Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function

INCLUSION CRITERIA

• Heart failure as defined by at least one of symptom (paroxysmal nocturnal dyspnea; orthopnea; or dyspnea on mild or moderate exertion) at the time of screening and at least one sign (any rales post cough; jugular venous pressure(JVP) greater than or equal to 10cm of water(H2O); lower extremity edema; or chest x-ray demonstrating pleural effusion, pulmonary congestion, or cardiomegaly) within 12 months prior to study entry:
• left ventricular ejection fraction greater than or equal to 45% (per local reading); the ejection fraction must have been obtained within 6 months prior to randomization and after any MI or other event that would affect ejection fraction
• Controlled systolic blood pressure(BP), defined as a target systolic BP less than 140 mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment if they are on three or more medications to control BP
• Serum potassium less than 5.0 mmol/L prior to randomization
• At least one hospital admission for which heart failure was a major component of the hospitalization some time within the 12 months prior to study entry OR brain natriuretic peptide (BNP) greater than or equal to 100pg/ml or N-terminal pro-BNP greater than or equal to 360pg/ml within the 60 days prior to study entry
• Women of child-bearing potential must have a negative serum/urine pregnancy test within 72 hours prior to randomization, must not be lactating, and must agree to use an effective method of contraception during the entire course of study participation
• Willing to comply with scheduled visits
• Informed consent form signed by the subject prior to participation in the trial

EXCLUSION CRITERIA

• Severe systemic illness with an expected life expectancy of less than 3 years
• Chronic pulmonary disease requiring home O2, oral steroid therapy, or hospitalization for exacerbation within 12 months of study entry, or significant chronic pulmonary disease in the opinion of the investigator
• Known infiltrative or hypertrophic obstructive cardiomyopathy or known pericardial constriction
• Primary hemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant, or any valvular disease expected to lead to surgery during the trial
• Atrial fibrillation with a resting heart rate greater than 90 bpm
• MI in the past 90 days
• Coronary artery bypass graft surgery in the past 90 days
• Percutaneous coronary intervention in the past 30 days
• Heart transplant recipient
• Currently implanted left ventricular assist device
• Stroke in past 90 days
• Systolic BP (SBP) greater than 160 mm Hg
• Known orthostatic hypotension
• Gastrointestinal disorder that could interfere with study drug absorption
• Use of any aldosterone antagonist or potassium sparing medication in the last 14 days or any known condition that would require the use of an aldosterone antagonist during study participation;
• Known intolerance to aldosterone antagonists
• Current lithium use
• Current participation (including prior 30 days) in any other therapeutic trial
• Any condition that, in the opinion of the investigator, may prevent the participant from adhering to the trial protocol
• History of hyperkalemia (serum potassium greater than or equal to 5.5mmol/L) in the past 6 months or serum potassium greater than or equal to 5.0mmol/L within the past 2 weeks
• Severe renal dysfunction, defined as an estimated glomerular filtration rate(GFR) less than 30ml/min. Participants with serum creatinine greater than or equal to 2.5mg/dl are also excluded even if their GFR is greater than or equal to 30ml/min
• Known chronic hepatic disease, defined as aspartate aminotransferase(AST) and alanine aminotransferase(ALT) levels greater than 3.0 times the upper limit of normal as read at the local lab.