5 New Neurology Studies' Practice-Changing Implications

Hans-Christoph Diener, MD, PhD


January 29, 2019

Dear colleagues, I am Christoph Diener, a neurologist from the University Essen in Germany. Today I'd like to discuss five noteworthy studies in the field of neurology, published this past fall.

More Proof of Aspirin's Ineffectiveness

The results of the ASPREE trial, which looked at aspirin for the primary prevention of cardiovascular events and mortality, had its results presented in a trio of publications in the New England Journal of Medicine.[1,2,3] Between 2010 and 2014, investigators in the United States and Australia enrolled more than 19,000 persons who were 70 years of age or older and free of cardiovascular diseases, dementia, or permanent disability. The trial compared 100 mg of aspirin per day versus placebo.

At a median of 4.7 years, the trial was terminated by the Data and Safety Monitoring Board due to lack of benefit. For the endpoints of dementia and persistent physical disability, the hazard ratio was 1.01, which definitely was not significant. The all-cause mortality was increased in people on aspirin, with a hazard ratio of 1.14. Cardiovascular events were not reduced in those receiving aspirin, with a hazard ratio of 0.95. Also, the rate of major bleeds was significantly increased in those taking aspirin, with a hazard ratio of 1.38.

ASPREE joins two other randomized trials[4,5] published within weeks of each other that showed that aspirin is not effective in primary prevention of cardiovascular diseases, including stroke, and simply causes more major bleeding.

Fingolimod's Efficacy in Pediatric Multiple Sclerosis

The second trial, also published in the New England Journal of Medicine, compared fingolimod with interferon beta-1a in pediatric multiple sclerosis.[6] The study included 215 patients between the ages of 10 and 17 years.

It clearly showed that, compared with beta interferon, fingolimod had a lower rate of annual relapses (0.67% vs 0.12%, respectively) and fewer new or newly enlarged lesions observed annually on MRI (9.3 vs 4.4, respectively). However, as you would expect, there were more serious adverse events on fingolimod.

Rivaroxaban Reduces Stroke in Patent Foramen Ovale

Lancet Neurology published a subgroup analysis[7] of the NAVIGATE ESUS trial,[8] in which patients with embolic stroke of undetermined source (ESUS) were randomized to daily doses of 15 mg rivaroxaban or 100 mg of aspirin. NAVIGATE ESUS was negative for recurrent stroke and showed an increased risk of bleeding with rivaroxaban.

This subgroup analysis looked at 534 patients from that trial who had patent foramen ovale (PFO), in whom the risk for recurrent stroke was reduced by approximately 50% if rivaroxaban was compared with aspirin.

The authors then combined their results in a random-effects meta-analysis with a pair of PFO closure studies that also compared anticoagulation with aspirin—the 2002 PICSS trial[9] and the 2017 CLOSE trial.[10] In doing so, they observed a significant benefit for anticoagulation over aspirin.

Encouraging Early Data in Amyotrophic Lateral Sclerosis

A very exciting preliminary study was published in Annals of Neurology regarding the use of bone marrow–derived mesenchymal stem cells (BM-MSCs).[11] Researchers randomized 64 patients with amyotrophic lateral sclerosis (ALS) to receive standard therapy with riluzole alone or combined with two repeated BM-MSC injections. They observed a possible clinical benefit to BM-MSCs after 4 and 6 months. This now has to be proven in a larger study.

Metformin: A New Option for Myotonic Dystrophy Type 1

Finally, the journal Brain published a study showing that metformin is effective in myotonic dystrophy type 1.[12] After noting the efficacy of this treatment in animal experiments, researchers enrolled 40 adult patients in a study to receive oral metformin or placebo three times daily, with a dose-escalation period over 4 weeks up to 3 g/day, followed by 48 weeks at maximum dose. The primary and secondary endpoints were a 6-minute walk test and muscle strength, respectively.

Unfortunately, only 23 of 40 patients completed the study, but there was a positive outcome in favor of metformin for both mobility and mechanical power. I think this is a very interesting experiment which indicates that, most probably, we now have a symptomatic treatment for myotonic dystrophy.


Ladies and gentlemen, these five studies collectively show us that aspirin is not effective for primary stroke prevention; fingolimod is superior to interferon beta-1a in pediatric multiple sclerosis; most probably anticoagulation is superior to aspirin in people with PFO where closure is not an option; there is a glimmer of hope for ALS with mesenchymal stem cells; and finally, metformin is effective in myotonic dystrophy to improve symptoms.

Thank you for listening and watching.


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