Literature DB >> 29393975

The pharmacodynamic and clinical trial evidence for statin dose.

Simon B Dimmitt1, Hans G Stampfer2, John B Warren3.   

Abstract

Statin doses around estimated effective dose 50 (ED50) can reduce myocardial infarction by over 25% and mortality by around 10%. Being a competitive enzyme inhibitor, statin efficacy plateaus at doses that are multiples above the ED50, whilst on- and off-target adverse events increase in number and severity with increasing dose. For example, myopathy has been shown to increase by up to 29-fold and liver dysfunction by up to nine-fold as statin dose is increased. Doses of up to 40-fold ED50 have been promoted, but above five-fold ED50, for example 10 mg of atorvastatin, there is no randomized controlled clinical trial evidence that coronary mortality is lowered, or that survival is increased.
© 2018 The British Pharmacological Society.

Entities:  

Keywords:  PCSK9 Inhibitors; coronary disease; dose response; effective dose 50 (ED50); ezetimibe; statin

Mesh:

Substances:

Year:  2018        PMID: 29393975      PMCID: PMC5980555          DOI: 10.1111/bcp.13539

Source DB:  PubMed          Journal:  Br J Clin Pharmacol        ISSN: 0306-5251            Impact factor:   4.335


  55 in total

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7.  Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database.

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8.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.

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Journal:  N Engl J Med       Date:  1995-11-16       Impact factor: 91.245

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7.  Effect of Upadacitinib on the Pharmacokinetics of Rosuvastatin or Atorvastatin in Healthy Subjects.

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