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

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. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02983214.

A Greek registry of current type 2 diabetes management, aiming to determine core clinical approaches, patterns and strategies.

BACKGROUND: To analyze data in terms of the glycaemic control and therapeutic regimens used for Type-2 Diabetes Mellitus (T2DM) management in Greece, identify factors that influence clinical decisions and determine the level of compliance of T2DM management with the latest international and local guidelines. METHODS: 'AGREEMENT' was a national-multicenter, non-interventional, cross-sectional disease registry. A total of 1191 adult T2DM patients were enrolled consecutively from 59 sites of the National Health System (NHS) or University Hospitals, representing the majority of Diabetes centers or Diabetes outpatient clinics in Greece with a broad geographic distribution. Patients were stratified by gender and analysis was done according to 3 treatment strategies: A (lifestyle changes or use of one oral antidiabetic agent), B (up to 3 antidiabetic agents including injectables but not insulin) and C (any regimens with insulin). RESULTS: Mean (±SD) HbA1c % of the total population was 7.1 (±1.2) while mean (±SD) FPG (mg/dl) was measured at 136 (±42). The proportion of patients who achieved HbA1c < 7% was 53% and ranged from 74.2% for group A, to 60.6% for group B and 35.5% for group C. Median age of the studied population was 65.0 year old (Interquartile Range-IQR 14.0) with an equal distribution of genders between groups. Patients on insulin therapy (treatment strategy C) were older (median age: 67 years vs 63 or 65 for A and B, respectively) with longer diabetes duration (mean duration: 15.3 years vs 5.2 and 10.1 for A and B, respectively). Patients who received insulin presented poor compliance. There was a consensus for a series of decision criteria and factors that potentially influence clinical decisions, used by physicians for selection of the therapeutic strategy among the three groups. Compliance with international and Greek guidelines received a high score among groups A, B and C. No significant differences were presented as per sites' geographic areas, NHS or University centers and physicians' specialty (endocrinologists, diabetologists and internists). CONCLUSIONS: The presented findings suggest the need for improvement of the glycaemic control rate, especially among insulin treated patients as this group seems to achieve low glycaemic control, by setting appropriate HbA1c targets along with timely and individualised intensification of treatment as well as post-therapy evaluation of the compliance with the proposed treatment.