We conducted a systematic review of trials of statin drugs to study placebo adverse effect reporting. The statin drug trials were chosen because, although many of the participants had coronary heart disease, hypercholesterolemia is asymptomatic and the drugs are often given for prophylaxis rather than treatment. Therefore, in the placebo arms of these trials, noncardiovascular symptoms are likely to be neither drug induced nor illness associated. Our goal was to identify all statin drug trials published between 1994 and 2003 that comprised more than 100 subjects in the placebo arm, using PubMed and additional literature research. Our search identified nearly identical publications as 2 recently published meta-analyses of statin drug trials.5- 6 The following trials were considered: LIPS (Lescol Intervention Prevention Study),7- 8 PROSPER (Prospective Study of Pravastatin in the Elderly at Risk),9 PPP (Prospective Pravastatin Pooling project; pooled data from CARE [Cholesterol and Recurrent Events study], LIPID [Long-term Intervention With Pravastatin in Ischemic Disease trial], and WOSCOP [West of Scotland Coronary Prevention study]),10- 11 MRC/BHF (Medical Research Council/British Heart Foundation Heart Protection Study),12 MIRACL (myocardial ischemia reduction with aggressive cholesterol lowering),13 SCAT (Simvastatin and Enalapril Coronary Atherosclerosis Trial),14- 15 German-Czech fluvastatin trial,16 LCAS (Lipoprotein and Coronary Atherosclerosis Study),17- 18 LIPID,19 CARE,20 WOSCOP,21 REGRESS (Regression Growth Evaluation Statin Study),22 PLAC (Pravastatin Limitation in Atherosclerosis in the Coronary Arteries study),23 PLAC-2 (Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries study),24 KAPS (Kuopio Atherosclerosis Prevention Study),25 ACAPS (Asymptomatic Carotid Artery Progression Study),26 4S (Scandinavian Simvastatin Survival Study Group),27 and EXCEL (Expanded Clinical Evaluation of Lovastatin trial28) (the EXCEL trial was included, although published in 1991, because it was a restudy of a larger lovastatin trial). Reported adverse effects for the placebo groups as well as further sample information of these studies were tabulated depending on whether only possibly drug-related symptoms were mentioned or whether symptoms in general were reported. Confidence intervals were computed to compare the base rates that differed most. We sought to distinguish whether variations were limited to nonspecific symptoms that were unlikely to be related to the pharmacologic action of the active drug or whether these variations can be also found for more clinically important adverse effects. One such adverse effect of statin drugs is muscle pain or myopathy, which can indicate rhabdomyolysis.29 Therefore, variations of base rates of muscle weakness also were analyzed.