Comparison Between Clopidogrel and Prasugrel Associated With CYP2C19 Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population
Background:The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.Methods and Results:This study consisted of 1,580 patients whoseCYP2C19gen...
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| Veröffentlicht in: | Circulation Journal 2020/08/25, Vol.84(9), pp.1575-1581 |
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| creator | Sawayama, Yuichi Yamamoto, Takashi Tomita, Yukinori Asada, Kohei Yagi, Noriaki Fukuyama, Megumi Miyamoto, Akashi Sakai, Hiroshi Ozawa, Tomoya Isono, Tetsuichiro Hira, Daiki Terada, Tomohiro Horie, Minoru Nakagawa, Yoshihisa |
| description | Background:The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.Methods and Results:This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85–4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10–9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14–3.26, P=0.62).Conclusions:Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping. |
| doi_str_mv | 10.1253/circj.CJ-20-0254 |
| format | Article |
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Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85–4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10–9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14–3.26, P=0.62).Conclusions:Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.</description><identifier>ISSN: 1346-9843</identifier><identifier>ISSN: 1347-4820</identifier><identifier>EISSN: 1347-4820</identifier><identifier>DOI: 10.1253/circj.CJ-20-0254</identifier><identifier>PMID: 32713878</identifier><language>eng</language><publisher>TOYKO: The Japanese Circulation Society</publisher><subject>Aged ; Aged, 80 and over ; Alleles ; Cardiac & Cardiovascular Systems ; Cardiovascular System & Cardiology ; Clopidogrel ; Clopidogrel - adverse effects ; Coronary Thrombosis - chemically induced ; Coronary Thrombosis - epidemiology ; Coronary Thrombosis - genetics ; CYP2C19 ; Cytochrome P-450 CYP2C19 - genetics ; Female ; Follow-Up Studies ; Genotype ; Hemorrhage - chemically induced ; Hemorrhage - epidemiology ; Hemorrhage - genetics ; Humans ; Japan - epidemiology ; Life Sciences & Biomedicine ; Loss of Function Mutation ; Male ; Middle Aged ; Myocardial Infarction - chemically induced ; Myocardial Infarction - epidemiology ; Myocardial Infarction - genetics ; P2Y12 inhibitor ; Percutaneous coronary intervention ; Percutaneous Coronary Intervention - adverse effects ; Platelet Aggregation Inhibitors - adverse effects ; Prasugrel ; Prasugrel Hydrochloride - adverse effects ; Retrospective Studies ; Science & Technology ; Stroke - chemically induced ; Stroke - epidemiology ; Stroke - genetics ; Treatment Outcome</subject><ispartof>Circulation Journal, 2020/08/25, Vol.84(9), pp.1575-1581</ispartof><rights>2020 THE JAPANESE CIRCULATION SOCIETY</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>11</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000563764000021</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c494t-7d8a2921a0f581a5928a5383a0091143b291fe0736a97e88fcafb33f922728823</citedby><cites>FETCH-LOGICAL-c494t-7d8a2921a0f581a5928a5383a0091143b291fe0736a97e88fcafb33f922728823</cites><orcidid>0000-0001-5771-3819</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,1884,27928,27929</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32713878$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sawayama, Yuichi</creatorcontrib><creatorcontrib>Yamamoto, Takashi</creatorcontrib><creatorcontrib>Tomita, Yukinori</creatorcontrib><creatorcontrib>Asada, Kohei</creatorcontrib><creatorcontrib>Yagi, Noriaki</creatorcontrib><creatorcontrib>Fukuyama, Megumi</creatorcontrib><creatorcontrib>Miyamoto, Akashi</creatorcontrib><creatorcontrib>Sakai, Hiroshi</creatorcontrib><creatorcontrib>Ozawa, Tomoya</creatorcontrib><creatorcontrib>Isono, Tetsuichiro</creatorcontrib><creatorcontrib>Hira, Daiki</creatorcontrib><creatorcontrib>Terada, Tomohiro</creatorcontrib><creatorcontrib>Horie, Minoru</creatorcontrib><creatorcontrib>Nakagawa, Yoshihisa</creatorcontrib><title>Comparison Between Clopidogrel and Prasugrel Associated With CYP2C19 Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population</title><title>Circulation Journal</title><addtitle>CIRC J</addtitle><addtitle>Circ J</addtitle><description>Background:The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.Methods and Results:This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85–4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10–9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14–3.26, P=0.62).Conclusions:Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Cardiac & Cardiovascular Systems</subject><subject>Cardiovascular System & Cardiology</subject><subject>Clopidogrel</subject><subject>Clopidogrel - adverse effects</subject><subject>Coronary Thrombosis - chemically induced</subject><subject>Coronary Thrombosis - epidemiology</subject><subject>Coronary Thrombosis - genetics</subject><subject>CYP2C19</subject><subject>Cytochrome P-450 CYP2C19 - genetics</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genotype</subject><subject>Hemorrhage - chemically induced</subject><subject>Hemorrhage - epidemiology</subject><subject>Hemorrhage - genetics</subject><subject>Humans</subject><subject>Japan - epidemiology</subject><subject>Life Sciences & Biomedicine</subject><subject>Loss of Function Mutation</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myocardial Infarction - chemically induced</subject><subject>Myocardial Infarction - epidemiology</subject><subject>Myocardial Infarction - genetics</subject><subject>P2Y12 inhibitor</subject><subject>Percutaneous coronary intervention</subject><subject>Percutaneous Coronary Intervention - adverse effects</subject><subject>Platelet Aggregation Inhibitors - adverse effects</subject><subject>Prasugrel</subject><subject>Prasugrel Hydrochloride - adverse effects</subject><subject>Retrospective Studies</subject><subject>Science & Technology</subject><subject>Stroke - chemically induced</subject><subject>Stroke - epidemiology</subject><subject>Stroke - genetics</subject><subject>Treatment Outcome</subject><issn>1346-9843</issn><issn>1347-4820</issn><issn>1347-4820</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><recordid>eNqNkctu1DAUhiMEoqWwZ4W8REIpvmViL4tFL6NKRAiEWFkez8nUo4wdbKdV34ZHredCZ8vGPpa__9z-qnpP8DmhDftsXbTrczWvKa4xbfiL6pQw3tZcUPxyF89qKTg7qd6ktMaYStzI19UJoy1hohWn1V8VNqOJLgWPvkB-APBIDWF0y7CKMCDjl6iLJk2710VKwTqTYYl-uXyH1O-OKiLRFfiQH0dIyHnUmezA54S-gwV37_wKdRDtlI2HMCWkQgzexEd04zPE-4K6UrwIDZqbsUAJUBfGaTDbj7fVq94MCd4d7rPq5-XXH-q6vv12daMubmvLJc91uxSGSkoM7htBTCOpMA0TzGAsCeFsQSXpAbdsZmQLQvTW9AvGeklpS4Wg7Kz6uM87xvBngpT1xiULw7DvWlNO24ZyhnlB8R61MaQUoddjdJsykSZYb33RO1-0mmuK9daXIvlwyD4tNrB8FvwzogCf9sADLEKfbNmghWcMY9zMWDvjJcCUFFr8P61c3m1ShcnnIr3cS9cpm9VRZGJ2doBD64JruT2OIxyBOxM1ePYEhu3F3g</recordid><startdate>20200825</startdate><enddate>20200825</enddate><creator>Sawayama, Yuichi</creator><creator>Yamamoto, Takashi</creator><creator>Tomita, Yukinori</creator><creator>Asada, Kohei</creator><creator>Yagi, Noriaki</creator><creator>Fukuyama, Megumi</creator><creator>Miyamoto, Akashi</creator><creator>Sakai, Hiroshi</creator><creator>Ozawa, Tomoya</creator><creator>Isono, Tetsuichiro</creator><creator>Hira, Daiki</creator><creator>Terada, Tomohiro</creator><creator>Horie, Minoru</creator><creator>Nakagawa, Yoshihisa</creator><general>The Japanese Circulation Society</general><general>Japanese Circulation Soc</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</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>7X8</scope><orcidid>https://orcid.org/0000-0001-5771-3819</orcidid></search><sort><creationdate>20200825</creationdate><title>Comparison Between Clopidogrel and Prasugrel Associated With CYP2C19 Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population</title><author>Sawayama, Yuichi ; Yamamoto, Takashi ; Tomita, Yukinori ; Asada, Kohei ; Yagi, Noriaki ; Fukuyama, Megumi ; Miyamoto, Akashi ; Sakai, Hiroshi ; Ozawa, Tomoya ; Isono, Tetsuichiro ; Hira, Daiki ; Terada, Tomohiro ; Horie, Minoru ; Nakagawa, Yoshihisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-7d8a2921a0f581a5928a5383a0091143b291fe0736a97e88fcafb33f922728823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Cardiac & Cardiovascular Systems</topic><topic>Cardiovascular System & Cardiology</topic><topic>Clopidogrel</topic><topic>Clopidogrel - adverse effects</topic><topic>Coronary Thrombosis - chemically induced</topic><topic>Coronary Thrombosis - epidemiology</topic><topic>Coronary Thrombosis - genetics</topic><topic>CYP2C19</topic><topic>Cytochrome P-450 CYP2C19 - genetics</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Genotype</topic><topic>Hemorrhage - chemically induced</topic><topic>Hemorrhage - epidemiology</topic><topic>Hemorrhage - genetics</topic><topic>Humans</topic><topic>Japan - epidemiology</topic><topic>Life Sciences & Biomedicine</topic><topic>Loss of Function Mutation</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myocardial Infarction - chemically induced</topic><topic>Myocardial Infarction - epidemiology</topic><topic>Myocardial Infarction - genetics</topic><topic>P2Y12 inhibitor</topic><topic>Percutaneous coronary intervention</topic><topic>Percutaneous Coronary Intervention - adverse effects</topic><topic>Platelet Aggregation Inhibitors - adverse effects</topic><topic>Prasugrel</topic><topic>Prasugrel Hydrochloride - adverse effects</topic><topic>Retrospective Studies</topic><topic>Science & Technology</topic><topic>Stroke - chemically induced</topic><topic>Stroke - epidemiology</topic><topic>Stroke - genetics</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sawayama, Yuichi</creatorcontrib><creatorcontrib>Yamamoto, Takashi</creatorcontrib><creatorcontrib>Tomita, Yukinori</creatorcontrib><creatorcontrib>Asada, Kohei</creatorcontrib><creatorcontrib>Yagi, Noriaki</creatorcontrib><creatorcontrib>Fukuyama, Megumi</creatorcontrib><creatorcontrib>Miyamoto, Akashi</creatorcontrib><creatorcontrib>Sakai, Hiroshi</creatorcontrib><creatorcontrib>Ozawa, Tomoya</creatorcontrib><creatorcontrib>Isono, Tetsuichiro</creatorcontrib><creatorcontrib>Hira, Daiki</creatorcontrib><creatorcontrib>Terada, Tomohiro</creatorcontrib><creatorcontrib>Horie, Minoru</creatorcontrib><creatorcontrib>Nakagawa, Yoshihisa</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sawayama, Yuichi</au><au>Yamamoto, Takashi</au><au>Tomita, Yukinori</au><au>Asada, Kohei</au><au>Yagi, Noriaki</au><au>Fukuyama, Megumi</au><au>Miyamoto, Akashi</au><au>Sakai, Hiroshi</au><au>Ozawa, Tomoya</au><au>Isono, Tetsuichiro</au><au>Hira, Daiki</au><au>Terada, Tomohiro</au><au>Horie, Minoru</au><au>Nakagawa, Yoshihisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison Between Clopidogrel and Prasugrel Associated With CYP2C19 Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population</atitle><jtitle>Circulation Journal</jtitle><stitle>CIRC J</stitle><addtitle>Circ J</addtitle><date>2020-08-25</date><risdate>2020</risdate><volume>84</volume><issue>9</issue><spage>1575</spage><epage>1581</epage><pages>1575-1581</pages><issn>1346-9843</issn><issn>1347-4820</issn><eissn>1347-4820</eissn><abstract>Background:The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.Methods and Results:This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85–4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10–9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14–3.26, P=0.62).Conclusions:Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.</abstract><cop>TOYKO</cop><pub>The Japanese Circulation Society</pub><pmid>32713878</pmid><doi>10.1253/circj.CJ-20-0254</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-5771-3819</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Alleles Cardiac & Cardiovascular Systems Cardiovascular System & Cardiology Clopidogrel Clopidogrel - adverse effects Coronary Thrombosis - chemically induced Coronary Thrombosis - epidemiology Coronary Thrombosis - genetics CYP2C19 Cytochrome P-450 CYP2C19 - genetics Female Follow-Up Studies Genotype Hemorrhage - chemically induced Hemorrhage - epidemiology Hemorrhage - genetics Humans Japan - epidemiology Life Sciences & Biomedicine Loss of Function Mutation Male Middle Aged Myocardial Infarction - chemically induced Myocardial Infarction - epidemiology Myocardial Infarction - genetics P2Y12 inhibitor Percutaneous coronary intervention Percutaneous Coronary Intervention - adverse effects Platelet Aggregation Inhibitors - adverse effects Prasugrel Prasugrel Hydrochloride - adverse effects Retrospective Studies Science & Technology Stroke - chemically induced Stroke - epidemiology Stroke - genetics Treatment Outcome |
| title | Comparison Between Clopidogrel and Prasugrel Associated With CYP2C19 Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population |
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