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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.


PROVIDER: S-EPMC5746969 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

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