Variability in Meta-analytic Results Concerning the Value of Cholesterol Reduction in Coronary Heart Disease: A Meta-Meta-Analysis

Despite official support for the efficacy of cholesterol reduction, considerable controversy exists, and meta-analyses of this topic have produced conflicting results. The authors assessed the variability of meta-analyses, evaluating the cardiovascular value of cholesterol reduction while attempting to explain the variability. Metaanalyses were identified by electronic search and citation tracking. Included were those conducted prior to 1995 that dealt with cholesterol reduction and total mortality, cardiovascular mortality, or nonfatal cardiovascular disease. In addition to extracting odds ratios for total mortality, cardiovascular mortality, and nonfatal cardiovascular disease, the authors encoded methodological variables, publication variables, and data concerning investigators' backgrounds. Twenty-three meta-analyses were reviewed, and 15 concluded that cholesterol reduction was beneficial. Summary odds ratios for total mortality were heterogeneous, generally failing to support the value of cholesterol reduction. Odds ratios depended on inclusion criteria and investigator variables. Odds ratios for cardiovascular mortality and for nonfatal cardiovascular disease were more homogeneous and supported the value of cholesterol reduction. Methodologically better meta-analyses tended to report more beneficial odds ratios. Although "supportiveness" of the value of cholesterol reduction was associated with inclusion/exclusion criteria and publication variables, the primary outcome variable related to supportiveness was the statistical significance of the odds ratios for cardiovascular mortality.