Clopidogrel: Difference between revisions

From Citizendium
Jump to navigation Jump to search
imported>Robert Badgett
No edit summary
(resolving ref errors)
 
(14 intermediate revisions by 4 users not shown)
Line 1: Line 1:
In [[medicine]], '''clopidogrel''' is a [[platelet aggregation inhibitor]]. It is used in the [[secondary prevention]] of [[stroke]] and [[coronary heart disease]].
{{subpages}}
{{Image|Clopidogrel2.png|right|300px|'''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==
==Metabolism==
It is metabolized by [[cytochrome P-450]] [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&TermToSearch=1557 2C19] [[allele]] and so may have drug interactions<ref>''''''[http://www.medicalletter.org/restricted/articles/w1303b.html PPI Interactions with Clopidogrel]. The Medical Letter.</ref> and inherited variations in metabolism.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref><ref name="pmid19108880">{{cite journal |author=Collet JP, Hulot JS, Pena A, ''et al'' |title=Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study |journal=Lancet |volume= |issue= |pages= |year=2008 |month=December |pmid=19108880 |doi=10.1016/S0140-6736(08)61845-0 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61845-0 |issn=}}</ref><ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al'' |title=Genetic Determinants of Response to Clopidogrel and Cardiovascular Events |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref>
It is metabolized by [[cytochrome P-450]] [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=DetailsSearch&Term=1559 2C19] [[allele]] and so may have drug interactions<ref>[http://www.medicalletter.org/restricted/articles/w1303b.html PPI Interactions with Clopidogrel]. The Medical Letter.</ref><ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref> and inherited variations in metabolism.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref><ref name="pmid19108880">{{cite journal |author=Collet JP, Hulot JS, Pena A, ''et al'' |title=Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study |journal=Lancet |volume= |issue= |pages= |year=2008 |month=December |pmid=19108880 |doi=10.1016/S0140-6736(08)61845-0 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61845-0 |issn=}}</ref><ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al'' |title=Genetic Determinants of Response to Clopidogrel and Cardiovascular Events |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref>


30% of patients may have a reduced-function allele.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref>
30% of patients may have a reduced-function allele.<ref name="pmid19106084"/> and patients with a loss of function CYP2C19 allele have higher rates of cardiac events.<ref name="pmid19106084"/><ref name="pmid19106083"/>
 
==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]]. <ref name="pmid15276392">{{cite journal| author=Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M et al.| title=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. | journal=Lancet | year= 2004 | volume= 364 | issue= 9431 | pages= 331-7 | pmid=15276392 | doi=10.1016/S0140-6736(04)16721-4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15276392 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15518452 Review in: ACP J Club. 2004 Nov-Dec;141(3):68] </ref>
 
==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.<ref name="pmid19106084"/><ref name="pmid19106083"/> [[Proton pump inhibitor]]s (especially inhibitors other than pantoprazole<ref name="pmid19176635">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</ref>), which are metabolized by the CYP2C19 isoenzyme of [[cytochrome P-450]], may<ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref> or may not<ref name="pmid19726078">{{cite journal| author=O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al.| title=Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. | journal=Lancet | year= 2009 | volume= 374 | issue= 9694 | pages= 989-97 | pmid=19726078
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19726078 | doi=10.1016/S0140-6736(09)61525-7 }}</ref><ref name="pmid20231564">{{cite journal| author=Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K et al.| title=Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. | journal=Ann Intern Med | year= 2010 | volume= 152 | issue= 6 | pages= 337-45 | pmid=20231564
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20231564 | doi=10.1059/0003-4819-152-6-201003160-00003 }} </ref> increase adverse cardiac events.


==External links==
==External links==
Line 10: Line 20:


==References==
==References==
<references/>
<small>
<references>
 
</references>
</small>  
 
[[Category:Suggestion Bot Tag]]

Latest revision as of 12:58, 20 September 2024

This article is developing and not approved.
Main Article
Discussion
Related Articles  [?]
Bibliography  [?]
External Links  [?]
Citable Version  [?]
 
This editable Main Article is under development and subject to a disclaimer.
© Image: David E. Volk
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.