Two studies provide further positive outcomes for empagliflozin in HF
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Among patients with HF, empagliflozin lowered diastolic pulmonary artery pressure and was effective at reducing CV death and HF hospitalizations regardless of sacubitril/valsartan use, researchers reported.
In the EMBRACE-HF study, empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) reduced diastolic pulmonary artery pressure in patients with HF with reduced or preserved ejection fraction with or without diabetes. In a new analysis from EMPEROR-Reduced, empagliflozin reduced CV death and HF hospitalizations in patients with HFrEF regardless of whether they were also taking sacubitril/valsartan (Entresto, Novartis).
EMBRACE-HF
In EMBRACE-HF, researchers randomly assigned 65 patients who had HF for at least 16 weeks and had diastolic pulmonary artery pressure of at least 12 mm Hg at baseline to empagliflozin (mean age, 70 years; 64% men) or placebo (mean age, 63 years; 63% men).
“The effects of SGLT2 inhibitors on filling pressures, one of the strongest predictors of clinical status, hospitalizations and death, have not been previously investigated,” Mikhail Kosiborod, MD, FACC, vice president of research at Saint Luke’s Health System and professor of medicine at the University of Missouri-Kansas City, said during a presentation.
The primary endpoint was change in diastolic pulmonary artery pressure from baseline to the end of the treatment period, an average of 8 to 12 weeks.
Among the cohort, 59 of the 65 patients completed the study.
The primary endpoint was reduced more in the empagliflozin group compared with the placebo group (P = .02), Kosiborod said, noting that the difference remained significant in an on-treatment analysis that eliminated the patients who did not complete the study (P = .01) and that the curves separated almost immediately.
For the secondary endpoint of change in systolic pulmonary artery pressure from baseline to the end of the treatment period, the difference between the groups was not significant (P = .21), but the curves started to separate in week 4, he said.
Change in mean pulmonary artery pressure from baseline to the end of the treatment period also favored the empagliflozin group but missed statistical significance (P = .07), he said.
Compared with the placebo group, the empagliflozin group was more likely to have at least a 20% decrease at 12 weeks in N-terminal pro-B-type natriuretic peptide (P = .007) and in type B natriuretic peptide (P = .05), according to the researchers.
Quality of life metrics, 6-minute walk distance, HbA1c levels and use of loop diuretics did not differ between the groups at 12 weeks, although the empagliflozin group lost more weight compared with the placebo group (P = .02), Kosiborod said, noting there were few serious adverse events, and they did not differ between the groups.
“EMBRACE-HF is the first randomized controlled trial to demonstrate the direct effect of SGLT2 inhibitors on lowering pulmonary artery diastolic pressure in patients with HF with reduced or preserved EF,” he said. “The findings complement data from large HF outcome trials of SGLT2 inhibitors, which demonstrated benefits on CV death or hospitalization for HF.”
EMPEROR-Reduced
Milton Packer, MD, distinguished scholar in cardiovascular science at Baylor University Medical Center and chair of the executive committee for the EMPEROR program, presented an analysis of whether outcomes in EMPEROR-Reduced differed by existing use of sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor.
As Healio previously reported, in EMPEROR-Reduced, empagliflozin reduced CV death/HF hospitalization, HF hospitalization and renal events compared with placebo regardless of whether patients had diabetes.
In the trial, 18.3 of those assigned empagliflozin and 20.7% of those assigned placebo were taking sacubitril/valsartan, Packer said.
The primary endpoint of time to CV death or HF hospitalization favored empagliflozin in those taking sacubitril/valsartan (HR = 0.64; 95% CI, 0.45-0.89) and in those not taking it (HR = 0.77; 95% CI, 0.66-0.9; P for interaction = .31), Packer said.
The same was true for the secondary endpoints of first and recurrent HF hospitalizations (HR for those taking sacubitril/valsartan = 0.65; 95% CI, 0.42-1; HR for those not taking it = 0.71; 95% CI, 0.58-0.88; P for interaction = .72) and prespecified renal outcomes (sacubitril/valsartan cohort, nine events in placebo group vs. three events in empagliflozin group; no sacubitril/valsartan cohort, 49 events in placebo group vs. 27 events in empagliflozin group), he said.
In those taking sacubitril/valsartan, the empagliflozin group had fewer adverse events leading to study drug discontinuation (15.9% vs. 19.9%), less hypokalemia (5.9% vs. 7.5%) and fewer cases of worsening renal function (9.4% vs. 13.2%), he said.
“Background use of neprilysin inhibition with sacubitril valsartan did not diminish, and may have enhanced, the efficacy and safety of empagliflozin, but all interaction P values were not statistically significant,” Packer said. “Taken together, the concordant results of DAPA-HF and EMPEROR-Reduced should be sufficient to establish SGLT2 inhibitors as a new standard of care for patients with heart failure and reduced ejection fraction, when added to all currently mandated treatments for heart failure, including neprilysin inhibition.”
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Nassif ME, et al.
Packer M, et al. Late-breaking clinical trials II. Both presented at: Heart Failure Society of America Scientific Meeting; Sept. 30-Oct. 6, 2020 (virtual meeting).
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