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

Abstract

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.

Has the association between saturated fatty acids, serum cholesterol and coronary heart disease been over emphasized?

“…Many systematic reviews and meta-analyses that analysed the results of these trials together with those relating to diet have been published. These analyses that used different inclusion and exclusion criteria as well as end points reached mixed conclusions on the effect of lipid lowering on CHD mortality (Katerndahl and Lawler, 1999).…”

How objective are systematic reviews? Differences between reviews on complementary medicine

“…Jadad et al 52 provide some guidance on how to cope with discordant quantitative meta-analyses, but the reader must be in possession of all the discordant reviews, as well as the time and specialized knowledge to decide which methods were most appropriate. We have looked only at reviews in complementary medicine but we suspect that the problem applies also to conventional medicine [3][4][5][6][7] .…”

Systematic Review and Meta-analysis

“…The most common flaws among these renal reviews were failure to assess the methodologic quality of included primary studies and failure to avoid bias in study inclusion (Mrkobrada M, Thiessen-Philbrook H, Haynes RB, Iansavichus AV, Rehman F, and Garg AX, submitted). In some cases, industry-supported reviews of drugs have had fewer reservations about methodologic limitations of the included trials than rigorously conducted Cochrane reviews on the same topic (10); however, the hypothesis that less rigorous reviews more often report positive conclusions than good-quality reviews of the same topic has not been borne out in empirical assessment (48,53,55). Nonetheless, like all good consumers, users of systematic reviews should carefully consider the quality of the product and adhere to the dictum "caveat emptor": Let the buyer beware.…”