Pfizer Inc. has reported the results from the REMINDER trial showing statistically significant risk reductions in the primary composite efficacy endpoint. The composite endpoint was defined as the time to first event of cardiovascular (CV) mortality, re-hospitalization 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.
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 randomized, double-blind trial, involving 1,012 patients with acute ST-segment elevation myocardial infarction (STEMI) without a history of HF or EF <40 per cent 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 12h).
The REMINDER trial demonstrated a statistically significant 42.9 per cent relative risk reduction in the primary endpoint with p < 0.0001 (95 per cent confidence interval [CI] 0.439, 0.742) in patients with acute STEMI when eplerenone was initiated within the first 24 hours of onset of symptoms. Overall, the adverse events reported in the REMINDER trial were consistent with those already known for eplerenone, primarily hyperkalemia.
Eplerenone is not approved for use in the patient population studied in the REMINDER trial in any market.
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. An elevation of BNP / NT-proBNP after 1 month was observed less frequently in the eplerenone group 81(16.0 per cent) than in the placebo group 131(25.9 per cent) (adjusted HR, 0.584; 95 per cent 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.
Commenting on the findings, the chair of the REMINDER Steering Committee Professor Gilles Montalescot, Institute of Cardiology, Centre Hospitalier Pitié-Salpêtriere, Paris, France said, “Eplerenone improved the outcome of patients presenting with acute STEMI and without concomitant heart failure. This benefit was obtained in a low-risk population that was well treated, without serious adverse drug effect. Adding eplerenone to standard therapy as early as within the first 24 hours of symptoms reduced heart failure-related morbidity.”
The REMINDER trial was a randomized, double-blind trial, involving 1012 patients with acute STEMI without a history of HF or EF <40% and without signs of HF. The REMINDER trial was conducted in 11 countries: Canada, Czech Republic, France, Germany, Greece, Hungary, Netherlands, Poland, Slovakia, Spain, UK.
The primary objective of the REMINDER trial was to assess the efficacy of Inspra 25 -50 mg once daily, compared to placebo, in the early treatment of acute ST-segment elevation myocardial infarction (STEMI) within 24 hours (preferably within the first 12h). The mean follow-up time was 10.5 months. The study was funded by Pfizer.
INSPRA (eplerenone) is a steroid nucleus-based mineralcorticoid receptor (MR) antagonist with a higher degree of selectivity than spironolactone.
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