CCB Doesn't Help Cognition After Stroke MMSE scores no better with nimodipine than placebo after 6 months

Just because finding the solution to this is 'vexing' and complicated is no reason to give up.

CCB Doesn't Help Cognition After Stroke MMSE scores no better with nimodipine than placebo after 6 months

• by Kristina Fiore
  Associate Editor, MedPage Today February 23, 2017

HOUSTON -- Nimodipine didn't improve cognition when ischemic stroke patients with vascular mild cognitive impairment (MCI) started taking the calcium channel blocker within a week of their event, researchers reported here.
In a randomized controlled trial from 23 sites in China, patients had no differences in change in Mini-Mental State Exam (MMSE) scores at 6 months whether they were on the drug or placebo, Huaguang Zheng, MD, of Beijing Tiantan Hospital in China and colleagues reported at the International Stroke Conference meeting here.
"In our trial, we found that nimodipine didn't benefit vascular MCI patients, but it may have marginal positive effects on specific cognitive domains, such as executive function, and it won't increase the risk of stroke or other adverse events," Zheng said during a press briefing.
More than half of stroke patients develop vascular MCI during the first three months of follow-up, he explained, and about 30% to 50% will develop dementia within 5 years.
While there are currently no effective therapies for vascular MCI and dementia, some studies have suggested that nimodipine may have cognitive benefits, he said.
To assess whether that's the case, Zheng and colleagues randomized 654 patients to either placebo or to 30 mg nimodipine three times a day. The primary endpoint was the change in cognition function on the MMSE and on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) over 6 months.
Overall, outcomes were similar between the two groups, with no significant advantage for nimodipine, Zheng said.
There was, however, an advantage for nimodipine in terms of the proportion of patients who had an ADAS-Cog score of 0 or greater at 6 months (34% versus 47%), and there was some indication that the drug may benefit specific brain areas, particularly executive function, he noted.
Zheng added that nimodipine didn't increase the risk of stroke and other adverse events.
He acknowledged that the study was limited because it didn't evaluate Global Cognitive Index scores, neurological outcome, or subcortical dementia, and the sample size was too small.
Mark Alberts, MD, of Hartford Healthcare, said it was "reasonable to investigate" nimodipine given that it's been shown to potentially have neuroprotective effects. But the problem of cognitive decline following stroke is a "vexing issue" because the pathophysiology is so complicated.
"If you have a stroke, and you develop dementia after the stroke, is that vascular dementia related to the stroke? Having a stroke, you take out millions of neurons," he told MedPage Today. "Most people, including myself, think it's a combination, that there's some underlying degenerative process, and vascular disease on top of that is just accelerating it perhaps."
Alberts said it's best to focus on risk factor control in patients with cognitive impairment after a stroke -- treating diabetes, hypertension, and hypercholesterolemia, for instance. For patients who progress to dementia, he offers rehabilitation programs or the cholinesterase inhibitor donepezil (Aricept).
Amytis Towfighi, MD, of the University of Southern California and director of neurological services at the Los Angeles County department of health, agreed that risk factor control is the main therapeutic strategy for cognitive impairment following stroke.
"Currently there are no proven treatments. We don't know if medications that have been tested in Alzheimer's would be effective," she told MedPage Today. "Generally we recommend lifestyle changes -- the same things you would recommend to prevent stroke. Prevention is the key."

The study was supported by the National Key Technology Research and Development Program of the Ministry of Science and Technology of China. Bayer provided additional support.
Zheng disclosed no financial relationships with industry.

• Primary Source

  International Stroke Conference

  Source Reference: Zheng H, et al "Efficacy and safety of nimodipine in vascular mild cognitive impairment: a randomized placebo controlled trial" ISC Meeting 2017; Abstract LB7.