To the Editor: In their randomized controlled trial, Dr Nissen and colleagues1 reported that a daily dose of 80 mg of atorvastatin was associated with a greater reduction in the volume of coronary atheromas than was a daily dose of 40 mg of pravastatin. The authors concluded that their results supported aggressive cholesterol-lowering therapy.
We have several concerns about their study. First, the authors measured change of atheroma volume rather than change of lumen area. The latter is more important, as it determines the amount of blood that can be delivered to the myocardium. Change of atheroma volume cannot be translated to clinical events because adaptive mechanisms try to maintain a normal lumen area during early atherogenesis.2 Second, the authors used 2 different statins. Thus, it is possible that the difference in outcome may have been due to variance in pleiotropic effects of the drugs rather than to differences in dosage or in degree of cholesterol lowering.
Furthermore, the finding of dose-response relationship between degree of cholesterol lowering and change of atheroma volume is inconsistent with the results of similar trials.3 - 4 In any event, the presence of dose-response relationship does not prove that the effect is due to cholesterol lowering. The statins inhibit the production of mevalonate, an early member of a biochemical pathway that leads to the synthesis of many important substances, one of which is cholesterol. Thus, any statin should exhibit a dose-response relationship, whether or not such inhibition is beneficial.
Furthermore, as in the current study, previous studies have reported only a weak relationship between statin dose and degree of cholesterol lowering. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)5 for instance, 10 mg of atorvastatin lowered low-density lipoprotein (LDL) cholesterol by 35%, whereas the 8-times higher dose used by Nissen et al lowered it only by a further 12%. Nonetheless, it seems likely that higher dosages would be associated with increasing numbers of adverse effects. In the study by Nissen et al, at least 1 transaminase measurement was more than 3 times higher than the upper limit of normal in 2.3% of the patients.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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