Τίτλος:
Efficacy and safety of adjunctive cilostazol to clopidogrel-treated diabetic patients with symptomatic lower extremity artery disease in the prevention of ischemic vascular events
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
BACKGROUND: Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, antiinflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel-treated 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. METHODS AND RESULTS: In a prospective 2-arm, multicenter, open-label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, 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 mg twice/day (403 patients). The median duration of follow-up was 27 months. 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-adjusted hazard ratio [HR], 0.468; 95% CI, 0.252-0.870; P=0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex-adjusted HR, 0.38; 95% CI, 0.15-0.98; P=0.046) and improved the ankle-brachial index and pain-free walking distance values (P=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-adjusted HR, 1.080; 95% CI, 0.579-2.015; P=0.809). CONCLUSIONS: Adjunctive cilostazol to clopidogrel-treated 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. REGISTRATION: URL: https://www.clini caltr ials.gov; Unique identifier: NCT02983214. © 2020 The Authors.
Συγγραφείς:
Kalantzi, K.
Tentolouris, N.
Melidonis, A.J.
Papadaki, S.
Peroulis, M.
Amantos, K.A.
Andreopoulos, G.
Bellos, G.I.
Boutel, D.
Bristianou, M.
Chrisis, D.
Dimitsikoglou, N.A.
Doupis, J.
Georgopoulou, C.
Gkintikas, S.A.
Iraklianou, S.
Kanellas, K.
Kotsa, K.
Koufakis, T.
Kouroglou, M.
Koutsovasilis, A.G.
Lanaras, L.
Liouri, E.
Lixouriotis, C.
Lykoudi, A.
Mandalaki, E.
Papageorgiou, E.
Papanas, N.
Rigas, S.
Stamatelatou, M.I.
Triantafyllidis, I.
Trikkalinou, A.
Tsouka, A.N.
Zacharopoulou, O.
Zoupas, C.
Tsolakis, I.
Tselepis, A.D.
Περιοδικό:
Journal of the American Heart Association
Εκδότης:
American Heart Association Inc.
Λέξεις-κλειδιά:
antidiabetic agent; antihypertensive agent; antilipemic agent; cilostazol; clopidogrel; proton pump inhibitor; antithrombocytic agent; cilostazol; clopidogrel, aged; Article; brain hemorrhage; diabetic patient; diarrhea; drug dose increase; drug efficacy; drug safety; female; gastrointestinal hemorrhage; headache; heart palpitation; human; intermittent claudication; ischemia; ischemic vascular event; leg artery; major clinical study; male; monotherapy; multicenter study; neoplasm; non insulin dependent diabetes mellitus; open study; peripheral occlusive artery disease; phase 4 clinical trial; priority journal; prospective study; side effect; symptom; tachycardia; urticaria; vascular disease; brain ischemia; clinical trial; combination drug therapy; complication; controlled study; drug monitoring; heart infarction; intermittent claudication; lower limb; mortality; non insulin dependent diabetes mellitus; pathophysiology; procedures; randomized controlled trial; treatment outcome; vascularization, Aged; Brain Ischemia; Cilostazol; Clopidogrel; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Intermittent Claudication; Lower Extremity; Male; Myocardial Infarction; Outcome and Process Assessment, Health Care; Platelet Aggregation Inhibitors; Treatment Outcome
DOI:
10.1161/JAHA.120.018184
