EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia

Inclusion Criteria:

• Non-pregnant women with chest discomfort who are 21 to 75 years of age and from diverse racial/ethnic groups.
• Suspected ischemic heart disease (IHD) but no severe coronary stenosis (> 50% diameter reduction) on coronary angiography used to qualify for WISE.
• Endothelial dysfunction, defined as failure to dilate to intracoronary acetylcholine (< 5% increase in mean lumen diameter).
• If possible, patients should be taking stable, maximally tolerated dose of either an angiotensin-converting enzyme inhibitor [ACEI] (or an angiotensin II receptor blocker [ARB] if ACEI intolerant)

Exclusion Criteria:

• Women who are breast-feeding or who are pregnant. Women of childbearing potential may be enrolled but must agree not to become pregnant during the course of the study and must practice a method of birth control considered reliable by the investigator. If established on hormonal contraceptives for more than 3 months, patients will be allowed to participate provided that this therapy remains constant throughout the study. If a patient becomes pregnant or begins breast-feeding during the study, she must be withdrawn immediately.
• Acute ischemic syndrome defined as acute myocardial infarction [MI] (by enzyme or electrocardiogram [ECG] criteria) or unstable angina within 1 month of entry.
• Uncontrolled moderate hypertension: sitting blood pressure > 160/95mmHg with measurements recorded on at least 2 occasions (for blood pressure control patients must first be stabilized, preferably with a diuretic, and remain on that dosing regimen throughout participation in the study).
• Severe heart failure defined as New York Heart Association (NYHA) Class III or IV on treatment.
• Coronary revascularization by either coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA) or stent placement.
• Conditions likely to influence outcomes independent of IHD: severe lung, renal (creatinine >1.8 or creatinine clearance [CrCl] ≤ 50ml/min) or hepatic disease; surgically uncorrected significant congenital or valvular heart disease; and other diseases likely to be fatal or require frequent hospitalizations within the next six months.
• Adherence or retention reasons: recent alcoholism or drug abuse; psychiatric illness including severe depression; dementia; active participation in any other research trial other than WISE; or unwilling to complete follow-up evaluations including repeat testing.
• Hypersensitivity to any medications to be used in the study
• Documented obstructive hypertrophic cardiomyopathy.
• Aortic stenosis (valve area < 1.5cm).
• Left ventricular (LV) dysfunction (ejection fraction <= 35%).
• History of significant cocaine or amphetamine abuse.
• Serum potassium > 5.0meq/l at baseline
• Taking potent CYP3A4 inhibitors (ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir)
• Intolerance to ACEI and ARB medications
• Use of potassium supplements or potassium sparing diuretics