Valsartan in Cardiovascular Disease With Renal Dysfunction (The V-CARD) Study

Effects of Valsartan on Cardiovascular Events in Patients With Renal Dysfunction

The purpose of this study is to investigate if an angiotensin II receptor blocker, valsartan 160 mg/day is more effective to reduce the incidence of cardiovascular events as compared to 40 mg/day in patients with moderate renal dysfunction.

It is well known that patients with renal dysfunction have a poor prognosis concerning cardiovascular diseases. That is called "cardiorenal syndrome". It was reported that valsartan was effective in reducing the urine albumin extraction rate in patients with hyper- or normotension. We hypothesized that valsartan was more effective to prevent cardiovascular events by the intermediary of improving renal function.

The primary endpoints are:

• cardiovascular events (cardiac death, non-fatal myocardial infarction, unstable angina requiring rehospitalization, congestive heart failure requiring rehospitalization, revascularization procedures including coronary angioplasty or coronary artery bypass grafting;Stroke or transient ischaemic attack, dissociation aneurysm of the aorta needing hospitalisation;Lower limbs artery obstruction needing hospitalisation .
• end-stage renal dysfunction (introduction of hemodialysis or kidney transplantation)
• 50% reduction of creatinine clearance

The secondary endpoints are:

• systolic and diastolic function of the left ventricle estimated by echocardiography (% FS and E/A ratio)
• specific biochemical markers for cardiac or renal function (urine microalbumin, plasma B-type natriuretic peptide, plasma type 1 plasminogen activator inhibitor, plasma cystatin C)
• % changes of creatinine clearance between start and end of the study period
• transition of 1/(serum Cr) in patients whose u-prot/u-Cr is equal to or more than 1.0
• transition of serum K
• HbA1c
• New onset Atrial Fibrillation
• New onset Diabetes

Inclusion Criteria (all required):

• Systolic blood pressure (SBP) >/= 140 and/or diastolic blood pressure (DBP) >/= 90 (untreated hypertension cases); or SBP>/=130 and/or DBP>/=80 (treated hypertension cases)
• Patients with coronary artery disease (more than 50% stenosis on coronary angiography [CAG], coronary computed tomography [CT] or coronary magnetic resonance angiography [MRA]; coronary spasm; or history of percutaneous coronary intervention [PCI]);Unstable angina patient
• Creatinine clearance between 30.0 and 89.9 ml/min

Exclusion Criteria (at least one of following):

• Reduced left ventricular (LV) function (ejection fraction [EF] equal to or less than 40%)
• Hyperpotassemia (serum potassium equal to or more than 5.5 mEq/l)
• Rapid progressive glomerular nephritis
• Nephrotic syndrome
• Renal artery stenosis
• Uncontrolled diabetes (HbA1c equal to or more than 9.0%)
• History of allergy to valsartan
• Pregnant women