Physicians' Academy for Cardiovascular Education

ARB in early-stage hypertrophic cardiomyopathy improves primary outcome

Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial

Literature - Ho CY, Day SM, Axelsson A et al., - Nat Med 2021, 27:1818-1824, doi: 10.1038/s41591-021-01505-4

Introduction and methods

Aim of the study

Hypertrophic cardiomyopathy (HCM), a primary heart muscle disorder, is often caused by pathogenic variants in genes encoding the sarcomere [1]. It is characterized by left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of heart failure, arrhythmias and sudden cardiac death [2]. There is an unmet need of therapies for HCM to slow progression or preventing this disease. Mouse and human studies have not showed substantial benefit using an ARB in well-established HCM, but this drug has not been tested in early HCM.

Study design

The Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial, a multi-center, double-blind, placebo-controlled phase 2 trial, examined the efficacy and safety of the ARB valsartan in patients with early-stage HCM (young age and absence of severe LVH or limiting symptoms) [3,4]. A total of 178 participants were randomized to valsartan or placebo. Mean age was 23.3 (10.1) years.

Primary outcome

Nine individual metrics were standardized and integrated into a composite z-score that assessed the change from baseline to year 2: body surface area (BSA)-indexed LV mass and BSA-indexed left atrial (LA) volume, BSA-indexed LV end diastolic and end systolic volumes determined by cardiac magnetic resonance imaging core laboratory, BSA-adjusted maximal LV wall thickness, age-adjusted Doppler diastolic (E’) and systolic (S’) velocities determined by the echocardiographic core laboratory and log-transformed serum high-sensitivity cardiac troponin T (TnT) and NTproBNP levels. An increase in the composite z-score indicates a greater than average improvement.

Main results


The VANISH trial showed that treatment of valsartan early in the course of HCM improved the composite outcome, an integration of nine measures of cardiac structure, function and remodeling, compared to placebo. Valsartan treatment in patients with early-stage sarcomeric HCM was safe and well-tolerated with no increase in adverse events.


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