Safety and efficacy of empagliflozin in heart failure among patients with a history of valvular heart disease: Insights from EMPEROR-Pooled

Abstract

Background

Valvular heart disease (VHD)-associated heart failure (HF) remains an important and growing cause of morbidity and mortality. There are no contemporary data on the efficacy and safety of SGLT2 inhibitors in patients with a history of VHD.

Methods

The EMPEROR-Pooled trial analyzed 9718 patients with HF who were enrolled in the randomized trials of empagliflozin versus placebo in HF with reduced left ventricular ejection fraction (HfrEF; EMPEROR-Reduced) and HF with preserved left ventricular ejection fraction (HFpEF; EMPEROR-Preserved). These trials evaluated a primary outcome of time to first HF hospitalization or cardiovascular death. Here we analyze outcomes of the EMPEROR-Pooled patients according to the presence and etiology of VHD history.

Results

Of the 9717 patients enrolled in EMPEROR-Pooled with available data, 1484 (15.3%) had a history of VHD. Of the patients with VHD history, a history of isolated mitral disease (39.2%) was the most common subtype. In patients randomized to placebo, the risk of the primary outcome was higher among patients with VHD history (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.53; P < .01), and particularly those with a history of multivalvular disease (HR, 1.51; 95% CI, 1.13-2.04; P < .01) compared with no valvular disease. No heterogeneity was introduced by VHD history with respect to the efficacy of empagliflozin on all major clinical outcomes evaluated in EMPEROR-Pooled (P_interaction > .05).

Conclusions

We present the first large analysis of SGLT2i (empagliflozin) use in HF patients by history of VHD. Although VHD history was associated with worse outcomes in HF patients, empagliflozin demonstrated consistent safety, efficacy, and patient-reported outcomes across all categories of VHD history.