{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:50:46Z","timestamp":1791154246402,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,1,22]],"date-time":"2007-01-22T00:00:00Z","timestamp":1169424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Internal Medicine"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>Abstract.<\/jats:title><jats:p><jats:bold>Objective.\u2002<\/jats:bold> To assess the prophylactic efficacy of aspirin and a high\u2010dose antioxidant vitamin combination in patients with peripheral arterial disease (PAD) in terms of reduction of the risk of a first vascular event (myocardial infarction, stroke, vascular death) and critical limb ischaemia.<\/jats:p><jats:p><jats:bold>Design.\u2002<\/jats:bold> Randomized, placebo\u2010controlled, double\u2010blind clinical trial with 2\u2003\u00d7\u20032 factorial design.<\/jats:p><jats:p><jats:bold>Setting.\u2002<\/jats:bold> Thirty\u2010seven European angiology\/vascular medicine units.<\/jats:p><jats:p><jats:bold>Subjects.\u2002<\/jats:bold> A total of 366 outpatients with stage I\u2010II PAD documented by angiography or ultrasound, with ankle\/brachial index &lt;0.85 or toe index &lt;0.6; 210 patients completed the follow\u2010up.<\/jats:p><jats:p><jats:bold>Interventions.\u2002<\/jats:bold> Four treatment groups: (i) oral aspirin (100\u2003mg daily), (ii) oral antioxidant vitamins (600\u2003mg vitamin E, 250\u2003mg vitamin C and 20\u2003mg <jats:italic>\u03b2<\/jats:italic>\u2010carotene daily), (iii) both or (iv) neither, given for 2\u2003years.<\/jats:p><jats:p><jats:bold>Main outcome measure.\u2002<\/jats:bold> Major vascular events (cardiovascular death, myocardial infarction or stroke) and critical leg ischaemia.<\/jats:p><jats:p><jats:bold>Results.\u2002<\/jats:bold> Seven of 185 patients allocated aspirin and 20 of 181 allocated placebo suffered a major vascular event (risk reduction 64%, <jats:italic>P<\/jats:italic>\u2003=\u20030.022); five and eight patients, respectively, suffered critical leg ischaemia (total 12 vs. 28, <jats:italic>P<\/jats:italic>\u2003=\u20030.014). There was no evidence that antioxidant vitamins were beneficial (16\/185 vs. 11\/181 vascular events). Neither treatment was associated with any significant increase in adverse events. Inclusion of this trial in a meta\u2010analysis of other randomized trials of anti\u2010platelet therapy in PAD makes the overall results highly significant (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001) and suggests that low\u2010dose aspirin reduces the incidence of vascular events by 26%.<\/jats:p><jats:p><jats:bold>Conclusions.\u2002<\/jats:bold> For the first time direct evidence shows that low\u2010dose aspirin should routinely be considered for PAD patients, including those with concomitant type 2 diabetes.<\/jats:p>","DOI":"10.1111\/j.1365-2796.2006.01763.x","type":"journal-article","created":{"date-parts":[[2007,1,22]],"date-time":"2007-01-22T10:27:48Z","timestamp":1169461668000},"page":"276-284","source":"Crossref","is-referenced-by-count":164,"title":["Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double\u2010blind trial"],"prefix":"10.1111","volume":"261","author":[{"name":"Critical Leg Ischaemia Prevention Study (CLIPS) Group","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,1,22]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-200303000-00005"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.6.2246"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.313.7070.1440"},{"key":"e_1_2_7_5_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/bmj.308.6921.81","article-title":"Collaborative overview of randomised trials of antiplatelet therapy. I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patient","volume":"308","author":"Antiplatelet Trialists\u2019 Collaboration","year":"1994","journal-title":"BMJ"},{"key":"e_1_2_7_6_2","first-page":"56802","article-title":"Internal analgesic, antipyretic and antirheumatic drug products for over\u2010the\u2010counter human use: final rule for professional labelling of aspirin, buffered aspirin and aspirin in combination with antacid drug products","volume":"63","author":"Food and Drug Administration","year":"1998","journal-title":"Fed Register"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.324.7329.71"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-199502000-00005"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198904063201407"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199805000-00017"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/154.2.145"},{"key":"e_1_2_7_12_2","first-page":"414","article-title":"Therapeutic uses of vitamin E in prevention of atherosclerosis","volume":"4","author":"Swain RA","year":"1999","journal-title":"Altern Med Rev"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)90866-1"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2000.00752.x"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)07072-5"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.11.1338"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09328-5"}],"container-title":["Journal of Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2796.2006.01763.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2796.2006.01763.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T21:42:25Z","timestamp":1697146945000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2796.2006.01763.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1,22]]},"references-count":16,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,3]]}},"alternative-id":["10.1111\/j.1365-2796.2006.01763.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2796.2006.01763.x","archive":["Portico"],"relation":{},"ISSN":["0954-6820","1365-2796"],"issn-type":[{"value":"0954-6820","type":"print"},{"value":"1365-2796","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,1,22]]}}}