SGLT2i safe and effective in HFpEF across all age groups

According to a prespecified analysis of the EMPEROR-Preserved trial, age does not influence the benefits seen with empagliflozin in HFpEF. Moreover, elderly patients tolerated the drug well.

Literature - Böhm M, Butler J, Filippatos G, et al. - J Am Coll Cardiol. 2022 Jul 5;80(1):1-18. doi: 10.1016/j.jacc.2022.04.040

Introduction and methods

//Background and aim of the study//

Empagliflozin reduces the combined risk of CVD or HF hospitalization in HFpEF patients, as shown in the recent EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction) trial [1]. There may be general concerns about decreased treatment effects and more adverse events with advanced age [2]. The aim of this analysis was to evaluate the interplay of age with the efficacy and safety of empagliflozin in the EMPEROR-Preserved trial.


The EMPEROR-Preserved trial was a double-blind RCT in which 5988 patients with HF (NYHA class II–IV symptoms) and EF >40% were randomized (1:1 ratio) to empagliflozin 10 mg daily or placebo. For the current, prespecified analysis, the patients were divided into 4 groups according to their baseline age: <65 years (n=1199), 65–74 years (n=2214), 75–79 years (n=1276), and ≥80 years (n=1299).


The primary endpoint was the time to first event of the composite outcome of adjudicated CV death or HF hospitalization. The first secondary endpoint was the occurrence of total (first and recurrent) adjudicated HF hospitalizations. The second secondary endpoint was the slope of the change in eGFR. Health-related quality of life (HRQoL )—based on the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS)—and frequency of adverse events were also assessed.

Main results

Efficacy outcomes

  • In patients on placebo, the incidence rate of the primary outcome (CV death or HF hospitalization) increased with age (P for interaction=0.02), as did the incidence rate of CV death (P for interaction=0.003).
  • The known relative risk reduction by empagliflozin was similar across the age groups for the primary endpoint (P for interaction=0.33), the first secondary endpoint (i.e., total HF hospitalizations; P for interaction=0.11), and first HF hospitalizations (P for interaction=0.22).
  • There was no significant treatment effect on CV death or all-cause mortality, nor an interaction by age.
  • When all patients were divided into different age groups, the treatment effect on the primary endpoint was maintained for the group ≥75 years compared with<75 years (P for interaction=0.22) and for ≥80 years compared with <80 years (P for interaction=0.51). Similar results were seen for first HF hospitalization and recurrent HF hospitalization.

eGFR slope

  • Empagliflozin reduced the second secondary endpoint (slope of eGFR change) compared with placebo (mean difference: 1.36 mL/min per 1.73 m2 per year; 95%CI: 1.06–1.66; P=0.0001). This effect was similar in all age groups (P for interaction=0.32).

Other outcomes

  • Patients in the empagliflozin group showed more improvement in the mean KCCQ-CSS at week 52, and there were no significant differences between the age groups (P for interaction=0.48).
  • There were also no clinically relevant differences in the frequency of adverse events between empagliflozin- and placebo-treated patients across the age groups (all P values for interaction>0.05).


In a prespecified analysis of the EMPEROR-Preserved trial, age did not influence the beneficial effects empagliflozin had on reducing CV death or HF hospitalization, total HF hospitalizations, and eGFR decline or on improving HRQoL. In addition, older age was not associated with clinically meaningful safety concerns.


1. Anker SD, Butler J, Filippatos G, et al. EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451–1461.

2. Ali Raza J, Movahed A. Use of cardiovascular medications in the elderly. Int J Cardiol. 2002;85:203–215.

Find this article online at JAMA Cardiol.

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