Effectiveness of Reloading to Overcome Clopidogrel Nonresponsiveness in Patients With Acute Myocardial Infarction
Whether increasing doses of clopidogrel can overcome nonresponsiveness was evaluated. Clopidogrel nonresponsiveness was found in up to 25% of treated patients and was associated with worse prognosis in patients with acute coronary syndrome and patients undergoing coronary intervention. Adenosine dip...
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| Veröffentlicht in: | The American journal of cardiology 2008-09, Vol.102 (5), p.524-529 |
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| container_title | The American journal of cardiology |
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| creator | Matetzky, Shlomi, MD Fefer, Paul, MD Shenkman, Boris, MD, PhD Varon, David, MD Savion, Naphtali, MD Hod, Hanoch, MD |
| description | Whether increasing doses of clopidogrel can overcome nonresponsiveness was evaluated. Clopidogrel nonresponsiveness was found in up to 25% of treated patients and was associated with worse prognosis in patients with acute coronary syndrome and patients undergoing coronary intervention. Adenosine diphosphate (ADP)-induced platelet aggregation was prospectively determined on day 4 of acute myocardial infarction in 200 consecutive patients, who received clopidogrel 300 mg as a loading dose and 75 mg/day thereafter. Thirty patients (15%) had ADP-induced platelet aggregation ≥80% using light transmittance aggregometry and were considered clopidogrel nonresponders. Nonresponders were reloaded with clopidogrel 600 mg, followed by 150 mg/day for 4 weeks. A 75-mg/day dose was resumed thereafter. ADP-induced platelet aggregation was reassessed 4 hours after reloading and biweekly for 10 weeks. Flow cytometry was used to determine platelet P-selectin expression and fibrinogen binding before and 4 hours after reloading. ADP-induced platelet aggregation significantly decreased 4 hours after reloading (from 83 ± 6% to 56 ± 14%; p |
| doi_str_mv | 10.1016/j.amjcard.2008.04.028 |
| format | Article |
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Clopidogrel nonresponsiveness was found in up to 25% of treated patients and was associated with worse prognosis in patients with acute coronary syndrome and patients undergoing coronary intervention. Adenosine diphosphate (ADP)-induced platelet aggregation was prospectively determined on day 4 of acute myocardial infarction in 200 consecutive patients, who received clopidogrel 300 mg as a loading dose and 75 mg/day thereafter. Thirty patients (15%) had ADP-induced platelet aggregation ≥80% using light transmittance aggregometry and were considered clopidogrel nonresponders. Nonresponders were reloaded with clopidogrel 600 mg, followed by 150 mg/day for 4 weeks. A 75-mg/day dose was resumed thereafter. ADP-induced platelet aggregation was reassessed 4 hours after reloading and biweekly for 10 weeks. Flow cytometry was used to determine platelet P-selectin expression and fibrinogen binding before and 4 hours after reloading. ADP-induced platelet aggregation significantly decreased 4 hours after reloading (from 83 ± 6% to 56 ± 14%; p <0.01). The decrease in platelet aggregation was maintained throughout the 4-week doubled maintenance dose. After resuming a maintenance dose of 75 mg/day, ADP-induced platelet aggregation returned to 66 ± 12% (p <0.001), and 5 patients (17%) had ADP-induced platelet aggregation ≥80%. Flow cytometry showed a significant decrease in P-selectin expression (from 37 ± 16% to 26 ± 13%; p <0.01) and fibrinogen binding (from 84 ± 7% to 70 ± 13%; p <0.01) in ADP-stimulated platelets 4 hours after reloading. In conclusion, clopidogrel reloading and increased maintenance dose may overcome clopidogrel nonresponsiveness in patients with acute myocardial infarction.</description><identifier>ISSN: 0002-9149</identifier><identifier>EISSN: 1879-1913</identifier><identifier>DOI: 10.1016/j.amjcard.2008.04.028</identifier><identifier>PMID: 18721506</identifier><identifier>CODEN: AJCDAG</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Biological and medical sciences ; Blood Platelets - metabolism ; Blood products ; Cardiology ; Cardiology. Vascular system ; Cardiovascular ; Cells ; Coronary heart disease ; Dose-Response Relationship, Drug ; Electrocardiography ; Female ; Fibrinogen - drug effects ; Fibrinogen - metabolism ; Flow Cytometry ; Follow-Up Studies ; Heart ; Heart attacks ; Humans ; Male ; Medical prognosis ; Medical sciences ; Middle Aged ; Myocardial Infarction - blood ; Myocardial Infarction - drug therapy ; Myocardial Infarction - physiopathology ; Myocarditis. Cardiomyopathies ; P-Selectin - biosynthesis ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - administration & dosage ; Prospective Studies ; Ticlopidine - administration & dosage ; Ticlopidine - analogs & derivatives ; Treatment Outcome</subject><ispartof>The American journal of cardiology, 2008-09, Vol.102 (5), p.524-529</ispartof><rights>Elsevier Inc.</rights><rights>2008 Elsevier Inc.</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Elsevier Sequoia S.A. 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Clopidogrel nonresponsiveness was found in up to 25% of treated patients and was associated with worse prognosis in patients with acute coronary syndrome and patients undergoing coronary intervention. Adenosine diphosphate (ADP)-induced platelet aggregation was prospectively determined on day 4 of acute myocardial infarction in 200 consecutive patients, who received clopidogrel 300 mg as a loading dose and 75 mg/day thereafter. Thirty patients (15%) had ADP-induced platelet aggregation ≥80% using light transmittance aggregometry and were considered clopidogrel nonresponders. Nonresponders were reloaded with clopidogrel 600 mg, followed by 150 mg/day for 4 weeks. A 75-mg/day dose was resumed thereafter. ADP-induced platelet aggregation was reassessed 4 hours after reloading and biweekly for 10 weeks. Flow cytometry was used to determine platelet P-selectin expression and fibrinogen binding before and 4 hours after reloading. ADP-induced platelet aggregation significantly decreased 4 hours after reloading (from 83 ± 6% to 56 ± 14%; p <0.01). The decrease in platelet aggregation was maintained throughout the 4-week doubled maintenance dose. After resuming a maintenance dose of 75 mg/day, ADP-induced platelet aggregation returned to 66 ± 12% (p <0.001), and 5 patients (17%) had ADP-induced platelet aggregation ≥80%. Flow cytometry showed a significant decrease in P-selectin expression (from 37 ± 16% to 26 ± 13%; p <0.01) and fibrinogen binding (from 84 ± 7% to 70 ± 13%; p <0.01) in ADP-stimulated platelets 4 hours after reloading. In conclusion, clopidogrel reloading and increased maintenance dose may overcome clopidogrel nonresponsiveness in patients with acute myocardial infarction.</description><subject>Biological and medical sciences</subject><subject>Blood Platelets - metabolism</subject><subject>Blood products</subject><subject>Cardiology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular</subject><subject>Cells</subject><subject>Coronary heart disease</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrocardiography</subject><subject>Female</subject><subject>Fibrinogen - drug effects</subject><subject>Fibrinogen - metabolism</subject><subject>Flow Cytometry</subject><subject>Follow-Up Studies</subject><subject>Heart</subject><subject>Heart attacks</subject><subject>Humans</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Myocardial Infarction - blood</subject><subject>Myocardial Infarction - drug therapy</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>P-Selectin - biosynthesis</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation Inhibitors - administration & dosage</subject><subject>Prospective Studies</subject><subject>Ticlopidine - administration & dosage</subject><subject>Ticlopidine - analogs & derivatives</subject><subject>Treatment Outcome</subject><issn>0002-9149</issn><issn>1879-1913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9v1DAQxSMEokvhI4AsJLhtGNtxEl9A1aq0lQpF_BFHy-uMi0Nib-3sSvvtcbRLkXrhZFn6vXkz86YoXlIoKdD6XV_qsTc6diUDaEuoSmDto2JB20YuqaT8cbEAALaUtJInxbOU-vylVNRPi5MMMSqgXhR359aimdwOPaZEgiVfcQi6c_6WTIHc7DCaMCJZDWHjunAbcSCfg4-YNsGnvzLnyRc9OfRTIj_d9Iucme2E5NM-zB06PZArb3XMPsE_L55YPSR8cXxPix8fz7-vLpfXNxdXq7PrpakaMS2tEWCbdaPXIGnTrNes6WTNWqsr28oWoONGC0TZCs7RopSatyCtsB1y3Ul-Wrw91N3EcLfFNKnRJYPDoD2GbVK1rIQUvMrg6wdgH7bR594U48Abnv0zJA6QiSGliFZtoht13CsKag5E9eoYiJoDUVCpHEjWvToW365H7P6pjglk4M0R0MnowUbtjUv3HIOaCibncT4cOMw72zmMKpm8cIOdizlA1QX331beP6hgBuddNv2Ne0z3Q1OVmAL1bb6e-XggL7sRVc3_AOLYwkk</recordid><startdate>20080901</startdate><enddate>20080901</enddate><creator>Matetzky, Shlomi, MD</creator><creator>Fefer, Paul, MD</creator><creator>Shenkman, Boris, MD, PhD</creator><creator>Varon, David, MD</creator><creator>Savion, Naphtali, MD</creator><creator>Hod, Hanoch, MD</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</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>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20080901</creationdate><title>Effectiveness of Reloading to Overcome Clopidogrel Nonresponsiveness in Patients With Acute Myocardial Infarction</title><author>Matetzky, Shlomi, MD ; Fefer, Paul, MD ; Shenkman, Boris, MD, PhD ; Varon, David, MD ; Savion, Naphtali, MD ; Hod, Hanoch, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-fc50f7b7ab09177bb27d9628fa4f89800d3ca5ee98533efe99a3809f5fde3ad93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Biological and medical sciences</topic><topic>Blood Platelets - metabolism</topic><topic>Blood products</topic><topic>Cardiology</topic><topic>Cardiology. 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Cardiomyopathies</topic><topic>P-Selectin - biosynthesis</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Aggregation Inhibitors - administration & dosage</topic><topic>Prospective Studies</topic><topic>Ticlopidine - administration & dosage</topic><topic>Ticlopidine - analogs & derivatives</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matetzky, Shlomi, MD</creatorcontrib><creatorcontrib>Fefer, Paul, MD</creatorcontrib><creatorcontrib>Shenkman, Boris, MD, PhD</creatorcontrib><creatorcontrib>Varon, David, MD</creatorcontrib><creatorcontrib>Savion, Naphtali, MD</creatorcontrib><creatorcontrib>Hod, Hanoch, MD</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>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biochemistry Abstracts 1</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matetzky, Shlomi, MD</au><au>Fefer, Paul, MD</au><au>Shenkman, Boris, MD, PhD</au><au>Varon, David, MD</au><au>Savion, Naphtali, MD</au><au>Hod, Hanoch, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effectiveness of Reloading to Overcome Clopidogrel Nonresponsiveness in Patients With Acute Myocardial Infarction</atitle><jtitle>The American journal of cardiology</jtitle><addtitle>Am J Cardiol</addtitle><date>2008-09-01</date><risdate>2008</risdate><volume>102</volume><issue>5</issue><spage>524</spage><epage>529</epage><pages>524-529</pages><issn>0002-9149</issn><eissn>1879-1913</eissn><coden>AJCDAG</coden><abstract>Whether increasing doses of clopidogrel can overcome nonresponsiveness was evaluated. Clopidogrel nonresponsiveness was found in up to 25% of treated patients and was associated with worse prognosis in patients with acute coronary syndrome and patients undergoing coronary intervention. Adenosine diphosphate (ADP)-induced platelet aggregation was prospectively determined on day 4 of acute myocardial infarction in 200 consecutive patients, who received clopidogrel 300 mg as a loading dose and 75 mg/day thereafter. Thirty patients (15%) had ADP-induced platelet aggregation ≥80% using light transmittance aggregometry and were considered clopidogrel nonresponders. Nonresponders were reloaded with clopidogrel 600 mg, followed by 150 mg/day for 4 weeks. A 75-mg/day dose was resumed thereafter. ADP-induced platelet aggregation was reassessed 4 hours after reloading and biweekly for 10 weeks. Flow cytometry was used to determine platelet P-selectin expression and fibrinogen binding before and 4 hours after reloading. ADP-induced platelet aggregation significantly decreased 4 hours after reloading (from 83 ± 6% to 56 ± 14%; p <0.01). The decrease in platelet aggregation was maintained throughout the 4-week doubled maintenance dose. After resuming a maintenance dose of 75 mg/day, ADP-induced platelet aggregation returned to 66 ± 12% (p <0.001), and 5 patients (17%) had ADP-induced platelet aggregation ≥80%. Flow cytometry showed a significant decrease in P-selectin expression (from 37 ± 16% to 26 ± 13%; p <0.01) and fibrinogen binding (from 84 ± 7% to 70 ± 13%; p <0.01) in ADP-stimulated platelets 4 hours after reloading. In conclusion, clopidogrel reloading and increased maintenance dose may overcome clopidogrel nonresponsiveness in patients with acute myocardial infarction.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>18721506</pmid><doi>10.1016/j.amjcard.2008.04.028</doi><tpages>6</tpages></addata></record> |
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| subjects | Biological and medical sciences Blood Platelets - metabolism Blood products Cardiology Cardiology. Vascular system Cardiovascular Cells Coronary heart disease Dose-Response Relationship, Drug Electrocardiography Female Fibrinogen - drug effects Fibrinogen - metabolism Flow Cytometry Follow-Up Studies Heart Heart attacks Humans Male Medical prognosis Medical sciences Middle Aged Myocardial Infarction - blood Myocardial Infarction - drug therapy Myocardial Infarction - physiopathology Myocarditis. Cardiomyopathies P-Selectin - biosynthesis Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - administration & dosage Prospective Studies Ticlopidine - administration & dosage Ticlopidine - analogs & derivatives Treatment Outcome |
| title | Effectiveness of Reloading to Overcome Clopidogrel Nonresponsiveness in Patients With Acute Myocardial Infarction |
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