Background:
Sodium glucose cotransporter 2 inhibitors (SGLT2i) prevent heart failure (HF) hospitalizations in patients with Type 2 Diabetes (T2D), and improve outcomes in those with HF and reduced ejection fraction (EF), regardless of T2D. Mechanisms of HF benefits remain unclear, and effects of SGLT2i on hemodynamics (filling pressures) are not known. EMBRACE-HF Trial was designed to address this knowledge gap.
Methods:
EMBRACE-HF is an investigator-initiated, randomized, multi-center, double-blind, placebo-controlled trial. From July 2017 to November 2019, patients with HF (regardless of EF, with or without T2D) and previously implanted pulmonary artery (PA) pressure sensor (CardioMEMS) were randomized across 10 US centers to empagliflozin 10 mg daily or placebo and treated for 12 weeks. The primary endpoint was change in PA diastolic pressure (PADP) from baseline to end of treatment (average PADP weeks 8-12). Secondary endpoints included health status (Kansas City Cardiomyopathy Questionnaire (KCCQ)), natriuretic peptides and 6-minute walking distance.
Results:
Overall, 93 patients were screened, and 65 were randomized (33 empagliflozin, 32 placebo). Mean age was 66 years, 63% were male, 52% had T2D, 54% NYHA class III/IV; mean EF 44%, median NT-proBNP 637 pg/mL and mean PADP 22 mmHg. Empagliflozin significantly reduced PADP, with effects beginning at week 1, and amplified over time; average PADP (weeks 8-12) was 1.5 mmHg lower (95% CI (0.2, 2.8); p = 0.02); and at week 12, PADP was 1.7 mmHg lower (95% CI (0.3, 3.2); p = 0.02) with empagliflozin vs placebo. Results were consistent for PA systolic and PA mean pressures. There was no difference in mean loop diuretic management (daily furosemide equivalents) between treatment groups. No significant differences between treatment groups were observed in KCCQ, natriuretic peptide levels and 6-minute walking distance.
Conclusions:
In patients with HF and CardioMEMS PA pressure sensor, empagliflozin produced rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management.
Clinical Trial Registration:
URL: https://www.clinicaltrials.gov. Unique identifier: NCT03030222.