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

Abstract

Hypertrophic cardiomyopathy (HCM) is often caused by pathogenic variants in sarcomeric genes and characterized by left ventricular (LV) hypertrophy, myocardial fibrosis and increased risk of heart failure and arrhythmias. There are no existing therapies to modify disease progression. In this study, we conducted a multi-center, double-blind, placebo-controlled phase 2 clinical trial to assess the safety and efficacy of the angiotensin II receptor blocker valsartan in attenuating disease evolution in early HCM. In total, 178 participants with early-stage sarcomeric HCM were randomized (1:1) to receive valsartan (320 mg daily in adults; 80-160 mg daily in children) or placebo for 2 years ( NCT01912534 ). Standardized changes from baseline to year 2 in LV wall thickness, mass and volumes; left atrial volume; tissue Doppler diastolic and systolic velocities; and serum levels of high-sensitivity troponin T and N-terminal pro-B-type natriuretic protein were integrated into a single composite z-score as the primary outcome. Valsartan (n = 88) improved cardiac structure and function compared to placebo (n = 90), as reflected by an increase in the composite z-score (between-group difference +0.231, 95% confidence interval (+0.098, +0.364); P = 0.001), which met the primary endpoint of the study. Treatment was well-tolerated. These results indicate a key opportunity to attenuate disease progression in early-stage sarcomeric HCM with an accessible and safe medication.

• Authors: Carolyn Y Ho, Sharlene M Day, Anna Axelsson, Mark W Russell, Kenneth Zahka, Harry M Lever, Alexandre C Pereira, Steven D Colan, Renee Margossian, Anne M Murphy, Charles Canter, Richard G Bach, Matthew T Wheeler, Joseph W Rossano, Anjali T Owens, Henning Bundgaard, Lee Benson, Luisa Mestroni, Matthew R G Taylor, Amit R Patel, Ivan Wilmot, Philip Thrush, Jose D Vargas, Jonathan H Soslow, Jason R Becker, Christine E Seidman, Neal K Lakdawala, Allison L Cirino, VANISH Investigators, Kristin M Burns, John J V McMurray, Calum A MacRae, Scott D Solomon, E John Orav, Eugene Braunwald
• Journal: Nature medicine (Nat Med) Vol. 27 Issue 10 Pg. 1818-1824 (10 2021) ISSN: 1546-170X [Electronic] United States
• PMID: 34556856 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chemical References

• Valsartan

Topics

• Adolescent
• Adult
• Cardiomyopathy, Hypertrophic (drug therapy, physiopathology)
• Double-Blind Method
• Female
• Heart (drug effects, physiopathology)
• Heart Failure (drug therapy, physiopathology)
• Humans
• Male
• Middle Aged
• Valsartan (administration & dosage, adverse effects)
• Young Adult