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

Abstract

AimsThe 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 results480 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.ConclusionsSupramaximal 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.

Treatment options for ischemic mitral regurgitation: A meta-analysis

“…The use of MitraClip procedure was associated with a significantly lower risk of reoperation compared to the use of GDMT alone at a mean follow-up of 15.8 months. The clinical benefit associated with the use of MitraClip procedure is by pathoanatomical and pharmacological means as it was more evident in correcting geometric changes of mitral valve than medical treatment alone including renin-angiotensin system inhibitors [21][22][23][24][25][26][27][28] and beta-adrenergic blockade [29][30][31][32][33][34][35] on reducing mitral regurgitation. These medications work by attenuating LV remodeling in chronic severe MR [36,37] often in association with temporary use of diuretics [38].…”

ESC Heart Failure: a new journal aims to broaden heart failure views

“…Inhibition of the renin–angiotensin–aldosterone system remains the mainstay of therapy in patients with chronic HF. He et al performed a randomized trial to assess the efficacy and safety of supramaximal titrated inhibition in patients with idiopathic dilated cardiomyopathy. They concluded that even supramaximal doses of benazepril and valsartan were tolerated and produced extra benefit on top of their low‐dose counterparts with regard to clinical outcome and cardiac reverse remodelling .…”

The appropriate dose of angiotensin‐converting‐enzyme inhibitors or angiotensin receptor blockers in patients with dilated cardiomyopathy. The higher, the better?

“…As described earlier, an ACE inhibitor, lisinopril, or an ARB, losartan, at high dose produced better clinical outcomes in patients with HF compared with each at low dose but did not decrease mortality significantly. 5,6 On the other hand, He et al reports that supramaximal dose of benazepril or valsartan improves not only cardiac function but also survival in patients with DCM compared with the low dose of each medication, 16 which indicates that ACE inhibitors or ARBs at supramaximal-dose might produce better outcomes in patients with EF compared with those at high dose (target dose). These unique findings are derived from a single-centre prospective, randomized, and controlled trial.…”