Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy

Phase 4CompletedNCT01917149

Xijing Hospital480 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

480

Conditions

Dilated Cardiomyopathy

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

All cause death or admission for heart failure

Admission for heart failure was defined as a minimum of 24 h inpatient admission to any health-care facility, with the primary cause being treated for worsening heart failure and during which an additional diuretic drug, intravenous or oral nitrate, or intravenous inotropic agent was given.

Time frame: 48 months after enrollment

Secondary Outcomes

Changes in NYHA functional class

Time frame: 6,12, 24 and 36 months after enrollment

Left-ventricular ejection fraction

Left ventricular ejection fraction (LVEF) were calculated from measurements of left ventricular end diastolic and end systolic volumes in apical 4 and 2 chamber views using the modified Simpson's rule according to current guidelines