Efficacy and Safety of Nimodipine in Subcortical Vascular Dementia

Abstract

Background and Purpose-Evidence of drug efficacy in vascular dementia (VaD) is scanty. Therapeutic trials should address VaD subtypes. We studied the efficacy and safety of the calcium antagonist nimodipine in subcortical VaD. Methods-242 patients defined as affected by subcortical VaD based on clinical (ICD-10) and computed tomography criteria were randomized to oral nimodipine 90 mg/d or placebo. Results-230 patients (121 nimodipine, mean age 75.2Ϯ6.1; 109 placebo, 75.4Ϯ6.0) were valid for the intention-to-treat analysis. At 52 weeks, the Sandoz Clinical Assessment Geriatric scale 5-point variation (primary outcome measure) did not differ significantly between the 2 groups. However, patients on nimodipine performed better than placebo patients in lexical production (PϽ0.01) and less frequently showed deterioration (3 or more point-drop versus baseline) on a Mini-Mental State Examination (28.1% versus 50.5%; 2 PϽ0.01) and Global Deterioration Scale (PϽ0.05). Dropouts and adverse events were all significantly more common among placebo than nimodipine patients, particularly cardiovascular (30 versus 13; RR, 2.26; 95% CI, 1.11 to 4.60) and cerebrovascular events (28 versus 10; RR, 2.48; 95% CI, 1.23 to 4.98), and behavioral disturbances requiring intervention (22 versus 5; RR, 3.88; 95% CI, 1.49 to 10.12). A worst-rank analysis, performed to correct for the effect of the high dropout rate in the placebo group, showed additional significant differences in favor of nimodipine in Set Test and MMSE total scores. Conclusions-Nimodipine may be of some benefit in subcortical VaD. Confirming previous results, the safety analysis of this study shows that in this high-risk population, nimodipine might protect against cardiovascular comorbidities.

Antihypertensive Treatment in People With Dementia

“…Both groups were allowed to continue with unspecified antihypertensive treatment as prescribed before the beginning of the study except alpha methyldopa. The results showed that the control group had significantly more adverse (cerebrovascular) events than the treatment group [11][12] . For cardiovascular events the trend was similar but reached significance in only one of the studies 12 .…”

“…The results showed that the control group had significantly more adverse (cerebrovascular) events than the treatment group [11][12] . For cardiovascular events the trend was similar but reached significance in only one of the studies 12 . In a subgroup analysis of participants with sub-cortical vascular dementia 13 , no significant differences in these adverse events were found, although again the same trend was observed (fewer events in the treatment group).…”

“…No randomized controlled placebo trials have been conducted in this area. In people with dementia, two randomized controlled trials investigated the effects of calcium channel blockers (CCBs) in an intention-to-treat, a efficacy and a safety analysis [10][11][12] . For both trials, main outcome was cognition but the safety analysis included cardio-and cerebrovascular events, which were reported as adverse events.…”

Latin American Delphi Consensus on Vascular Cognitive Impairment: Definitions, Clinical Features, Pathophysiology, Prevention and Treatment

“…A Cochrane 2002 review analyzed three studies using nimodipine (90 mg/day) between 12 and 24 weeks in patients with vascular dementia, and a benefit was found in some cognition and global assessment scales [226] A multicenter, double-blind, randomized study comparing nimodipine (90 mg/day) to placebo for the treatment of subcortical vascular dementia for 52 weeks was published, without finding a benefit in the cognition scales [227].…”

Sarpogrelate Dilates Cerebral Arteries in the Absence of Exogenous Serotonin

“…27) Only nimodipine has been established as a neuroprotectant after subarachnoid hemorrhage. 22) In addition, L-type calcium channel blockers have potential therapeutic uses for subcortical vascular dementia 19) and Parkinson's disease. 23) Thus, as a L-type calcium channel antagonist, sarpogrelate may represent a new and important therapeutic agent in the treatment of cerebral ischemia, subarachnoid hemorrhage, dementia, and Parkinson's disease.…”