Clopidogrel: Difference between revisions
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{{Image|Clopidogrel2.png|right|300px|'''Clopidogrel'''.}} | {{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]]. | In [[medicine]], '''clopidogrel''' is a [[thienopyridine]] class [[platelet aggregation inhibitor]]. It is used in the [[secondary prevention]] of [[stroke]] and [[coronary heart disease]]. | ||
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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> | 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" | 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"/> | ||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id= | |||
==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== | ==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" | 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&retmode=ref&cmd=prlinks&id=19726078 | doi=10.1016/S0140-6736(09)61525-7 }} < | | 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== | ||
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==References== | ==References== | ||
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Latest revision as of 12:58, 20 September 2024
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.
- Clopidogrel - FDA approved drug information (drug label) from DailyMed (U.S. National Library of Medicine).
- Clopidogrel - Drug information for consumers from MedlinePlus (U.S. National Library of Medicine).
- Clopidogrel - Detailed information from DrugBank.
References
- ↑ PPI Interactions with Clopidogrel. The Medical Letter.
- ↑ 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.
- ↑ 3.0 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.
- ↑ 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.
- ↑ 5.0 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.
- ↑ 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
- ↑ 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
- ↑ 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.
- ↑ 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.