Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in Routine Care
Abstract Background Direct-acting oral anticoagulants (DOACs) are widely prescribed for stroke prevention in patients with atrial fibrillation. An important advantage of DOACs is that routine monitoring of anticoagulation response is not necessary. Nevertheless, due to their mechanism of action, DOA...
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| Veröffentlicht in: | Canadian journal of cardiology 2017-08, Vol.33 (8), p.1036-1043 |
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| creator | Gulilat, Markus, BMSc Tang, Anthony, MD Gryn, Steven E., MD Leong-Sit, Peter, MD Skanes, Allan C., MD Alfonsi, Jeffrey E., MD Dresser, George K., MD, PhD Henderson, Sara L., PharmD Rose, Rhiannon V., MMath Lizotte, Daniel J., PhD Teft, Wendy A., PhD Schwarz, Ute I., MD, PhD Tirona, Rommel G., PhD Kim, Richard B., MD |
| description | Abstract Background Direct-acting oral anticoagulants (DOACs) are widely prescribed for stroke prevention in patients with atrial fibrillation. An important advantage of DOACs is that routine monitoring of anticoagulation response is not necessary. Nevertheless, due to their mechanism of action, DOAC anticoagulation effect can be inferred based on observed plasma concentration. However, there is paucity of data relating to observed interpatient variation in DOAC plasma concentrations in the post-market clinical setting. Methods We determined rivaroxaban and apixaban plasma concentrations in atrial fibrillation patients during routine clinic visits. Results Among 243 patients (rivaroxaban, n=94; apixaban, n=149) enrolled in this study, 60- and 50-fold interpatient variation in plasma concentration was observed for rivaroxaban and apixaban respectively. Approximately 12% of rivaroxaban and 13% of apixaban patients exceeded the 95th percentile for predicted maximum plasma concentration observed in clinical trials. Conclusions In this routine care setting, rivaroxaban and apixaban plasma concentrations tended to be more variable than those observed in clinical trials. Identification of additional clinical and molecular determinants that more fully predict patients at risk for excessively high or low DOAC concentrations may enable a more precise DOAC dosing regimen for the individual patient. |
| doi_str_mv | 10.1016/j.cjca.2017.04.008 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1924601118</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0828282X17302003</els_id><sourcerecordid>1924601118</sourcerecordid><originalsourceid>FETCH-LOGICAL-c411t-93eaba7e7cf2cf4097158cd6eb1e230ba454d7de37d14447c8e12c3dbdfc0f713</originalsourceid><addsrcrecordid>eNp9kcFu1DAQhi0EokvhBTigHLkkzDjeOJEQUrWCUqkSqAXUm-XYE8khay92UtG3r9MtHDhw8lj6v1-abxh7jVAhYPNurMxodMUBZQWiAmifsA122JQS5PYp20DL25K3_OaEvUhpBBAoZfOcnfBWbkXddht2c-Fnigc9O_Jz8UNHl8fgC-eLK3erY_ite-0L7W1xdnDHz9dJp70udsGbDMUHID0QYZmdp2KnI71kzwY9JXr1-J6y758-ftt9Li-_nF_szi5LIxDnsqspd0qSZuBmENBJ3LbGNtQj8Rp6LbbCSku1tCiEkKYl5Ka2vR0MDBLrU_b22HuI4ddCaVZ7lwxNk_YUlqSw46IBRGxzlB-jJoaUIg3qEN1exzuFoFajalSrUbUaVSBUNpqhN4_9S78n-xf5ozAH3h8DlLe8dRRVMlmmIesimVnZ4P7f_-Ef3EzOO6Onn3RHaQxL9NmfQpW4AnW93nQ9KcoaOEBd3wP4tp1T</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1924601118</pqid></control><display><type>article</type><title>Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in Routine Care</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Gulilat, Markus, BMSc ; Tang, Anthony, MD ; Gryn, Steven E., MD ; Leong-Sit, Peter, MD ; Skanes, Allan C., MD ; Alfonsi, Jeffrey E., MD ; Dresser, George K., MD, PhD ; Henderson, Sara L., PharmD ; Rose, Rhiannon V., MMath ; Lizotte, Daniel J., PhD ; Teft, Wendy A., PhD ; Schwarz, Ute I., MD, PhD ; Tirona, Rommel G., PhD ; Kim, Richard B., MD</creator><creatorcontrib>Gulilat, Markus, BMSc ; Tang, Anthony, MD ; Gryn, Steven E., MD ; Leong-Sit, Peter, MD ; Skanes, Allan C., MD ; Alfonsi, Jeffrey E., MD ; Dresser, George K., MD, PhD ; Henderson, Sara L., PharmD ; Rose, Rhiannon V., MMath ; Lizotte, Daniel J., PhD ; Teft, Wendy A., PhD ; Schwarz, Ute I., MD, PhD ; Tirona, Rommel G., PhD ; Kim, Richard B., MD</creatorcontrib><description>Abstract Background Direct-acting oral anticoagulants (DOACs) are widely prescribed for stroke prevention in patients with atrial fibrillation. An important advantage of DOACs is that routine monitoring of anticoagulation response is not necessary. Nevertheless, due to their mechanism of action, DOAC anticoagulation effect can be inferred based on observed plasma concentration. However, there is paucity of data relating to observed interpatient variation in DOAC plasma concentrations in the post-market clinical setting. Methods We determined rivaroxaban and apixaban plasma concentrations in atrial fibrillation patients during routine clinic visits. Results Among 243 patients (rivaroxaban, n=94; apixaban, n=149) enrolled in this study, 60- and 50-fold interpatient variation in plasma concentration was observed for rivaroxaban and apixaban respectively. Approximately 12% of rivaroxaban and 13% of apixaban patients exceeded the 95th percentile for predicted maximum plasma concentration observed in clinical trials. Conclusions In this routine care setting, rivaroxaban and apixaban plasma concentrations tended to be more variable than those observed in clinical trials. Identification of additional clinical and molecular determinants that more fully predict patients at risk for excessively high or low DOAC concentrations may enable a more precise DOAC dosing regimen for the individual patient.</description><identifier>ISSN: 0828-282X</identifier><identifier>EISSN: 1916-7075</identifier><identifier>DOI: 10.1016/j.cjca.2017.04.008</identifier><identifier>PMID: 28754389</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Administration, Oral ; Aged ; Atrial Fibrillation - blood ; Atrial Fibrillation - complications ; Atrial Fibrillation - drug therapy ; Cardiovascular ; Dose-Response Relationship, Drug ; Factor Xa Inhibitors - administration & dosage ; Factor Xa Inhibitors - pharmacokinetics ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; Pyrazoles - administration & dosage ; Pyrazoles - pharmacokinetics ; Pyridones - administration & dosage ; Pyridones - pharmacokinetics ; Rivaroxaban - administration & dosage ; Rivaroxaban - pharmacokinetics ; Stroke - etiology ; Stroke - prevention & control ; Time Factors</subject><ispartof>Canadian journal of cardiology, 2017-08, Vol.33 (8), p.1036-1043</ispartof><rights>2017 Canadian Cardiovascular Society</rights><rights>Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-93eaba7e7cf2cf4097158cd6eb1e230ba454d7de37d14447c8e12c3dbdfc0f713</citedby><cites>FETCH-LOGICAL-c411t-93eaba7e7cf2cf4097158cd6eb1e230ba454d7de37d14447c8e12c3dbdfc0f713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cjca.2017.04.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28754389$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gulilat, Markus, BMSc</creatorcontrib><creatorcontrib>Tang, Anthony, MD</creatorcontrib><creatorcontrib>Gryn, Steven E., MD</creatorcontrib><creatorcontrib>Leong-Sit, Peter, MD</creatorcontrib><creatorcontrib>Skanes, Allan C., MD</creatorcontrib><creatorcontrib>Alfonsi, Jeffrey E., MD</creatorcontrib><creatorcontrib>Dresser, George K., MD, PhD</creatorcontrib><creatorcontrib>Henderson, Sara L., PharmD</creatorcontrib><creatorcontrib>Rose, Rhiannon V., MMath</creatorcontrib><creatorcontrib>Lizotte, Daniel J., PhD</creatorcontrib><creatorcontrib>Teft, Wendy A., PhD</creatorcontrib><creatorcontrib>Schwarz, Ute I., MD, PhD</creatorcontrib><creatorcontrib>Tirona, Rommel G., PhD</creatorcontrib><creatorcontrib>Kim, Richard B., MD</creatorcontrib><title>Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in Routine Care</title><title>Canadian journal of cardiology</title><addtitle>Can J Cardiol</addtitle><description>Abstract Background Direct-acting oral anticoagulants (DOACs) are widely prescribed for stroke prevention in patients with atrial fibrillation. An important advantage of DOACs is that routine monitoring of anticoagulation response is not necessary. Nevertheless, due to their mechanism of action, DOAC anticoagulation effect can be inferred based on observed plasma concentration. However, there is paucity of data relating to observed interpatient variation in DOAC plasma concentrations in the post-market clinical setting. Methods We determined rivaroxaban and apixaban plasma concentrations in atrial fibrillation patients during routine clinic visits. Results Among 243 patients (rivaroxaban, n=94; apixaban, n=149) enrolled in this study, 60- and 50-fold interpatient variation in plasma concentration was observed for rivaroxaban and apixaban respectively. Approximately 12% of rivaroxaban and 13% of apixaban patients exceeded the 95th percentile for predicted maximum plasma concentration observed in clinical trials. Conclusions In this routine care setting, rivaroxaban and apixaban plasma concentrations tended to be more variable than those observed in clinical trials. Identification of additional clinical and molecular determinants that more fully predict patients at risk for excessively high or low DOAC concentrations may enable a more precise DOAC dosing regimen for the individual patient.</description><subject>Administration, Oral</subject><subject>Aged</subject><subject>Atrial Fibrillation - blood</subject><subject>Atrial Fibrillation - complications</subject><subject>Atrial Fibrillation - drug therapy</subject><subject>Cardiovascular</subject><subject>Dose-Response Relationship, Drug</subject><subject>Factor Xa Inhibitors - administration & dosage</subject><subject>Factor Xa Inhibitors - pharmacokinetics</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Pyrazoles - administration & dosage</subject><subject>Pyrazoles - pharmacokinetics</subject><subject>Pyridones - administration & dosage</subject><subject>Pyridones - pharmacokinetics</subject><subject>Rivaroxaban - administration & dosage</subject><subject>Rivaroxaban - pharmacokinetics</subject><subject>Stroke - etiology</subject><subject>Stroke - prevention & control</subject><subject>Time Factors</subject><issn>0828-282X</issn><issn>1916-7075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhi0EokvhBTigHLkkzDjeOJEQUrWCUqkSqAXUm-XYE8khay92UtG3r9MtHDhw8lj6v1-abxh7jVAhYPNurMxodMUBZQWiAmifsA122JQS5PYp20DL25K3_OaEvUhpBBAoZfOcnfBWbkXddht2c-Fnigc9O_Jz8UNHl8fgC-eLK3erY_ite-0L7W1xdnDHz9dJp70udsGbDMUHID0QYZmdp2KnI71kzwY9JXr1-J6y758-ftt9Li-_nF_szi5LIxDnsqspd0qSZuBmENBJ3LbGNtQj8Rp6LbbCSku1tCiEkKYl5Ka2vR0MDBLrU_b22HuI4ddCaVZ7lwxNk_YUlqSw46IBRGxzlB-jJoaUIg3qEN1exzuFoFajalSrUbUaVSBUNpqhN4_9S78n-xf5ozAH3h8DlLe8dRRVMlmmIesimVnZ4P7f_-Ef3EzOO6Onn3RHaQxL9NmfQpW4AnW93nQ9KcoaOEBd3wP4tp1T</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Gulilat, Markus, BMSc</creator><creator>Tang, Anthony, MD</creator><creator>Gryn, Steven E., MD</creator><creator>Leong-Sit, Peter, MD</creator><creator>Skanes, Allan C., MD</creator><creator>Alfonsi, Jeffrey E., MD</creator><creator>Dresser, George K., MD, PhD</creator><creator>Henderson, Sara L., PharmD</creator><creator>Rose, Rhiannon V., MMath</creator><creator>Lizotte, Daniel J., PhD</creator><creator>Teft, Wendy A., PhD</creator><creator>Schwarz, Ute I., MD, PhD</creator><creator>Tirona, Rommel G., PhD</creator><creator>Kim, Richard B., MD</creator><general>Elsevier Inc</general><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></search><sort><creationdate>20170801</creationdate><title>Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in Routine Care</title><author>Gulilat, Markus, BMSc ; Tang, Anthony, MD ; Gryn, Steven E., MD ; Leong-Sit, Peter, MD ; Skanes, Allan C., MD ; Alfonsi, Jeffrey E., MD ; Dresser, George K., MD, PhD ; Henderson, Sara L., PharmD ; Rose, Rhiannon V., MMath ; Lizotte, Daniel J., PhD ; Teft, Wendy A., PhD ; Schwarz, Ute I., MD, PhD ; Tirona, Rommel G., PhD ; Kim, Richard B., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-93eaba7e7cf2cf4097158cd6eb1e230ba454d7de37d14447c8e12c3dbdfc0f713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Administration, Oral</topic><topic>Aged</topic><topic>Atrial Fibrillation - blood</topic><topic>Atrial Fibrillation - complications</topic><topic>Atrial Fibrillation - drug therapy</topic><topic>Cardiovascular</topic><topic>Dose-Response Relationship, Drug</topic><topic>Factor Xa Inhibitors - administration & dosage</topic><topic>Factor Xa Inhibitors - pharmacokinetics</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Pyrazoles - administration & dosage</topic><topic>Pyrazoles - pharmacokinetics</topic><topic>Pyridones - administration & dosage</topic><topic>Pyridones - pharmacokinetics</topic><topic>Rivaroxaban - administration & dosage</topic><topic>Rivaroxaban - pharmacokinetics</topic><topic>Stroke - etiology</topic><topic>Stroke - prevention & control</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gulilat, Markus, BMSc</creatorcontrib><creatorcontrib>Tang, Anthony, MD</creatorcontrib><creatorcontrib>Gryn, Steven E., MD</creatorcontrib><creatorcontrib>Leong-Sit, Peter, MD</creatorcontrib><creatorcontrib>Skanes, Allan C., MD</creatorcontrib><creatorcontrib>Alfonsi, Jeffrey E., MD</creatorcontrib><creatorcontrib>Dresser, George K., MD, PhD</creatorcontrib><creatorcontrib>Henderson, Sara L., PharmD</creatorcontrib><creatorcontrib>Rose, Rhiannon V., MMath</creatorcontrib><creatorcontrib>Lizotte, Daniel J., PhD</creatorcontrib><creatorcontrib>Teft, Wendy A., PhD</creatorcontrib><creatorcontrib>Schwarz, Ute I., MD, PhD</creatorcontrib><creatorcontrib>Tirona, Rommel G., PhD</creatorcontrib><creatorcontrib>Kim, Richard B., MD</creatorcontrib><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>Canadian journal of cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gulilat, Markus, BMSc</au><au>Tang, Anthony, MD</au><au>Gryn, Steven E., MD</au><au>Leong-Sit, Peter, MD</au><au>Skanes, Allan C., MD</au><au>Alfonsi, Jeffrey E., MD</au><au>Dresser, George K., MD, PhD</au><au>Henderson, Sara L., PharmD</au><au>Rose, Rhiannon V., MMath</au><au>Lizotte, Daniel J., PhD</au><au>Teft, Wendy A., PhD</au><au>Schwarz, Ute I., MD, PhD</au><au>Tirona, Rommel G., PhD</au><au>Kim, Richard B., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in Routine Care</atitle><jtitle>Canadian journal of cardiology</jtitle><addtitle>Can J Cardiol</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>33</volume><issue>8</issue><spage>1036</spage><epage>1043</epage><pages>1036-1043</pages><issn>0828-282X</issn><eissn>1916-7075</eissn><abstract>Abstract Background Direct-acting oral anticoagulants (DOACs) are widely prescribed for stroke prevention in patients with atrial fibrillation. An important advantage of DOACs is that routine monitoring of anticoagulation response is not necessary. Nevertheless, due to their mechanism of action, DOAC anticoagulation effect can be inferred based on observed plasma concentration. However, there is paucity of data relating to observed interpatient variation in DOAC plasma concentrations in the post-market clinical setting. Methods We determined rivaroxaban and apixaban plasma concentrations in atrial fibrillation patients during routine clinic visits. Results Among 243 patients (rivaroxaban, n=94; apixaban, n=149) enrolled in this study, 60- and 50-fold interpatient variation in plasma concentration was observed for rivaroxaban and apixaban respectively. Approximately 12% of rivaroxaban and 13% of apixaban patients exceeded the 95th percentile for predicted maximum plasma concentration observed in clinical trials. Conclusions In this routine care setting, rivaroxaban and apixaban plasma concentrations tended to be more variable than those observed in clinical trials. Identification of additional clinical and molecular determinants that more fully predict patients at risk for excessively high or low DOAC concentrations may enable a more precise DOAC dosing regimen for the individual patient.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>28754389</pmid><doi>10.1016/j.cjca.2017.04.008</doi><tpages>8</tpages></addata></record> |
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| subjects | Administration, Oral Aged Atrial Fibrillation - blood Atrial Fibrillation - complications Atrial Fibrillation - drug therapy Cardiovascular Dose-Response Relationship, Drug Factor Xa Inhibitors - administration & dosage Factor Xa Inhibitors - pharmacokinetics Female Follow-Up Studies Humans Male Middle Aged Prospective Studies Pyrazoles - administration & dosage Pyrazoles - pharmacokinetics Pyridones - administration & dosage Pyridones - pharmacokinetics Rivaroxaban - administration & dosage Rivaroxaban - pharmacokinetics Stroke - etiology Stroke - prevention & control Time Factors |
| title | Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in Routine Care |
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