PHARMACOLOGICAL COMBINATION FOR DISTAL ARTERIOPATHY IN DIABETICS

Abstract

In a prospective, open, multicenter study, investigators from Aristotle University of Thessaloniki, included type 2 diabetic patients with intermittent claudication that had been receiving clopidogrel 75 mg/day for at least 6 months, who were randomly assigned 1:1 to continue monotherapy or to add cilostazol 100 mg twice daily. The mean follow-up duration was 27 months. The first composite efficacy parameter was ischemic cerebrovascular accident or transient cerebrovascular accident, myocardial infarction and death for a vascular cause. Secondarily, the ankle/brachial index (ABI) and pain-free walking distance were measured, as well as hemorrhagic events, hospitalization due to acute ischemia of lower limbs, revascularization of lower limbs and death for non-cardiovascular causes. The clopidogrel monotherapy group included 391 patients and 403 received combined clopidogrelcilostazol treatment. In the latter group treatment was initiated with cilostazol at a dose of 50 mg twice daily during 15 days in order to avoid adverse reactions such as tachycardia, palpitations or headache, and then treatment continued at full dose during a minimum of 18 months and up to a maximum duration of 36 months. Controls were conducted monthly during the first year and every three months thereafter. Follow-up was initially scheduled for a duration of one year, but upon observing the number of major events recorded during this period, it was decided to prolong follow-up for another 6 months. The composite primary endpoint of cerebrovascular accident, transient accident, infarction and death for a vascular reason was recorded in 15 patients (3.7%) of the 403 assigned to combined treatment and in 31 (7.9%) of those assigned to clopidogrel monotherapy, with a significant difference (p=0.016). Both, the ankle/ arm index, as well as the pain-free walking distance improved in both treatment groups, but improvements in both parameters was significantly greater in the group assigned to addition of cilostazol. Other clinical data (thrombosis of coronary stents, hospitalization for acute ischemia of limbs, death for cardiovascular cause or any cause) did not reveal significant differences between both groups. No significant differences were observed in bleeding episodes either. Authors affirm that the combination of cilostazol and clopidogrel improved the results of the primary endpoints of the study as well as the ankle/arm index and the pain-free walking distance and stress the significant reduction of cerebrovascular accidents and transient cerebral ischemia achieved with the study combination.