Treating Statistical Markers of Disease Is Not the Same as Treating Disease Itself


What stands to reason is not always borne out by facts, for reality is often refractory to human wishes. There was a good illustration of this unfortunate principle in a recent edition of the New England Journal of Medicine.

It has long been known that low concentrations of high-density lipoproteins (HDL) and high concentrations of low-density lipoproteins (LDL) are associated, in a more or less linear fashion, with cardiovascular disease such as strokes and heart attacks. It would seem to stand to reason, therefore, that raising the HDL and lowering the LDL would lead to fewer cardiovascular "events," as strokes and heart attacks are called.

One way to achieve this wished-for biochemical change is to treat patients at risk of such events with niacin, a B vitamin, in addition to the statins that they are already taking. The largest placebo-controlled trial of niacin ever undertaken, with 25,673 patients who had already had a stroke or heart attack, has shown that the addition of niacin, though it does indeed increase HDL and decrease LDL, has no effect on the rate of heart attack or stroke. Worse still, it gave rise to serious side effects, such as worsening of diabetes and unpleasant gastrointestinal, musculoskeletal and dermatological effects. One of the most unexpected findings of the trial was the excess of infections in people treated by niacin. If anything, the overall death rate in the niacin-treated group was higher than that in the placebo control group, though the difference was not statistically significant (which is not quite the same thing as saying that it was not real). The patients were followed up, on average, for nearly four years and at no time was treatment with niacin superior to that with placebo.