{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:35:51Z","timestamp":1778891751340,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,11,27]],"date-time":"2013-11-27T00:00:00Z","timestamp":1385510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Clopidogrel is a prodrug that needs to be activated to inhibit platelet aggregation. The objective of this study was to evaluate the prevalence and clinical consequences of potential drug\u2013drug interactions of clopidogrel with drugs affecting <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Co\u2010administrations of clopidogrel together with well\u2010established <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inhibitors, <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inducers, and atorvastatin were investigated in a population\u2010based pharmacoepidemiological study utilizing data from the national healthcare registers and in more detail from a university hospital register in Finland. The main outcome measures were all\u2010cause mortality and mortality and morbidity related to thrombosis or bleeding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the nationwide analysis, 6.1%, 1.0%, and 20.8% of the clopidogrel\u2010treated patients were exposed to concomitant use of <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inhibitors, <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inducers, and atorvastatin, respectively. In the survival analysis, the adjusted hazard ratio for overall mortality was 2.29 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) for <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inducer users and 0.74 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) for atorvastatin users compared with controls (patients receiving clopidogrel without interacting medication). <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inhibitor use seemed to prevent from thrombosis: <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 0.67, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001. The hospitalizations due to bleedings were rarer in atorvastatin and <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inhibitor groups compared with controls. Thrombosis complications leading to hospitalizations were more often seen in the atorvastatin group than in the control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>No uniform untoward effect of concomitant <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inhibitor use on the clinical efficacy of clopidogrel was found. In patients receiving concomitant atorvastatin and clopidogrel, the antithrombotic effect of clopidogrel was moderately attenuated, but the combination significantly reduced the overall mortality. <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 inhibitors and atorvastatin may reduce bleedings in clopidogrel users.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12028","type":"journal-article","created":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T11:52:03Z","timestamp":1371210723000},"page":"344-351","source":"Crossref","is-referenced-by-count":14,"title":["Epidemiology of <scp>CYP<\/scp>3A4\u2010Mediated Clopidogrel Drug\u2013Drug Interactions and Their Clinical Consequences"],"prefix":"10.1111","volume":"31","author":[{"given":"Tuire","family":"Tirkkonen","sequence":"first","affiliation":[{"name":"Department of Pharmacology Drug Development and Therapeutics University of Turku Turku Finland"},{"name":"Clinical Pharmacology Unit Turku University 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