Analysis of Data from the EMPEROR-Preserved Study Revealed Whether Blood Pressure Affects the Effectiveness of Empagliflozin in Patients with Heart Failure with Preserved Ejection Fraction

Methodology and Course of the Study

Patients with HF with left ventricular ejection fraction (LVEF) > 40% were included in the randomized double-blind study. The patients were divided into 2 groups in a 1:1 ratio. The first group received empagliflozin in a dose of 10 mg daily in addition to their chronic medication, while the second group received a placebo. Patients with and without diabetes (DM) were included. At each doctor's visit, patients’ blood pressure was measured, vital functions were monitored, estimated glomerular filtration rate (eGFR) was determined, adverse effects of treatment were recorded, changes in chronic medication were noted, and the overall condition of the patient was assessed. Administration of empagliflozin or placebo was discontinued at the end of the study, and patients underwent a follow-up check-up after 23–45 days.

The primary efficacy endpoint comprised the first hospitalization for heart failure (HF) or death from CV causes, and the time to this event was determined. Secondary endpoints included all potential hospitalizations related to HF and changes in eGFR.

For the analysis, patients were divided into 3 groups based on baseline sBP values: < 110 mmHg, 110–130 mmHg, and > 130 mmHg. The influence of baseline BP on the later occurrence of hypotension, symptomatic hypotension, acute renal failure, and hypovolemia was also examined.

Results

A total of 5,988 patients were included in the study, with 2,997 receiving empagliflozin and 2,991 receiving a placebo. It was shown that patients with lower baseline BP were at a more advanced stage of HF. These patients had higher levels of NT-proBNP, heart rate, albuminuria, lower eGFR, higher probability of hospitalization for HF in the last 12 months, and higher prevalence of diabetes.

In the placebo group, the incidence of the primary endpoint in the case of sBP > 130 mmHg was 8.58/100 patient-years, in the 110–130 mmHg group it was 8.26/100 patient-years, and among patients with sBP < 110 mmHg it was 11.59/100 patient-years. The incidence of death from CV causes was also highest in the group with sBP < 110 mmHg, at 6.61/100 patient-years, compared to 3.04/100 patient-years in the BP 110–130 mmHg group (p < 0.0001), and 4.01/100 patient-years in the BP > 130 mmHg group (p = 0.008).

In the group with sBP < 110 mmHg, a slight increase in systolic and diastolic BP values was noted during treatment in both treatment arms, and a small increase was also visible in the sBP 110–130 mmHg group. For patients with baseline sBP > 130 mmHg, a decrease in BP was also observed in both treatment arms. Patients receiving empagliflozin experienced fewer adverse effects and instances of acute renal failure. Hypovolemia and symptomatic hypotension were numerically more frequent in those taking empagliflozin, especially in those with baseline sBP < 110 mmHg.

The risk of death from CV causes and HF hospitalization was lower in the group receiving empagliflozin, regardless of baseline BP. This was also true for the time to the first hospitalization for HF.

Discussion and Conclusion

In the group of patients with lower baseline sBP (< 110 mmHg), there were higher incidences of CV complications and a shorter time to the first HF hospitalization or death from CV causes. Treatment with empagliflozin yielded positive results irrespective of baseline BP values, reducing the risk of cardiovascular complications without increasing the risk of hypotension or hypovolemia. Hypertension is a very common comorbidity in patients with HFpEF (52.0%) but occurs less frequently in patients with heart failure with reduced ejection fraction (HFrEF) (28.2% according to the EMPEROR-Reduced study). Patients with systolic BP < 110 mmHg generally have a worse HF prognosis but are often under-treated, primarily due to the absence of hypertension.

According to the results of this study, baseline sBP cannot be considered a factor modifying the cardio-renal effectiveness and mechanism of action of empagliflozin. Its effect is preserved even at sBP < 110 mmHg. According to the authors, low systolic blood pressure should not be an obstacle to starting treatment with empagliflozin in patients with heart failure and LVEF > 40%.

(kali)

Source: Böhm M., Anker S., Mahfoud F. et al. Empagliflozin, irrespective of blood pressure, improves outcomes in heart failure with preserved ejection fraction: the EMPEROR-Preserved trial. Eur Heart J 2023 Feb 1; 44 (5): 396–407, doi: 10.1093/eurheartj/ehac693.