EWISE: Study of Eplerenone in Women With Chest Pain, Coronary Vascular Dysfunction and Evidence of Myocardial Ischemia
Condition: Ischemic Heart Disease
MeSH terms: Heart Diseases; Myocardial Ischemia; Coronary Artery Disease; Ischemia; Chest Pain
Intervention: Eplerenone; Placebo or sugar pill
Intervention description: Eplerenone 25 mg (1 pill) daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.; Placebo blinded as 25 mg tablet(1 pill) once daily for 1 week then uptitrated to 50 mg (2 pills) daily for 15 weeks.
Intervention MeSH terms: Eplerenone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 70.0
Sex: Female
Minimum age: 21 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Microvascular Disease; Women; Ischemic Heart Disease; WISE

Summary:

      Some women have chest pain even without having a blockage in one of the major blood vessels
      that supplies blood to the heart. In many of these women the microscopic (small) blood
      vessels in the heart do not function normally. This study seeks to determine if treatment
      with eplerenone, a commercially available diuretic, can improve the function of these
      microscopic blood vessels and, possibly, improve the chest pain.
    

Eligibility criteria:

        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