Observed and predicted reduction of ischemic cardiovascular events in the Simvastatin and Ezetimibe in Aortic Stenosis trial.
In the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, combined ezetimibe (10 mg) and simvastatin (40 mg) decreased low-density lipoprotein cholesterol levels by 50% and ischemic cardiovascular event (ICE) risk by 22% compared to placebo. A larger decrease in ICE risk might have been expected for the degree of lipid-lowering observed. This analysis investigated relations between changes in lipoprotein components (LCs), and ICE risk decrease in the SEAS trial in all patients, by severity of aortic stenosis (AS), and compared to results of other clinical trials. A total of 1,570 patients with baseline aortic jet velocity (JV) data, baseline and 1-year low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B, and no ICEs during the first year were included in the analysis. Relations between on-treatment measurements of 1-year LCs and time-to-ICE occurrence were assessed in all patients and in JV tertiles (<2.8, 2.8 to 3.3, and >3.3 m/s). Observed and predicted ICE risk decreases were compared by Cox model. Decreases in LCs after 1 year of ezetimibe plus simvastatin were associated with decreased ICE risk in all patients and in the 2 lower JV tertiles (p <0.05 to <0.001) but not in tertile 3. In JV tertiles 1 and 2, ICE risk decreased by 47% and 36%, respectively, was reasonably well predicted by all LCs, and was consistent with findings from meta-regression analyses in other populations. In conclusion, the degree of lipid lowering by ezetimibe plus simvastatin may predict the extent of ICE risk decrease in patients with mild AS, but ICE risk prediction in patients with more severe AS is confounded by AS-associated cardiovascular events and a shorter interval of exposure to lipid lowering.
Centre of Preventive Medicine, Oslo University Hospital, Ullevål, Oslo, Norway. Ingar.holme@ulleval.no
Ingar
I
Holme
Kurt
K
Boman
Philippe
P
Brudi
Kenneth
K
Egstrup
Christa
C
Gohlke-Baerwolf
Y Antero
YA
Kesäniemi
William
W
Malbecq
Anne B
AB
Rossebø
Kristian
K
Wachtell
Ronnie
R
Willenheimer
Terje R
TR
Pedersen
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001024:Aortic Valve Stenosis / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects; D050197:Atherosclerosis / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D001384:Azetidines / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D000069438:Ezetimibe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019821:Simvastatin / Q000627:therapeutic use*; D013997:Time Factors
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019821:Simvastatin; D000069438:Ezetimibe