Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel
Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countri...
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| Veröffentlicht in: | The American journal of cardiology 2012-08, Vol.110 (4), p.502-508 |
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| creator | Jang, Jae-Sik, MD, PhD Cho, Kyoung-Im, MD, PhD Jin, Han-Young, MD Seo, Jeong-Sook, MD, PhD Yang, Tae-Hyun, MD, PhD Kim, Dae-Kyeong, MD, PhD Kim, Dong-Soo, MD, PhD Seol, Sang-Hoon, MD, PhD Kim, Doo-Il, MD, PhD Kim, Bo-Hyun, MD, PhD Park, Yong Hyun, MD, PhD Je, Hyung-Gon, MD, PhD Jeong, Young-Hoon, MD, PhD Lee, Seung-Whan, MD, PhD |
| description | Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity. |
| doi_str_mv | 10.1016/j.amjcard.2012.04.020 |
| format | Article |
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We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.</description><identifier>ISSN: 0002-9149</identifier><identifier>EISSN: 1879-1913</identifier><identifier>DOI: 10.1016/j.amjcard.2012.04.020</identifier><identifier>PMID: 22591668</identifier><identifier>CODEN: AJCDAG</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Aryl Hydrocarbon Hydroxylases - genetics ; Biological and medical sciences ; Cardiology. Vascular system ; Cardiovascular ; Cardiovascular disease ; Cohort Studies ; Coronary Artery Disease - drug therapy ; Coronary Artery Disease - ethnology ; Coronary Artery Disease - genetics ; Coronary heart disease ; Coronary vessels ; Cytochrome P-450 CYP2C19 ; Ethnic Groups ; Heart ; Heart attacks ; Humans ; Medical sciences ; Platelet Aggregation Inhibitors - therapeutic use ; Polymorphism, Genetic - genetics ; Prospective Studies ; Randomized Controlled Trials as Topic ; Risk Assessment ; Studies ; Ticlopidine - analogs & derivatives ; Ticlopidine - therapeutic use ; Treatment Outcome</subject><ispartof>The American journal of cardiology, 2012-08, Vol.110 (4), p.502-508</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>Aug 15, 2012 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-9d2f2e23e6d1a91c727a2165bfed2f6d7014b9a5d77b0886df31a8335d4ef7383</citedby><cites>FETCH-LOGICAL-c478t-9d2f2e23e6d1a91c727a2165bfed2f6d7014b9a5d77b0886df31a8335d4ef7383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1036912713?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976,64364,64366,64368,72218</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26281663$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22591668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jang, Jae-Sik, MD, PhD</creatorcontrib><creatorcontrib>Cho, Kyoung-Im, MD, PhD</creatorcontrib><creatorcontrib>Jin, Han-Young, MD</creatorcontrib><creatorcontrib>Seo, Jeong-Sook, MD, PhD</creatorcontrib><creatorcontrib>Yang, Tae-Hyun, MD, PhD</creatorcontrib><creatorcontrib>Kim, Dae-Kyeong, MD, PhD</creatorcontrib><creatorcontrib>Kim, Dong-Soo, MD, PhD</creatorcontrib><creatorcontrib>Seol, Sang-Hoon, MD, PhD</creatorcontrib><creatorcontrib>Kim, Doo-Il, MD, PhD</creatorcontrib><creatorcontrib>Kim, Bo-Hyun, MD, PhD</creatorcontrib><creatorcontrib>Park, Yong Hyun, MD, PhD</creatorcontrib><creatorcontrib>Je, Hyung-Gon, MD, PhD</creatorcontrib><creatorcontrib>Jeong, Young-Hoon, MD, PhD</creatorcontrib><creatorcontrib>Lee, Seung-Whan, MD, PhD</creatorcontrib><title>Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel</title><title>The American journal of cardiology</title><addtitle>Am J Cardiol</addtitle><description>Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.</description><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular</subject><subject>Cardiovascular disease</subject><subject>Cohort Studies</subject><subject>Coronary Artery Disease - drug therapy</subject><subject>Coronary Artery Disease - ethnology</subject><subject>Coronary Artery Disease - genetics</subject><subject>Coronary heart disease</subject><subject>Coronary vessels</subject><subject>Cytochrome P-450 CYP2C19</subject><subject>Ethnic Groups</subject><subject>Heart</subject><subject>Heart attacks</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Platelet Aggregation Inhibitors - therapeutic use</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Prospective Studies</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Risk Assessment</subject><subject>Studies</subject><subject>Ticlopidine - analogs & derivatives</subject><subject>Ticlopidine - therapeutic use</subject><subject>Treatment Outcome</subject><issn>0002-9149</issn><issn>1879-1913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkttuEzEQhlcIREPhEUCWEBI3G3zY4w1VtC0FqagRFHFpOfZs43R3HWxvpTxXX7CzTaBSb7gajfzNP-P5J0neMjpnlBWfNnPVb7TyZs4p43OazSmnz5IZq8o6ZTUTz5MZpZSnNcvqo-RVCBtMGcuLl8kR53nNiqKaJXffIap0MahuF2wgriXNLjq99q4HssxySnjDarJ03a53fru2oSdqMOSHDTcTvTC34AOQprOD1aojl2PUWBvIonfDNWmcd4PyO7LwETCc2gAK-aWKFob40PHUti14zMhZXKMKOfdu3AZy5UFFMOS3jWts4LbWuGsP3evkRau6AG8O8Tj59eXsqvmaXlyef2sWF6nOyiqmteEtBy6gMEzVTJe8VJwV-aoFfClMSVm2qlVuynJFq6owrWCqEiI3GbSlqMRx8nGvu_Xuzwghyt4GDV2nBnBjkIwKKnJcZYno-yfoxo0et_pAFTXjJRNI5XtKexeCh1Zuve1xOwjJyVW5kQdX5eSqpJlEV7Hu3UF9XPVg_lX9tRGBDwdABTSh9WrQNjxyBa-QmwY42XOAa7u14GXQaIMGYz3oKI2z_x3l8xMFfXD-BnYQHn8tA9bIn9MJThfIUIRVlIp7wqrX4Q</recordid><startdate>20120815</startdate><enddate>20120815</enddate><creator>Jang, Jae-Sik, MD, PhD</creator><creator>Cho, Kyoung-Im, MD, PhD</creator><creator>Jin, Han-Young, MD</creator><creator>Seo, Jeong-Sook, MD, PhD</creator><creator>Yang, Tae-Hyun, MD, PhD</creator><creator>Kim, Dae-Kyeong, MD, PhD</creator><creator>Kim, Dong-Soo, MD, PhD</creator><creator>Seol, Sang-Hoon, MD, PhD</creator><creator>Kim, Doo-Il, MD, PhD</creator><creator>Kim, Bo-Hyun, MD, PhD</creator><creator>Park, Yong Hyun, MD, PhD</creator><creator>Je, Hyung-Gon, MD, PhD</creator><creator>Jeong, Young-Hoon, MD, PhD</creator><creator>Lee, Seung-Whan, MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7Z</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20120815</creationdate><title>Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel</title><author>Jang, Jae-Sik, MD, PhD ; Cho, Kyoung-Im, MD, PhD ; Jin, Han-Young, MD ; Seo, Jeong-Sook, MD, PhD ; Yang, Tae-Hyun, MD, PhD ; Kim, Dae-Kyeong, MD, PhD ; Kim, Dong-Soo, MD, PhD ; Seol, Sang-Hoon, MD, PhD ; Kim, Doo-Il, MD, PhD ; Kim, Bo-Hyun, MD, PhD ; Park, Yong Hyun, MD, PhD ; Je, Hyung-Gon, MD, PhD ; Jeong, Young-Hoon, MD, PhD ; Lee, Seung-Whan, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-9d2f2e23e6d1a91c727a2165bfed2f6d7014b9a5d77b0886df31a8335d4ef7383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Biological and medical sciences</topic><topic>Cardiology. 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Academic</collection><jtitle>The American journal of cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jang, Jae-Sik, MD, PhD</au><au>Cho, Kyoung-Im, MD, PhD</au><au>Jin, Han-Young, MD</au><au>Seo, Jeong-Sook, MD, PhD</au><au>Yang, Tae-Hyun, MD, PhD</au><au>Kim, Dae-Kyeong, MD, PhD</au><au>Kim, Dong-Soo, MD, PhD</au><au>Seol, Sang-Hoon, MD, PhD</au><au>Kim, Doo-Il, MD, PhD</au><au>Kim, Bo-Hyun, MD, PhD</au><au>Park, Yong Hyun, MD, PhD</au><au>Je, Hyung-Gon, MD, PhD</au><au>Jeong, Young-Hoon, MD, PhD</au><au>Lee, Seung-Whan, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel</atitle><jtitle>The American journal of cardiology</jtitle><addtitle>Am J Cardiol</addtitle><date>2012-08-15</date><risdate>2012</risdate><volume>110</volume><issue>4</issue><spage>502</spage><epage>508</epage><pages>502-508</pages><issn>0002-9149</issn><eissn>1879-1913</eissn><coden>AJCDAG</coden><abstract>Loss-of-function (LOF) variants of cytochrome P450 2C19 (CYP2C19) have been hypothesized to be associated with lesser degrees of platelet inhibition and increased risk for recurrent ischemic events in patients with coronary artery disease on clopidogrel therapy; however, studies from Western countries have yielded mixed results. We aimed to assess the impact of CYP2C19 LOF variants on clinical outcomes from different ethnic groups. Sixteen prospective cohort studies including 7,035 patients carrying ≥1 CYP2C19 LOF allele and 13,750 patients with the wild-type genotype were included in this meta-analysis. Carriers of ≥1 CYP2C19 LOF allele were at significantly higher risk for adverse clinical events compared to noncarriers during clopidogrel therapy (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.13 to 1.78). The summary OR showed a significant association between CYP2C19 LOF variants and an increased risk of cardiac death (OR 2.18, 95% CI 1.37 to 3.47), myocardial infarction (OR 1.42, 95% CI 1.12 to 1.81), and stent thrombosis (OR 2.41, 95% CI 1.76 to 3.30). Stratified analysis by ethnicity of study population suggested higher odds of adverse clinical events in the Asian population with LOF variants of CYP2C19 (OR 1.89, 95% CI 1.32 to 2.72) compared to Western populations (OR 1.28, 95% CI 1.00 to 1.64). In conclusion, carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients with coronary artery disease on clopidogrel therapy despite differences in clinical significance according to ethnicity.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>22591668</pmid><doi>10.1016/j.amjcard.2012.04.020</doi><tpages>7</tpages></addata></record> |
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| identifier | ISSN: 0002-9149 |
| ispartof | The American journal of cardiology, 2012-08, Vol.110 (4), p.502-508 |
| issn | 0002-9149 1879-1913 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland |
| subjects | Aryl Hydrocarbon Hydroxylases - genetics Biological and medical sciences Cardiology. Vascular system Cardiovascular Cardiovascular disease Cohort Studies Coronary Artery Disease - drug therapy Coronary Artery Disease - ethnology Coronary Artery Disease - genetics Coronary heart disease Coronary vessels Cytochrome P-450 CYP2C19 Ethnic Groups Heart Heart attacks Humans Medical sciences Platelet Aggregation Inhibitors - therapeutic use Polymorphism, Genetic - genetics Prospective Studies Randomized Controlled Trials as Topic Risk Assessment Studies Ticlopidine - analogs & derivatives Ticlopidine - therapeutic use Treatment Outcome |
| title | Meta-Analysis of Cytochrome P450 2C19 Polymorphism and Risk of Adverse Clinical Outcomes Among Coronary Artery Disease Patients of Different Ethnic Groups Treated With Clopidogrel |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T21%3A56%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Meta-Analysis%20of%20Cytochrome%20P450%202C19%20Polymorphism%20and%20Risk%20of%20Adverse%20Clinical%20Outcomes%20Among%20Coronary%20Artery%20Disease%20Patients%20of%20Different%20Ethnic%20Groups%20Treated%20With%20Clopidogrel&rft.jtitle=The%20American%20journal%20of%20cardiology&rft.au=Jang,%20Jae-Sik,%20MD,%20PhD&rft.date=2012-08-15&rft.volume=110&rft.issue=4&rft.spage=502&rft.epage=508&rft.pages=502-508&rft.issn=0002-9149&rft.eissn=1879-1913&rft.coden=AJCDAG&rft_id=info:doi/10.1016/j.amjcard.2012.04.020&rft_dat=%3Cproquest_cross%3E2747931031%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1036912713&rft_id=info:pmid/22591668&rft_els_id=1_s2_0_S0002914912011800&rfr_iscdi=true |