Original ArticleIs Blockade of the Renin-angiotensin System Able to Reverse the Structural and Functional Remodeling of the Left Ventricle in Severe Aortic Stenosis?Helske-Suihko, Satu MD, PhD*; Laine, Mika MD, PhD†; Lommi, Jyri MD, PhD†; Kaartinen, Maija MD, PhD†; Werkkala, Kalervo MD, PhD‡; Kovanen, Petri T. MD, PhD*; Kupari, Markku MD, PhD†Author Information *Wihuri Research Institute, Helsinki, Finland; Divisions of †Cardiology, Helsinki University Central Hospital, Helsinki, Finland; and ‡Cardiac Surgery, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland. Reprints: Markku Kupari, MD, PhD, Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki 00029, Finland (e-mail: [email protected]). Supported by the Finnish Foundation for Cardiovascular Research, Helsinki, Finland; by the Finnish Medical Foundation (S.H.-S.); and by the EVO research funds of the Helsinki University Central Hospital. Wihuri Research Institute (Helsinki, Finland) is maintained by the Jenny and Antti Wihuri Foundation. The investigational drugs were kindly provided by the AstraZeneca company (Espoo, Finland). The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcvp.org). Clinical Trial Registration—The Potential of Candesartan to Retard the Progression of Aortic Stenosis (ROCK-AS). ClinicalTrials.gov Identifier: NCT00699452. Received June 05, 2014 Accepted October 21, 2014 Journal of Cardiovascular Pharmacology: March 2015 - Volume 65 - Issue 3 - p 233-240 doi: 10.1097/FJC.0000000000000182 Buy SDC Metrics Abstract Abstract: In experimental aortic stenosis (AS), blockade of the renin-angiotensin system attenuates AS-related left ventricular (LV) dysfunction and improves survival. We tested whether candesartan, an angiotensin II type 1 receptor blocker, favorably influences LV structure and function and improves exercise capacity in AS patients. Fifty-one patients with severe AS were randomized to receive candesartan (target dose 16 mg/d) or placebo. Eight patients discontinued treatment and the remaining 43 patients underwent echocardiography, walking test, and measurement of plasma N-terminal B-type natriuretic peptide (Nt-proBNP) before and after an average of 5-month treatment. No statistically significant changes in LV diameters, mass, or function were seen. The median 6-minute walking distance decreased from 390 to 368 m with candesartan (P = 0.003) and from 380 to 370 m with placebo (P = 0.523), reflecting natural progression of AS. Concomitantly, median Nt-proBNP increased from 319 to 414 ng/L with candesartan (P = 0.170) and from 413 to 561 ng/L with placebo (P = 0.035). No change with candesartan was statistically significantly different from the corresponding change with placebo. In conclusion, candesartan was well tolerated but had no favorable effects on the LV or effort tolerance. The benefits found in experimental AS of blocking the renin-angiotensin system could not be reproduced in patients with severe AS. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.