VERY FINE FINE PRINT

Why have we never heard about the outcome of the first statin trial, the largest of them all?

This trial involved a large number of American clinics and research institutions, including the Merck Sharpe & Dohme Research Laboratories at West Point, NY, where the drug was produced. More than 8000 individuals with cholesterol levels between 240 and 300 mg/dL received one of four different dosages of lovastatin or a placebo.With a view to reporting the possible adverse effects of the treatment, preliminary study results were published after one year of the trial (Arch Intern Med, 1991; 151: 43-9). No significant side effects were reported but, in the fine print, the authors were obliged to mention that death due to all causes was 0.5 per cent in the four lovastatin groups combined (32 or 33 individuals out of a group of about 6000 no exact figures were given in the report) compared with 0.2 per cent in the placebo group (three or four individuals out of a group of 1650).

Lumping all the lovastatin groups together, the difference would have been statistically significant if the number of deaths in these groups had been 33, but not if it had been 32. But even if the difference was not statistically significant after one year, it would certainly have become significant if the tendency towards higher mortality in the treatment groups had continued throughout the trial. In any case, the aim of the treatment was to lower mortality and, most certainly, no lowering was achieved.

Today, at least 20 reports from the EXCEL trial have been published in various medical journals. These reports tell us how well lovastatin is tolerated and how effective it is in lowering blood cholesterol levels in various populations, but not one of them has reported the final outcome of the trial, even though more than 10 years have passed since it began. We do not know whether the increased mortality, seen after just one year of treatment, has continued throughout the trial.

Are there more trials we haven’t heard about? And are there any unfavourable effects in the published trials that we haven’t heard about, either?