Benefits of empagliflozin consistent regardless of cause of HFrEF
Empagliflozin on top of guideline recommended therapy improved CV and renal outcomes in HF with reduced ejection fraction, regardless of whether the cause of HF was ischemic or not, a study found.
The results of a post hoc analysis of the EMPEROR-Reduced trial that evaluated the efficacy and safety of empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) for patients with HFrEF from an ischemic cause compared with from a nonischemic cause were published in the Journal of the American Heart Association.
“The main takeaway from this paper is that in the presence of baseline optimal medical therapy, empagliflozin improved health status and clinical outcomes in patients with HFrEF similarly in patients with ischemic and non-ischemic etiologies,” Cardiology Today Editorial Board Member, Javed Butler, MD, MPH, MBA, FACC, FAHA, FESC, president of the Baylor Scott and White Research Institute, senior vice president for Baylor Scott and White Health and distinguished professor of medicine at the University of Mississippi, told Healio. “Thus, the cause of HF should not determine who should receive the therapy and all eligible HFrEF patients irrespective of etiology should be considered for this therapy.”
The EMPEROR-Reduced trial
For the EMPEROR-Reduced trial, researchers enrolled 3,730 patients with HFrEF to evaluate the effects of empagliflozin plus guideline-recommended therapy to reduce the primary outcome of CV death or hospitalization compared with placebo plus guideline-recommended therapy.
As Healio previously reported, treatment with empagliflozin reduced risk for CV death or HF hospitalization by 25% (P < .001), reduced total HF hospitalizations by 30% (P < .001) and reduced renal events by 50% (P < .001) compared with placebo.
EMPEROR-Reduced outcomes assessed by HF cause
For the present post hoc analysis, researchers compared the effects of empagliflozin in patients with HF from an ischemic cause (mean age, 68 years; 82% men; 75% white; 55% with diabetes) with those with HF from a nonischemic cause (mean age, 65 years; 70% men; 66% white; 44% with diabetes).
Within the EMPEROR-Reduced cohort, 51.7% of participants had HF from ischemic cause.
Researchers reported that in the placebo arm, patients with HF from ischemic causes did not have any higher risk for CV mortality (HR = 1.21; 95% CI, 0.9-1.63) and HF hospitalization (HR = 0.9; 95% CI, 0.72-1.12) compared with those with HF from nonischemic causes.
Compared with placebo, empagliflozin reduced risk for CV mortality or hospitalization for HF both in patients with HF from an ischemic cause (HR = 0.82; 95% CI, 0.68-0.99) and from a nonischemic cause (HR = 0.67; 95% CI, 0.55-0.82; P for interaction = .15).
“Previous studies have suggested worse outcomes for patients with ischemic etiology of HFrEF and more beneficial treatment effects of various therapies in patients with non-ischemic HFrEF. We did not find either of these to be statistically significantly different between the two groups,” Butler told Healio. “In patients with type 2 diabetes, acute or chronic HF, HFrEF and HFpEF and chronic kidney disease — we now know that empagliflozin provides significant clinical benefit. We now need data in patients after MI.”
The benefit of empagliflozin on estimated glomerular filtration rate slope change was consistent across both groups (P for interaction = .572) and empagliflozin was associated with decreased risk for renal events in both groups (P for interaction = .399), according to the study.
Improvements in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score were observed in both groups without any treatment modification, with similar rates of adverse events across arms.
“These data suggest that once left ventricular dilation and consequent dysfunction have ensued, regardless of prior cause journey progression of HF syndrome, a quadruple therapy regimen is effective and can be broadly used,” Muhammad Shahzeb Khan, MD, MSc, assistant professor of medicine at Duke University School of Medicine, and colleagues wrote.
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