Rationale and protocol of a trial for prevention of diabetic atherosclerosis by using antiplatelet drugs: study of Diabetic Athe

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Abstract

Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects.

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Methods
Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81├óÔé¼ÔÇ£100 mg/day) or the cilostazol group (100├óÔé¼ÔÇ£200 mg/day) in this international, 2-year, prospective follow-up interventional study.

Results
The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index.

Conclusion
This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease.

Background
Westernization of lifestyle has led to an explosive increase in the number of diabetic patients and an increase in diabetic atherosclerosis in Eastern Asian countries [1,2]. This is of great concern for the future of patients and health systems in East Asia, and is a problem that requires immediate and careful evaluation. With this in mind a cooperative, multinational research group in Japan, Korea, China, and Phillippine has been formed to investigate the potential for antiplatelet medication to prevent the occurrence and progression of diabetic atherosclerosis in Asian patients.

The rationale for the study is based upon the finding that the primary incidence rate of coronary artery disease (CAD) in diabetic patients is similar to the secondary incidence rate of CAD in nondiabetic patients. This finding suggests that secondary treatment of atherosclerosis is applicable to the primary prevention of arteriosclerosis in diabetic patients. Antiplatelet drugs are widely reported to be effective in preventing the recurrence of atherosclerosis. In one study [3], type 2 diabetic patients with early-stage carotid atherosclerosis who were given aspirin showed a slight progression of intima-media thickness (IMT) of the carotid artery (0.033 ± 0.010 mm/year). In another study [4], similar patients given cilostazol showed negligible change in IMT (0.00 ± 0.16 mm/3 years). However, the primary preventive and secondary therapeutic effects of these two drugs have not been sufficiently investigated in the Asian diabetic patient population. We therefore initiated an international, 2-year prospective follow-up interventional study to clarify the efficacy and usefulness of aspirin and cilostazol in the primary prevention and secondary treatment of diabetic atherosclerosis in Asian patients. Assessment will be performed by chronologically observing the intima-media thickness (IMT) of the carotid artery, which is used as a surrogate endpoint of atherosclerosis, and by analyzing the occurrence and progression of large-vessel complications in patients with type 2 diabetes and mild atherosclerosis [5,6].

Study design and protocol
The DAPC study has been registered on the University Hospital Medical Information NetworkClinical Trials Registry (UMIN-CTR) which is a non-profit organization in Japan and meets the requirements of the International Committee of Medical Journal Editors (ICMJE). Patients enrolled in the study will have been dignosed with type 2 diabetes, aged between 40 to 85 years and with clinical findings suggestive of arteriosclerosis obliterans (ASO) (Table 1, Table 2). In the study ASO will be defined as detection of the following findings in either of the patient's lower limbs: an ABI (ankle brachial pressure index) of <1.0 and a weakened or bilaterally different pulsation of the popliteal artery or dorsal artery of the foot; or clinical signs and symptoms suggestive of ASO. />/>/>/>/>/>/>/>/>/>/>/>/>/>/>

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References
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  2. Islam MM, Horibe H, Koyabashi F: Current trend in prevalence of diabetes mellitus in Japan, 1964├óÔé¼ÔÇ£1992. J Epidemiol 1999, 9:155-162.
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