New European guidelines for the management of dyslipidaemia in cardiovascular prevention

The new guidelines from the European Atherosclerosis Society and the European Society of Cardiology include a number of updated items. In this paper, we summarize 4 of these changes that we consider to be the most pertinent. Firstly, cardiovascular risk is now stratified according to 4 (previously 2) categories: "very high risk" (patients with cardiovascular disease, patients with diabetes > 40 years old who have at least one other risk factor, patients with kidney failure, or patients in primary prevention with a SCORE value > or = 10%); "high risk" (patients in primary prevention with a SCORE value > or = 5% and or = 1% and < 5%); and "low risk" (primary prevention with SCORE < 1%). The SCORE value for patients in primary prevention is estimated using the SCORE table (calibrated for Belgium). Risk in this table may now be corrected according to HDL cholesterol level. Secondly, the therapeutic targets for each category are now more stringent: LDL cholesterol < 70 mg/dl (or reduced by at least 50%) if the risk is "very high"; < 100 mg/dl if the risk is "high"; and < 115 mg/dl if the risk is "moderate". Thirdly, for patients at "high" or "very high" risk, particularly in patients with combined dyslipidaemia, two further therapeutic targets should be considered: non-HDL cholesterol and apolipoprotein B levels. Fourthly, the follow-up of efficacy (lipid profile) and tolerance (hepatic and muscular enzymes) is described in more details so as to harmonize case management in clinical practice.Peer reviewe

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies.

Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood-brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19--all initially developed for other indications--are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood-brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date

How I treat ... dyslipidaemia according to the cardiovascular risk profile

peer reviewedThe new guidelines from the European Atherosclerosis Society and the European Society of Cardiology include a number of new items. Here we demonstrate their application in several different clinical examples. We focus on the 4 items most pertinent for medical practice: 1) the stratification of risk of cardiovascular disease into 4 categories ('very high', 'high', 'moderate' and 'low risk'), involving--for primary prevention cases--the use of the SCORE table, which has been calibrated for Belgium and where the risk can be adjusted according to HDL cholesterol and the presence of other risk factors; 2) the choice of more stringent therapeutic targets for LDL cholesterol (< 70 mg/dl for 'very high' risk patients, 100 mg/dl for 'high' risk patients and 115 mg/dl for patients at 'moderate' risk); 3) the choice of other therapeutic targets (non-HDL cholesterol and apolipoprotein B levels) for patients at 'very high' or 'high' risk with combined dyslipidaemia; and 4) follow-up of lipid parameters and muscular and hepatic enzymatic profiles

Cost-effectiveness of pravastatin in secondary prevention of coronary heart disease: comparison between Belgium and the United States of a projected risk model

Methodological differences and variations in health care regulations among countries often preclude direct comparisons of cost-effectiveness studies. A projected risk model was applied, designed to determine the economic value in the United States of pravastatin in the secondary prevention of coronary heart disease (CHD), to Belgium using local health care costs. A Markov process was used to model the effectiveness of treatment for 3 years with pravastatin versus placebo in 1000 male CHD patients aged 60 years and clinically similar to those in the pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I) and pravastatin, lipids and atherosclerosis in the carotid arteries (PLAC II) studies. The PLAC I and II trials have shown that pravastatin treatment for 3 years at a weighted mean dose of 36.64 mg daily significantly reduced the incidence of non-fatal myocardial infarction in patients with CHD. Framingham data were used to project the risk of mortality 10 years post-myocardial infarction. The incremental cost per life year gained (LYG), after discounting costs and benefits by 5% annually, in the setting of Belgian health care regulations, was Belgian francs (BEF) 720 794 (US$24 359) for CHD patients with one additional risk factor; BEF 526 464 (US$ 17 792) for those with two additional risk factors; and BEF 392 765 (US$ 13 274) for those with three or more additional risk factors. The cost per LYG in Belgium appeared to be more sensitive to drug acquisition cost than to costs of medical interventions. The cost-effectiveness ratios of pravastatin monotherapy for 3 years in secondary prevention of CHD, obtained with the same projected risk model, are from 86 to 92% higher in Belgium than in the United States, due to differences in medical patterns of practice and in intervention costs. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved