Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis

J Am Coll Cardiol. 2005 Nov 15;46(10):1855-62. doi: 10.1016/j.jacc.2005.05.085. Epub 2005 Oct 24.


Objectives: This study sought to determine whether statins reduce coronary heart disease (CHD) risk more than other interventions that also primarily lower low-density lipoprotein cholesterol (LDL-C).

Background: Statins have anti-inflammatory, immunomodulatory, antithrombotic, vascular, and other non-LDL-C-lowering effects. It is unclear whether these pleiotropic effects contribute to cardiovascular risk reduction beyond that expected from LDL-C reduction alone.

Methods: Trials published in English language journals were retrieved by searching Medline (1966 to October 2004), bibliographies, and the author's reference files. Randomized, placebo-controlled trials of interventions to primarily lower LDL-C of three or more years' duration in which clinical disease or death were primary outcomes were used. Information on sample size, treatment type and duration, participant characteristics at baseline, reduction in lipids, and outcome was independently abstracted by two authors (J.R. and N.M.) using a standardized protocol. Data from 5 diet, 3 bile acid sequestrant, 1 surgery, and 10 statin trials, with 81,859 participants, were included in the CHD meta-regression analysis.

Results: The regression lines for non-statin and statin trials were similar and consistent with a one-to-one relationship between LDL-C lowering and CHD and stroke reduction over five years of treatment.

Conclusions: The pleiotropic effects of statins do not seem to contribute an additional cardiovascular risk reduction benefit beyond that expected from the degree of LDL-C lowering observed in other trials that primarily lowered LDL-C.

Publication types

  • Meta-Analysis

MeSH terms

  • Cholesterol, LDL / blood
  • Clinical Trials as Topic
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Regression Analysis


  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors