Empagliflozin improves outcomes in HFpEF patients regardless of age

Treatment with empagliflozin results in a reduction in heart failure (HF) risk and renal outcomes and in better health-related quality of life (HRQoL) among patients with chronic HF with preserved ejection fraction (HFpEF), a study has shown. In addition, the study drug is well tolerated by older patients.

“Empagliflozin reduced primary outcomes and first and recurrent HF hospitalization (HFH) and improved symptoms across a broad age spectrum,” the researchers said. “High age was not associated with reduced efficacy or meaningful intolerability.”

A total of 5,988 patients were grouped based on their baseline age (<65 years: n=1,199; 65‒74 years: n=2,214; 75‒79 years: n=1,276; ≥80 years: n=1,299).

The researchers assessed the impact of age on empagliflozin effects on cardiovascular disease (CVD) or HFH, total HFH, rate of decline in estimated glomerular filtration rate (eGFR), HRQoL with the Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (KCCQ-CSS), and frequency of adverse events.

The incidence of HFH (p_trend=0.02) and CVD (p_trend=0.003) increased with age among patients on placebo. However, those on empagliflozin had decreased CVD or HFH (p_trend=0.33), first HFH (p_trend=0.22), and first and recurrent HFH (p_trend=0.11) across all age groups, with the effect being similar at ≥75 years (p_interaction=0.22) or >80 years (p_interaction=0.51). [J Am Coll Cardiol 2022;80:1-18]

At week 52, empagliflozin treatment led to improved KCCQ-CSS (p=0.48) and lessened the decline of eGFR without age interaction (p=0.32). In addition, adverse events did not differ significantly between empagliflozin and placebo across the age groups.

“Age was associated with an increased rate of adverse events without meaningful alteration by empagliflozin, including in the elderly,” the researchers said. “Serious acute renal adverse events were less likely at <65 years and 65‒74 years and similar at older ages with empagliflozin.”

Treatment efficacy

Patients with HFpEF were usually older than those with HF with reduced ejection fraction (HFrEF). In addition, many pharmacologic treatments did not provide significant benefit in HFpEF patients. [Eur J Heart Fail 2011;13:18-28; Clin Res Cardiol 2019;108:1394-1405; Clin Res Cardiol 2020;109:1079-1098]

A previous study, the EMPEROR-Preserved, showed the efficacy of empagliflozin in reducing the composite of cardiovascular death and HFH in HFpEF patients. [N Engl J Med 2021;385:1451-1461]

“In the population of EMPEROR-Preserved, we found that patients in the higher age category were more often female, had higher blood pressure and higher left ventricular ejection fraction at baseline, but had lower eGFR,” the researchers said.

“Therefore, concerns have been expressed in elderly HF patients and, particularly, in patients with higher age and HFpEF that treatment effects across the age spectrum are diminished and that benefits come at a high cost of impairment of quality of life and tolerability of the drug,” they added. [Clin Res Cardiol 2019;108:1394-1405; J Am Coll Cardiol 2019;74:601-612; Eur J Heart Fail 2013;15:1296-1303]

The current study, on the other hand, proved that the efficacy of empagliflozin on HF outcomes was consistent across the full age spectrum. Notably, its effectiveness did not vanish in patients aged ≥75 and ≥85 years.

Furthermore, treatment effects among patients with HFrEF were similar across the age spectrum for sacubitril/valsartan, beta-blockers, dapagliflozin, and ivabradine. [Eur J Heart Fail 2013;15:1296-1303; Circulation 2020;141:100-111; BMJ 2016;353:i1855; Eur Heart J 2015;36:2576-2584]