SummaryBackground-Metformin might reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, but whether it has cardiovascular benefits is unknown. We aimed to investigate whether metformin treatment (added to titrated insulin therapy) reduced atherosclerosis, as measured by progression of common carotid artery intima-media thickness (cIMT), in adults with type 1 diabetes at increased risk for cardiovascular disease.

. (2016) Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Lancet, 388(10056), pp. 2142Lancet, 388(10056), pp. -2152Lancet, 388(10056), pp. . (doi:10.1016 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/124000/ 30Background. The optimal blood pressure (BP) target in hypertension remains debated, especially in

Objective To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management.Design Multicentre, parallel group, observer blind, randomised controlled trial. Setting 39 UK hospitals, recruiting from June 2009 to November 2012.Participants 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone).Intervention Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively.Main outcome measures The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months).Results Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was −0.21 (1.00) cm2/day in the ciclosporin group compared with −0.14 (0.42) cm2/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm2/day, 95% confidence interval −0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group.Conclusion Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference. Trial registration Current Controlled Trials ISRCTN35898459.

Enlighten -Research publications by members of the University of Glasgow http://eprints.gla.ac.ukT h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 374;16 nejm. BACKGROUNDAmong patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODSAfter a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTSAfter a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P = 0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P = 0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONSIn patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. 1522T h e ne w e ngl a nd jou r na l o f m e dicine A ngiotensin-converting-enzyme (ACE) inhibitors are effective in lowering the risks of death and hospitalization among patients with chronic heart failure and reduced ejection fraction.1,2 As a consequence, there has been interest in other approaches to interruption of the renin-angiotensin system in patients with heart failure. Angiotensin-receptor blockers (ARBs) were the first alternative tested, and in one placebo-controlled trial, candesartan was associated with lower risks of death from cardiovascular causes and hospitalization for heart failure among patients who could not take ACE inhibitors.3 However, in a head-to-head comparison, losartan was not as effective as captopril. 4 The combination of an ARB and an ACE inhibitor has also been examined in two trials involving patients with heart failure. 5,6 In both trials, the addition of an ARB to standard therapy with an ACE inhibitor was associated with a lower risk of hospitalization for heart failure than was standard therapy alone and, in one trial, with a lower risk of death from cardiovascular causes. Neither trial, ...

AimsMen and women differ in terms of presentation and management in coronary artery disease (CAD). Whether these differences translate into different clinical outcomes in stable CAD is unclear. We analysed data from the international prospective CLARIFY registry to compare cardiovascular clinical outcomes in men and women with stable CAD.Methods and resultsWe analysed 1-year outcomes in 30 977 outpatients with stable CAD [23 975 (77.4%) men; 7002 (22.6%) women]. Women were older than men, more likely to have hypertension and diabetes, and less likely to exercise or smoke. They had more frequent angina, but were less likely to have undergone diagnostic non-invasive testing or coronary angiography. Women received less optimized treatment for stable CAD. One-year outcomes were similar for men and women for the composite of cardiovascular death, non-fatal myocardial infarction, or stroke [adjusted rates 1.7 vs. 1.8%, respectively, odds ratio (OR) 0.93, 95% confidence interval (CI) 0.75–1.15]; all-cause death (adjusted 1.5 vs. 1.6%, OR: 0.91, 95% CI: 0.72–1.13); fatal or non-fatal myocardial infarction (adjusted 1.0 vs. 0.9%, OR: 0.81, 95 CI: 0.60–1.08); and cardiovascular death or non-fatal myocardial infarction (adjusted 1.4 vs. 1.4%, OR: 0.89, 95% CI: 0.70–1.12). Fewer women underwent revascularization (2.6 vs. 2.2%, OR: 0.77, 95% CI: 0.64–0.93), although appropriateness was not analysed.ConclusionThe risk profiles of women and men with stable CAD differ substantially. However, 1-year outcomes were similar. Fewer women underwent revascularization. Further research is needed to better understand gender determinants of outcome and devise strategies to minimize bias in the management and treatment of women.

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AimsTherapy with i.v. iron in patients with chronic heart failure (CHF) and iron deficiency (ID) improves symptoms, functional capacity, and quality of life. We sought to investigate whether these beneficial outcomes are independent of anaemia.Methods and resultsFAIR-HF randomized 459 patients with CHF [NYHA class II or III, LVEF ≤40% (NYHA II) or ≤45% (NYHA III)] and ID to i.v. iron as ferric carboxymaltose (FCM) or placebo in a 2:1 ratio. We analysed the efficacy and safety according to the presence or absence of anaemia (haemoglobin ≤120 g/L) at baseline. Of 459 patients, 232 had anaemia at baseline (51%). The effect of FCM on the primary endpoints of self-reported Patient Global Assessment (PGA) and NYHA class at week 24 was similar in patients with and without anaemia [odds ratio (OR) for improvement, 2.48 vs. 2.60, P = 0.97 for PGA and 1.90 vs. 3.39, P = 0.51 for NYHA). Results were also similar for the secondary endpoints, including PGA and NYHA at weeks 4 and 12, 6 min walk test distance, Kansas City Cardiomyopathy Questionnaire overall score, and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points. Regarding safety, no differences were noticed in the rates of death or first hospitalization between FCM and placebo both in anaemic and in non-anaemic patients.ConclusionsTreatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia. Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered.

A low-intensity, pharmacist-led collaborative intervention in primary care resulted in modest improvements in prescribing of disease-modifying medications but did not improve clinical outcomes in a population that was relatively well treated at baseline.