Gaziano and colleagues [1] recently presented yet another study on cholesterol reduction. The authors stated that "there is little doubt that elevated cholesterol levels increase the risk for coronary heart disease." This statement is made on the basis of results from the consensus conference of 1985 [2], in which the statistically significant difference in rate of myocardial infarction in treated patients compared with control patients was evaluated. Little emphasis was placed on death in that study, although death is clearly the best end point.

Are these small numbers clinically important? The authors state that "although most randomized cholesterol reduction trials do not show a statistically significantly lower total mortality rate, it is important to distinguish between the finding of no effect and the inability to detect an effect." Are they forgetting the very small numbers of cardiovascular deaths that were described? What clinical importance would there be if the small number of deaths was statistically significantly different, as was reported in the 4S (Scandinavian Simvastatin Survival) trial [3]? The 4S trial was cogently criticized by Stehbens [4]. In addition, that the placebo group contained 58 more Q-wave infarctions, 32 more patients with a 1- to 5-year history of angina, and 21 more patients with both angina and myocardial infarction (numbers not mutually exclusive) than did the control group suggests that the difference of 189 deaths among patients receiving placebo compared with 111 deaths among patients treated with simvastatin out of 4444 patients may have resulted from differences in the two groups and that the attempt at randomization may have failed. Furthermore, no difference in mortality rate was seen among women: Twenty-seven deaths were seen among 407 patients receiving the study drug, and 25 deaths were seen among 420 patients receiving placebo.

Clinicians look for advances to help patients. Perhaps nothing will again achieve the remarkable effect of penicillin in the 1940s, which made a clinically important difference in the treatment of appropriate infections. It did not require pressure from academic experts to convince physicians to prescribe the drug.

In view of the small number of cardiovascular deaths and given that "most randomized cholesterol reduction trials do not show a statistically significantly lower total mortality rate," does this trial provide a good reason to again urge clinicians to increase their treatment of serum cholesterol levels?