Loading…
Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding
Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations...
Saved in:
| Published in: | Circulation (New York, N.Y.) N.Y.), 2013-04, Vol.127 (13), p.1404-1412 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c491t-7613ea04dd192d80f3dc3ebcd6b68b5807665853897de947724887f3c20072e53 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c491t-7613ea04dd192d80f3dc3ebcd6b68b5807665853897de947724887f3c20072e53 |
| container_end_page | 1412 |
| container_issue | 13 |
| container_start_page | 1404 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 127 |
| creator | PARE, Guillaume ERIKSSON, Niclas SIEGBAHN, Agneta SYVANEN, Ann-Christine WADELIUS, Claes WADELIUS, Mia ZIMDAHL-GELLING, Heike YUSUF, Salim WALLENTIN, Lars LEHR, Thorsten CONNOLLY, Stuart EIKELBOOM, John EZEKOWITZ, Michael D AXELSSON, Tomas HAERTTER, Sebastian OLDGREN, Jonas REILLY, Paul |
| description | Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations of the active metabolite of dabigatran etexilate and influence the safety and efficacy of dabigatran.
We successfully conducted a genome-wide association study in 2944 Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) participants. The CES1 single-nucleotide polymorphism rs2244613 was associated with trough concentrations, and the ABCB1 single-nucleotide polymorphism rs4148738 and the CES1 single-nucleotide polymorphism rs8192935 were associated with peak concentrations at genome-wide significance (P |
| doi_str_mv | 10.1161/CIRCULATIONAHA.112.001233 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_DiVA_org_uu_197322</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1323278628</sourcerecordid><originalsourceid>FETCH-LOGICAL-c491t-7613ea04dd192d80f3dc3ebcd6b68b5807665853897de947724887f3c20072e53</originalsourceid><addsrcrecordid>eNpVkFtvEzEQRi1ERUPhLyDzgMQDW3zZ9eVxSaCNFBFUpbxaXns2GO0ltXdb8e9xlVDUp9GMzjejOQi9p-SSUkE_L9c3y9tNvVtvv9fXdZ6xS0Io4_wFWtCKlUVZcf0SLQghupCcsXP0OqXfuRVcVq_QOeOlkEqQBdpewQBTcHgFE8Q-DHaYEh5bvLJN2Nsp2gH_6GzqLd7APXQJ28Hj3S8IEd9AZ6cwDnga8ZcOwIdh_wadtbZL8PZUL9Dtt6-75XWx2V6tl_WmcKWmUyEF5WBJ6T3VzCvScu84NM6LRqimUkQKUamKKy096FJKViolW-4YIZJBxS_Qp-Pe9ACHuTGHGHob_5jRBrMKP2szxr2ZZ0P14_8Z_3jED3G8myFNpg_JQdfZAcY5GcoZZ9kIUxnVR9TFMaUI7dNuSsyjfvNcf54xc9Sfs-9OZ-amB_-U_Oc7Ax9OgE3Odm3W60L6z0mqdaUr_hckjY27</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1323278628</pqid></control><display><type>article</type><title>Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding</title><source>EZB Electronic Journals Library</source><creator>PARE, Guillaume ; ERIKSSON, Niclas ; SIEGBAHN, Agneta ; SYVANEN, Ann-Christine ; WADELIUS, Claes ; WADELIUS, Mia ; ZIMDAHL-GELLING, Heike ; YUSUF, Salim ; WALLENTIN, Lars ; LEHR, Thorsten ; CONNOLLY, Stuart ; EIKELBOOM, John ; EZEKOWITZ, Michael D ; AXELSSON, Tomas ; HAERTTER, Sebastian ; OLDGREN, Jonas ; REILLY, Paul</creator><creatorcontrib>PARE, Guillaume ; ERIKSSON, Niclas ; SIEGBAHN, Agneta ; SYVANEN, Ann-Christine ; WADELIUS, Claes ; WADELIUS, Mia ; ZIMDAHL-GELLING, Heike ; YUSUF, Salim ; WALLENTIN, Lars ; LEHR, Thorsten ; CONNOLLY, Stuart ; EIKELBOOM, John ; EZEKOWITZ, Michael D ; AXELSSON, Tomas ; HAERTTER, Sebastian ; OLDGREN, Jonas ; REILLY, Paul</creatorcontrib><description>Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations of the active metabolite of dabigatran etexilate and influence the safety and efficacy of dabigatran.
We successfully conducted a genome-wide association study in 2944 Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) participants. The CES1 single-nucleotide polymorphism rs2244613 was associated with trough concentrations, and the ABCB1 single-nucleotide polymorphism rs4148738 and the CES1 single-nucleotide polymorphism rs8192935 were associated with peak concentrations at genome-wide significance (P<9×10(-8)) with a gene-dose effect. Each minor allele of the CES1 single-nucleotide polymorphism rs2244613 was associated with lower trough concentrations (15% decrease per allele; 95% confidence interval, 10-19; P=1.2×10(-8)) and a lower risk of any bleeding (odds ratio, 0.67; 95% confidence interval, 0.55-0.82; P=7×10(-5)) in dabigatran-treated participants, with a consistent but nonsignificant lower risk of major bleeding (odds ratio, 0.66; 95% confidence interval, 0.43-1.01). The interaction between treatment (warfarin versus all dabigatran) and carrier status was statistically significant (P=0.002), with carriers having less bleeding with dabigatran than warfarin (hazard ratio, 0.59; 95% confidence interval, 0.46-0.76; P=5.2×10(-)5) in contrast to no difference in noncarriers (hazard ratio, 0.96; 95% confidence interval, 0.81-1.14; P=0.65). There was no association with ischemic events, and neither rs4148738 nor rs8192935 was associated with bleeding or ischemic events.
Genome-wide association analysis identified that carriage of the CES1 rs2244613 minor allele occurred in 32.8% of patients in RE-LY and was associated with lower exposure to active dabigatran metabolite. The presence of the polymorphism was associated with a lower risk of bleeding.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.</description><identifier>ISSN: 0009-7322</identifier><identifier>ISSN: 1524-4539</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.112.001233</identifier><identifier>PMID: 23467860</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Aged ; Anticoagulants - adverse effects ; Anticoagulants - blood ; Antithrombin Proteins - adverse effects ; Antithrombin Proteins - metabolism ; Benzimidazoles - adverse effects ; Benzimidazoles - blood ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood. Blood coagulation. Reticuloendothelial system ; Cardiac dysrhythmias ; Cardiology. Vascular system ; Dabigatran ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Female ; Genome-Wide Association Study - methods ; Heart ; Hemorrhage - epidemiology ; Hemorrhage - genetics ; Humans ; Male ; Medical sciences ; Neurology ; Pharmacology. Drug treatments ; Polymorphism, Single Nucleotide - genetics ; Prodrugs - adverse effects ; Prodrugs - metabolism ; Pyridines - adverse effects ; Pyridines - blood ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Circulation (New York, N.Y.), 2013-04, Vol.127 (13), p.1404-1412</ispartof><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-7613ea04dd192d80f3dc3ebcd6b68b5807665853897de947724887f3c20072e53</citedby><cites>FETCH-LOGICAL-c491t-7613ea04dd192d80f3dc3ebcd6b68b5807665853897de947724887f3c20072e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27199595$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23467860$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-197322$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>PARE, Guillaume</creatorcontrib><creatorcontrib>ERIKSSON, Niclas</creatorcontrib><creatorcontrib>SIEGBAHN, Agneta</creatorcontrib><creatorcontrib>SYVANEN, Ann-Christine</creatorcontrib><creatorcontrib>WADELIUS, Claes</creatorcontrib><creatorcontrib>WADELIUS, Mia</creatorcontrib><creatorcontrib>ZIMDAHL-GELLING, Heike</creatorcontrib><creatorcontrib>YUSUF, Salim</creatorcontrib><creatorcontrib>WALLENTIN, Lars</creatorcontrib><creatorcontrib>LEHR, Thorsten</creatorcontrib><creatorcontrib>CONNOLLY, Stuart</creatorcontrib><creatorcontrib>EIKELBOOM, John</creatorcontrib><creatorcontrib>EZEKOWITZ, Michael D</creatorcontrib><creatorcontrib>AXELSSON, Tomas</creatorcontrib><creatorcontrib>HAERTTER, Sebastian</creatorcontrib><creatorcontrib>OLDGREN, Jonas</creatorcontrib><creatorcontrib>REILLY, Paul</creatorcontrib><title>Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations of the active metabolite of dabigatran etexilate and influence the safety and efficacy of dabigatran.
We successfully conducted a genome-wide association study in 2944 Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) participants. The CES1 single-nucleotide polymorphism rs2244613 was associated with trough concentrations, and the ABCB1 single-nucleotide polymorphism rs4148738 and the CES1 single-nucleotide polymorphism rs8192935 were associated with peak concentrations at genome-wide significance (P<9×10(-8)) with a gene-dose effect. Each minor allele of the CES1 single-nucleotide polymorphism rs2244613 was associated with lower trough concentrations (15% decrease per allele; 95% confidence interval, 10-19; P=1.2×10(-8)) and a lower risk of any bleeding (odds ratio, 0.67; 95% confidence interval, 0.55-0.82; P=7×10(-5)) in dabigatran-treated participants, with a consistent but nonsignificant lower risk of major bleeding (odds ratio, 0.66; 95% confidence interval, 0.43-1.01). The interaction between treatment (warfarin versus all dabigatran) and carrier status was statistically significant (P=0.002), with carriers having less bleeding with dabigatran than warfarin (hazard ratio, 0.59; 95% confidence interval, 0.46-0.76; P=5.2×10(-)5) in contrast to no difference in noncarriers (hazard ratio, 0.96; 95% confidence interval, 0.81-1.14; P=0.65). There was no association with ischemic events, and neither rs4148738 nor rs8192935 was associated with bleeding or ischemic events.
Genome-wide association analysis identified that carriage of the CES1 rs2244613 minor allele occurred in 32.8% of patients in RE-LY and was associated with lower exposure to active dabigatran metabolite. The presence of the polymorphism was associated with a lower risk of bleeding.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.</description><subject>Aged</subject><subject>Anticoagulants - adverse effects</subject><subject>Anticoagulants - blood</subject><subject>Antithrombin Proteins - adverse effects</subject><subject>Antithrombin Proteins - metabolism</subject><subject>Benzimidazoles - adverse effects</subject><subject>Benzimidazoles - blood</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Cardiac dysrhythmias</subject><subject>Cardiology. Vascular system</subject><subject>Dabigatran</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Female</subject><subject>Genome-Wide Association Study - methods</subject><subject>Heart</subject><subject>Hemorrhage - epidemiology</subject><subject>Hemorrhage - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Prodrugs - adverse effects</subject><subject>Prodrugs - metabolism</subject><subject>Pyridines - adverse effects</subject><subject>Pyridines - blood</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0009-7322</issn><issn>1524-4539</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpVkFtvEzEQRi1ERUPhLyDzgMQDW3zZ9eVxSaCNFBFUpbxaXns2GO0ltXdb8e9xlVDUp9GMzjejOQi9p-SSUkE_L9c3y9tNvVtvv9fXdZ6xS0Io4_wFWtCKlUVZcf0SLQghupCcsXP0OqXfuRVcVq_QOeOlkEqQBdpewQBTcHgFE8Q-DHaYEh5bvLJN2Nsp2gH_6GzqLd7APXQJ28Hj3S8IEd9AZ6cwDnga8ZcOwIdh_wadtbZL8PZUL9Dtt6-75XWx2V6tl_WmcKWmUyEF5WBJ6T3VzCvScu84NM6LRqimUkQKUamKKy096FJKViolW-4YIZJBxS_Qp-Pe9ACHuTGHGHob_5jRBrMKP2szxr2ZZ0P14_8Z_3jED3G8myFNpg_JQdfZAcY5GcoZZ9kIUxnVR9TFMaUI7dNuSsyjfvNcf54xc9Sfs-9OZ-amB_-U_Oc7Ax9OgE3Odm3W60L6z0mqdaUr_hckjY27</recordid><startdate>20130402</startdate><enddate>20130402</enddate><creator>PARE, Guillaume</creator><creator>ERIKSSON, Niclas</creator><creator>SIEGBAHN, Agneta</creator><creator>SYVANEN, Ann-Christine</creator><creator>WADELIUS, Claes</creator><creator>WADELIUS, Mia</creator><creator>ZIMDAHL-GELLING, Heike</creator><creator>YUSUF, Salim</creator><creator>WALLENTIN, Lars</creator><creator>LEHR, Thorsten</creator><creator>CONNOLLY, Stuart</creator><creator>EIKELBOOM, John</creator><creator>EZEKOWITZ, Michael D</creator><creator>AXELSSON, Tomas</creator><creator>HAERTTER, Sebastian</creator><creator>OLDGREN, Jonas</creator><creator>REILLY, Paul</creator><general>Lippincott Williams & Wilkins</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>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DF2</scope></search><sort><creationdate>20130402</creationdate><title>Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding</title><author>PARE, Guillaume ; ERIKSSON, Niclas ; SIEGBAHN, Agneta ; SYVANEN, Ann-Christine ; WADELIUS, Claes ; WADELIUS, Mia ; ZIMDAHL-GELLING, Heike ; YUSUF, Salim ; WALLENTIN, Lars ; LEHR, Thorsten ; CONNOLLY, Stuart ; EIKELBOOM, John ; EZEKOWITZ, Michael D ; AXELSSON, Tomas ; HAERTTER, Sebastian ; OLDGREN, Jonas ; REILLY, Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-7613ea04dd192d80f3dc3ebcd6b68b5807665853897de947724887f3c20072e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>Anticoagulants - adverse effects</topic><topic>Anticoagulants - blood</topic><topic>Antithrombin Proteins - adverse effects</topic><topic>Antithrombin Proteins - metabolism</topic><topic>Benzimidazoles - adverse effects</topic><topic>Benzimidazoles - blood</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cardiac dysrhythmias</topic><topic>Cardiology. Vascular system</topic><topic>Dabigatran</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Female</topic><topic>Genome-Wide Association Study - methods</topic><topic>Heart</topic><topic>Hemorrhage - epidemiology</topic><topic>Hemorrhage - genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Prodrugs - adverse effects</topic><topic>Prodrugs - metabolism</topic><topic>Pyridines - adverse effects</topic><topic>Pyridines - blood</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PARE, Guillaume</creatorcontrib><creatorcontrib>ERIKSSON, Niclas</creatorcontrib><creatorcontrib>SIEGBAHN, Agneta</creatorcontrib><creatorcontrib>SYVANEN, Ann-Christine</creatorcontrib><creatorcontrib>WADELIUS, Claes</creatorcontrib><creatorcontrib>WADELIUS, Mia</creatorcontrib><creatorcontrib>ZIMDAHL-GELLING, Heike</creatorcontrib><creatorcontrib>YUSUF, Salim</creatorcontrib><creatorcontrib>WALLENTIN, Lars</creatorcontrib><creatorcontrib>LEHR, Thorsten</creatorcontrib><creatorcontrib>CONNOLLY, Stuart</creatorcontrib><creatorcontrib>EIKELBOOM, John</creatorcontrib><creatorcontrib>EZEKOWITZ, Michael D</creatorcontrib><creatorcontrib>AXELSSON, Tomas</creatorcontrib><creatorcontrib>HAERTTER, Sebastian</creatorcontrib><creatorcontrib>OLDGREN, Jonas</creatorcontrib><creatorcontrib>REILLY, Paul</creatorcontrib><collection>Pascal-Francis</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><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Uppsala universitet</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PARE, Guillaume</au><au>ERIKSSON, Niclas</au><au>SIEGBAHN, Agneta</au><au>SYVANEN, Ann-Christine</au><au>WADELIUS, Claes</au><au>WADELIUS, Mia</au><au>ZIMDAHL-GELLING, Heike</au><au>YUSUF, Salim</au><au>WALLENTIN, Lars</au><au>LEHR, Thorsten</au><au>CONNOLLY, Stuart</au><au>EIKELBOOM, John</au><au>EZEKOWITZ, Michael D</au><au>AXELSSON, Tomas</au><au>HAERTTER, Sebastian</au><au>OLDGREN, Jonas</au><au>REILLY, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2013-04-02</date><risdate>2013</risdate><volume>127</volume><issue>13</issue><spage>1404</spage><epage>1412</epage><pages>1404-1412</pages><issn>0009-7322</issn><issn>1524-4539</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Fixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in the prevention of stroke in atrial fibrillation patients compared with warfarin. We hypothesized that genetic variants could contribute to interindividual variability in blood concentrations of the active metabolite of dabigatran etexilate and influence the safety and efficacy of dabigatran.
We successfully conducted a genome-wide association study in 2944 Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) participants. The CES1 single-nucleotide polymorphism rs2244613 was associated with trough concentrations, and the ABCB1 single-nucleotide polymorphism rs4148738 and the CES1 single-nucleotide polymorphism rs8192935 were associated with peak concentrations at genome-wide significance (P<9×10(-8)) with a gene-dose effect. Each minor allele of the CES1 single-nucleotide polymorphism rs2244613 was associated with lower trough concentrations (15% decrease per allele; 95% confidence interval, 10-19; P=1.2×10(-8)) and a lower risk of any bleeding (odds ratio, 0.67; 95% confidence interval, 0.55-0.82; P=7×10(-5)) in dabigatran-treated participants, with a consistent but nonsignificant lower risk of major bleeding (odds ratio, 0.66; 95% confidence interval, 0.43-1.01). The interaction between treatment (warfarin versus all dabigatran) and carrier status was statistically significant (P=0.002), with carriers having less bleeding with dabigatran than warfarin (hazard ratio, 0.59; 95% confidence interval, 0.46-0.76; P=5.2×10(-)5) in contrast to no difference in noncarriers (hazard ratio, 0.96; 95% confidence interval, 0.81-1.14; P=0.65). There was no association with ischemic events, and neither rs4148738 nor rs8192935 was associated with bleeding or ischemic events.
Genome-wide association analysis identified that carriage of the CES1 rs2244613 minor allele occurred in 32.8% of patients in RE-LY and was associated with lower exposure to active dabigatran metabolite. The presence of the polymorphism was associated with a lower risk of bleeding.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>23467860</pmid><doi>10.1161/CIRCULATIONAHA.112.001233</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2013-04, Vol.127 (13), p.1404-1412 |
| issn | 0009-7322 1524-4539 1524-4539 |
| language | eng |
| recordid | cdi_swepub_primary_oai_DiVA_org_uu_197322 |
| source | EZB Electronic Journals Library |
| subjects | Aged Anticoagulants - adverse effects Anticoagulants - blood Antithrombin Proteins - adverse effects Antithrombin Proteins - metabolism Benzimidazoles - adverse effects Benzimidazoles - blood Biological and medical sciences Blood and lymphatic vessels Blood. Blood coagulation. Reticuloendothelial system Cardiac dysrhythmias Cardiology. Vascular system Dabigatran Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Female Genome-Wide Association Study - methods Heart Hemorrhage - epidemiology Hemorrhage - genetics Humans Male Medical sciences Neurology Pharmacology. Drug treatments Polymorphism, Single Nucleotide - genetics Prodrugs - adverse effects Prodrugs - metabolism Pyridines - adverse effects Pyridines - blood Vascular diseases and vascular malformations of the nervous system |
| title | Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T07%3A11%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20Determinants%20of%20Dabigatran%20Plasma%20Levels%20and%20Their%20Relation%20to%20Bleeding&rft.jtitle=Circulation%20(New%20York,%20N.Y.)&rft.au=PARE,%20Guillaume&rft.date=2013-04-02&rft.volume=127&rft.issue=13&rft.spage=1404&rft.epage=1412&rft.pages=1404-1412&rft.issn=0009-7322&rft.eissn=1524-4539&rft.coden=CIRCAZ&rft_id=info:doi/10.1161/CIRCULATIONAHA.112.001233&rft_dat=%3Cproquest_swepu%3E1323278628%3C/proquest_swepu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c491t-7613ea04dd192d80f3dc3ebcd6b68b5807665853897de947724887f3c20072e53%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1323278628&rft_id=info:pmid/23467860&rfr_iscdi=true |