Volume 194 - Issue 1
Managing residual risk in patients receiving statin therapy
Author: Marilyn K Mann
Med J Aust 2011; 194 (1): 54. || doi: 10.5694/j.1326-5377.2011.tb04158.x
Published online: 3 January 2011
Published online: 3 January 2011
To the Editor: I am writing about important errors contained in a letter of reply by Hamilton-Craig.1 In his response to a letter by Montgomery,2 he states:
The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial (in which patients with aortic stenosis were treated for 52.2 months with statin plus ezetimibe or statin plus placebo) showed a 4.7% reduction in ischaemic [cardiovascular disease] events in the ezetimibe group (P = 0.02; number needed to treat, 23), driven by a reduced need for coronary artery bypass grafting.
However, in the SEAS trial, patients were treated with statin plus ezetimibe or with placebo, not with statin plus placebo. Therefore, the reduction in ischaemic events in the statin/ezetimibe group cannot be attributed to ezetimibe, as it could have been caused by the effect of simvastatin alone (or by the combined effect of the two drugs). I note also that the absolute reduction in ischaemic events over the course of the trial was 4.4% (15.7% v 20.1%), not 4.7%.3
With respect to the ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) trial, Hamilton-Craig states:
As no placebo group was included, neither lack of benefit nor harm from ezetimibe therapy can be inferred.1
In the ENHANCE trial, patients with familial hypercholesterolaemia were treated with simvastatin plus ezetimibe or simvastatin plus placebo. There was no significant difference in progression of mean carotid intima media thickness (CIMT) between the two groups (0.0058 mm in the simvastatin/placebo group v 0.0111 mm in the simvastatin/ezetimibe group [P = 0.29]).4 Therefore, contrary to Hamilton-Craig’s statement, there was a placebo group, and a lack of benefit from ezetimibe was shown in the trial.
Thus, the SEAS trial was unable to confirm a benefit of ezetimibe, as the active treatment arm included both a statin and ezetimibe, while the ENHANCE trial showed no additional benefit of ezetimibe on the surrogate endpoint of CIMT progression in patients taking a statin.
Author’s note: The United States Securities and Exchange Commission disclaims responsibility for any private publication or statement of any Commission employee or Commissioner. This letter expresses my views and does not necessarily reflect those of the Commission, the Commissioners, or other members of the Commission staff.
References
- Hamilton-Craig IR. Managing residual risk in patients receiving statin therapy [letter]. Med J Aust 2010; 193: 375-376. 0_i1095837
- Montgomery BD. Managing residual risk in patients receiving statin therapy [letter]. Med J Aust 2010; 193: 375. 0_i1095839
- Rossebø AB, Pedersen TR, Boman K, et al; SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008; 359: 1343-1356. 0_CBBIFHDH
- Kastelein JJ, Akdim F, Stroes ES, et al; ENHANCE Investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358: 1431-1443. 0_CBBGIIFF