Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events
Identifieur interne : 001C73 ( PascalFrancis/Curation ); précédent : 001C72; suivant : 001C74Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events
Auteurs : Deepak L. Bhatt [États-Unis] ; Keith A. A. Fox [Royaume-Uni] ; Werner Hacke [Allemagne] ; Peter B. Berger [États-Unis] ; Henry R. Black [États-Unis] ; William E. Boden [États-Unis] ; Patrice Cacoub [France] ; Eric A. Cohen [Canada] ; Mark A. Creager [États-Unis] ; J. Donald Easton [États-Unis] ; Marcus D. Flather [Royaume-Uni] ; Steven M. Haffner [États-Unis] ; Christian W. Hamm [Allemagne] ; Graeme J. Hankey [Australie] ; S. Claiborne Johnston [États-Unis] ; Koon-Hou Mak [Singapour] ; Jean-Louis Mas [France] ; Gilles Montalescot [France] ; Thomas A. Pearson [États-Unis] ; P. Gabriel Steg ; Steven R. Steinhubl ; Michael A. Weber ; Danielle M. Brennan [États-Unis] ; Liz Fabry-Ribaudo [États-Unis] ; Joan Booth [États-Unis] ; Eric J. TopolSource :
- The New England journal of medicine [ 0028-4793 ] ; 2006.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Médecine.
English descriptors
- KwdEn :
Abstract
BACKGROUND Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. METHODS We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. RESULTS The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046). CONCLUSIONS In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes.
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<author><name sortKey="Bhatt, Deepak L" sort="Bhatt, Deepak L" uniqKey="Bhatt D" first="Deepak L." last="Bhatt">Deepak L. Bhatt</name>
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<author><name sortKey="Pearson, Thomas A" sort="Pearson, Thomas A" uniqKey="Pearson T" first="Thomas A." last="Pearson">Thomas A. Pearson</name>
<affiliation wicri:level="1"><inist:fA14 i1="19"><s1>University of Rochester School of Medicine</s1>
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<author><name sortKey="Booth, Joan" sort="Booth, Joan" uniqKey="Booth J" first="Joan" last="Booth">Joan Booth</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events</title>
<author><name sortKey="Bhatt, Deepak L" sort="Bhatt, Deepak L" uniqKey="Bhatt D" first="Deepak L." last="Bhatt">Deepak L. Bhatt</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cleveland Clinic</s1>
<s2>Cleveland</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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<author><name sortKey="Fox, Keith A A" sort="Fox, Keith A A" uniqKey="Fox K" first="Keith A. A." last="Fox">Keith A. A. Fox</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>University and Royal Infirmary of Edinburgh</s1>
<s2>Edinburgh</s2>
<s3>GBR</s3>
<sZ>2 aut.</sZ>
</inist:fA14>
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<author><name sortKey="Hacke, Werner" sort="Hacke, Werner" uniqKey="Hacke W" first="Werner" last="Hacke">Werner Hacke</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Heidelberg</s1>
<s2>Heidelberg</s2>
<s3>DEU</s3>
<sZ>3 aut.</sZ>
</inist:fA14>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Berger, Peter B" sort="Berger, Peter B" uniqKey="Berger P" first="Peter B." last="Berger">Peter B. Berger</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Duke University</s1>
<s2>Durham, N.C</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Black, Henry R" sort="Black, Henry R" uniqKey="Black H" first="Henry R." last="Black">Henry R. Black</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Rush Medical College</s1>
<s2>Chicago</s2>
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</inist:fA14>
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</affiliation>
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<author><name sortKey="Boden, William E" sort="Boden, William E" uniqKey="Boden W" first="William E." last="Boden">William E. Boden</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Hartford Hospital</s1>
<s2>Hartford, Conn</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
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<author><name sortKey="Cacoub, Patrice" sort="Cacoub, Patrice" uniqKey="Cacoub P" first="Patrice" last="Cacoub">Patrice Cacoub</name>
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</inist:fA14>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Cohen, Eric A" sort="Cohen, Eric A" uniqKey="Cohen E" first="Eric A." last="Cohen">Eric A. Cohen</name>
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</inist:fA14>
<country>Canada</country>
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<author><name sortKey="Creager, Mark A" sort="Creager, Mark A" uniqKey="Creager M" first="Mark A." last="Creager">Mark A. Creager</name>
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</inist:fA14>
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<author><name sortKey="Easton, J Donald" sort="Easton, J Donald" uniqKey="Easton J" first="J. Donald" last="Easton">J. Donald Easton</name>
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<author><name sortKey="Flather, Marcus D" sort="Flather, Marcus D" uniqKey="Flather M" first="Marcus D." last="Flather">Marcus D. Flather</name>
<affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Royal Brompton Hospital</s1>
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<author><name sortKey="Haffner, Steven M" sort="Haffner, Steven M" uniqKey="Haffner S" first="Steven M." last="Haffner">Steven M. Haffner</name>
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<author><name sortKey="Hamm, Christian W" sort="Hamm, Christian W" uniqKey="Hamm C" first="Christian W." last="Hamm">Christian W. Hamm</name>
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<s2>Bad Nauheim</s2>
<s3>DEU</s3>
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<author><name sortKey="Hankey, Graeme J" sort="Hankey, Graeme J" uniqKey="Hankey G" first="Graeme J." last="Hankey">Graeme J. Hankey</name>
<affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Royal Perth Hospital and School of Medicine and Pharmacology, University of Western Australia</s1>
<s2>Perth</s2>
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<sZ>14 aut.</sZ>
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<author><name sortKey="Johnston, S Claiborne" sort="Johnston, S Claiborne" uniqKey="Johnston S" first="S. Claiborne" last="Johnston">S. Claiborne Johnston</name>
<affiliation wicri:level="1"><inist:fA14 i1="15"><s1>University of California, San Francisco</s1>
<s2>San Francisco</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Mak, Koon Hou" sort="Mak, Koon Hou" uniqKey="Mak K" first="Koon-Hou" last="Mak">Koon-Hou Mak</name>
<affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Gleneagles Medical Centre</s1>
<s3>SGP</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Singapour</country>
</affiliation>
</author>
<author><name sortKey="Mas, Jean Louis" sort="Mas, Jean Louis" uniqKey="Mas J" first="Jean-Louis" last="Mas">Jean-Louis Mas</name>
<affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Sainte-Anne Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Montalescot, Gilles" sort="Montalescot, Gilles" uniqKey="Montalescot G" first="Gilles" last="Montalescot">Gilles Montalescot</name>
<affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Institut de Cardiologie-CHU Pitié-Salpêtrière</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Pearson, Thomas A" sort="Pearson, Thomas A" uniqKey="Pearson T" first="Thomas A." last="Pearson">Thomas A. Pearson</name>
<affiliation wicri:level="1"><inist:fA14 i1="19"><s1>University of Rochester School of Medicine</s1>
<s2>Rochester, N.Y</s2>
<s3>USA</s3>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Steg, P Gabriel" sort="Steg, P Gabriel" uniqKey="Steg P" first="P. Gabriel" last="Steg">P. Gabriel Steg</name>
</author>
<author><name sortKey="Steinhubl, Steven R" sort="Steinhubl, Steven R" uniqKey="Steinhubl S" first="Steven R." last="Steinhubl">Steven R. Steinhubl</name>
</author>
<author><name sortKey="Weber, Michael A" sort="Weber, Michael A" uniqKey="Weber M" first="Michael A." last="Weber">Michael A. Weber</name>
</author>
<author><name sortKey="Brennan, Danielle M" sort="Brennan, Danielle M" uniqKey="Brennan D" first="Danielle M." last="Brennan">Danielle M. Brennan</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cleveland Clinic</s1>
<s2>Cleveland</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>23 aut.</sZ>
<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Fabry Ribaudo, Liz" sort="Fabry Ribaudo, Liz" uniqKey="Fabry Ribaudo L" first="Liz" last="Fabry-Ribaudo">Liz Fabry-Ribaudo</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cleveland Clinic</s1>
<s2>Cleveland</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>23 aut.</sZ>
<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Booth, Joan" sort="Booth, Joan" uniqKey="Booth J" first="Joan" last="Booth">Joan Booth</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Cleveland Clinic</s1>
<s2>Cleveland</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>23 aut.</sZ>
<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Topol, Eric J" sort="Topol, Eric J" uniqKey="Topol E" first="Eric J." last="Topol">Eric J. Topol</name>
</author>
</analytic>
<series><title level="j" type="main">The New England journal of medicine</title>
<title level="j" type="abbreviated">N. Engl. j. med.</title>
<idno type="ISSN">0028-4793</idno>
<imprint><date when="2006">2006</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">The New England journal of medicine</title>
<title level="j" type="abbreviated">N. Engl. j. med.</title>
<idno type="ISSN">0028-4793</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetylsalicylic acid</term>
<term>Analgesic</term>
<term>Antiplatelet agent</term>
<term>Antipyretic</term>
<term>Atherosclerosis</term>
<term>Clopidogrel</term>
<term>Comparative study</term>
<term>Medicine</term>
<term>Non steroidal antiinflammatory agent</term>
<term>Prevention</term>
<term>Thrombosis</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Athérosclérose</term>
<term>Clopidogrel</term>
<term>Inhibiteur thromboagrégation</term>
<term>Thrombose</term>
<term>Acétylsalicylique acide</term>
<term>Etude comparative</term>
<term>Prévention</term>
<term>Médecine</term>
<term>Antipyrétique</term>
<term>Analgésique</term>
<term>Antiinflammatoire non stéroïde</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Médecine</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">BACKGROUND Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. METHODS We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. RESULTS The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046). CONCLUSIONS In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0028-4793</s0>
</fA01>
<fA02 i1="01"><s0>NEJMAG</s0>
</fA02>
<fA03 i2="1"><s0>N. Engl. j. med.</s0>
</fA03>
<fA05><s2>354</s2>
</fA05>
<fA06><s2>16</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>BHATT (Deepak L.)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>FOX (Keith A. A.)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>HACKE (Werner)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>BERGER (Peter B.)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>BLACK (Henry R.)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>BODEN (William E.)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>CACOUB (Patrice)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>COHEN (Eric A.)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>CREAGER (Mark A.)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>EASTON (J. Donald)</s1>
</fA11>
<fA11 i1="11" i2="1"><s1>FLATHER (Marcus D.)</s1>
</fA11>
<fA11 i1="12" i2="1"><s1>HAFFNER (Steven M.)</s1>
</fA11>
<fA11 i1="13" i2="1"><s1>HAMM (Christian W.)</s1>
</fA11>
<fA11 i1="14" i2="1"><s1>HANKEY (Graeme J.)</s1>
</fA11>
<fA11 i1="15" i2="1"><s1>JOHNSTON (S. Claiborne)</s1>
</fA11>
<fA11 i1="16" i2="1"><s1>MAK (Koon-Hou)</s1>
</fA11>
<fA11 i1="17" i2="1"><s1>MAS (Jean-Louis)</s1>
</fA11>
<fA11 i1="18" i2="1"><s1>MONTALESCOT (Gilles)</s1>
</fA11>
<fA11 i1="19" i2="1"><s1>PEARSON (Thomas A.)</s1>
</fA11>
<fA11 i1="20" i2="1"><s1>STEG (P. Gabriel)</s1>
</fA11>
<fA11 i1="21" i2="1"><s1>STEINHUBL (Steven R.)</s1>
</fA11>
<fA11 i1="22" i2="1"><s1>WEBER (Michael A.)</s1>
</fA11>
<fA11 i1="23" i2="1"><s1>BRENNAN (Danielle M.)</s1>
</fA11>
<fA11 i1="24" i2="1"><s1>FABRY-RIBAUDO (Liz)</s1>
</fA11>
<fA11 i1="25" i2="1"><s1>BOOTH (Joan)</s1>
</fA11>
<fA11 i1="26" i2="1"><s1>TOPOL (Eric J.)</s1>
</fA11>
<fA14 i1="01"><s1>Cleveland Clinic</s1>
<s2>Cleveland</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>23 aut.</sZ>
<sZ>24 aut.</sZ>
<sZ>25 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>University and Royal Infirmary of Edinburgh</s1>
<s2>Edinburgh</s2>
<s3>GBR</s3>
<sZ>2 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>University of Heidelberg</s1>
<s2>Heidelberg</s2>
<s3>DEU</s3>
<sZ>3 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Duke University</s1>
<s2>Durham, N.C</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
</fA14>
<fA14 i1="05"><s1>Rush Medical College</s1>
<s2>Chicago</s2>
<s3>USA</s3>
<sZ>5 aut.</sZ>
</fA14>
<fA14 i1="06"><s1>Hartford Hospital</s1>
<s2>Hartford, Conn</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="07"><s1>Hôpital Pitié-Salpêtrière</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="08"><s1>Sunnybrook and Women's College Health Science Centre</s1>
<s2>Toronto</s2>
<s3>CAN</s3>
<sZ>8 aut.</sZ>
</fA14>
<fA14 i1="09"><s1>Brigham and Women's Hospital and Harvard Medical School</s1>
<s2>Boston</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="10"><s1>Rhode Island Hospital and Brown University</s1>
<s2>Providence</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="11"><s1>Royal Brompton Hospital</s1>
<s2>London</s2>
<s3>GBR</s3>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="12"><s1>University of Texas Health Science Center at San Antonio</s1>
<s2>San Antonio</s2>
<s3>USA</s3>
<sZ>12 aut.</sZ>
</fA14>
<fA14 i1="13"><s1>Kerckhoff-Klinik Center</s1>
<s2>Bad Nauheim</s2>
<s3>DEU</s3>
<sZ>13 aut.</sZ>
</fA14>
<fA14 i1="14"><s1>Royal Perth Hospital and School of Medicine and Pharmacology, University of Western Australia</s1>
<s2>Perth</s2>
<s3>AUS</s3>
<sZ>14 aut.</sZ>
</fA14>
<fA14 i1="15"><s1>University of California, San Francisco</s1>
<s2>San Francisco</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</fA14>
<fA14 i1="16"><s1>Gleneagles Medical Centre</s1>
<s3>SGP</s3>
<sZ>16 aut.</sZ>
</fA14>
<fA14 i1="17"><s1>Sainte-Anne Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>17 aut.</sZ>
</fA14>
<fA14 i1="18"><s1>Institut de Cardiologie-CHU Pitié-Salpêtrière</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>18 aut.</sZ>
</fA14>
<fA14 i1="19"><s1>University of Rochester School of Medicine</s1>
<s2>Rochester, N.Y</s2>
<s3>USA</s3>
<sZ>19 aut.</sZ>
</fA14>
<fA17 i1="01" i2="1"><s1>CHARISMA Investigators</s1>
<s3>INC</s3>
</fA17>
<fA20><s1>1706-1717</s1>
</fA20>
<fA21><s1>2006</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>6013</s2>
<s5>354000156809380070</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2006 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>14 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>06-0239775</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>The New England journal of medicine</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>BACKGROUND Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. METHODS We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. RESULTS The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046). CONCLUSIONS In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B01</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002B12B01</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Athérosclérose</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Atherosclerosis</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Ateroesclerosis</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Clopidogrel</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Clopidogrel</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Clopidogrel</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Inhibiteur thromboagrégation</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Antiplatelet agent</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Inhibidor tromboagregación</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Thrombose</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Thrombosis</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Trombosis</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Acétylsalicylique acide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Acetylsalicylic acid</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Acetilsalicilico ácido</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Etude comparative</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Comparative study</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Estudio comparativo</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Prévention</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Prevention</s0>
<s5>08</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Prevención</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Médecine</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Medicine</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Medicina</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Antipyrétique</s0>
<s5>25</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Antipyretic</s0>
<s5>25</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Antipirético</s0>
<s5>25</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Analgésique</s0>
<s5>26</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Analgesic</s0>
<s5>26</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Analgésico</s0>
<s5>26</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Antiinflammatoire non stéroïde</s0>
<s5>27</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Non steroidal antiinflammatory agent</s0>
<s5>27</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Antiinflamatorio no esteroide</s0>
<s5>27</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Thiénopyridine dérivé</s0>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Thienopyridine derivative</s0>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Thienopyridin derivado</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Inhibiteur enzyme</s0>
<s5>38</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Enzyme inhibitor</s0>
<s5>38</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Inhibidor enzima</s0>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Prostaglandin-endoperoxide synthase</s0>
<s2>FE</s2>
<s5>39</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Prostaglandin-endoperoxide synthase</s0>
<s2>FE</s2>
<s5>39</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Prostaglandin-endoperoxide synthase</s0>
<s2>FE</s2>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Salicylés</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Salicylates</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Salicilatos</s0>
<s5>40</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Appareil circulatoire pathologie</s0>
<s5>41</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Cardiovascular disease</s0>
<s5>41</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Aparato circulatorio patología</s0>
<s5>41</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Vaisseau sanguin pathologie</s0>
<s5>42</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Vascular disease</s0>
<s5>42</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Vaso sanguíneo patología</s0>
<s5>42</s5>
</fC07>
<fN21><s1>149</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>
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