Results of the eagerly-awaited and highly controversial IMPROVE-IT trial are finally going to be revealed. The American Heart Association hasannounced that the trial will be presented by Chris Cannon on November 17 at 11:51 AM (central time) in Chicago at the group’s annual scientific sessions . IMPROVE-IT compared the effect on cardiovascular outcomes of the statin simvastatin with Vytorin (the combination of simvastatin and ezetimibe, manufactured by Merck) in more than 18,000 patients with acute coronary syndromes.
Both Vytorin and IMPROVE-IT have been the subject of considerable controversy. The drug was approved, and widely used, despite the absence of clinical trials demonstrating benefit. The IMPROVE-IT trial, which was designed to assess the effect of clinical outcomes, has taken many years to reach completion. Some observers have pointed out that the trial’s length has closely paralleled the patent life of the drug.
But IMPROVE-IT may have important implications beyond our understanding of ezetimibe. It is widely believed that the trial will provide a significant contribution to the debate about the reliability of surrogate endpoints in general and the independent importance of lowering LDL cholesterol in particular. I have argued in the past that the fate of the new PCSK9 inhibitors may depend on the results of IMPROVE-IT:
If IMPROVE-IT meets its primary endpoint then the FDA will be far more inclined to accept LDL-lowering as a surrogate endpoint and the PCSK9 inhibitors may well gain early approval (if all else goes well, of course, though this is by no means assured). On the other hand, if IMPROVE-IT does not meet its primary endpoint then the FDA will be much less likely to approve a new class of cholesterol-lowering drugs without evidence of significant clinical benefits.