{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:51:33Z","timestamp":1781571093094,"version":"3.54.5"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,1,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti\u2010inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel\u2010treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In a prospective 2\u2010arm, multicenter, open\u2010label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75\u00a0mg\/d) for at least 6\u00a0months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100\u00a0mg twice\/day (403 patients). The median duration of follow\u2010up was 27\u00a0months. The primary efficacy end point, the composite of acute ischemic stroke\/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex\u2010adjusted hazard ratio [HR], 0.468; 95% CI, 0.252\u20130.870;\n              <jats:italic>P<\/jats:italic>\n              =0.016). Adjunctive cilostazol also significantly reduced the stroke\/transient ischemic attack events (sex\u2010adjusted HR, 0.38; 95% CI, 0.15\u20130.98;\n              <jats:italic>P<\/jats:italic>\n              =0.046) and improved the ankle\u2010brachial index and pain\u2010free walking distance values (\n              <jats:italic>P<\/jats:italic>\n              =0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex\u2010adjusted HR, 1.080; 95% CI, 0.579\u20132.015;\n              <jats:italic>P<\/jats:italic>\n              =0.809).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Adjunctive cilostazol to clopidogrel\u2010treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT02983214.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.018184","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T10:36:33Z","timestamp":1608201393000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Efficacy and Safety of Adjunctive Cilostazol to Clopidogrel\u2010Treated Diabetic Patients With Symptomatic Lower Extremity Artery Disease in the Prevention of Ischemic Vascular Events"],"prefix":"10.1161","volume":"10","author":[{"given":"Kallirroi","family":"Kalantzi","sequence":"first","affiliation":[{"name":"Atherothrombosis Research Center Laboratory of Biochemistry Department of Chemistry University of Ioannina 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