At sea with SEAS: the first clinical endpoint trial for ezetimibe, treatment of patients with mild to moderate aortic stenosis, ends with mixed results and more controversy.
SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) hypothesised that aggressive lipid lowering with simvastatin/ezetimibe reduced cardiovascular disease (CVD) risk and the need for aortic valve replacement (AVR) in patients with asymptomatic aortic stenosis (AS). The study enrolled from 173 centres in seven European countries 1873 elderly non-diabetics with mild to moderate AS (mean aortic-valve area 1.28+/-0.47 cm(2)), who had no indication for lipid-lowering therapy. Patients were randomised to treatment with either simvastatin/ezetimibe 40/10mg daily or matching placebo after a four-week diet/placebo run-in period. Compared with placebo, LDL cholesterol was reduced by 61% (2.0 mmol/l). There was no difference in the primary endpoint (a combination of AVR, CV death, non-fatal MI, congestive heart failure from AS progression, coronary revascularisation, hospitalised unstable angina and non-haemorrhagic stroke). Compared with placebo, CVD events were reduced by 4.4% from 20.1% to 15.7% in the simvastatin/ezetimibe group (p=0.02). Cancer incidence and cancer deaths were more frequent in the simvastatin/ezetimibe group (9.9% vs. 7.0%, p=0.03 and 4.1% vs. 2.5%, p=0.05, respectively). These differences were not related to any form of cancer and did not increase with increased duration of therapy.
Hamilton-Craig
Ian
I
Department of Cardiology, Griffith University School of Medicine, Gold Coast Hospital, Southport, Queensland 4215, Australia. ihamilton-craig@griffith.edu.au
Kostner
Karam
K
Colquhoun
David
D
Woodhouse
Stan
S
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001024:Aortic Valve Stenosis / Q000097:blood / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D002784:Cholesterol / Q000097:blood; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects
D000924:Anticholesteremic Agents; D001384:Azetidines; D008077:Lipoproteins, LDL; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe