This trial is a multicenter, international, randomized, double blind placebo-controlled trial of thealdosterone antagonist, spironolactone, in 4500 adults with heart failure and left ventricularejection fraction of at least 45%, recruited from over 150 clinical centers. The primary endpointis a composite of cardiovascular mortality, aborted cardiac arrest or hospitalization for themanagement of heart failure. Secondary endpoints include all-cause mortality, new onset ofdiabetes mellitus, atrial fibrillation, and quality of life. The trial duration is 4.25 years, with 2.0years for subject enrollment and an additional 2.25 years of follow-up, with an average subjectfollow-up of 3.0 years.Study drug dosing will start at 15 mg/day and may be titrated up to 45 mg according to subjecttolerance, safety parameters, and symptoms, and will be continued throughout the trial.Following each change in the dosing regimen, subjects will have blood drawn for safety labs 1week later. Subjects will take study medication every day according to specific instructions. Allother treatments will follow accepted local standards for medical care for specific morbidities asdescribed by the American College of Cardiology (ACC), the American Heart Association(AHA), and the European Society of Cardiology (ESC) Practice Guidelines, as appropriate.Such treatments may also be adjusted by the local medical practitioner, if necessary. Allrandomized subjects will be followed even if study drug is discontinued ahead of schedule,except in the case that the subject refuses to participate further in the study.
