Systolic BP has been shown not to effect the reduction in cardiovascular outcomes for heart failure patients treated with empagliflozin.
As a drug class, the sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown in a systematic review to have a moderate effect on major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease. Moreover, the same review identified how SGLT2is can also reduce hospitalisation for heart failure (HF) and progression of renal disease regardless of existing atherosclerotic cardiovascular disease. In addition to these positive effects on cardiovascular outcomes, SGLT2is have been shown to reduce 24-hour blood pressure (BP) in diabetic patients. Nevertheless, this blood pressure-lowering effect is of concern in those with HF, especially as between 15 and 20% of HF patients have low systolic BP and therefore at a higher risk of in-hospital and post-discharge mortality.
In an effort to evaluate whether the baseline systolic BP affected outcomes associated with the use of empagliflozin, an international team, led by researchers from Saarland University, Germany, enrolled patients in the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. Patients with class II, III, or IV heart failure and an ejection fraction of less than 40% were randomised in a 1:1 fashion to either empagliflozin (10mg daily) or placebo in addition to their usual therapy for heart failure. For the study, patients were grouped according to their baseline systolic BP, as <110mmHg, 110–130mmHg or > 130mmHg and the primary outcome in the EMPEROR-Reduced trial was a composite of adjudicated cardiovascular death or hospitalisation for heart failure. For the present study, the researchers focused on whether the baseline systolic BP influenced the outcomes of cardiovascular death and hospitalisations for HF in patients given empagliflozin compared to placebo.
A total of 3730 patients were randomised to either empagliflozin (1863) or placebo and all patients had a left ventricular ejection fraction of less than 30%. Over a median of 16 months, the event rate per 100 patients years (pys) of follow-up, the primary outcome increased from 16.5 among the high SBP group to 20.8 for the intermediate group, and to 26.3 per 100 among the patients with low SBP (p=0.0015). Compared with placebo, treatment with empagliflozin significantly decreased the risk of cardiovascular death among the low systolic BP (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) groups. However, while there were reductions in rates of HF hospitalisation with empagliflozin compared with placebo, this was only significant for patients with intermediate (110–130mmHg) systolic BP (HR = 0.66, 95% CI 0.50–0.88).
The authors concluded that empagliflozin reduced the risk of cardiovascular death and the number of HF hospitalisations and that this effect occurred independently of the baseline systolic BP.
Bohm M et al. Empagliflozin Improves Cardiovascular and Renal Outcomes in Heart Failure Irrespective of Systolic Blood Pressure. J Am Coll Cardiol 2021.