For January 2016 we have selected: Buettner C, Rony-Reuven N, Bernstein C, et al. Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial. Ann Neurol 2015 Sept 29;doi: 10.1002/ana.24534.
Migraine is a worldwide primary headache disorder that can be highly disabling and with an important impact on quality of life. Migraine has been linked to an increased risk for vascular diseases by sharing the same ethiopathogenesis, related to alterations mediated by the endothelium. This endothelial dysfunction seems to be improved by statins. Moreover, vitamin D has been shown to potentiate the statin positive effects. Migraine treatment can prevent and end headache. However, current available preventive medications are often accompanied by important side effects.
In this randomized, monocenter, double-blind, placebo-controlled, parallel-arm study, the investigators studied the effects of the combined treatment simvastatin/vitamin D on migraine prevention. Patients with at least 3-year history of migraine and more then 4 days/month were pre-randomized for a 12-week period (baseline) of migraine clinical characteristics assessments. Subsequently, patients who did not meet the criteria for chronic daily headache (³15 days/month for 3 months) were randomized to placebo or simvastatin/vitamin D3 (20mg/1000 international units twice a day) and followed with visits scheduled at 12 and 24 weeks. For the whole study duration patients were asked to complete detailed paper diaries for headache and medications, and at each visit they were assessed with migraine disability questionnaires (MIDAS).
Of the 89 patients who were pre-randomized, 57 subjects were afterwards randomized to placebo (n. 29) or simvastatin/vitamin D (n. 28) treatment. Fifty-two patients completed the whole study. At both time points, the active treatment significantly decreased the number of migraine days (-8 days, IQR: -15.0 to -2.0 at 12 weeks; -9 days, IQR: -13.0 to -5.0 at 24 weeks) compared to the pre-randomized period (+1.0 days, IQR: -1.0 to +6.0 at 12 weeks; +3.0 days, IQR: -1.0 to +5.0 at 24 weeks; P<0.001). At the last time point, 29% patients of the active group versus 3% patients of the placebo group showed ³50% reduction (P=0.03) in migraine days. Moreover, the active treatment group used less anti-migraine medications and for shorter period of time. However, migraine disability was significantly decreased only at the 12-week follow-up and migraine clinical characteristics did not change during the study in either group. No clinical independent variables were found to be associated to the active treatment effect. Adverse events were no different between groups.
“Many clinical patients had longstanding history of migraine resistant to previous preventive treatment or with unacceptable side effects. Results coming from this study are encouraging and indicate a new and more mechanism based way to prevent migraine.” says Prof. Fabio Antonaci, Department of Brain and Behavioral Sciences, C. Mondino National Institute of Neurology Foundation, University of Pavia, Italy. “On average, simvastatin plus vitamin D allowed patients to have three migraine-free days per month (30% reduction). This effects size goes beyond the effects of other medications that are usually used for migraine prevention. These results need to be replicated in a larger population. Indeed, the two groups showed significant difference concerning days of migraine recorded at baseline. Migraine is a chronic disease which trends to worsen over the years. Thus, a longer follow-up of the proposed combined treatment is required. Moreover, the role of simvastatin alone versus vitamin D3 alone needs further investigation.”
The other nominees for the January paper of the month are:
Nichol A, French G, Little R, et al., for the EPO-TBI Investigators and the ANZICS Clinical Trials Group. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomized controlled trial. Lancet 2015; Oct 6. doi: 10.1016/S0140-6736(15)00386-4The possible neurocytoprotective effects of erythropoietin were studied in 606 patients with moderate or severe traumatic brain injury in 29 centers from seven countries. Patients were randomized to 40,000 units erythropoietin subcutaneously or placebo once per week for a maximum of three doses. Functional outcome at 6 months, as measured by the Extended Glasgow Outcome Scale was similar between groups, although a possible reduction in mortality was observed in the erythropoietin group.
Andrews PJD, Sinclair HL, Rodriguez A, et al., for the Eurotherm3235 Trial Collaborators. Hypothermia for intracranial hypertension after traumatic brain injury. NEJM 2015; 373(25):2403-12. In this multicenter European trial, 387 patients with intracranial hypertension of more than 20 mmHg after traumatic brain injury were randomly assigned to receive either standard care or hypothermia (32 to 35° C) plus standard care. There was no significant difference in the Extended Glasgow Outcome Scale between groups at 6 months.
Roa W, Kepka L, Kumar N, et al. International Atomic Energy Agency randomized phase III study of radiation therapy in elderly and/or frail patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 2015; 33(35):4145-50. 2015. Ninety-eight patients with glioblastoma multiforme were randomly assigned to two radiotherapy treatments: short-course (25 Gy in five daily fractions over one week) and conventional (40 Gy in 15 daily fractions over three weeks). Survival time, progression-free survival time, and quality of life did not significantly differ between groups, suggesting that short 1-week radiotherapy can be preferred for elderly and frail patients.