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. 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. 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. 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.