Dear colleagues, I am Christoph Diener, a neurologist from the University of Duisburg-Essen in Germany. This month I am reporting on five new studies in the field of neurology.
The first study, called REVERSE AD, was published in the New England Journal of Medicine. Patients with atrial fibrillation who are taking dabigatran to prevent stroke can have major bleeding complications. Idarucizumab is a new agent that reverses the anticoagulant effect of dabigatran. REVERSE AD was an open-label study of 503 patients who were taking dabigatran; 301 had a major bleeding event and 202 required urgent surgery and thus needed anticoagulant reversal. The study showed that idarucizumab neutralized the anticoagulant effect of dabigatran within 10 minutes. This is a very important result for neurologists. The mortality of intracranial bleeds was only 16% compared with a mortality of intracranial bleeds between 35% and 41% depending on the dose of dabigatran in the RE-LY study, where the reversal agent was not available. Thus, with the help of the reversal agent, we can reduce mortality in dabigatran-related intracranial bleeds.
The second study was a systematic review published in Stroke. This was a major analysis of five randomized trials that compared endarterectomy versus stenting in patients with asymptomatic carotid stenosis. The meta-analysis included 3019 patients and showed a strong trend toward an increased risk for periprocedural stroke and death for stenting compared with endarterectomy. Unfortunately, this analysis did not look at whether best medical therapy might be at least equivalent or superior to either endarterectomy or stenting. Studies comparing best medical therapy, stenting, and endarterectomy are ongoing.
The third study, published in Lancet Neurology, investigated the impact of a high (80 mg) dose of simvastatin on cognitive, neuropsychiatric, and quality-of-life measures in patients with secondary progressive multiple sclerosis. The initial publication of this study showed that this treatment has little impact on the clinical course of the disease. In this substudy, the investigators looked at neuropsychological tests, depression scales, and quality of life. They found that, already at baseline, 45% of these patients have impaired frontal lobe function; and over 2 years, patients experienced a clear worsening of verbal and nonverbal memory. Moreover, only two out of many outcome parameters were improved with simvastatin; these were the frontal assessment battery and the physical component of the Short Form Health Survey (SF-36). The bottom line is that simvastatin has no real benefit in patients with secondary progressive multiple sclerosis.
The fourth study, published in the New England Journal of Medicine, investigated the use of tocilizumab for treatment of patients with giant cell arteritis. Prednisone is the standard of care for giant cell arteritis, but patients with this condition are elderly and side effects with long-term treatment are a major problem. Tocilizumab is an interleukin-6 receptor alpha inhibitor. These investigators recruited 251 patients who were randomly assigned to receive tocilizumab—162 mg subcutaneously, either weekly or every other week—or placebo. The study looked at sustained remission and the sparing of prednisone. After 12 months, sustained remission was achieved in 56% of patients receiving tocilizumab weekly and 53% of those who received it biweekly, compared with only 14%-18% with placebo. The cumulative prednisone dose was reduced by almost 50%.
This result is very encouraging, but unfortunately this drug is extremely expensive. In practical terms, for patients who need an ongoing high dose of prednisone, we would first use methotrexate or azathioprine to save prednisone.
The last study, published in JAMA Neurology, will have a major impact on pain therapy. This US study comprised a population-based cohort of patients with painful polyneuropathy and control patients who were or were not treated with long-term opioids. In all, the study included 2892 patients with polyneuropathy and 14,435 control patients. Patients with polyneuropathy received long-term opioid treatment more often than controls.
Investigators could not show a difference in physical impairment between patients treated with opioids or not treated with opioids. They did see a clear increased risk for adverse outcomes with opioids, including depression, opioid dependence, and opioid overdose. These adverse outcomes are becoming a major problem, not only in patients with painful polyneuropathy but also in those with chronic low back pain. Until 10 years ago, we were quite reluctant to prescribe long-acting opioids for non-cancer pain, but now the tendency has moved in the other direction. There is now an overuse of opioids in patients with non-cancer pain. We have to select these patients very carefully.
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