Sunday, April 20, 2008

Vytorin and Cholesterol Conundrums

In recent months The New York Times,, and Wall Street Journal,, published many articles on the controversial Vytorin -ENHANCE clinical trials and the possibility that Vytorin and Zetia were not effective in reducing carotid artery (and coronary artery) plaque, even though they were effective in reducing serum cholesterol. If lowering cholesterol does not reduce coronary artery plaque, then there may be a fallacy in the entire theory that reduction of cholesterol leads to reduction of heart attacks. Or more likely, the ENHANCE study may have not been designed properly since the group of patients that Vytorin was tested on had a genetic, familial disorder that caused elevated cholesterol, and the patients were pre-treated for elevated cholesterol prior to ENHANCE. The genetic disorder may also account for variation in plaque distribution and growth in the surrogate carotid arteries that were studied in the ENHANCE trial. In view of that, correlating the results of the ENHANCE study to the average patient who has elevated cholesterol secondary to age, being overweight, having a poor diet and leading a sedentary life style, may not be valid. Our healthcare marketing research in the form an online physician survey of cardiologists
reveals that 68% of cardiologists believe that the group of patients that Vytorin was tested on was not reflective of the average patient who has non-familial elevated cholesterol (see questions #8). However, cardiologists have ambivalent feelings towards Vytorin since there was a 10% reduction in the number of cardiologists who would use Vytorin for themselves or family members after the ENHANCE study was released (see questions #12-13). In summary, it seems like the debate is dying down on whether the ENHANCE study was an accurate gauge of whether Vytorin works as it should or is advertised. It seems like all the parties involved (Schering-Plough/Merck, cardiologists who ran the study, American College of Cardiology expert panel, FDA, Wall Street analysts) were less than competent at times, had occasional conflicts of interest, and were sometimes influenced by their egos rather than facts. The real issue will probably boil down to whether Merck and Schering-Plough delayed release of data to hide something or whether the data was so poor that it could not be objectively evaluated to draw significant conclusions. I suspect the latter. Time will tell as the IMPROVE IT study,, due in 2012 will reveal whether Vytorin and Zetia reduce the incidence of heart attacks and strokes in the study population. Even then, the study population for these drugs will be questioned.
Robert Cykiert, M.D.

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