This study is designed to etablish the effects of spironolactone in comparison to placebo on the composite endpoint of nonfatal Myocardial Infarction (MI) and acute coronary syndrome, hospitalization for heart failure, nonfatal stroke or cardiovascular-induced death. The primary endpoint will be the time to onset of the first incident.

• During a run-in period : Spironolactone will be initially administered per os at a 25 mg dose per two days in practice after the session, three times per week
• Patients will be randomized (spironolactone vs. placebo) and titrated over one month to a maximum single dose of 25 mg/d
• However if kalemia is greater than or equal to 5.5 mmol / l twice on this run-in period or on the day of randomization, patient won't be randomized.
• A pre-specified algorithm for the management of the risk of incident hyperkalemia will be followed, including dose adjustment, temporary cessation of study treatment, in addition to usual dietary measures and the use of chelating resins and low-potassium dialysis baths
• Patients will be followed for a mean of 2 years.

Inclusion Criteria:

• Written informed consent.
• Adult men and women on HD for at least 45 days for ESRD regardless of the etiology including diabetes, with at least 3 HD sessions per week
• Presenting at least one of the follow comorbidities, cardiovascular abnormalities or CV risk factors:
• Left ventricular hypertrophy defined by left ventricular mass > 130 g/m2 in men and 100 g/m2 in women (echocardiography)
• OR Cornell (RaVL + SV3) >28 mm in men, > 20 mm in women(ECG)
• OR left ventricular ejection fraction < 40%
• OR large QRS > 0.14 sec
• OR Left bundle branch block (ECG) measured during the twelve months preceding inclusion; diabetes;
• OR history of cardiovascular disease: coronary artery disease, symptomatic lower limb peripheral arterial disease, carotid or renal artery stenosis > 50%, stroke, hospitalization for heart failure, permanent atrial fibrillation (AF), oral anticoagulant treatment for AF, valvular heart prosthesis,
• OR CRP > 5 mg/l for 3 months without infectious or neoplastic disease documented in progress

Exclusion Criteria:

• history of hypersensitivity to spironolactone or galactose intolerance
• the Lapp lactase deficiency or malabsorption of glucose or galactose
• hyperkalemia > 5.5 mmol/l during the two weeks prior to enrolment
• history of unscheduled hemodialysis for hyperkalemia during the last six months
• hospitalization for hyperkalemia during the last six months
• patients with imperative indication of a combination of ACEI and sartan or renin inhibitor (each being authorized separately), NSAIDS, Cox-2 inhibitors
• kidney transplant scheduled within the year
• symptomatic interdialytic hypotension
• acute systemic disease
• uncompensated hypothyroidism
• acute hyperthyroidism
• any prior or concomitant clinical condition compromising the inclusion, in the discretion of the investigator
• cardiac transplant
• severe uncontrolled arrhythmia
• stroke within 3 months prior to enrolment
• acute coronary syndrome in the previous month inclusion
• recent (1 month) or planned coronary revascularization by angioplasty
• recent (3 months) or planned cardiovascular surgery (excluding HD vascular access)
• non menopausal women or without effective contraceptive methods
• pregnancy, breastfeeding or planning a pregnancy within 2 years
• non compliance
• protected adult
• SBP > 200 mmHg and/or DBP > 110 mmHg
• Concomitant treatment can not be stopped by another potassium-sparing diuretic, a potassium supplements, AINS or Cox 2 inhibitors

Statistical Analysis Plan