Unfavorable Outcomes During Treatment Of Multiple Sclerosis With High Doses Of Vitamin D

[No abstract available

The Real-life Experience With Cardiovascular Complications In The First Dose Of Fingolimod For Multiple Sclerosis [a Experiência Da Vida Real Com Complicações Cardiovasculares Na Primeira Dose De Fingolimode]

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.729712714Thomas, K., Ziemssen, T., Management of fingolimod in clinical practice (2013) Clin Neurol Neurosurg., 115, pp. S60-S64Ontaneda, D., Hara-Cleaver, C., Rudick, R.A., Cohen, J.A., Bermel, R.A., Early tolerability and safety of fingolimod in clinical practice (2012) J Neurol Sci., 323, pp. 167-172Bünemann, M., Liliom, K., Brandts, B.K., A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes (1996) EMBO J., 15, pp. 5527-5534Sanna, M., Liao, J., Jo, E., Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate (2004) J Biol Chem, 279, pp. 13839-13848Laroni, A., Brogi, D., Morra, V.B., Safety of the first dose of fingolimod for multiple sclerosis: Results of an open-label clinical trial (2014) BMC Neurol, 14, p. 65Polman, C.H.R., Reingold, S.C., Banwell, B., Dianosticcriteria for multiple sclerosis: 2010 Revisions to the Mac Donald criteria (2011) Ann Neurol, 69, pp. 292-302Espinosa, P.S., Berger, J.R., Delayed fingolimod-associated asystole (2011) Mult Scler, 17, pp. 1387-1389Kappos, L., Radue, E.W., O'Connor, P., A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis (2010) N Engl J Med, 362, pp. 387-401Singer, B.A., Initiating oral fingolimod treatment in patients with multiple sclerosis (2013) Ther Adv Neurol Disord, 6, pp. 269-27

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)