On a statin mg for mg basis, Lipitor and Crestor are more than capable of matching Vytorin. In the MSP studies, they typically made the studies huge under-dosed the comparative statin for a guaranteed narrow win. Besides, the problems they now have are all about not being forthcoming with the results. It really looks like they completely blew it all the way around!

Enhance was only 720 patients in total, which means ~ 360 took Vytorin and ~360 took Simva 80 mg. Statin outcomes trials have generally been in the multiple thousands of patients (e.g. 4S was over 4400 patients and Heart Protection Study was ~ 20,000 patients). Also, the entry level of plaque was too low to expect meaningful differences in a short period of time, plus IMT is not as good as IVUS. In Enhance Vytorin lowered LDL significantly more than simva alone, with no difference in safety profile. Unfortunately, it did not show any incremental benefit re plaque, but again I think that was a size and design issue. I agree, unfortunately we won’t know the results of a true outcomes study with Vytorin until 2012.

Agree Prava is probably the safest but not very effective; and Lipitor and Crestor are a bit more effective, with Zocor very close in LDL lowering efficacy.

I also believe strongly in the lipid hypothesis that “lower is better” and therefore believe that ultimately Vytorin will demonstrate incremental benefit over statins alone and believe that taking people off Vytorin when there is no safety concern raised by Enhance is premature. I have seen people say that someone was taken off Vytorin and put on a statin, clearly indicating that they don’t know this market at all, since Vytorin contains a statin (simva). The Enhance trial was a small, poorly designed and executed study. It doesn’t, however, change my belief in Vytorin.