ENHANCE results now available (follow-up)
Results from ENHANCE are now available. I don’t think anyone is terribly surprised, given the delay in reporting the results, that addition of ezitimibe to simvasatin (i.e. Vytorin) did not have a sigificant impact on carotid intimal media thickness compared with simvastatin (Zocor) alone in subjects with heterozygous familial hypercholesterolemia (a disorder of LDL receptors that affects about 1 in 500 people globally).
See my prior post on the implications of ENHANCE for most current Zetia users. As I indicated previously, these results will likely have very little impact on prescribing of Vytorin or Zetia, despite pronouncements to the contrary yesterday, primarily from Steve Nissen of the Cleveland Clinic. Dr. Nissen apparently gave lots of interviews yesterday, saying things like:
This wraps it up…That’s all there is. There just isn’t any evidence that adding ezetimibe to simvastatin produces any advantage.
to the Washington Post.
Of course that isn’t all there is. One trial with an iffy surrogate endpoint in a highly selected population does not a definitive treatment recommendation make (said Master Yoda).
Since my last post, I was happy to learn about another trial of Vytorin underway, one with a hard outcome. The IMPROVE-IT trial, sponsored by Merck and Schering-Plough, is a randomized, active-control, double-blind study of subjects with stabilized high-risk acute coronary syndrome. The primary objective in IMPROVE-IT is to evaluate the clinical benefit of Vytorin 10/40mg compared with Simvastatin 40 mg alone, where clinical benefit is the reduction in the risk of the occurrence of a composite endpoint of CV death, major coronary events, and stroke. Nice. Now enroll this sucker.
I’m not stopping my Zetia because of ENHANCE, and I’m confident that most other users of Zetia and Vytorin will not either. Once the ENHANCE dust settles, it’ll be clear that ezitimibe remains our first best hope for atherosclerosis therapy beyond statins, at least until a definitive study demonstrates otherwise.
Disclosures: I have no financial ties to Merck or Schering-Plough.
Pharma’s Cutting Edge » ENHANCE results published; experts weigh in said,
March 31, 2008 at 9:03 am
[…] This is a f/u to the piece I wrote in January describing the preliminary (but widely publicized) results from the ENHANCE study of simvastatin and ezetimibe (Zetia) (combination tablet sold as Vytorin by Schering-Plough and Merck) in patients with familial hypercholesterolemia. The study looked at the effects of the combination versus simvastatin alone on carotid intima-media thickness. My previous opinions of the study’s meaning aren’t changed with publication of the final results in the NEJM to coincide with the ACC meeting. In case you were asleep for the past couple of months, ENHANCE was negative for signs of IMT improvement with the combo. […]