Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy

• Status: Completed
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Dilated cardiomyopathy (DCM) is a poorly understood cause of systolic heart failure and is the most common indication for heart transplantation worldwide. Despite advances in medical and device therapy, the 5-year mortality of patients with DCM remains high.

Patients diagnosed of dilated cardiomyopathy with a NYHA functional class of II to IV and left ventricular ejection fraction(LVEF) <35% were selected for randomized controlled study of the efficacy and safety of high dose Renin-angiotensin system (RAS) inhibitor (benazepril or valsartan), in comparison with low dose RAS inhibitor(benazepril or valsartan) and standard beta-adrenergic blocker therapy (metoprolol). The primary endpoint was all cause death or admission for heart failure. Additional prespecified outcomes included all-cause death, cardiovascular death, all-cause admission, heart failure admission. Secondary cardiovascular outcomes included the changes from baseline to the last available observation after treatment in NYHA functional class, quality-of-life scores, LVEF, LVEDD, mitral regurgitation and wall-motion score index assessed by ECG. Adverse events were reported during in-hospital observation and follow-ups.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Xijing Hospital
• Treatments: Benazepril; Metoprolol; Valsartan

Criteria

Inclusion Criteria:

• Diagnosis of dilated cardiomyopathy

• Left ventricular ejection fraction < 35%

• NYHA Functional classes of II-IV

• Symptomatic but not rapidly deteriorating 1 month before enrollment

• Signed informed consent

Exclusion Criteria:

• Contradictions and intolerance of the studied drugs:

• supine systolic arterial blood pressure < 90 mmHg,

• renal artery stenosis >50%,

• pregnancy or lactation,

• impaired renal function (estimated glomerular filtration rate < 60 ml/min/1.73m2,

• impaired liver function (total bilirubin >2 times upper limit of normal,

• serum aspartate AST or alanine ALT >3 times the upper limit of normal),

• hemoglobin less than 8 mg/dl, hyperkalaemia (serum potassium >5.5mmol/l),

• obstructive lung disease,

• advanced atrioventricular block,

• any co-morbidity with impact on survival, and

• known intolerance to benazepril, valsartan and metoprolol succinate;

• HF secondary to a known cause:

• coronary artery disease based on coronary angiography (≥50% stenosis in ≥1 of the major coronary arteries) and/or a history of myocardial infarction or angina pectoris,

• acute or subacute stage of myocarditis,

• primary valve disease,

• diabetes mellitus,

• excessive use of alcohol or illicit drugs;

• Expected or performed cardiac resynchronization therapy and heart transplantation.