Quadruple combination therapy with SGLT2i, GLP-1RA, ARNI and MRA in heart failure with preserved ejection fraction patients with type 2 diabetes mellitus: A prospective and observational cohort study.

BACKGROUND

Treatments for heart failure with preserved ejection fraction (HFpEF) remain inconclusive.

AIMS: We aim to explore in this prospective and observational cohort study how combined therapy with sodium-dependent glucose transporter 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), angiotensin receptor-neprilysin inhibitor (ARNI), or mineralocorticoid receptor antagonists (MRA) impact clinical outcomes in HFpEF patients with type 2 diabetes mellitus (T2DM).

METHODS

We enrolled 1445 HFpEF patients with T2DM from a prospective cohort between October 2018 and October 2022. The patients were divided into five groups based on their medications at 3 months after discharge: defined as a combination of SGLT2i, GLP-1RA, ARNI, and MRA. The primary outcome is major adverse cardiovascular (CV) events (MACEs), corresponding to the CV mortality and/or HF rehospitalization. The secondary outcome is CV mortality as well as left ventricular ejection fraction (LVEF) change or HF category transition.

RESULTS

During a median follow-up period of 54 (27-75) months, participants with quadruple combination showed the most benefits, corresponding to MACEs (79/174; P <0.001), CV mortality (46/174; P = 0.03), LVEF change, or HF transitions. Quadruple combination was a protective factor for MACEs, while higher N-terminal pro-B-type natriuretic peptide level was an independent risk factor. For participants with LVEF less than 60%, quadruple combination reduced the incidence of composite endpoint events compared to those with LVEF over 60%.

CONCLUSIONS

Quadruple combination therapy with SGLT2i, GLP-1RA, ARNI, and MRA in HFpEF patients with T2DM was associated with favorable clinical outcomes, especially in participants with LVEF less than 60%.