Empagliflozin safe, effective in HFrEF regardless of systolic BP, NT-proBNP levels
Empagliflozin was safe and effective in patients with HF with reduced ejection fraction regardless of systolic BP or N-terminal pro-B-type natriuretic peptide level, according to two new analyses of results from the EMPEROR-Reduced trial.
Healio previously reported results of the EMPEROR-Reduced trial wherein empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) demonstrated an improvement in CV and renal outcomes among patients with HFrEF regardless of a patient’s diabetes status.
Systolic BP
In an analysis of the EMPEROR-Reduced trial exploring the influence of systolic BP on empagliflozin effect on CV death or HF hospitalization, researchers evaluated 3,730 patients from the trial who were randomly assigned to empagliflozin at 10 mg once daily (n = 1,863) or placebo (n = 1,867). Patients were categorized based on their systolic BP at baseline into a less than 110 mm Hg group (n = 928), a 110 mm Hg to 130 mm Hg group (n = 1,755) or a greater than 130 mm Hg group (n = 1,047).
“There is an inverse relationship between systolic BP and the risk of cardiovascular death and hospitalizations for heart failure in patients who have heart failure and a reduced ejection fraction,” Michael Böhm, MD, from the department of cardiology, angiology and internal intensive care medicine in the Clinic for Internal Medicine at Saarland University Hospital, Homberg, Germany, and colleagues wrote. “Thus, patients with the lowest systolic BP are at the highest risk but may be least likely to receive effective treatments.”
After a median of 16 months, baseline systolic BP and CV death or HF hospitalization risk were inversely related when considering only patients who received placebo (P = .0015). However, there was a slight increase among patients with less than 110 mm Hg systolic BP, no change among patients with 110 mm Hg to 130 mm Hg and a slight reduction among patients with greater than 130 mm Hg when corrected for placebo.
According to the researchers, these differences were of borderline significance after 4 and 12 weeks but not significant later (P for interaction trend = .05 to .1).
There was no influence on systolic BP and empagliflozin effect on reducing risk for HF events or renal endpoints. In addition, patients with a systolic BP of less than 110 mm Hg demonstrated no increased rate of symptomatic hypotension with empagliflozin treatment.
NT-proBNP levels
In a separate analysis of the EMPEROR-Reduced trial, researchers assessed the relationship between NT-proBNP and effects of empagliflozin in the same 3,730 patients. NT-proBNP levels were measured at baseline, 4, 12, 52 and 100 weeks, and patients were divided into quartiles based on their NT-proBNP levels of less than 1,115 pg/mL (n = 930), 1,115 pg/mL to 1,909 pg/mL (n = 932), 1,910 pg/mL to 3,479 pg/mL (n = 934) or at least 3,480 pg/mL (n = 932).
“Elevated or rising concentrations of NT-proBNP in patients with HFrEF are associated with a more decompensated hemodynamic profile, higher filling pressures and greater risk for progressive adverse cardiac remodeling, hospitalization and death,” James L. Januzzi Jr., MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research at Massachusetts General Hospital, and colleagues wrote. “In contrast, a reduction of NT-proBNP values following treatment for HFrEF predicts an improved outcome, better health status and a higher likelihood for favorable reverse cardiac remodeling.”
Among patients in the highest NT-proBNP quartiles, there were four- to sixfold higher incidence rates for each outcome in EMPEROR-Preserved compared with patients in the lowest quartiles. In addition, those in the higher quartiles had two- to threefold total higher hospitalizations compared with those in the lowest quartiles.
Empagliflozin reduced major cardiorenal event risk for time to first event of CV death of HF hospitalization across NT-proBNP quartiles (P for interaction = .94), and the same was true for major adverse renal outcomes (P for interaction = .71). Empagliflozin also demonstrated significant reductions in NT-proBNP during all timepoints, with an adjusted mean difference compared with placebo of 13% at 52 weeks (P <. 001).
Researchers observed an association between the lowest NT-proBNP quartile 12 weeks after randomization and reduced risk for CV death or HF hospitalization regardless of baseline NT-proBNP levels. Compared with placebo, empagliflozin treatment demonstrated 27% higher adjusted odds for NT-proBNP level of less than 1,115 pg/mL at 12 weeks (P = .01).
Reference:
Collapse