Empagliflozin significantly reduced cardiovascular (CV) death and heart failure (HF) hospitalization risk among patients with HF with reduced ejection fraction (HFrEF) regardless of baseline systolic blood pressure (SBP), an international team of researchers has found. Their findings were published in the Journal of the American College of Cardiology.
While empagliflozin reduces the risk of CV death or HF in patients with HFrEF, the impact of SBP levels on the effects of empagliflozin were previously not known, according to the study authors.
To evaluate the interplay between empagliflozin and SBP, the investigators sourced data from the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction (EMPEROR-Reduced; ClinicalTrials.gov Identifier: NCT03057977). Patients (N=3730) with HFrEF were randomized to receive either 10 mg daily empagliflozin or placebo for a median of 16 months, in addition to usual therapy for HF. Prior to randomization, patients were stratified by baseline SBP into low SBP (<110 mmHg; n=928), intermediate SBP (110-130 mmHg; n=1755), and high SBP (>130 mmHg; n=1047) groups. The primary endpoints were the impacts of SBP on empagliflozin effects on CV death and on HF hospitalization.
The low, intermediate, and high SBP cohorts differed significantly in terms of most baseline characteristics — including age, gender, race/ethnicity, body mass index, diastolic blood pressure, left ventricular ejection fraction, device therapy (implantable cardioverter-defibrillator, cardiac resynchronization therapy), diabetes, and hypertension (all P £.0392). In general, lower SBP was associated with more severe symptoms of HF.
The incidence rate for the primary endpoint increased from 16.5 per 100 person-years (py) among the high SBP cohort to 20.8 per 100 py for the intermediate group, and to 26.3 per 100 py among the patients with low SBP (P =.0015).
Compared with placebo, empagliflozin decreased the risk for CV death and HF hospitalization among the low (hazard ratio [HR], 0.78; 95% CI, 0.61-1.00), intermediate (HR, 0.71; 95% CI, 0.58-0.87), and high (HR, 0.82; 95% CI, 0.62-1.09) SBP patients, indicating no interaction between therapy and baseline SBP (P =.83).
Empagliflozin therapy tended to have a stabilization effect on DBP after 4 and 12 weeks, in which no change in DBP was observed among the intermediate group and DBP tended to slightly increase and decrease among the low and high SBP cohorts, respectively (P for interaction trend =0.05-0.10).
No significant change to estimated glomerular filtration rate (eGFR) was observed among the low (P =.0690) or high (P =.1112) SBP groups. There was a significant increase in eGFR among the intermediate SBP cohort (adjusted mean, 4.3; 95% CI, 2.1-6.5; P =.0001).
Among the recipients of placebo, individuals in the low, intermediate, and high SBP cohorts had symptomatic hypotension at a rate of 8.2, 4.0, and 2.9 per 100 py, respectively.
The investigators said their findings may not be generalizable to all individuals with HFrEF, given that patients with an eGFR <20 mL/min/1.73 m2, symptomatic hypotension, or SBP <100 mmHg were excluded from the EMPEROR-Reduced trial.
In summary, this study found no evidence for an interaction between empagliflozin and baseline SBP with respect to reducing the risk for CV death and HF hospitalization among patients with HFrEF.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Böhm, M, Anker SD, Butler J, et al. Empagliflozin improves cardiovascular and renal outcomes in heart failure irrespective of systolic blood pressure.J Am Coll Cardiol. 2021;78(13):1337-1348. doi:10.1016/j.jacc.2021.07.049