title: Impact of baseline severity of aortic valve stenosis on effect of intensive lipid lowering therapy (from the SEAS study).
abstract: Retrospective studies have suggested a beneficial effect of lipid-lowering treatment on the progression of aortic stenosis (AS) in milder stages of the disease. In the randomized, placebo-controlled Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, 4.3 years of combined treatment with simvastatin 40 mg and ezetimibe 10 mg did not reduce aortic valve events (AVEs), while ischemic cardiovascular events (ICEs) were significantly reduced in the overall study population. However, the impact of baseline AS severity on treatment effect has not been reported. Baseline and outcomes data in 1,763 SEAS patients (mean age 67 years, 39% women) were used. The study population was divided into tertiles of baseline peak aortic jet velocity (tertile 1: ≤ 2.8 m/s; tertile 2: > 2.8 to 3.3 m/s; tertile 3: > 3.3 m/s). Treatment effect and interaction were tested in Cox regression analyses. The rates of AVEs and ICEs increased with increasing baseline severity of AS. In Cox regression analyses, higher baseline peak aortic jet velocity predicted higher rates of AVEs and ICEs in all tertiles (all p values < 0.05) and in the total study population (p < 0.001). Simvastatin-ezetimibe treatment was not associated with a statistically significant reduction in AVEs in any individual tertile. A significant quantitative interaction between the severity of AS and simvastatin-ezetimibe treatment effect was demonstrated for ICEs (p < 0.05) but not for AVEs (p = 0.10). In conclusion, the SEAS study results demonstrate a strong relation between baseline the severity of AS and the rate of cardiovascular events but no significant effect of lipid-lowering treatment on AVEs, even in the group with the mildest AS.
authors.affiliation: Institute of Medicine, University of Bergen, Bergen, Norway. eva.gerdts@helse-bergen.no
authors.forename: Eva
authors.initials: E
authors.lastname: Gerdts
authors.forename: Anne Bjørhovde
authors.initials: AB
authors.lastname: Rossebø
authors.forename: Terje Rolf
authors.initials: TR
authors.lastname: Pedersen
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.forename: Philippe
authors.initials: P
authors.lastname: Brudi
authors.forename: John Boyd
authors.initials: JB
authors.lastname: Chambers
authors.forename: Kenneth
authors.initials: K
authors.lastname: Egstrup
authors.forename: Christa
authors.initials: C
authors.lastname: Gohlke-Bärwolf
authors.forename: Ingar
authors.initials: I
authors.lastname: Holme
authors.forename: Y Antero
authors.initials: YA
authors.lastname: Kesäniemi
authors.forename: William
authors.initials: W
authors.lastname: Malbecq
authors.forename: Christoph
authors.initials: C
authors.lastname: Nienaber
authors.forename: Simon
authors.initials: S
authors.lastname: Ray
authors.forename: Terje
authors.initials: T
authors.lastname: Skjærpe
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
authors.forename: Ronnie
authors.initials: R
authors.lastname: Willenheimer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004452:Echocardiography; D000069438:Ezetimibe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001384:Azetidines; D000960:Hypolipidemic Agents; D008055:Lipids; D019821:Simvastatin; D000069438:Ezetimibe