LDL and Stroke Prevention: How Low to Go

Hans-Christoph Diener, MD, PhD


January 28, 2020

This transcript has been edited for clarity.

Dear colleagues, I'm Christoph Diener, a neurologist from the University of Duisburg-Essen in Germany, here to discuss five interesting studies published in November 2019.

Vitamin D3's Role Unclear in Multiple Sclerosis

There are a number of registry studies indicating that low vitamin D3 levels are, perhaps, a risk factor in multiple sclerosis. In a publication in Neurology, investigators behind the SOLAR study reported results in 229 patients with relapsing-remitting multiple sclerosis treated with interferon-beta-1a. Patients were then randomized to receive either 14,000 units of vitamin D3 per day or placebo.

The primary endpoint—no evidence of disease activity at week 48—was achieved by 35% in both treatment groups. Although there was no benefit to vitamin D3 overall, a subgroup analysis did show a tendency toward fewer new lesions on MRI imaging with vitamin D3.

Three Options for Treating Status Epilepticus Refractory to Benzodiazepines

A study published in The New England Journal of Medicine addressed the very important question of what is the best treatment for patients with status epilepticus who initially do not respond to benzodiazepines. Investigators randomized patients to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121).

The primary endpoint of absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion was achieved in 45%-47% of patients across the three treatments. There was no difference in efficacy. In terms of adverse events, there was a higher, but statistically insignificant, number of patients with hypotension and need for intubation in the fosphenytoin group, and a slightly higher mortality in the levetiracetam group.

Aim for an LDL < 70 mg after Ischemic Stroke or Transient Ischemic Attack

Also published in The New England Journal of Medicine were results from the Treat Stroke to Target study. Investigators addressed the question of how low should the LDL cholesterol be in secondary stroke prevention after ischemic stroke or transient ischemic attack. They recruited 2860 patients and randomized them to two target groups: an LDL of < 70 mg/dL or an LDL between 90 and 110 mg/dL. Patients were followed for a median of 3.5 years.

The primary endpoint of major cardiovascular events or deaths from cardiovascular causes was reached in 8.5% in the lower-target group, who achieved an LDL of 65 mg/dL, and in 10.9% in the higher-target group, who achieved an LDL of 96 mg/dL. This translates to a hazard ratio of 0.78, representing a significant 22% risk reduction (P = .04).

Ubrogepant Superior to Placebo for Migraine, but Important Questions Remain

The ACHIEVE II Study investigated the oral calcitonin gene-related peptide receptor antagonist ubrogepant versus placebo for the treatment of acute migraine attacks. Investigators recruited 1686 patients (90% female) who received ubrogepant at 25 or 50 mg or placebo.

The primary endpoint of being pain-free 2 hours after taking the medication was achieved by approximately 21% of the patients receiving ubrogepant at either dose, compared with 14% of the placebo group. There were very few side effects with ubrogepant outside of a little bit of nausea and dizziness.

However, this study was unable to answer the most important question of whether this new drug is equivalent in efficacy to sumatriptan. The other important question is whether this drug can be used in people who have contraindications for triptans, which, unfortunately, this study also could not answer.

Consider Tranexamic Acid Immediately After Traumatic Brain Injury

Published in The Lancet, the CRASH-3 study investigated the possible benefit of tranexamic acid in acute brain injury with intracranial bleeding. Tranexamic acid, unfortunately, was not effective in spontaneous intracerebral haemorrhage. The current study recruited more than 12,000 patients who were randomized to receive tranexamic acid or placebo within 3 hours of brain injury. Participants had to have a Glasgow Coma Scale score of 12 or less and an intracranial bleed.

The death rate was 18.5% for tranexamic acid versus 19.8% for placebo, which translates to a 6% risk reduction that almost reached statistical significance. There was a statistically significant benefit if patients with very severe head injury were excluded. Here the risk reduction was 11% and was significant.

Tranexamic acid is obviously an option for people with traumatic intracranial haemorrhage. It's cheap, it's safe, and it did not lead to an increased risk for vascular occlusive disease.

Ladies and gentlemen, I'm Christoph Diener from the University of Duisburg-Essen. Thank you very much for listening about these five interesting studies from November 2019.

Dr Diener is an expert in the treatment of stroke and headache, and chairs the German Headache Consortium and the German Stroke Data Bank.

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