"The study involved 720 patients with heterozygous familial hypercholesterolemia and showed no significant difference in the primary endpoint between patients treated with ezetimibe and simvastatin versus patients treated with simvastatin alone over a two-year period. The study was designed to prove that Vytorin could slow the growth of plaque in carotid arteries supplying the brain more than simvastatin alone. Media reports indicate that the results of the trial show no benefit from the combination of ezetimibe (Zetia) and simvastatin (sold together as Vytorin) over simvastatin alone.
The American College of Cardiology recommends that major clinical decisions not be made on the basis of the ENHANCE study alone."
According to the American College of Cardiology (ACC), this study deserves serious thought and follow-up. The overall incidence rates of cardiac events were nearly identical between both treatment groups, and both medicines were generally well tolerated. There should no be reason for patients to panic. The difference in IMT changes between the simvastatin group and the Vytorin group was 0.006 mm vs. 0.011 mm.
Health care professionals should speak to their concerned patients using this drug. The ACC is also releasing a public statement explaining that this is not an urgent situation and patients should never stop taking any prescribed medications without first discussing the issue with their health care professional. Further research will be needed in this area to provide conclusive evidence about which lipid lowering strategy is preferred (statin alone vs. statin plus ezetimibe).
Furthermore, the ACC notes that this trial is an imaging study and not a clinical-outcome study. Conclusions should not be made until the three large clinical-outcome trials are presented within the next two to three years. The ACC recommends that Zetia remain a reasonable option for patients who are currently on a high dose statin but have not reached their goal. The ACC also notes that Zetia is a reasonable option for patients who cannot tolerate statins or can only tolerate a low dose statin.
On the subject of endpoints and markers. The Critical Path is not about using surrogate endpoints. Anyone who has listened to Dr. Woodcock more than once knows it is about finding and qualifying biomarkers -- molecular and imaging -- that predict disease progression and outcome as well as response to treatment -- as well as developing novel statistical ways that can be deployed across divisions and technologies to advance understanding of technology impact on disease.
The issue in the ENHANCE study was whether or not imaging studies were accurate measures of disease progression in this small population. Nothing more or less. In this regard, development of better standards and predictive imaging studies will help advance their use in clinical trials. Also let's remember that Dr. Nissen, who has trashed the results might be a bit biased since his own imaging studies demonstrated a regression of atherosclerosis by reducing LDL levels with another drug, something the NY Times failed to point out. And let's remember Dr. Nissen also tossed out imaging studies in another clinical trial looking at plaque regression because they were unreadable, so he just looked at the results of the readable ones.
At the risk of repeating myself again and again -- here's a link to the story we repeated when the MSM was looking for a Vytorin coverup months ago.
The problem with the Atherogenic drug that Nissen worked on was the same one -- more or less -- the scientists running the ENHANCE study struggled with. Namely, the statistical correlation was hard to measure because of the unwieldy nature of the biomarker. In each study, patients taking the drug did better than patients taking a placebo on most endpoints, just not on the endpoint most difficult to measure. But unlike the Nissen re-analysis, ENHANCE did not do an interim analysis with fewer patients to produce a benefit. The debate was whether or not to chuck the analysis altogether because of questions about the reliability of the biomarker.
Which is what the Critical Path is all about.
No need to panic or disregard your doctor in favor of the medical advice dispensed by the fearmongers and Pharm-haters on the NY Times editorial page.