• Clinical science

Statins

Abstract

Statins are the lipid-lowering drugs of choice. Statins reduce hepatic cholesterol synthesis by inhibiting enzyme HMG-CoA reductase. This leads to a consequent upregulation of LDL receptors on hepatocytes, which, in turn, lowers LDL cholesterol levels and triglycerides while raising HDL cholesterol. Headache and gastrointestinal side-effects are common. Statins carry a risk of hepatic and muscular toxicity, the latter being associated with a high risk of acute kidney injury (AKI). In this case, statins should immediately be discontinued.

Overview

Statin Half-life in hours CYP-450 Bioavailability
Atorvastatin 15–30 CYP3A4 ∼ 10%
Simvastatin 2–3 CYP3A4, CYP3A5 ∼ 5%
Pravastatin ∼ 2 ∼ 20%
Lovastatin 3 CYP3A4 ∼ 5%
Fluvastatin 0.5–2.5 CYP2C9 ∼20–30%
Pitavastatin 12 Limited CYP2C9 ∼ 50%
Rosuvastatin 19 Limited CYP2C9 ∼ 20%

Potency (and cost) increases in the following order: fluvastatinlovastatin and pravastatinsimvastatin and atorvastatin!

References:[1][2]

Effects

Competitive inhibition of HMG-CoA reductase reduced intrahepatic cholesterol biosynthesis → upregulation of expression of LDL receptor gene via sterol regulatory element-binding protein (SREBP)

  • ↓↓ LDL cholesterol (by ∼ 21–63%)
  • HDL cholesterol (by ∼ 5–10%)
  • triglyceride level (by ∼ 10–20%)
  • Pleiotropic effect: ↓ C-reactive protein, plaque stabilization; , ↑ anti-inflammatory effect, antioxidant effect and improved endothelial function of coronary arteries

Treatment of hyperlipidemia with statins significantly reduces the risk of mortality!

References:[3][4][2]

Side effects

Treatment must be discontinued if myopathy/rhabdomyolysis occurs!

Interaction with certain drugs (see below) can increase the risk of myopathy!
References:[4][5][6]

We list the most important adverse effects. The selection is not exhaustive.

Indications

→ For details see therapy of atherosclerotic disease and Guidelines for lipid-lowering therapy (ATP III guidelines)

Statins are the first-line therapy for hypercholesterolemia!

References:[7]

Contraindications

  • Hypersensitivity
  • Active liver disease
  • Muscle disorder
  • Pregnancy, breastfeeding

References:[2]

We list the most important contraindications. The selection is not exhaustive.

Interactions

Maintain a high index of suspicion for rhabdomyolysis if muscle pain occurs after administering statins!
References:[4][5][2][6][8]

Guidelines & therapy recommendations

  • Ideally administered in the evenings (especially simvastatin)
  • Combination therapy with bile acid resins has a stronger hypolipidemic effect compared to treatment with statins alone; (both groups of drugs increase LDL receptor expression)

References:[2]

  • 1. Whitfield LR, Stern RH, Sedman AJ, Abel R, Gibson DM. Effect of food on the pharmacodynamics and pharmacokinetics of atorvastatin, an inhibitor of HMG-CoA reductase. Eur J Drug Metab Pharmacokinet. 2000; 25(2): pp. 97–101. pmid: 11112089.
  • 2. Rosenson RS. Statins: Actions, Side Effects, and Administration. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/statins-actions-side-effects-and-administration. Last updated February 1, 2017. Accessed March 21, 2017.
  • 3. McTaggart F, Jones P. Effects of Statins on High-Density Lipoproteins: A Potential Contribution to Cardiovascular Benefit. Cardiovasc Drugs Ther. 2008; 22(4): pp. 321–338. doi: 10.1007/s10557-008-6113-z.
  • 4. Onusko E. Statins and elevated liver tests: what's the fuss?. J Fam Pract. 2008; 57(7): pp. 449–452. pmid: 18625167.
  • 5. Chang CY, Schiano TD. Review article: drug hepatotoxicity. Aliment Pharmacol Ther. 2007; 25(10): pp. 1135–1151. doi: 10.1111/j.1365-2036.2007.03307.x.
  • 6. Rosenson RS, Baker SK. Statin myopathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/statin-myopathy. Last updated March 11, 2016. Accessed March 21, 2017.
  • 7. Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Journal of the American College of Cardiology. 2014; 63(25). doi: 10.1016/j.jacc.2013.11.002.
  • 8. UpToDate. Warfarin: Drug information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/warfarin-drug-information. Last updated March 21, 2017. Accessed March 21, 2017.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
  • Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill Education; 2015.
  • Rosenson RS. Lipid lowering with drugs other than statins and fibrates. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/lipid-lowering-with-drugs-other-than-statins-and-fibrates. Last updated September 14, 2015. Accessed February 20, 2017.
last updated 11/20/2018
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