Patients With Acute STEMI Without Heart Failure Benefit From Inspra® (Eplerenone) Within First 24 Hours, Study Shows
Primary composite efficacy endpoint met in REMINDER trial
Pfizer has announced results from the REMINDER[i] trial (Role of Eplerenone in acute Myocardial INfarction – Double-blind, Early treatment initiation, Randomised, placebo-controlled, multi-centre study) showing statistically significant risk reductions in the primary composite efficacy endpoint. This is the first randomised trial to test a mineralocorticoid receptor antagonist during the acute phase of heart attack.
Eplerenone is not approved for use in the patient population studied in the REMINDER trial in any market.
The composite endpoint was defined as the time to first event of cardiovascular (CV) mortality, re-hospitalisation or extended initial hospital stay due to diagnosis of heart failure (HF), sustained ventricular tachycardia or fibrillation, ejection fraction (EF) ≤40% after 1 month, or an elevation of BNP/NT- proBNP after 1 month.
After a mean follow-up of 10.5 months, the primary composite endpoint occurred in 18.4% of patients in the eplerenone group as compared with 29.6% in the placebo group. This represented a statistically significant 42.9% relative risk reduction in the primary endpoint, with p < 0.0001 (95% confidence interval [CI] 0.439, 0.742), when eplerenone was initiated within the first 24 hours of onset of symptoms in patients with acute STEMI. Overall, the adverse events reported in the REMINDER trial were consistent with those already known for eplerenone, primarily hyperkalaemia.
Commenting on the findings, Professor Gregory Lip, Professor of Cardiovascular Medicine, University of Birmingham Centre for Cardiovascular Sciences, said: “Reducing the risk of death and future heart failure is the overriding concern in the management of STEMI. The results of REMINDER show that adding eplerenone to standard STEMI care within the first 24 hours could significantly improve patient outcomes.”
The results were presented for the first time during the Late Breaker Clinical Trial session at the 62nd Annual Scientific Session of the American College of Cardiology in San Francisco.
The REMINDER trial was a randomised, double-blind trial, involving 1,012 patients with acute ST-segment elevation myocardial infarction (STEMI) without a history of HF or EF <40% and without signs of HF. Patients received, preferably before myocardial reperfusion, either eplerenone (25-50 mg OD) or placebo in addition to standard therapy. Treatment was initiated within the first 24 hours of symptom onset (preferably within first 12 hours).
The improvement in outcome was mainly driven by a significant reduction of the BNP/NT-proBNP biomarker component at 1 month. BNP/NT-proBNP has been shown to be an important marker for short- and long-term prognosis in patients with myocardial infarction in the presence or absence of preserved ejection fraction.[ii] An elevation of BNP/NT-proBNP after 1 month was observed less frequently in the eplerenone group (81[16.0%]) than in the placebo group (131[25.9%]) (adjusted HR, 0.584; 95% CI 0.441-0.773; p=0.0002).
Over the course of the study, the incidence of hyperkalemia (elevated potassium defined as serum potassium levels exceeding 5.5 mEq/L) occurred in 5.6% vs. 3.2% (p=0.09) in the eplerenone and placebo groups, respectively. Hypokalemia (serum potassium level below 3.5 mEq/L) occurred more frequently in the placebo group with 1.4% vs. 5.5% (p=0.0002) in the eplerenone and placebo groups, respectively. The rates of other adverse events were similar in both groups.
STEMI, a severe type of acute myocardial infarction, is most often caused by complete and persistent occlusion of a coronary artery by a blood clot. As soon as the coronary blood supply is interrupted, myocardial damage begins and the longer the blood supply is blocked the greater the amount of heart muscle lost.[iii]
About Inspra® (eplerenone)
Eplerenone is a selective aldosterone antagonist/ mineralocorticoid receptor antagonist (MRA). It is indicated in addition to standard therapy including beta-blockers, to reduce the risk of cardiovascular mortality and morbidity in stable patients with left ventricular dysfunction (LVEF £40%) and clinical evidence of heart failure after recent myocardial infarction.[iv]
Eplerenone is also indicated in addition to standard optimal therapy, to reduce the risk of cardiovascular mortality and morbidity in adult patients with NYHA class II (chronic) heart failure and left ventricular systolic dysfunction (LVEF ≤30%).
Health economic analysis of eplerenone in patients with CHF (NYHA class II) have shown that eplerenone as an add-on to standard optimal therapy is cost-effective compared to standard therapy alone, with a cost per Quality Adjusted Life Year (QALY) gained of £3,534,[v] providing a good economic as well as a clinical case for the use of eplerenone.
Please note that eplerenone is not licensed for the treatment of patients with ST-segment elevation myocardial infarction (STEMI) without a history of heart failure. UK prescribing information is available here.
[i] Early Administration of Eplerenone in Patients with Acute Myocardial Infarction Without Heart Failure: Results of the Randomised, Double-Blind, Placebo-Controlled REMINDER Trial. Data presented at ACC 2013.
[ii] Richards AM, Nicholls MG, Espiner EA, et al. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation 2003;107:2786-92.
[iii] NICE draft guidance: Myocardial infarction with ST-segment-elevation. The acute management of myocardial infarction with ST-segment-elevation. Draft for consultation. January 2013. (date accessed March 2013).
[iv] Inspra Summary of Product Characteristics. Last updated on the eMC: 04/04/2012.
[v]Data on file:Pfizer cost effectiveness model for Inspra for CHF; 2012.