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.

Plasma neutrophil gelatinase-associated lipocalin (NGAL) as an early predictive marker of contrast-induced nephropathy in hospitalized patients undergoing computed tomography.

BACKGROUND: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) represents a promising biomarker for AKI. Its role in the early diagnosis of CIN has already been examined in adults and children undergoing coronary angiography. This study was designed to prospectively evaluate plasma NGAL compared with serum creatinine (SCr) for early CIN detection among hospitalized patients undergoing contrast-enhanced computed tomography (CT). METHODS: We prospectively enrolled consecutive hospitalized patients undergoing elective CT with intravenous (IV), low-osmolar contrast administration. Patients with pre-procedure SCr >150 µmol/L (1.7 mg/dL), congestive heart failure, haemodynamic instability, sepsis, or urinary tract infection were excluded. Plasma NGAL was measured using the standardized Triage(®) NGAL test (Biosite Incorporated, San Diego, CA, USA) at baseline and 6 h post-procedure. SCr, blood urea nitrogen (BUN), albumin and sodium (Na) were measured and eGFR MDRD4 was calculated at the same intervals, as well as at 24 and 48 h post-procedure. CIN was defined as an increase in SCr of >25% or >44 µmol/L (0.5 mg/dL) from baseline within 48 h post-procedure, in the absence of other obvious causes. RESULTS: Forty-seven patients, male/female 27/20, median age 68 (31-88) years, 16/47 diabetics, with baseline SCr 91.94 ± 20.33 µmol/L (1.04 ± 0.23 mg/dL) and eGFR MDRD4 68.40 ± 18.22 mL/min/1.73 m(2) were enrolled. A contrast volume of 120 mL (range 100-150 mL) was administered. CIN was found in four subjects (8.51%), but detection by SCr was only possible 24 h in 1 and 48 h post-procedure in three. In contrast, significant elevation of plasma NGAL was found at 6 h post-procedure in those with versus those without CIN (779.25 ± 361.49 versus 82.30 ± 40.64 ng/mL, P < 0.001). Using a cutoff value of 200 ng/mL, sensitivity, specificity and area under the receiver-operating characteristic (ROC) curve of 6-h plasma NGAL for CIN prediction were excellent (100, 100 and 1.00%, respectively). Subjects with CIN did not differ in baseline demographics, renal function and diabetes status compared with those without CIN. No differences in any variable were noted between diabetics and non-diabetics. Plasma NGAL at 6 h (R (2) = 0.24, P < 0.001) was found to be an independent predictor of CIN. CONCLUSIONS: Plasma NGAL 6 h after contrast administration measured by the rapid, point-of-care Triage(®) NGAL test appears to be a useful biomarker in the early prediction of CIN among hospitalized patients undergoing elective contrast-enhanced CT. However, the small sample size and the very small number of CIN events are important limitations. In any case, according to our evaluation, CIN incidence in this well-controlled population underlines the importance of early detection by an adequate and simple procedure such as the 6-h plasma NGAL test.