Rivastigmine effective in patients with Parkinson’s disease dementia, orthostatic hypotension
A study of more than 1,000 patients with Parkinson’s disease dementia found that patients who also had orthostatic hypotension experienced greater cognitive benefits from rivastigmine compared with patients who did not.
The results were published in Annals of Neurology.
“We were indeed surprised [by] the results of this analysis. Our hypothesis was that patients with orthostatic hypotension would have less or no benefit [from] rivastigmine compared to those without, given the detrimental effect of hypotension on cognitive function,” Alberto J. Espay, MD, MSc, FAAN, professor of neurology and director and endowed chair of the James J. and Joan A. Gardner Center for Parkinson’s Disease and Movement Disorders at the University of Cincinnati, told Healio Neurology. “However, we found the exact opposite: the magnitude of cognitive benefit was significantly greater in those with orthostatic hypotension compared to those without.”
The cholinesterase inhibitor rivastigmine is approved for the treatment of cognitive impairment in patients with Parkinson’s disease dementia. Espay and colleagues aimed to examine the cognitive benefits of the drug in patients who also have orthostatic hypotension.
Espay and colleagues conducted a post-hoc analysis of two randomized, controlled trials that compared rivastigmine vs. placebo at week 24 (n = 501) and rivastigmine patch vs. capsule at week 76 (n = 546), for a total study population of 1,047 patients with Parkinson’s disease dementia. The researchers classified patients with a drop of greater than or equal to 20 mm Hg in systolic blood pressure or a drop of greater than or equal to 10 mm Hg in diastolic blood pressure upon standing as positive for orthostatic hypotension; otherwise, patients were classified as negative. They used the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) at week 24 and the Mattis Dementia Rating Scale (MDRS) at week 76 to assess cognitive function.
The researchers found no significant differences in demographic or clinical characteristics and cognitive assessment scale scores. Changes in cognitive function from baseline after treatment with rivastigmine in patients with orthostatic hypotension compared with patients without served as the main outcome measure.
Overall safety was comparable between patients with orthostatic hypotension (n = 288) and patients without (n = 730), although patients with orthostatic hypotension in the placebo arm experienced a greater rate of syncope (9.2%). However, patients with orthostatic hypotension had a higher frequency of syncope in the placebo arm (9.2%), according to Espay and colleagues.
ADAS-Cog scores improved by a larger margin at week 24 among patients with orthostatic hypotension compared with patients without (5.6 vs. 1.9 points; P = .0165). Mini-Mental State Examination scores also improved among patients with orthostatic hypotension who received rivastigmine compared with placebo (2.2 vs. -0.7 points; P < .001). Patients with orthostatic hypotension who switched from placebo to rivastigmine at week 48 saw improved ADAS-Cog scores (3.2 vs. -1.1), though this was not significant.
At week 76, the researchers observed a significantly greater change from baseline in MDRS scores among patients with orthostatic hypotension, but only in 42 patients who received rivastigmine capsules compared with 35 patients who received a transdermal patch (10.6 ± 2.9 vs. -1.5 ± 3; P = .031). Espay and colleagues observed no differences in terms of cognitive effect for the rivastigmine patch in patients with and without orthostatic hypotension.
“These findings are relevant,” Espay said. “Individuals with Parkinson’s disease dementia and orthostatic hypotension may in fact be better candidates for rivastigmine than previously recognized.”