Mortality benefit derived from SGLT2 inhibition could extend to HF with improved EF
Key takeaways:
- The mortality benefit from dapagliflozin may extend to patients with HF with improved ejection fraction.
- Dapagliflozin significantly reduced risk for sudden death vs. placebo.
Dapagliflozin plus guideline-directed medical therapy may reduce CV death in patients with HF with improved ejection fraction by lowering risk for sudden death, researchers reported.
Findings from a post hoc analysis of the DELIVER trial assessing mode of death among patients with HF with improved EF treated with dapagliflozin (Farxiga, AstraZeneca) compared with placebo were published in JAMA Cardiology.
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“Patients with heart failure with improved ejection fraction, defined as prior left ventricular ejection fraction 40% or lower that has increased to greater than 40%, represent an understudied group,” Orly Vardeny, PharmD, MS, associate professor of medicine at the University of Minnesota, and colleagues wrote. “These patients experience similar rates of adverse nonfatal clinical outcomes as those with HF with mildly reduced or preserved ejection fraction. Little is known regarding the potential benefit of initiating new therapies in those with LVEF that has improved to greater than 40%.”
The DELIVER trial
For the DELIVER trial, 6,263 patients with HF and LVEF more than 40%, with or without type 2 diabetes, were randomly assigned to dapagliflozin 10 mg once daily or placebo on top of usual therapy, for a median of 2.3 years. The primary outcome was a composite of worsening HF, defined as time to unplanned HF hospitalization or urgent HF visit, or CV death.
As Healio previously reported, dapagliflozin significantly reduced risk for CV death and worsening HF compared with placebo in patients with HF with mildly reduced or preserved EF, with fewer total HF hospitalizations and improved symptom burden.
The post hoc analysis
For the present post hoc analysis, Vardeny and colleagues evaluated the association between dapagliflozin and change in cause-specific death in patients with HF with improved EF. The primary outcome was a composite of worsening HF events — defined as hospitalization or urgent HF visits — or CV death.
HF with improved EF was defined as a patient having a history of LVEF of 40% and later presenting with LVEF of 50% or more.
Overall, 1,151 DELIVER trail participants had HF with improved EF in DELIVER, of whom 16.5% died, compared with 16.3% of 5,112 participants with LVEF consistently greater than 40%, according to the study.
The distribution of participants who had non-CV death or CV death was similar among those with HF with improved EF compared with patients with LVEF consistently greater than 40%, and the majority of deaths among patients with HF with improved EF were non-CV (54%).
Among CV deaths in the HF with improved EF group, 19% were sudden, followed by 15% that were HF-related.
Dapagliflozin was associated with lower risk for CV death compared with placebo among those with HF with improved EF (HR = 0.62; 95% CI, 0.41-0.96) and not among patients with EF consistently above 40% (HR = 0.95; 95% CI, 0.78-1.15; P for interaction = .09).
The observed benefit of dapagliflozin in patients with HF with improved EF was primarily driven by lower risk for sudden death (HR = 0.38; 95% CI, 0.18-0.79; P for interaction = .01), according to the study.
“The association of reduced risk of sudden death with dapagliflozin compared with placebo was consistent across LVEF values. The apparent greater magnitude of the dapagliflozin mortality benefit in patients with HF with improved EF should be considered hypothesis generating,” the researchers wrote. “These data suggest that the risk for sudden death may be modifiable with SGLT inhibitor therapy in addition to other HF treatments known to reduce cardiovascular death.”
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