There have long been suspicions, but it was still very disturbing to learn this week that a heavily promoted cholesterol-lowering drug had flunked a clinical trial of its effectiveness in reducing fatty deposits in arteries. The two companies that reap billions from the drug had been cynically sitting on the results for more than a year.
The trial was conducted in 720 European patients with genes that cause abnormally high cholesterol levels. For two years, the patients received either Zocor, an older cholesterol drug, or Vytorin, a combination of Zocor and Zetia. The assumption was that Vytorin would reduce the growth of fatty plaques — a risk factor for heart attacks and strokes — more than Zocor alone. As it turned out, the plaques grew almost twice as fast in patients taking the Vytorin.
There are reasons to be cautious about interpreting these results. The number of patients was relatively small. And many of them may have used different drug treatments for years before entering the trial, possibly diminishing the effectiveness of adding Zetia.
The companies’ grudging release of the data has raised disturbing questions. A House committee will explore whether they withheld the results lest they interfere with sales and only released them under pressure from Congress and news media reports. Whatever the committee discovers, the experience is one more argument for why scientists involved in studies sponsored by drug companies must insist on the right to review and release data. A new law that strengthens the penalties for companies that do not release data promptly should help.
The findings also raise doubts about the current belief that lowering cholesterol is the key to cardiovascular health. The study showed that Vytorin reduced bad cholesterol significantly more than Zocor alone. The problem was that it failed to reduce the formation of plaque.
The companies are conducting three large clinical trials to test whether Vytorin can nevertheless reduce heart attacks and strokes. Results won’t be available until at least 2011. Meanwhile, with no evidence of effectiveness in plaque-reduction, it seems clear that Zetia and Vytorin should be used sparingly, in cases where all other cholesterol drugs have failed.
