Efficacy and Safety of Adjunctive Cilostazol to Clopidogrel-Treated Diabetic Patients With Symptomatic Lower Extremity Artery Disease in the Prevention of Ischemic Vascular Events

被引：12

作者：

Kalantzi, Kallirroi ^{[1
]}

Tentolouris, Nikolaos ^{[2
]}

Melidonis, Andreas J. ^{[3
]}

Papadaki, Styliani ^{[1
]}

Peroulis, Michail ^{[1
]}

Amantos, Konstantinos A. ^{[3
]}

Andreopoulos, George ^{[3
]}

Bellos, George I. ^{[4
]}

Boutel, Dimitrios ^{[5
]}

Bristianou, Magdalini ^{[6
]}

Chrisis, Dimitrios ^{[7
,8
]}

Dimitsikoglou, Nikolaos A. ^{[1
]}

Doupis, John ^{[1
]}

Georgopoulou, Chrysoula ^{[3
]}

Gkintikas, Stergios A. ^{[9
,10
]}

Iraklianou, Styliani ^{[11
]}

Kanellas, Konstantinos ^{[11
]}

Kotsa, Kalliopi ^{[9
,10
]}

Koufakis, Theocharis ^{[9
,10
]}

Kouroglou, Maria ^{[12
]}

Koutsovasilis, Anastasios G. ^{[7
,8
]}

Lanaras, Leonidas ^{[6
]}

Liouri, Eirini ^{[7
,8
]}

Lixouriotis, Charalampos ^{[13
]}

Lykoudi, Akrivi ^{[7
,8
]}

Mandalaki, Efthymia ^{[1
]}

Papageorgiou, Evanthia ^{[7
,8
]}

Papanas, Nikolaos ^{[14
]}

Rigas, Spyridon ^{[7
,8
]}

Stamatelatou, Maria I. ^{[15
]}

Triantafyllidis, Ioannis ^{[1
,16
]}

Trikkalinou, Aikaterini ^{[3
]}

Tsouka, Aikaterini N. ^{[1
]}

Zacharopoulou, Ourania ^{[3
]}

Zoupas, Christos ^{[3
]}

Tsolakis, Ioannis ^{[16
]}

Tselepis, Alexandros D. ^{[1
]}

机构：

[1] Univ Ioannina, Dept Chem, Lab Biochem, Atherothrombosis Res Ctr, Ioannina, Greece

[2] Natl & Kapodistrian Univ Athens, Med Sch, Dept Propaedeut Internal Med 1, Athens, Greece

[3] Metropolitan Hosp Athens, Diabet Ctr, Athens, Greece

[4] Koropi Hlth Ctr, Attica, Greece

[5] Gen Hosp Giannitsa, Giannitsa, Greece

[6] Gen Hosp Lamia, Dept Internal Med, Lamia, Greece

[7] Gen Hosp Nikaia, Internal Med Dept 3, Athens, Greece

[8] Gen Hosp Nikaia, Diabet Ctr, Athens, Greece

[9] Aristotle Univ Thessaloniki, Ahepa Univ Hosp, Div Endocrinol & Metab, Med Sch, Thessaloniki, Greece

[10] Aristotle Univ Thessaloniki, Ahepa Univ Hosp, Diabet Ctr, Dept Internal Med 1,Med Sch, Thessaloniki, Greece

[11] Gen Hosp Tzaneio, Dept Internal Med Ctr 3, Piraeus, Greece

[12] Gen Reg Hosp Mytilene, Mitilini, Greece

[13] Hlth Ctr Distomo, Voiotia, Greece

[14] Democritus Univ Thrace, Dept Internal Med 2, Alexandroupolis, Greece

[15] Gen Hosp Sitia, Internal Med Clin, Iraklion, NE, Greece

[16] Univ Patras, Vasc Surg Dept, Patras, Greece

来源：

JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2021年 / 10卷 / 01期

关键词：

cilostazol; clopidogrel; coronary artery disease; diabetes mellitus; intermittent claudication; ischemic stroke; DUAL ANTIPLATELET THERAPY; PLATELET REACTIVITY; RISK; METAANALYSIS; RESTENOSIS; DIAGNOSIS; MELLITUS; CORONARY; IMPACT; AGENTS;

D O I：

10.1161/JAHA.120.018184

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND: Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti-inflammatory, 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.

引用

页码：1 / 11

页数：11

共 20 条

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