for the early identification and prompt management of this patient population without delay,” wrote investigators.
The DELIVER trial, which was originally presented at ESC Congress 2022, randomized 6263 patients from 350 centers in 20 countries to dapagliflozin 10 mg or placebo therapy. This cohort had a mean age of 71.7 (SD, 9.6) years, 43.9% were women, and the median follow-up time was 2.3 (IQR, 1.7-2.8) years. Results of the trial suggested use of dapagliflozin was associated with an 18% (HR, 0.82 [95% CI, 0.73-0.92]; P <.001) relative risk reaction for the primary composite endpoint of cardiovascular death or worsening heart failure, with this effect consistent in those with an ejection fraction greater than 60% compared to the overall study population (HR, 0.83 [95% CI, 0.73-0.95]; P=.009).
The current analysis, which was presented at the Heart Failure Society of America (HFSA) 2022 annual scientific meeting by Muthiah Vaduganathan, MD, MPH, cardiologist and codirector of the Center for Cardiometabolic Implementation Science at Brigham and Women’s Hospital, was designed with the specific intent of assessing time to first and sustained statistical significance of dapagliflozin for the trial’s primary composite end point and worsening heart failure alone.
In the analysis, results suggested the time to first nominal statistical significance for the primary composite end point was 13 days (HR, 0.45 [95% CI, 0.20-0.99]; P=.046) and this observed significance was sustained from day 15 onwards. Further analysis suggested first and sustained statical significance for worsening heart failure events was achieved by day 16 (HR, 0.45 [95% CI, 0.21-0.96]; P=.04). Additionally, investigators pointed out the benefits for both the primary endpoint (HR, 0.82 [95% CI, 0.73-0.92]) and for worsening heart failure events (HR, 0.79 [95% CI, 0.69-0.91]) were sustained at 30 days, 90 days, 6 months, 1 year, 2 years, and the final follow-up.
“This timeline of clinical benefit was highly consistent with similar observations from the EMPEROR-Preserved trial in which the nominal significance was first reached at day 18 after randomization and in trials of SGLT-2 inhibitors in patients with HF with reduced ejection fraction (12 to 28 days),” investigators added. “Furthermore, these data align with rapid improvements in symptoms, physical limitations, and quality of life seen with SGLT-2 inhibition as early as 2 to 4 weeks.”
This study, “Time to Clinical Benefit of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction,” was presented at HFSA 2022 and published in JAMA Cardiology.