Efficacy and safety of supramaximal titrated inhibition of renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy.

Abstract

AIMS:

The optimal dosing strategies for blocking the renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy (IDCM) are poorly known. We sought to determine the long-term efficacy and safety of supramaximal titration of benazepril and valsartan in patients with IDCM.

METHODS AND RESULTS:

480 patients with IDCM in New York Heart Association functional class II-IV and with left ventricular ejection fraction ≤35% were randomly assigned to extended-release metoprolol (mean 152 mg/day, range 23.75-190), low-dose benazepril (20 mg/day), low-dose valsartan (160 mg/day), high-dose benazepril (mean 69 mg/day, range 40-80), and high-dose valsartan (mean 526 mg/day, range 320-640). After a median follow-up of 4.2 years, high-dose benazepril and valsartan, compared with their respective low dosages, resulted in 41% and 52% risk reduction in the primary endpoint of all-cause death or admission for heart failure (P = 0.042 and 0.002), promoted functional improvement, and reversed remodelling as assessed by New York Heart Association classes, quality-of-life scores, and echocardiographic recording of left ventricular ejection fraction, left ventricular end-diastolic volume, mitral regurgitation, and wall motion score index. Compared with metoprolol, high-dose valsartan reduced risk for the primary endpoint by 46% (P = 0.006), whereas high-dose benazepril and both low-dose groups showed no significant difference. Major adverse events involved hypotension and renal impairment but were largely tolerated.

CONCLUSIONS:

Supramaximal doses of benazepril and valsartan were well tolerated and produced extra benefit than their low dosages in clinical outcome and cardiac reverse remodelling in patients with IDCM and modest-severe heart failure. ClinicalTrials.gov identifier: NCT01917149.

• Authors: Zheng He, Yun Sun, Hui Gao, Jun Zhang, Yuhong Lu, Jihua Feng, Hongli Su, Chao Zeng, Anlin Lv, Kang Cheng, Yan Li, Huan Li, Ronghua Luan, Ling Wang, Qiujun Yu
• Journal: ESC heart failure (ESC Heart Fail) Vol. 2 Issue 4 Pg. 129-138 (Dec 2015) ISSN: 2055-5822 [Electronic] England
• PMID: 28834619 (Publication Type: Journal Article)
• Copyright: © 2015 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.