title: Is blockade of the Renin-Angiotensin system able to reverse the structural and functional remodeling of the left ventricle in severe aortic stenosis?
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.
authors.affiliation: *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.
authors.forename: Satu
authors.initials: S
authors.lastname: Helske-Suihko
authors.forename: Mika
authors.initials: M
authors.lastname: Laine
authors.forename: Jyri
authors.initials: J
authors.lastname: Lommi
authors.forename: Maija
authors.initials: M
authors.lastname: Kaartinen
authors.forename: Kalervo
authors.initials: K
authors.lastname: Werkkala
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Markku
authors.initials: M
authors.lastname: Kupari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D001024:Aortic Valve Stenosis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds; D018450:Disease Progression; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D005387:Finland; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D020127:Recovery of Function; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D010446:Peptide Fragments; D013777:Tetrazoles; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C081643:candesartan