Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction

Background Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrino...

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Veröffentlicht in:European heart journal 2003-10, Vol.24 (20), p.1807-1814
Hauptverfasser: Savonitto, S., Armstrong, P.W., Lincoff, A.M., Jia, G., Sila, C.A., Booth, J., Terrosu, P., Cavallini, C., White, H.D., Ardissino, D., Califf, R.M., Topol, E.J.
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container_end_page 1814
container_issue 20
container_start_page 1807
container_title European heart journal
container_volume 24
creator Savonitto, S.
Armstrong, P.W.
Lincoff, A.M.
Jia, G.
Sila, C.A.
Booth, J.
Terrosu, P.
Cavallini, C.
White, H.D.
Ardissino, D.
Califf, R.M.
Topol, E.J.
description Background Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting. Methods and results We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10U bolus twice, 30min apart) with standard-dose heparin (5000U bolus followed by an infusion of 1000Uh−1for patients ≥80kg and 800Uh−1for those
doi_str_mv 10.1016/j.ehj.2003.07.004
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The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting. Methods and results We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10U bolus twice, 30min apart) with standard-dose heparin (5000U bolus followed by an infusion of 1000Uh−1for patients ≥80kg and 800Uh−1for those &lt;80kg) or combination therapy with abciximab (0.25mg/kg bolus and 0.125μg/kg/min for 12h) and half-dose reteplase (two boluses of 5U 30min apart) with reduced-dose heparin (60Ukg−1bolus, maximum 5000U, followed by an infusion of 7Ukg−1h−1) in the 16 588 patients randomized in the GUSTO V trial. Overall, the incidence of intracranial haemorrhage was similar in the two groups (0.6% vs 0.6%; OR 1.05, 95% CI 0.71, 1.56). The median (25th–75th) time from drug administration to intracranial haemorrhage was 5.5 (3.4–11) hours with combination therapy and 9.2 (5.9–22) hours with reteplase (P=0.048). Among the multivariable predictors of intracranial haemorrhage, only age showed a significant interaction with treatment effect (age per treatment interaction chi-square 4.60, P=0.032) with a lower risk of combination therapy for younger patients and a higher risk for the elderly. Conclusions Although no additional risk of intracranial haemorrhage has been observed with combination therapy in the whole population, a significant age pertreatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly.</description><identifier>ISSN: 0195-668X</identifier><identifier>EISSN: 1522-9645</identifier><identifier>DOI: 10.1016/j.ehj.2003.07.004</identifier><language>eng</language><publisher>Oxford University Press</publisher><subject>Abciximab ; Fibrinolysis ; Heparin ; Myocardial infarction ; Stroke</subject><ispartof>European heart journal, 2003-10, Vol.24 (20), p.1807-1814</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids></links><search><creatorcontrib>Savonitto, S.</creatorcontrib><creatorcontrib>Armstrong, P.W.</creatorcontrib><creatorcontrib>Lincoff, A.M.</creatorcontrib><creatorcontrib>Jia, G.</creatorcontrib><creatorcontrib>Sila, C.A.</creatorcontrib><creatorcontrib>Booth, J.</creatorcontrib><creatorcontrib>Terrosu, P.</creatorcontrib><creatorcontrib>Cavallini, C.</creatorcontrib><creatorcontrib>White, H.D.</creatorcontrib><creatorcontrib>Ardissino, D.</creatorcontrib><creatorcontrib>Califf, R.M.</creatorcontrib><creatorcontrib>Topol, E.J.</creatorcontrib><title>Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction</title><title>European heart journal</title><addtitle>Eur Heart J</addtitle><description>Background Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting. Methods and results We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10U bolus twice, 30min apart) with standard-dose heparin (5000U bolus followed by an infusion of 1000Uh−1for patients ≥80kg and 800Uh−1for those &lt;80kg) or combination therapy with abciximab (0.25mg/kg bolus and 0.125μg/kg/min for 12h) and half-dose reteplase (two boluses of 5U 30min apart) with reduced-dose heparin (60Ukg−1bolus, maximum 5000U, followed by an infusion of 7Ukg−1h−1) in the 16 588 patients randomized in the GUSTO V trial. Overall, the incidence of intracranial haemorrhage was similar in the two groups (0.6% vs 0.6%; OR 1.05, 95% CI 0.71, 1.56). The median (25th–75th) time from drug administration to intracranial haemorrhage was 5.5 (3.4–11) hours with combination therapy and 9.2 (5.9–22) hours with reteplase (P=0.048). Among the multivariable predictors of intracranial haemorrhage, only age showed a significant interaction with treatment effect (age per treatment interaction chi-square 4.60, P=0.032) with a lower risk of combination therapy for younger patients and a higher risk for the elderly. Conclusions Although no additional risk of intracranial haemorrhage has been observed with combination therapy in the whole population, a significant age pertreatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly.</description><subject>Abciximab</subject><subject>Fibrinolysis</subject><subject>Heparin</subject><subject>Myocardial infarction</subject><subject>Stroke</subject><issn>0195-668X</issn><issn>1522-9645</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqVjUtOwzAURS0EEuGzAGbeQFI7H6edgoBmShFUTKIXx6lfmtjVixFkA6y7RWIDjK50dHQuY3dSJFJItegTY_skFSJLRJkIkZ-xSBZpGq9UXpyzSMhVESu13F6yq2nqhRBLJVXEfl5w2nPfcXSBQBM4hIFbMKMnsrAz_AuD5dqPDTrT8g4bQueHOaDm4Fq-G2btD-SDQcerqllUVQWnmsUGgycerCE4zCfCQX8Gw8fZa6D29wZdB6QDenfDLjoYJnP7t9csfnp8fVjHOAXzXR8IR6C5BtrXqszKol5vP-q3cnO_yZ7f6zz7r38E_LRiAg</recordid><startdate>20031001</startdate><enddate>20031001</enddate><creator>Savonitto, S.</creator><creator>Armstrong, P.W.</creator><creator>Lincoff, A.M.</creator><creator>Jia, G.</creator><creator>Sila, C.A.</creator><creator>Booth, J.</creator><creator>Terrosu, P.</creator><creator>Cavallini, C.</creator><creator>White, H.D.</creator><creator>Ardissino, D.</creator><creator>Califf, R.M.</creator><creator>Topol, E.J.</creator><general>Oxford University Press</general><scope>BSCLL</scope></search><sort><creationdate>20031001</creationdate><title>Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction</title><author>Savonitto, S. ; Armstrong, P.W. ; Lincoff, A.M. ; Jia, G. ; Sila, C.A. ; Booth, J. ; Terrosu, P. ; Cavallini, C. ; White, H.D. ; Ardissino, D. ; Califf, R.M. ; Topol, E.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-istex_primary_ark_67375_HXZ_V7SBS3GW_43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Abciximab</topic><topic>Fibrinolysis</topic><topic>Heparin</topic><topic>Myocardial infarction</topic><topic>Stroke</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Savonitto, S.</creatorcontrib><creatorcontrib>Armstrong, P.W.</creatorcontrib><creatorcontrib>Lincoff, A.M.</creatorcontrib><creatorcontrib>Jia, G.</creatorcontrib><creatorcontrib>Sila, C.A.</creatorcontrib><creatorcontrib>Booth, J.</creatorcontrib><creatorcontrib>Terrosu, P.</creatorcontrib><creatorcontrib>Cavallini, C.</creatorcontrib><creatorcontrib>White, H.D.</creatorcontrib><creatorcontrib>Ardissino, D.</creatorcontrib><creatorcontrib>Califf, R.M.</creatorcontrib><creatorcontrib>Topol, E.J.</creatorcontrib><collection>Istex</collection><jtitle>European heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Savonitto, S.</au><au>Armstrong, P.W.</au><au>Lincoff, A.M.</au><au>Jia, G.</au><au>Sila, C.A.</au><au>Booth, J.</au><au>Terrosu, P.</au><au>Cavallini, C.</au><au>White, H.D.</au><au>Ardissino, D.</au><au>Califf, R.M.</au><au>Topol, E.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction</atitle><jtitle>European heart journal</jtitle><addtitle>Eur Heart J</addtitle><date>2003-10-01</date><risdate>2003</risdate><volume>24</volume><issue>20</issue><spage>1807</spage><epage>1814</epage><pages>1807-1814</pages><issn>0195-668X</issn><eissn>1522-9645</eissn><abstract>Background Intracranial haemorrhage is an important limitation to pharmacologic reperfusion therapy for acute myocardial infarction. The combination of a glycoprotein IIb/IIIa inhibitor, half-dose plasminogen activator and reduced-dose heparin has been evaluated as an alternative to standard fibrinolytic therapy in this setting. Methods and results We evaluated the relation between univariate and multivariate predictors of intracranial haemorrhage and the effect of treatment with either reteplase alone (10U bolus twice, 30min apart) with standard-dose heparin (5000U bolus followed by an infusion of 1000Uh−1for patients ≥80kg and 800Uh−1for those &lt;80kg) or combination therapy with abciximab (0.25mg/kg bolus and 0.125μg/kg/min for 12h) and half-dose reteplase (two boluses of 5U 30min apart) with reduced-dose heparin (60Ukg−1bolus, maximum 5000U, followed by an infusion of 7Ukg−1h−1) in the 16 588 patients randomized in the GUSTO V trial. Overall, the incidence of intracranial haemorrhage was similar in the two groups (0.6% vs 0.6%; OR 1.05, 95% CI 0.71, 1.56). The median (25th–75th) time from drug administration to intracranial haemorrhage was 5.5 (3.4–11) hours with combination therapy and 9.2 (5.9–22) hours with reteplase (P=0.048). Among the multivariable predictors of intracranial haemorrhage, only age showed a significant interaction with treatment effect (age per treatment interaction chi-square 4.60, P=0.032) with a lower risk of combination therapy for younger patients and a higher risk for the elderly. Conclusions Although no additional risk of intracranial haemorrhage has been observed with combination therapy in the whole population, a significant age pertreatment interaction exists, with a lower risk with combination therapy in younger patients, and a higher risk in the elderly.</abstract><pub>Oxford University Press</pub><doi>10.1016/j.ehj.2003.07.004</doi></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals
subjects Abciximab
Fibrinolysis
Heparin
Myocardial infarction
Stroke
title Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction
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