Empagliflozin and Age in Heart Failure With Preserved Ejection Fraction

A study was conducted to assess the effect of age and empagliflozin therapy in patients with chronic heart failure with preserved ejection fraction.

Empagliflozin decreases rates of heart failure (HF) symptoms, cardiovascular death, and hospitalizations related to HF across a wide age range of patients with HF with preserved ejection fraction (HFpEF). These findings were published in the Journal of the American College of Cardiology.

Researchers aimed to investigate the safety, efficacy, and effects of empagliflozin treatment in relation to patient age among patients with HFpEF. The primary outcome was HF hospitalization or cardiovascular death.

They conducted a prespecified analysis of the randomized controlled Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved; ClinicalTrials.gov Identifier: NCT03057951). The researchers grouped participants by age (<65 years, n=1199, 36.6% women; 65-74 years, n=2214, 42.3% women; 75-79 years, n=1276, 48.5% women; ≥80 years, n=1299, 52.4% women) to investigate age influence on the effects of empagliflozin on HF hospitalizations or cardiovascular death, total HF hospitalization, frequency of adverse events, rate of decline in estimated glomerular filtration rate, and health-related quality of life. Patients were randomly assigned in a double-blind, 1:1 fashion to add either empagliflozin or placebo to their regular therapy.

Incidence of primary outcomes and cardiovascular death increase with age (P trend =.02 and P trend =.003, respectively) in the placebo group. Across all age groups, the researchers report that empagliflozin reduces primary outcomes (P trend =.33), first HF hospitalization (P trend =.22), and first and recurrent HF hospitalization (P trend =.11). The effects at age 75 years or older (P interaction =.22) or 80 years or older (P interaction =.51) are similar.

There is decline of estimated glomerular filtration rate without age interaction in the empagliflozin groups (P =.32), and the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at week 52 is improved (P =.48) with empagliflozin. Comparing adverse events across age groups shows no clinically relevant differences between empagliflozin and placebo.

Study limitations include that treatment is not randomized to age groups and are therefore subject to unidentified confounders. Categorization by age predefined in the EMPEROR-Preserved trial also resulted in some age groups and event numbers being statistically insignificant.

“Empagliflozin reduced primary outcomes and first and recurrent HF [hospitalization] and improved symptoms across a broad age spectrum,” the researchers noted. They also acknowledged the need for studies of older cohorts to “better define the role of empagliflozin in the management of heart failure and preserved ejection fraction in elderly patients.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Trial (EMPEROR-Preserved trial) supported by industry: Boehringer Ingelheim and Eli Lilly.


Böhm M, Butler J, Filippatos G, et al; EMPEROR-Preserved Trial Committees and Investigators. Empagliflozin improves outcomes in patients with heart failure and preserved ejection fraction irrespective of age. J Am Coll Cardiol. Published online June 27, 2022. doi:10.1016/j.jacc.2022.04.04