Comparison of Eplerenone Versus Spironolactone in Heart Failure Patients With Glucose Intolerance or Type 2 Diabetes

Inclusion Criteria:

1. Male or female at least 18 years old.
2. Symptomatic HF corresponding to NYHA class II-IV symptoms for at least 4 weeks priorrandomization.
3. A diagnosis of 1) impaired glucose tolerance described as overnight fasting betweenblood glucose 5.6 and 6.9 mmol/L on two occasions; or 2) type 2 diabetes defined asovernight fasting between blood glucose of 7.0 mmol/L or more on two occasions; aHbA1c equal to or higher than 6.5% or more on two occasions; or as a history of typeII diabetes treated with hypoglycemic agents.
4. LVEF equal to or lower than 40% documented by, contrast ventriculography, magneticresonance imaging, radionuclide ventriculography or quantitative echocardiographywithin the previous 12 months if no cardiac event occurred since the measurement ofthe LVEF. The most recent measurements should be used.
5. Treatment with an optimal and stable dose of ACE inhibitor (or ARB) for at least 4weeks prior to enrolment in the study. In addition, patients should be treated with astable dose of beta-blockers for at least 4 weeks prior enrolment in the study.Patients incapable to tolerate bisoprolol, carvedilol or metoprolol will be allowedwithin the trial.
6. Informed consent must be obtained before any study specific procedures are performed

Exclusion Criteria:

1. Current treatment with a combination of an ARB, an ACE or a renin inhibitor.
2. Type 1 diabetes
3. Known intolerance or allergy to eplerenone or spironolactone, including gynecomastiawith spironolactone.
4. Estimated GFR < 30 mL/min/1.73 m2 as calculated using the MDRD equation (Appendix 1).
5. Current serum potassium higher than 5.0 mmol/L (higher than 5.0 mEq/L).
6. Current symptomatic hypotension and/or systolic B.P. < 90 mmHg.
7. Persistent systolic or diastolic hypertension (systolic > 170 mmHg or diastolic > 100mmHg despite use of antihypertensive therapy).
8. HF secondary to any of the following conditions: hemodynamically significant primarystenotic valvular cardiomyopathy, isolated right sided CHF, non cardiac disease (e.g.uncorrected thyroid disease), pericardial disease, complex congenital heart disease,myocarditis.
9. Decompensated heart failure described as hospitalization or I.V. administration ofmedication in emergency room or heart failure clinic within 4 weeks (ex.: diuretics,inotropes, vasodilatators)
10. Current treatment with insulin
11. Stroke, acute coronary syndrome, PCI within the last 4 weeks before randomization.
12. Cardiac surgery within 3 months.
13. Significant liver disease (ALT x 3 times limit of normal).
14. Planned cardiac surgery expected to be performed within the next 6 months.
15. Previous heart transplant or heart transplant expected to be performed within the next 6 months.
16. Presence of any non-cardiac diseases likely to significantly shorten life expectancyto < 1 year.
17. Pregnant or lactating women or women of childbearing potential who are not protectedfrom pregnancy by an accepted method of contraception, such as the oral contraceptivepill, an intrauterine device or surgical sterilization (all women of childbearingpotential must have a negative pregnancy test before randomization).
18. Any condition that in the opinion of the investigator would jeopardize the evaluationon efficacy or safety or be associated with poor adherence to the protocol.
19. Treatment with any investigational agent or device within 4 weeks of randomization.