Multiple daily doses of acetyl‐salicylic acid (ASA) overcome reduced platelet response to once‐daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial

Summary Background The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post‐operative platelet turnover. Objectives To determine whether acetyl‐salicylic acid (ASA) 325 mg once‐daily or 81 mg four‐times daily ov...

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Veröffentlicht in:Journal of thrombosis and haemostasis 2015-03, Vol.13 (3), p.448-456
Hauptverfasser: Paikin, J. S., Hirsh, J., Ginsberg, J. S., Weitz, J. I., Chan, N. C., Whitlock, R. P., Pare, G., Johnston, M., Eikelboom, J. W.
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container_end_page 456
container_issue 3
container_start_page 448
container_title Journal of thrombosis and haemostasis
container_volume 13
creator Paikin, J. S.
Hirsh, J.
Ginsberg, J. S.
Weitz, J. I.
Chan, N. C.
Whitlock, R. P.
Pare, G.
Johnston, M.
Eikelboom, J. W.
description Summary Background The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post‐operative platelet turnover. Objectives To determine whether acetyl‐salicylic acid (ASA) 325 mg once‐daily or 81 mg four‐times daily overcomes the impaired response to ASA 81 mg once‐daily in post‐operative coronary artery bypass graft (CABG) patients. Methods We randomized 110 patients undergoing CABG surgery to either ASA 81 mg once‐daily, 81 mg four times daily or 325 mg once‐daily and compared their effects on serum thromboxane B2 (TXB2) suppression and arachidonate‐induced platelet aggregation. Results One hundred patients were included in the final analysis. Platelet counts fell after surgery, reached a nadir on day 2, and then gradually increased. Although there was near complete suppression of TXB2 on the second or third post‐operative day, TXB2 levels increased in parallel with the rise in platelet count on subsequent days. This increase was most marked in patients receiving ASA 81 mg once‐daily and less evident in those receiving ASA four times daily. On post‐operative day 4, (i) median TXB2 levels were lower with four times daily ASA than with either ASA 81 mg once‐daily (1.1 ng/mL; Quartile(Q) Q1,Q3: 0.5, 2.4 and 13.3 ng/mL; Q1,Q3: 7.8, 30.8 ng/mL, respectively; P 
doi_str_mv 10.1111/jth.12832
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S. ; Hirsh, J. ; Ginsberg, J. S. ; Weitz, J. I. ; Chan, N. C. ; Whitlock, R. P. ; Pare, G. ; Johnston, M. ; Eikelboom, J. W.</creator><creatorcontrib>Paikin, J. S. ; Hirsh, J. ; Ginsberg, J. S. ; Weitz, J. I. ; Chan, N. C. ; Whitlock, R. P. ; Pare, G. ; Johnston, M. ; Eikelboom, J. W.</creatorcontrib><description>Summary Background The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post‐operative platelet turnover. Objectives To determine whether acetyl‐salicylic acid (ASA) 325 mg once‐daily or 81 mg four‐times daily overcomes the impaired response to ASA 81 mg once‐daily in post‐operative coronary artery bypass graft (CABG) patients. Methods We randomized 110 patients undergoing CABG surgery to either ASA 81 mg once‐daily, 81 mg four times daily or 325 mg once‐daily and compared their effects on serum thromboxane B2 (TXB2) suppression and arachidonate‐induced platelet aggregation. Results One hundred patients were included in the final analysis. Platelet counts fell after surgery, reached a nadir on day 2, and then gradually increased. Although there was near complete suppression of TXB2 on the second or third post‐operative day, TXB2 levels increased in parallel with the rise in platelet count on subsequent days. This increase was most marked in patients receiving ASA 81 mg once‐daily and less evident in those receiving ASA four times daily. On post‐operative day 4, (i) median TXB2 levels were lower with four times daily ASA than with either ASA 81 mg once‐daily (1.1 ng/mL; Quartile(Q) Q1,Q3: 0.5, 2.4 and 13.3 ng/mL; Q1,Q3: 7.8, 30.8 ng/mL, respectively; P &lt; 0.0001) or ASA 325 mg once‐daily (3.4 ng/mL; Q1,Q3: 2.0, 8.2 ng/mL; P = 0.002), and (ii) ASA given four times daily was more effective than ASA 81 mg once‐daily and 325 mg once‐daily at suppressing platelet aggregation. Conclusions Four times daily ASA is more effective than ASA 81 and 325 mg once‐daily at suppressing serum TXB2 formation and platelet aggregation immediately following CABG surgery.</description><identifier>ISSN: 1538-7933</identifier><identifier>ISSN: 1538-7836</identifier><identifier>EISSN: 1538-7836</identifier><identifier>DOI: 10.1111/jth.12832</identifier><identifier>PMID: 25546465</identifier><language>eng</language><publisher>England: Elsevier Limited</publisher><subject>Aged ; aspirin ; Aspirin - administration &amp; dosage ; Aspirin - adverse effects ; Biomarkers - blood ; Blood Platelets - drug effects ; Blood Platelets - metabolism ; coronary artery bypass ; Coronary Artery Bypass - adverse effects ; Drug Administration Schedule ; Drug Resistance ; Female ; Humans ; Male ; Middle Aged ; Ontario ; perioperative period ; Pilot Projects ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - administration &amp; dosage ; Platelet Aggregation Inhibitors - adverse effects ; Platelet Count ; Platelet Function Tests ; Thromboxane B2 - blood ; Time Factors ; Treatment Outcome</subject><ispartof>Journal of thrombosis and haemostasis, 2015-03, Vol.13 (3), p.448-456</ispartof><rights>2014 International Society on Thrombosis and Haemostasis</rights><rights>2014 International Society on Thrombosis and Haemostasis.</rights><rights>Copyright © 2015 International Society on Thrombosis and Haemostasis</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3882-e542de971d621552501072acb6e858a8eeb9b6b36f92c7053528bebfd917eecb3</citedby><cites>FETCH-LOGICAL-c3882-e542de971d621552501072acb6e858a8eeb9b6b36f92c7053528bebfd917eecb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25546465$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Paikin, J. S.</creatorcontrib><creatorcontrib>Hirsh, J.</creatorcontrib><creatorcontrib>Ginsberg, J. S.</creatorcontrib><creatorcontrib>Weitz, J. I.</creatorcontrib><creatorcontrib>Chan, N. C.</creatorcontrib><creatorcontrib>Whitlock, R. P.</creatorcontrib><creatorcontrib>Pare, G.</creatorcontrib><creatorcontrib>Johnston, M.</creatorcontrib><creatorcontrib>Eikelboom, J. W.</creatorcontrib><title>Multiple daily doses of acetyl‐salicylic acid (ASA) overcome reduced platelet response to once‐daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial</title><title>Journal of thrombosis and haemostasis</title><addtitle>J Thromb Haemost</addtitle><description>Summary Background The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post‐operative platelet turnover. Objectives To determine whether acetyl‐salicylic acid (ASA) 325 mg once‐daily or 81 mg four‐times daily overcomes the impaired response to ASA 81 mg once‐daily in post‐operative coronary artery bypass graft (CABG) patients. Methods We randomized 110 patients undergoing CABG surgery to either ASA 81 mg once‐daily, 81 mg four times daily or 325 mg once‐daily and compared their effects on serum thromboxane B2 (TXB2) suppression and arachidonate‐induced platelet aggregation. Results One hundred patients were included in the final analysis. Platelet counts fell after surgery, reached a nadir on day 2, and then gradually increased. Although there was near complete suppression of TXB2 on the second or third post‐operative day, TXB2 levels increased in parallel with the rise in platelet count on subsequent days. This increase was most marked in patients receiving ASA 81 mg once‐daily and less evident in those receiving ASA four times daily. On post‐operative day 4, (i) median TXB2 levels were lower with four times daily ASA than with either ASA 81 mg once‐daily (1.1 ng/mL; Quartile(Q) Q1,Q3: 0.5, 2.4 and 13.3 ng/mL; Q1,Q3: 7.8, 30.8 ng/mL, respectively; P &lt; 0.0001) or ASA 325 mg once‐daily (3.4 ng/mL; Q1,Q3: 2.0, 8.2 ng/mL; P = 0.002), and (ii) ASA given four times daily was more effective than ASA 81 mg once‐daily and 325 mg once‐daily at suppressing platelet aggregation. Conclusions Four times daily ASA is more effective than ASA 81 and 325 mg once‐daily at suppressing serum TXB2 formation and platelet aggregation immediately following CABG surgery.</description><subject>Aged</subject><subject>aspirin</subject><subject>Aspirin - administration &amp; dosage</subject><subject>Aspirin - adverse effects</subject><subject>Biomarkers - blood</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - metabolism</subject><subject>coronary artery bypass</subject><subject>Coronary Artery Bypass - adverse effects</subject><subject>Drug Administration Schedule</subject><subject>Drug Resistance</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Ontario</subject><subject>perioperative period</subject><subject>Pilot Projects</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation Inhibitors - administration &amp; dosage</subject><subject>Platelet Aggregation Inhibitors - adverse effects</subject><subject>Platelet Count</subject><subject>Platelet Function Tests</subject><subject>Thromboxane B2 - blood</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><issn>1538-7933</issn><issn>1538-7836</issn><issn>1538-7836</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1u1TAQhS1ERUthwQsgS2zo4raxfZ047K4q6I-KWFDWkX8mxVe-cbCdorDiEXigPg1PwtC07LBkeXx85htZh5BXrDpmuE625esx40rwJ-SASaFWjRL108e6FWKfPM95W1Wslbx6Rva5lOt6XcsDcvdxCsWPAajTPszUxQyZxp5qC2UOv3_-yjp4O-NGyTv6dvN5c0TjLSQbd0ATuMmCo2PQBQIUFPIYhwy0RBoHC0hYyNhHdV8gURtTHHSaqU54namZR50zvUn4TPOUblB8RzUdfYgI1IOLO_8Dh9g4lBRDwLIkr8MLstfrkOHlw3lIvnx4f316vrr6dHZxurlaWaEUX4Fccwdtw1zNmZRcVqxquLamBiWVVgCmNbURdd9y21RSSK4MmN61rAGwRhySNwt3TPHbBLl02zilAUd2rJZt06i2keg6Wlw2xZwT9N2Y_A7_2bGq-5tThzl19zmh9_UDcTI7cP-cj8Gg4WQxfPcB5v-Tusvr8wX5B5jXom8</recordid><startdate>201503</startdate><enddate>201503</enddate><creator>Paikin, J. S.</creator><creator>Hirsh, J.</creator><creator>Ginsberg, J. S.</creator><creator>Weitz, J. I.</creator><creator>Chan, N. C.</creator><creator>Whitlock, R. P.</creator><creator>Pare, G.</creator><creator>Johnston, M.</creator><creator>Eikelboom, J. W.</creator><general>Elsevier Limited</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>7T5</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>201503</creationdate><title>Multiple daily doses of acetyl‐salicylic acid (ASA) overcome reduced platelet response to once‐daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial</title><author>Paikin, J. S. ; Hirsh, J. ; Ginsberg, J. S. ; Weitz, J. I. ; Chan, N. C. ; Whitlock, R. P. ; Pare, G. ; Johnston, M. ; Eikelboom, J. 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S.</creatorcontrib><creatorcontrib>Hirsh, J.</creatorcontrib><creatorcontrib>Ginsberg, J. S.</creatorcontrib><creatorcontrib>Weitz, J. I.</creatorcontrib><creatorcontrib>Chan, N. C.</creatorcontrib><creatorcontrib>Whitlock, R. P.</creatorcontrib><creatorcontrib>Pare, G.</creatorcontrib><creatorcontrib>Johnston, M.</creatorcontrib><creatorcontrib>Eikelboom, J. W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><jtitle>Journal of thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paikin, J. S.</au><au>Hirsh, J.</au><au>Ginsberg, J. S.</au><au>Weitz, J. I.</au><au>Chan, N. C.</au><au>Whitlock, R. P.</au><au>Pare, G.</au><au>Johnston, M.</au><au>Eikelboom, J. W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple daily doses of acetyl‐salicylic acid (ASA) overcome reduced platelet response to once‐daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial</atitle><jtitle>Journal of thrombosis and haemostasis</jtitle><addtitle>J Thromb Haemost</addtitle><date>2015-03</date><risdate>2015</risdate><volume>13</volume><issue>3</issue><spage>448</spage><epage>456</epage><pages>448-456</pages><issn>1538-7933</issn><issn>1538-7836</issn><eissn>1538-7836</eissn><abstract>Summary Background The efficacy of ASA for prevention of graft failure following CABG surgery may be limited by incomplete platelet inhibition due to increased post‐operative platelet turnover. Objectives To determine whether acetyl‐salicylic acid (ASA) 325 mg once‐daily or 81 mg four‐times daily overcomes the impaired response to ASA 81 mg once‐daily in post‐operative coronary artery bypass graft (CABG) patients. Methods We randomized 110 patients undergoing CABG surgery to either ASA 81 mg once‐daily, 81 mg four times daily or 325 mg once‐daily and compared their effects on serum thromboxane B2 (TXB2) suppression and arachidonate‐induced platelet aggregation. Results One hundred patients were included in the final analysis. Platelet counts fell after surgery, reached a nadir on day 2, and then gradually increased. Although there was near complete suppression of TXB2 on the second or third post‐operative day, TXB2 levels increased in parallel with the rise in platelet count on subsequent days. This increase was most marked in patients receiving ASA 81 mg once‐daily and less evident in those receiving ASA four times daily. On post‐operative day 4, (i) median TXB2 levels were lower with four times daily ASA than with either ASA 81 mg once‐daily (1.1 ng/mL; Quartile(Q) Q1,Q3: 0.5, 2.4 and 13.3 ng/mL; Q1,Q3: 7.8, 30.8 ng/mL, respectively; P &lt; 0.0001) or ASA 325 mg once‐daily (3.4 ng/mL; Q1,Q3: 2.0, 8.2 ng/mL; P = 0.002), and (ii) ASA given four times daily was more effective than ASA 81 mg once‐daily and 325 mg once‐daily at suppressing platelet aggregation. Conclusions Four times daily ASA is more effective than ASA 81 and 325 mg once‐daily at suppressing serum TXB2 formation and platelet aggregation immediately following CABG surgery.</abstract><cop>England</cop><pub>Elsevier Limited</pub><pmid>25546465</pmid><doi>10.1111/jth.12832</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
aspirin
Aspirin - administration & dosage
Aspirin - adverse effects
Biomarkers - blood
Blood Platelets - drug effects
Blood Platelets - metabolism
coronary artery bypass
Coronary Artery Bypass - adverse effects
Drug Administration Schedule
Drug Resistance
Female
Humans
Male
Middle Aged
Ontario
perioperative period
Pilot Projects
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - administration & dosage
Platelet Aggregation Inhibitors - adverse effects
Platelet Count
Platelet Function Tests
Thromboxane B2 - blood
Time Factors
Treatment Outcome
title Multiple daily doses of acetyl‐salicylic acid (ASA) overcome reduced platelet response to once‐daily ASA after coronary artery bypass graft surgery: a pilot randomized controlled trial
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