Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on-treatment platelet reactivity.

BACKGROUND: High on-treatment platelet reactivity (HTPR) is frequent in patients on hemodialysis (HD) receiving clopidrogel. OBJECTIVES: The primary aim of this study was to determine the antiplatelet effects of prasugrel vs. high-dose clopidogrel in patients on HD with HTPR. PATIENTS/METHODS: We performed a prospective, single-center, single-blind, investigator-initiated, randomized, crossover study to compare platelet inhibition by prasugrel 10 mg day(-1) with that by high-dose 150 mg day(-1) clopidogrel in 21 patients on chronic HD with HTPR. Platelet function was assessed with the VerifyNow assay, and genotyping was performed for CYP2C19*2 carriage. RESULTS: The primary endpoint of platelet reactivity (PR, measured in P2Y12 reaction units [PRU]) was lower in patients receiving prasugrel (least squares [LS] estimate 156.6, 95% confidence interval [CI] 132.2-181.1) than in those receiving high-dose clopidogrel (LS 279.9, 95% CI 255.4-304.3), P < 0.001). The LS mean differences between the two treatments were - 113.4 PRU (95% CI - 152.9 to - 73.8, P < 0.001) and - 163.8 PRU (95% CI - 218.1 to - 109.2, P < 0.001) in non-carriers and carriers of at least one CYP2C19*2 allele, respectively. HTPR rates were lower for prasugrel than clopidogrel, in all patients (19% vs. 85.7%, P < 0.001) and in non-carriers (25.7% vs. 80%, P = 0.003). All carriers continued to show HTPR while receiving high-dose clopidogrel, but none showed it while receiving prasugrel. CONCLUSIONS: In HD patients exhibiting HTPR following standard clopidogrel treatment, prasugrel 10 mg day(-1) is significantly more efficient than doubling the clopidogrel dosage in achieving adequate platelet inhibition. Neither effect seems to be influenced by carriage of the loss-of-function CYP2C19*2 allele.

Comparative effects of rosuvastatin and atorvastatin on glucose metabolism and adipokine levels in non-diabetic patients with dyslipidaemia: a prospective randomised open-label study.

AIMS: The impact of statins on glucose metabolism and adipokines remains controversial. We compared the effects of rosuvastatin and atorvastatin on glucose homeostasis, insulin sensitivity (IS), adiponectin and leptin levels as well as systemic inflammation in non-diabetic patients with dyslipidaemia. METHODS: Thirty-six patients were randomly assigned to 10 mg/day of rosuvastatin (n = 18) or 20 mg/day of atorvastatin (n = 18) for 12 weeks. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), quantitative IS check index (QUICKI), adiponectin, leptin and high-sensitivity C-reactive protein (hsCRP) were measured at baseline and after 4 and 12 weeks. RESULTS: Both statins significantly lowered TC, LDL-C, non-HDL-C and TG compared with baseline. Only rosuvastatin caused a significant reduction in insulin and HOMA-IR levels (-35%, p = 0.005 and -33%, p = 0.011 respectively) and a significant increase in QUICKI (+11%, p = 0.003) at 12 weeks. In terms of adipokines and hsCRP, no difference was observed after 4 and 12 weeks of treatment with either statin. CONCLUSIONS: Rosuvastatin compared with atorvastatin resulted in significant improvements in IS indices. No significant changes in adiponectin, leptin or hsCRP levels were observed at 4 and 12 weeks of treatment with either statin.

Non-functioning pituitary adenomas: a single center experience.

INTRODUCTION: To describe the clinical imaging and hormonal characteristics and the natural course of patients with clinically non-functioning pituitary adenomas (NFPAs) presenting at our department from 1984 to 2009. MATERIALS AND METHODS: Retrospective review of electronic medical records of patients with NFPAs. The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary axis. Size and functional alterations were estimated at yearly intervals. RESULTS: 114 patients (55 men and 59 women, aged 47±2) were studied. The mean follow-up time was 55±6 months (range 0-240). 45% of the adenomas were incidentally discovered and 75% were macroadenomas (73% with extrasellar extension). At diagnosis, 53% had headache and 76% of those with macroadenomas had visual field defects. Disruption of ≥1 pituitary axes was identified in 31% of patients at diagnosis. Surgery was performed in 59% and radiotherapy in 9% of the cases. 88% of surgically treated patients reported improvement in headache and 59% in visual fields. However, the prevalence of permanent diabetes insipidus increased from 2% at diagnosis to 15% postoperatively. The prevalence of ≥1 pituitary deficiencies and panhypopituitarism increased significantly postoperatively. 58% of the adenomas relapsed in size. 29% of the patients were managed conservatively and tumor size remained stable in 83% of them. CONCLUSIONS: The majority of NFPAs not selected for surgery at diagnosis remained stable in size. Pituitary dysfunction and visual defects at diagnosis were common. Surgical debulking led to clinical improvement, but relapse occurred in 2/3 of the cases.

Glucagon-like peptide-1-based therapies and cardiovascular disease: looking beyond glycaemic control.

Type 2 diabetes mellitus is a well-established risk factor for cardiovascular disease (CVD). New therapeutic approaches have been developed recently based on the incretin phenomenon, such as the degradation-resistant incretin mimetic exenatide and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, as well as the dipeptidyl dipeptidase (DPP)-4 inhibitors, such as sitagliptin, vildagliptin, saxagliptin, which increase the circulating bioactive GLP-1. GLP-1 exerts its glucose-regulatory action via stimulation of insulin secretion and glucagon suppression by a glucose-dependent way, as well as by weight loss via inhibition of gastric emptying and reduction of appetite and food intake. These actions are mediated through GLP-1 receptors (GLP-1Rs), although GLP-1R-independent pathways have been reported. Except for the pancreatic islets, GLP-1Rs are also present in several other tissues including central and peripheral nervous systems, gastrointestinal tract, heart and vasculature, suggesting a pleiotropic activity of GLP-1. Indeed, accumulating data from both animal and human studies suggest a beneficial effect of GLP-1 and its metabolites on myocardium, endothelium and vasculature, as well as potential anti-inflammatory and antiatherogenic actions. Growing lines of evidence have also confirmed these actions for exenatide and to a lesser extent for liraglutide and DPP-4 inhibitors compared with placebo or standard diabetes therapies. This suggests a potential cardioprotective effect beyond glucose control and weight loss. Whether these agents actually decrease CVD outcomes remains to be confirmed by large randomized placebo-controlled trials. This review discusses the role of GLP-1 on the cardiovascular system and addresses the impact of GLP-1-based therapies on CVD outcomes.

Pituitary incidentalomas: a single-centre experience.

AIM: Pituitary incidentalomas (PIs) are diagnosed in about 10% of the patients undergoing radiological investigation for non-pituitary disorders. The aim of this study was to describe the morphological and hormonal characteristics of PIs in a cohort of patients, followed up in a single centre from 1982-2009. METHODS: Retrospective analysis of electronic medical records of patients with PIs was carried out. All patients underwent basal and dynamic evaluation of the hypothalamus-pituitary axis. Mass size was assessed at yearly intervals. RESULTS: Sixty-one patients (38 men/23 women, aged 53±2 years) were studied. The mean follow-up time was 48±8 months, and mean size of PIs was 20±2 mm. Twelve PIs (20%) were microadenomas, 48 (78%) were macroadenomas and one (2%) was a Rathke's cyst. The most common reasons that led to their discovery were headaches, dizziness, syncope, stroke and head injury. Forty-seven of the 61 PIs (77%) were non-functioning, 11 (18%) prolactinomas, and two (3%) GH-secreting adenomas. Hypopituitarism was present in 12% at diagnosis. Forty-eight per cent of the patients were submitted to surgery with conventional radiotherapy in 8%. Relapse in size was observed in 48% of the surgically treated patients. Of the PIs followed conservatively, 78% remained stable, 11% showed decrease and 11% increase in size during follow up. Hypopituitarism rose to 57% postoperatively. CONCLUSIONS: Majority of PIs are non-functioning adenomas that remain stable in size. Relapse in size and hypopituitarism postoperatively are common. PIs, for which conservative management was initially considered appropriate, did not progress in size.

Long term follow-up of patients with adrenal incidentalomas--a single center experience and review of the literature.

INTRODUCTION: Adrenal incidentalomas (AIs) constitute an emerging clinical entity due to the increased use of abdominal imaging for diagnostic purposes. Most often it consists of benign-nonfunctioning lesions and an increase in size during follow-up is reported in about 9% (0-26%), whereas their functional evolution is rare. MATERIALS AND METHODS: Sixty-four patients (22 males and 42 females; mean age 61.6 ± 1.2 years), with AIs and follow-up of 3.1 ± 0.4 years (range 0-19) were retrospectively evaluated. The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary-adrenal axis, renin-angiotensin-aldosterone system and adrenomedullary function. Mass enlargement and adrenal hyperfunction were estimated at yearly intervals. RESULTS: Adrenalectomy was performed in 5 patients (4 benign cortical adenomas and 1 pheochromocytoma). Abnormal manifestation, based on clinical, laboratory and histological evaluation, was observed in 4 patients [1 (1.56%) with SCS, 2 (3.12%) with pheochromocytoma and 1 (1.56%) with aldosteronoma], 3 of which were diagnosed at their initial evaluation and 1 at the 3 (rd) year of follow-up. The remainders [60 patients (93.75%)] were harbouring a non-secretory mass (8 potential myelolipomas, 8 nodular hyperplasias, 3 cystic lesions). Eleven patients (17.2%) had bilateral AIs. Mass enlargement (5-13 mm) was observed in 9 patients (14%), ≥10 mm 4 (6.25%), while mass shrinkage (5-19 mm) in 3 (4.7%) during follow-up. No hormonal evolution was noticed. CONCLUSIONS: AIs present usually as benign, non-secretory lesions. Criteria for surgical intervention were met at initial assessment for the majority of AIs. Size alterations during follow-up are uncommon and functional evolution is rare.