Breaking news! ENHANCE trial results released

After nearly two years of controversy surrounding the results of the ENHANCE clinical trial — a melodrama filled with theories of cover-ups and manipulations of clinical trial data in the possession only of the drug company sponsor, a secret panel behind attempts to change the study endpoints after the trial was over, a Congressional investigation and years of delays in the release of the findings — in a surprise move this morning, Merck/Schering-Plough Pharmaceuticals announced the results:

There were no benefits seen among the people treated with the cholesterol-lowering statin Vytorin, which combines Zetia and Zocor, over a generic Zocor. The study population consisted of people at the highest risks for cholesterol-related heart disease deaths and many believed the ideal group to demonstrate Zetia's benefits. As Heart.org explained this morning, the ENHANCE trial is the first major study to be conducted with Zetia, which is why the results have been so eagerly anticipated. As the Wall Street Journal reports:

No Significant Difference Found Between Statins

Merck & Co. and Schering-Plough Corp. announced today that a combination of Zetia and Zocor doesn't offer significant benefits in fighting heart disease over just the statin Zocor alone. The long-awaited study results are bound to have an impact on sales on Zetia and Vytorin, the drug that combines Zocor, now sold generically as simvastatin, and ezetimibe.

The study — known as Enhance... — was a surrogate endpoint trial conducted in 720 patients with Heterozygous Familial Hypercholesterolemia, a genetic condition that leads to very high cholesterol levels. The Enhance study measured the mean change in the intima-media thickness measured at three sites in the carotid arteries (the right and left common carotid, internal carotid and carotid bulb) between patients treated with ezetimibe/simvastatin 10/80 mg versus patients treated with simvastatin 80 mg alone over a two year period.

There was no statistically significant difference between treatment groups on the primary endpoint. There was also no statistically significant difference between the treatment groups for each of the components of the primary endpoint, including the common carotid artery. Key secondary imaging endpoints showed no statistical difference between treatment groups....

The Journal made an important point that is easy to miss: This only reports on the surrogate endpoints and still doesn’t given us the full story. While it is clear that the statin didn’t produce the desired change in the surrogate endpoint, intima-media thickness, we don’t know the most crucial piece of information: Did it improve clinical outcomes and save lives?

The mortality data is part of the safety monitoring for all clinical trials and is the easiest result of all to report. The company press release provided some answers. There were two cardiovascular deaths among the Vytorin group compared to one in the generic Zocor group; and three nonfatal heart attacks among the Vytorin group compared to two among those on the generic. No other deaths were reported, but the company noted that this study was not powered nor designed to assess clinical event outcomes.

Vytorin and Zetia generate $5 billion in annual sales for Merck and Schering. Sadly, it appears that for years, millions of people have been prescribed Vytorin or Zetia by their doctors, believing they will better prevent heart attacks and strokes and help them live longer, with no evidence at all.