Disclosures: Ferreira reports he received consultant fees from Boehringer Ingelheim. Greene reports he received research support from the American Heart Association, Amgen, AstraZeneca, Bristol Myers Squibb, Merck and Novartis; served on advisory boards for Amgen and Cytokinetics; and serves as a consultant for Amgen and Merck. Khan reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
March 19, 2021
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Mineralocorticoid receptor antagonist use does not affect empagliflozin HF, renal benefits

Disclosures: Ferreira reports he received consultant fees from Boehringer Ingelheim. Greene reports he received research support from the American Heart Association, Amgen, AstraZeneca, Bristol Myers Squibb, Merck and Novartis; served on advisory boards for Amgen and Cytokinetics; and serves as a consultant for Amgen and Merck. Khan reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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The use of mineralocorticoid receptor antagonists did not influence the ability of empagliflozin to reduce adverse HF and renal outcomes, according to data from EMPEROR-Reduced published in the Journal of the American College of Cardiology.

João Pedro Ferreira

João Pedro Ferreira, MD, assistant professor in the department of physiology and cardiothoracic surgery at the São João Porto Hospital, Portugal, assistant professor at the University of Lorraine in the Centre for Clinical and Plurithematic Investigation, Nancy, France, and research fellow at the University of Glasgow, U.K., and colleagues conducted a substudy of EMPEROR-Reduced, which enrolled 3,730 patients with HF and a reduced ejection fraction of 40% or less. Among the cohort, 71% of patients used mineralocorticoid receptor antagonists (MRAs).

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Researchers evaluated whether the effects of the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim) would be affected by patients also using MRAs.

Similar effects

There were similar effects of empagliflozin on reducing adverse HF, renal outcomes and on safety outcomes for patients receiving or not receiving MRAs (P for interaction > .2), according to the researchers.

The effect of empagliflozin compared with placebo for CV death trended toward being more beneficial in patients using MRAs (HR = 0.82; 95% CI, 0.65-1.05) than in patients not using them (HR = 1.19; 95% CI, 0.82-1.71; P for interaction = .1). Researchers observed a similar trend for all-cause mortality (P for interaction = .098).

At baseline, of 1,069 patients who did not use MRAs, those in the empagliflozin group were 35% less likely to initiate MRA treatment after randomization compared with patients in the placebo group (HR = 0.65; 95% CI, 0.49-0.85). For the 2,661 patients who used MRAs at baseline, those in the empagliflozin group were 22% less likely to discontinue MRA treatment after randomization compared with those in the placebo group (HR = 0.78; 95% CI, 0.64-0.96).

Patients in the empagliflozin group were numerically less likely to develop severe hyperkalemia, regardless of MRA use at baseline (HR = 0.7; 95% CI, 0.47-1.04; P for interaction = .56).

“In the clinical setting, a favorable symptomatic response to SGLT2 inhibition should not obviate the use of MRAs by practitioners,” the researchers wrote. “Furthermore, the possibility that the use of SGLT2 inhibitors may enhance the ability of patients to be maintained on treatment with an MRA provides further support for the value of combining these two classes of drugs to improve outcomes in patients with heart failure.”

Core treatment

According to a related editorial, these findings further support SGLT2 inhibitors as a centerpiece in treating patients with HFrEF.

Muhammad Shahzeb Khan

“For patients with HFrEF in 2021, the central therapeutic goal is for eligible patients to receive target or maximally tolerated doses of a four-member team of medications,” Stephen J. Greene, MD, assistant professor of medicine in the division of cardiology at Duke University School of Medicine and member in the Duke Clinical Research Institute, Durham, North Carolina, and Muhammad Shahzeb Khan, MD, assistant professor of medicine in the department of medicine at the University of Mississippi, wrote. “If we can harness SGLT2 inhibitors to help [guideline-directed medical therapy] teammates get on the field and stay in the game, it will be yet another reason to embrace this new therapy.”

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