Empagliflozin beneficial in HF with reduced ejection fraction, despite other therapies
Adults with heart failure with reduced ejection fraction derived similar benefits with empagliflozin regardless of other disease-modifying heart failure therapies prescribed at baseline, post hoc analysis of the EMPEROR-Reduced trial show.
“The EMPEROR-Reduced trial required patients to be treated for heart failure, but did not mandate specific doses or specific drugs,” Subodh Verma, MD, PhD, FRCSC, professor and the Canada Research Chair in Cardiovascular Surgery at the University of Toronto, and colleagues wrote in the study background. “Consequently, the trial provided an opportunity to determine if the benefits of empagliflozin are influenced by established disease-modifying therapies when used in combination and when prescribed at target or sub-target doses, as similarly evaluated with dapagliflozin in the DAPA-HF trial.”
As Healio previously reported, in EMPEROR-Reduced, among 3,730 patients with heart failure and an ejection fraction of 40% or less, treatment with empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) in addition to recommended therapy reduced the primary composite endpoint of CV death or heart failure hospitalization by 25% (P < .001), reduced total heart failure hospitalizations by 30% (P < .001) and reduced renal events by 50% (P < .001) compared with placebo. The study included participants with New York Heart Association class II to IV with an ejection fraction of 40% or less, randomly assigned the addition of either oral empagliflozin 10 mg per day or placebo to background therapy, which could include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers and mineralocorticoid receptor antagonists (MRAs).
“In this post hoc analysis, we aimed to evaluate the efficacy and safety of empagliflozin in patients given these foundational drug classes, used alone or in combination or prescribed at 50% or greater or at less than 50% of target dose,” the researchers wrote. The findings were published in The Lancet Diabetes & Endocrinology.
The primary composite outcome was CV death and hospitalization for heart failure; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient heart failure with reduced ejection fraction (HFrEF) events. The researchers analyzed outcomes according to background therapy use.
Researchers found that empagliflozin reduced risk for the primary outcome by 25% (HR = 0.75; 95% CI, 0.65-0.96), regardless of background therapy or its target doses for ACE inhibitors or angiotensin II receptor blockers at doses of less than 50% of the target dose (HR = 0.85; 95% CI, 0.69-1.06) and for doses of 50% or more of the target dose (HR = 0.67; 95% CI, 0.52-0.88). Researchers observed a similar result for beta-blockers at doses of less than 50% of the target dose, with an HR of 0.66 (95% CI, 0.54-0.8) and for doses of 50% or more of the target dose, with an HR of 0.81 (95% CI, 0.66-1).
Empagliflozin also reduced the risk for the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus beta-blocker plus an MRA, with an HR of 0.73 for those given the combination (95% CI, 0.61-0.88) and an HR or 0.76 for those not prescribed the combination (95% CI, 0.62-0.94). Similar patterns of benefit were observed for the secondary and extended composite outcomes.
Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension and hyperkalemia were similar across all subgroups, according to the researchers.
“Taken together, these data indicate that empagliflozin provides clinically important benefits in HFrEF in addition to existing disease-modifying therapies, regardless of breadth or intensity of use,” the researchers wrote.
The researchers noted that the findings should be considered exploratory and hypothesis-generating, as the number of comparisons could inflate the false-positive error rate and rates of adherence and therapeutic changes were not available in these analyses.
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