Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Jun;84(6):1128-1135.
doi: 10.1111/bcp.13539. Epub 2018 Apr 16.

The pharmacodynamic and clinical trial evidence for statin dose

Simon B Dimmitt  1 , Hans G Stampfer  2 , John B Warren  3
Affiliations
Review

The pharmacodynamic and clinical trial evidence for statin dose

Simon B Dimmitt et al. Br J Clin Pharmacol. 2018 Jun.

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.

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

PubMed Disclaimer

Comment in

References

    1. Stone NJ, Robinson J, Lichtenstein AH, Merz NB, Blum CB, Eckel RH, et al 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 2014; 124: S1–S45. - PubMed
    1. Warren JB, Dimmitt SB, Stampfer HG. Cholesterol trials and mortality. Br J Clin Pharmacol 2016; 82: 168–177. - PMC - PubMed
    1. Warren JB. Composite endpoints and the distortion of risk benefit analysis. Br J Clin Pharmacol 2017; 83: 221–223. - PMC - PubMed
    1. Pedersen TR, Kjekshus J, Berg K, Haghfelt T, Faergeman O, Thorgeirsson G, et al Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–1389. - PubMed
    1. Ballantyne CM. Low‐density lipoproteins and risk for coronary artery disease. Am J Cardiol 1998; 82 (9A): 3Q–12Q. - PubMed

MeSH terms