{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:53:34Z","timestamp":1788951214355,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T00:00:00Z","timestamp":1339372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel.<\/jats:p><jats:p>\u2022\u2003No studies have measured drug exposure in a time\u2010varying manner that detects discontinuation and restart of clopidogrel and statin therapy, allowing clinical quantification of the interaction effect.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Clopidogrel and CYP3A4\u2010metabolizing statin use were each associated with a substantially reduced rate of major adverse cardiovascular events within 12 months after coronary stent implantation.<\/jats:p><jats:p>\u2022\u2003Although we observed an interaction between use of clopidogrel and statins, statin use <jats:italic>vs.<\/jats:italic> non\u2010use was not associated with an increased rate of major adverse cardiovascular events in patients using clopidogrel after coronary stent implantation.<\/jats:p><jats:p><jats:bold>AIMS<\/jats:bold> To examine whether CYP3A4\u2010metabolizing statin use modified the association between clopidogrel use and major adverse cardiovascular events (MACE) after coronary stent implantation, using time\u2010varying drug exposure ascertainment.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> We conducted this population\u2010based cohort study in Western Denmark (population: 3 million) using medical databases. We identified all 13\u2003001 patients with coronary stent implantation between 2002 and 2005 and their comorbidities. During 12 months of follow\u2010up, we tracked the use of clopidogrel and CYP3A4\u2010metabolizing statins and the rate of MACE. We used Cox regression to compute hazard ratios (HRs) controlling for potential confounders.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold> The rate of MACE per 1000 person years was 104 for concomitant clopidogrel and statin use, 130 for clopidogrel without statin use, 108 for statin without clopidogrel use and 446 for no use of either drug. The adjusted HR comparing clopidogrel use with non\u2010use was 0.68 (95% confidence interval (CI) 0.58, 0.79) among statin users and 0.34 (95% CI 0.29, 0.40) among statin non\u2010users, yielding an interaction effect (i.e. relative rate increase) of 1.97 (95% CI 1.59, 2.44). The adjusted HR for MACE comparing statin use with non\u2010use was 0.97 (95% CI 0.83, 1.13) among clopidogrel users and 0.49 (95% CI 0.42, 0.57) among clopidogrel non\u2010users.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold> Clopidogrel and CYP3A4\u2010metabolizing statin use were each associated with a substantially reduced rate of MACE within 12 months after coronary stent implantation. Although we observed an interaction between use of clopidogrel and statins, statin use <jats:italic>vs.<\/jats:italic> non\u2010use was not associated with an increased rate of MACE in patients using clopidogrel after coronary stent implantation.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2012.04169.x","type":"journal-article","created":{"date-parts":[[2012,1,13]],"date-time":"2012-01-13T16:56:21Z","timestamp":1326473781000},"page":"161-170","source":"Crossref","is-referenced-by-count":14,"title":["Concomitant use of clopidogrel and statins and risk of major adverse cardiovascular events following coronary stent implantation"],"prefix":"10.1111","volume":"74","author":[{"given":"Morten","family":"Schmidt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin B.","family":"Johansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Maeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kaltoft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisette O.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Henrik","family":"Tilsted","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans E.","family":"B\u00f8tker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Baron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik Toft","family":"S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,6,11]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17275-9"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.11.024"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.1.53"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000047060.60595.CC"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-668X(03)00442-1"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2005.01522.x"},{"key":"e_1_2_8_8_2","first-page":"2240","article-title":"Comparison on long\u2010term effects of atorvastatin or pravastatin combined with clopidogrel for patients undergoing coronary stenting: a randomized controlled trial","volume":"89","author":"Han YL","year":"2009","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000088780.57432.43"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.01.097"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2007.12.009"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-08-0503"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2004.035014"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn212"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(03)00626-X"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1716"},{"key":"e_1_2_8_17_2","first-page":"71","volume-title":"Modern Epidemiology","author":"Greenland S","year":"2008"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S10190"},{"key":"e_1_2_8_19_2","unstructured":"Danish Medicines Agency.Over\u2010the\u2010counter medicine and reimbursement criteria in Denmark [online]. 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