Ezetimibe: effects on major atherosclerotic events and mortality
Effect of ezetimibe on major atherosclerotic disease events and all-cause mortality
Hayek S, Canepa Escaro F, Sattar A, et al.
Am J Cardiol. 2013 Feb 15;111(4):532-9. doi: 10.1016/j.amjcard.2012.11.002.
Ezetimibe reduces LDL-cholesterol levels without a proportionate improvement in carotid intima-media thickness (CIMT), a measure of atherosclerotic disease (AD) burden [1-3], although 1 trial showed a reduction of major AD events . It is therefore essential to investigate the independent effect of ezetimibe. As there are no data of the effect of ezetimibe on either cardiovascular outcomes or all-cause mortality in the absence of concomitant statin use, this study examined and compared the estimated effect of ezetimibe use and statin use on these events, using data from a large health maintenance organization. A total of 367 new ezetimibe users, aged ≥18 years with no previous statin use, were identified from November 1, 2002, to December 31, 2009. One to 4 statin user matches were identified for each ezetimibe user, resulting in a total of 1,238 statin user matches. The primary outcome was a composite of major AD and all-cause mortality.
- Ezetimibe use and statin use were associated with reductions in the likelihood of the composite outcome (odds ratio 0.33, 95% CI0.13 to 0.86, and odds ratio 0.61, 95% CI 0.36 to 1.04, respectively). These associations were most significant for cerebrovascular disease events and all-cause death.
- Subgroup analyses showed consistent protective relations for ezetimibe use and statin use, with no statistical significant differences.
- Among women, a significant protective relation was found for ezetimibe use and statin use
- For statin users with history of AD, ezetimibe users without history of AD, and ezetimibe users with history of diabetes a protective association was found.
Ezetimibe appeared to have a protective effect on major AD events and all-cause death that was not significantly different from that observed for statin use. Additional studies of ezetimibe are needed to support these findings, especially those focusing on hard clinical end points rather than uncertain predictive measures of major AD events, such as CIMT.
1. Fleg JL, Mete M, Howard BV, et al. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J Am Coll Cardiol 2008;52:2198e2205.
2. Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008;358:1431e1443.
3. Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009;361:2113e2122.
4. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011;377:2181e2192.