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Clinical Pharmacology
Statins: established indications and controversial subgroups
  1. J Wouter Jukema1,2,
  2. Sandrin C Bergheanu1,2,3
  1. 1
    Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2
    Einthoven Laboratory for Experimental Vascular Medicine, The Netherlands
  3. 3
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  1. Professor J Wouter Jukema, Department of Cardiology C5-P, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands; j.w.jukema{at}

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Statins are, to date, the most powerful cholesterol lowering drugs. In brief, they inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, which is a key enzyme in the initial chain of the steroid synthesis of cholesterol. As a response to the decreased synthesis of cholesterol in the liver, the low density lipoprotein (LDL) receptors are stimulated and the result is an increased clearance of LDL cholesterol (LDL-C) accompanied by its decreasing blood concentrations. Akira Endo and Masao Kuroda from Japan are acknowledged pioneers of the research into inhibitors of HMG-CoA reductase and their work dates back as early as 1971. Despite more than 35 years of research, statins still remain a Pandora’s box for physicians, both in regard to their exact mode of action as well as clinical efficacy. Bearing in mind the sky-rocketing social and economic burden of cardiovascular disease worldwide, one can easily understand why statins are now more appealing than ever, but also feared because of the high total prescription costs accompanying the broadening indication area.

This paper presents the unanimously accepted evidence with regard to statins, and then discusses more controversial topics such as categories of patients in whom statin use still remains unclear.


Statins are first choice medication for reducing LDL-C values, and clinical trials have demonstrated beyond doubt that lowering LDL-C with statins considerably diminishes the risk for cardiovascular disease in a wide range of patients. The first large clinical study to show truly significant beneficial effects of statins was the Scandinavian Simvastatin Survival Study (4S) published in 1994.1 A total of 4444 high risk patients with documented coronary heart disease (CHD) and high baseline cholesterol were randomised to double blind treatment with simvastatin or placebo and followed for a median of 5.4 years. Simvastatin produced mean changes of total cholesterol (TC), LDL-C and high density …

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  • Competing interests: In compliance with EBAC/EACCME guidelines, all authors participating in Education in Heart have disclosed potential conflicts of interest that might cause a bias in the article. J Wouter Jukema has received research grants from Astra-Zeneca, and is an established clinical investigator of the Netherlands Heart Foundation (2001D032). Sandrin C Bergheanu has no information to disclose.