Pfizer Inc. (NYSE: PFE) announced results from a new post-hoc analysis of the EMPHASIS-HF trial showing statistically significant reductions in rates of cumulative heart failure (HF) hospitalisations in patients with HF treated with eplerenone compared with placebo on a background of standard optimal therapy.1 The results were presented at The European Society of Cardiology Congress (ESC) in Munich.
Results of this sub-analysis showed that despite fewer deaths in the eplerenone group compared with placebo, there were fewer recurrent hospitalisations. Heart failure hospitalisation rates in the eplerenone and placebo groups were 11.1 and 17.9 per 100 patient years respectively.
Cumulative hospitalisation rates over time revealed that the bulk of the reduced risk on eplerenone occurred in the first year of follow-up.
The first year following a diagnosis of chronic heart failure is particularly crucial with studies showing that only around 65 percent of patients are expected to survive the first 12 months3,4 with mortality particularly high in the first three months after diagnosis.3 Furthermore, the median length of duration per hospitalisation is 8 days with almost half of the patients managed in the intensive care unit for a median of 4 days.5 These statistics illustrate the importance of early diagnosis and prompt treatment according to the new ESC guideline on acute and chronic heart failure5 that recommends the use of triple therapy to include mineralocorticoid receptor antagonists (MRAs) alongside ACE inhibitors and beta blockers for almost all patients.
Commenting on the findings, sub-analysis author, Dr Jennifer Rogers, London School of Hygiene and Tropical Medicine, said: “Eplerenone is known to reduce the time to first hospitalisation or cardiovascular death in patients with heart failure. However, the impact of heart failure on rates of hospitalisation is significant and crucially, more complex than can be understood by assessing time to first hospital admission alone. We have been able to show that the benefit of treatment with eplerenone markedly reduces the risk of heart failure hospitalisations in patients in the crucial first year of treatment and beyond.”
Approximately 1–2% of the adult population in developed countries has HF, with the prevalence rising to ≥10% among persons 70 years of age or older.6 Heart failure is associated with a poorer survival rate than many cancers, including prostate and bladder cancer in men, and breast cancer in women.7
No new safety information emerged as a result of this post-hoc analysis. In the EMPHASIS-HF study, there was a higher incidence of hyperkalaemia (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). There was no significant difference in rates of severe hyperkalemia (defined as serum potassium level > 6.0mmol/l) or in rates of discontinuation due to hyperkalemia. The incidence of hypokalaemia (low potassium, defined as serum potassium level <3.5mmol/l) was lower in the eplerenone group compared to placebo (7.5% vs 11.0%, respectively; p=0.002).2
- Rogers, JK; McMurray, JJV; and Pocock, SJ et al. Eplerenone in patients with systolic heart failure and mild symptoms: analysis of repeat hospitalisations. Presented at the European Society of Cardiology congress, Munich, 27 August 2012. Abstract number: 3155
- Zannad, F; McMurray, J.J.V; and Drexler, H; et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2010 [10.1056/nejmoa1009492 nejm.org]
- Dar O; Cowie MR. The Epidemiology and Diagnosis of Heart Failure. In Hurst's The Heart. 12th:713-723. Fuster V (ed). Andover Publishing (2007)
- Setoguchi S; Stevenson LW; Schneeweiss S. Repeated hospitalizations predict mortality in the community population with heart failure. Am Heart J. 2007 Aug;154(2):260-6
- Maggioni AP, Dahlstro U, Filippatos G, et al. EURObservational Research programme: The Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail 2010;12:1076-1084.
- McMurray JJV, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33:1787-1847
- Stewart S; MacIntyre K; Hole DJ, et al. More 'malignant' than cancer? Five- year survival following a first admission for heart failure. Eur J Heart Fail 2001;3:315-22