Efficacy and Safety Study of Supramaximal Titrated Inhibition of RAAS in Idiopathic Dilated Cardiomyopathy
Overview
- Phase
- Phase 4
- Intervention
- Benazepril
- Conditions
- Dilated Cardiomyopathy
- Sponsor
- Xijing Hospital
- Enrollment
- 480
- Locations
- 1
- Primary Endpoint
- All cause death or admission for heart failure
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief 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.
Investigators
Hezheng
Professor
Xijing Hospital
Eligibility 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,
Arms & Interventions
High dose Benazepril
Patients randomized to high-dose benazepril were started on benazepril 10mg twice daily, and uptitrated to target doses within 7 days under in-hospital observation. The target high doses of benazepril is determined by left-ventricular end-diastolic diameter (LVEDD) (the maximal value of anteroposterior and lateral diameters) obtained by ECG at the randomization visit. A target dose of benazepril 40mg, 60mg, 80mg daily were assigned to patients with LVEDD of 50-59, 60-69, ≥70 mm respectively.
Intervention: Benazepril
Metoprolol
Patients in the metoprolol group were started on 11.875-23.75mg of metoprolol succinct extended-release tablet once daily (11.875mg was recommended for patients with NYHA functional classes III-IV), and then doses were doubled every 2 weeks to achieve asymptomatic bradycardia (50-60 bpm of heart rate) over 4-6 weeks. Investigators were encouraged to up-titrate metoprolol to a maximum dose of 190mg whenever possible.
Intervention: Metoprolol
Low-dose valsartan
Patients randomized to low dose valsartan receive valsartan 80 mg until study completion.
Intervention: Valsartan
Low dose Benazepril
Patients randomized to low dose Benazepril receive Benazepril 10 mg until study completion.
Intervention: Benazepril
High dose valsartan
Patients randomized to high-dose valsartan were started on valsartan 80mg twice daily, and uptitrated to target doses within 7 days under in-hospital observation. The target high doses of valsartan is determined by left-ventricular end-diastolic diameter (LVEDD) (the maximal value of anteroposterior and lateral diameters) obtained by ECG at the randomization visit. A target dose of valsartan 320mg, 480mg, 640mg daily were assigned to patients with LVEDD of 50-59, 60-69, ≥70 mm respectively.
Intervention: Valsartan
Outcomes
Primary Outcomes
All cause death or admission for heart failure
Time Frame: 48 months after enrollment
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.
Secondary Outcomes
- Left-ventricular end-diastolic diameter(6, 12 , 24 and 36 months after enrollment)
- Left-ventricular ejection fraction(6,12, 24 and 36 months after enrollment)
- Changes in NYHA functional class(6,12, 24 and 36 months after enrollment)