Clopidogrel

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Clopidogrel.

In medicine, clopidogrel is a thienopyridine class platelet aggregation inhibitor. It is used in the secondary prevention of stroke and coronary heart disease.

Metabolism

It is metabolized by cytochrome P-450 2C19 allele and so may have drug interactions[1][2] and inherited variations in metabolism.[3][4][5]

30% of patients may have a reduced-function allele.[3] and patients with a loss of function CYP2C19 allele have higher rates of cardiac events.[3][5]

Effectiveness

"Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality." according to the MATCH randomized controlled trial. [6]

Adverse effects

Inadequate effect in patients with coronary heart disease can be due to CYP2C19 loss-of-function alleles which are associated with more cardiovascular events.[3][5] Proton pump inhibitors (especially inhibitors other than pantoprazole[7]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[2] or may not[8][9] increase adverse cardiac events.

External links

The most up-to-date information about Clopidogrel and other drugs can be found at the following sites.


References

  1. PPI Interactions with Clopidogrel. The Medical Letter.
  2. Jump up to: 2.0 2.1 Ho PM, Maddox TM, Wang L, et al. (March 2009). "Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome". JAMA 301 (9): 937–44. DOI:10.1001/jama.2009.261. PMID 19258584. Research Blogging.
  3. Jump up to: 3.0 3.1 3.2 3.3 Mega JL, Close SL, Wiviott SD, et al (December 2008). "Cytochrome P-450 Polymorphisms and Response to Clopidogrel". N. Engl. J. Med.. DOI:10.1056/NEJMoa0809171. PMID 19106084. Research Blogging.
  4. Collet JP, Hulot JS, Pena A, et al (December 2008). "Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study". Lancet. DOI:10.1016/S0140-6736(08)61845-0. PMID 19108880. Research Blogging.
  5. Jump up to: 5.0 5.1 5.2 Simon T, Verstuyft C, Mary-Krause M, et al (December 2008). "Genetic Determinants of Response to Clopidogrel and Cardiovascular Events". N. Engl. J. Med.. DOI:10.1056/NEJMoa0808227. PMID 19106083. Research Blogging.
  6. Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M et al. (2004). "Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial.". Lancet 364 (9431): 331-7. DOI:10.1016/S0140-6736(04)16721-4. PMID 15276392. Research Blogging. Review in: ACP J Club. 2004 Nov-Dec;141(3):68
  7. Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635
  8. O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al. (2009). "Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials.". Lancet 374 (9694): 989-97. DOI:10.1016/S0140-6736(09)61525-7. PMID 19726078. Research Blogging.
  9. Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K et al. (2010). "Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study.". Ann Intern Med 152 (6): 337-45. DOI:10.1059/0003-4819-152-6-201003160-00003. PMID 20231564. Research Blogging.