Results from the EMPHASIS-HF trial have shown a statistically significant reduction in risk of cardiovascular death or heart failure (HF) hospitalisation for patients with chronic heart failure with mild symptoms treated with eplerenone (Inspra, Pfizer) versus those given placebo in addition to standard HF therapy. The results were presented at the American Heart Association Scientific Sessions in Chicago, USA, and were simultaneously published online in the New England Journal of Medicine.
The EMPHASIS-HF trial demonstrated a statistically significant 37% relative risk reduction for the eplerenone group (p<0.0001) compared to placebo in the primary composite endpoint of death from cardiovascular causes or HF hospitalisation. There were also statistically significant reductions in other secondary endpoints of all-cause mortality (24%; p=0.008), cardiovascular mortality (24%; p=0.012), all-cause hospitalisation (23%, p<0.0001) and HF hospitalisation (42%; p<0.0001).
Faiez Zannad, professor of Therapeutics and cardiologist at the CHU (University Hospital) of the Henri Poincaré University of Nancy, France and co-chair of the EMPHASIS-HF Steering Committee said: “It is encouraging to see a clinical trial deliver results that are sufficiently strong to meet strict pre-defined stopping criteria. Patients such as those enrolled in EMPHASIS-HF typically have a poor prognosis and these results should therefore provide real encouragement for doctors and patients alike.”
The primary objective of the EMPHASIS-HF trial was to evaluate the efficacy and safety of eplerenone plus standard HF therapy versus placebo plus standard HF therapy on the cumulative incidence of the composite endpoint of cardiovascular death or HF hospitalisation. Patients enrolled in the study had New York Heart Association (NYHA) class II chronic systolic heart failure with mild symptoms.
No new safety information emerged as a result of this study. As anticipated, there was a higher incidence of hyperkalemia (elevated potassium, defined as serum potassium level >5.5mmol/L) among patients assigned to eplerenone compared to placebo (11.8% vs. 7.2%, respectively; p<0.001). In contrast, the incidence of hypokalemia (low potassium, defined as serum potassium level <3.5mmol/L) was lower in the eplerenone group compared to placebo (7.5% vs. 11%, respectively; p=0.002).
In May 2010, recruitment to the EMPHASIS-HF trial was halted early after the second pre-specified interim analysis showed that the study’s pre-defined stopping rules had been met and a significant difference (two-sided p<0.001 in favour of eplerenone) in the primary endpoint was evident.
Eplerenone is not authorised for use in the patient population studied in the EMPHASIS-HF trial in any individual market.