title: Effects of rosuvastatin on progression of stenosis in adult patients with congenital aortic stenosis (PROCAS Trial).
abstract: Recent trials have failed to show that statin therapy halts the progression of calcific aortic stenosis (AS). We hypothesized that statin therapy in younger patients with congenital AS would be more beneficial, because the valve is less calcified. In the present double-blind, placebo-controlled trial, 63 patients with congenital AS (age 18 to 45 years) were randomly assigned to receive either 10 mg of rosuvastatin daily (n = 30) or matched placebo (n = 33). The primary end point was the progression of peak aortic valve velocity. The secondary end points were temporal changes in the left ventricular mass, ascending aortic diameter, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The median follow-up was 2.4 years (interquartile range 1.9 to 3.0). The mean increase in peak velocity was 0.05 ± 0.21 m/s annually in the rosuvastatin group and 0.09 ± 0.24 m/s annually in the placebo group (p = 0.435). The annualized change in the ascending aorta diameter (0.4 ± 1.7 mm with rosuvastatin vs 0.5 ± 1.6 mm with placebo; p = 0.826) and left ventricular mass (1.1 ± 15.8 g with rosuvastatin vs -3.7 ± 30.9 g with placebo; p = 0.476) were not significantly different between the 2 groups. Within the statin group, the NT-proBNP level was 50 pg/ml (range 19 to 98) at baseline and 21 pg/ml (interquartile range 12 to 65) at follow-up (p = 0.638). NT-proBNP increased from 40 pg/ml (interquartile range 20 to 92) to 56 pg/ml (range 26 to 130) within the placebo group (p = 0.008). In conclusion, lipid-lowering therapy with rosuvastatin 10 mg did not reduce the progression of congenital AS in asymptomatic young adult patients. Interestingly, statins halted the increase in NT-proBNP, suggesting a potential positive effect of statins on cardiac function in young patients with congenital AS.
authors.affiliation: Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Denise
authors.initials: D
authors.lastname: van der Linde
authors.forename: Sing C
authors.initials: SC
authors.lastname: Yap
authors.forename: Arie P J
authors.initials: AP
authors.lastname: van Dijk
authors.forename: Werner
authors.initials: W
authors.lastname: Budts
authors.forename: Petronella G
authors.initials: PG
authors.lastname: Pieper
authors.forename: Pieter H
authors.initials: PH
authors.lastname: van der Burgh
authors.forename: Barbara J M
authors.initials: BJ
authors.lastname: Mulder
authors.forename: Maarten
authors.initials: M
authors.lastname: Witsenburg
authors.forename: Judith A A E
authors.initials: JA
authors.lastname: Cuypers
authors.forename: Jan
authors.initials: J
authors.lastname: Lindemans
authors.forename: Johanna J M
authors.initials: JJ
authors.lastname: Takkenberg
authors.forename: Jolien W
authors.initials: JW
authors.lastname: Roos-Hesselink
mesh_terms: D000293:Adolescent; D000328:Adult; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000151:congenital* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001530:Belgium; D001783:Blood Flow Velocity / Q000187:drug effects; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000188:drug therapy; D018450:Disease Progression; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006350:Heart Valve Prosthesis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009426:Netherlands; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010446:Peptide Fragments; D011743:Pyrimidines; D013449:Sulfonamides; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068718:Rosuvastatin Calcium