In addition, eligible patients were stratified by two eligibility categories: (1) history of hospitalization within the previous 12 months, with management of heart failure a major component of the care provided, or (2) elevated brain natriuretic peptide (BNP) level within 60 days before randomization.Įxclusion criteria included severe systemic illness with a life expectancy of less than 3 years, severe renal dysfunction, and specific coexisting conditions, medications, or acute events.Ī total of 3445 participants were enrolled, with 1722 assigned to the spironolactone group and 1723 assigned to the placebo group. Patients 50 years of age or older were eligible if they had at least one sign and at least one symptom of heart failure on a pre-specified list of clinically defined signs and symptoms, a LVEF ≥ 45%, controlled systolic blood pressure (< 140 mm Hg or 140-160 mm Hg if subject was being treated with 3 or more medications), and a serum potassium level of less than 5.0 mmol per liter.
#TOPCAT WELL SERVICE TRIAL#
Therefore, the TOPCAT trial was initiated to determine whether treatment with spironolactone, an aldosterone antagonist, would improve clinical outcomes in patients with symptomatic heart failure and a relatively preserved LVEF. However, rigorous testing was needed regarding their effect on clinical outcomes in patients with preserved LVEF. In small mechanistic studies involving patients with heart failure and preserved left ventricular function, mineralocorticoid receptor antagonists improved measures of diastolic function. Due to a lack of favorable evidence from clinical trials, clinical guidelines offered no specific recommendations for the management of heart failure in patients with preserved LVEF except for attention to coexisting conditions.Īmong patients with heart failure and a reduced LVEF and those with myocardial infarction complicated by heart failure and left ventricular dysfunction, mineralocorticoid receptor antagonists have been shown to be effective in reducing overall mortality and hospitalizations for heart failure. However at the time of TOPCAT, the benefit of medical therapies for heart failure was limited to those with a reduced LVEF. Such patients share similar signs and symptoms as patients who have heart failure and a reduced LVEF, as well as an impaired quality of life and a poor prognosis. Many patients with heart failure have a normal or near-normal left ventricular ejection fraction (LVEF). The TOPCAT trial evaluated the effectiveness of aldosterone antagonist therapy in reducing cardiovascular mortality, aborted cardiac arrest, and heart failure hospitalization in patients who have heart failure with preserved systolic function.