Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial.
OBJECTIVE
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 75.2+/-6.1; 109 placebo, 75.4+/-6.0) 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 (P<0.01) and less frequently showed deterioration (3 or more point-drop versus baseline) on a Mini-Mental State Examination (28.1% versus 50.5%; chi2 P<0.01) and Global Deterioration Scale (P<0.05). 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.
Pantoni
Leonardo
L
Department of Neurological and Psychiatric Sciences, University of Florence, Viale Morgagni 35, 50134 Florence, Italy. pantoni@neuro.unifi.it
del Ser
Teodoro
T
Soglian
Andrea G
AG
Amigoni
Silvia
S
Spadari
Giovanni
G
Binelli
Daniela
D
Inzitari
Domenico
D
D000368:Aged; D015140:Dementia, Vascular / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D009553:Nimodipine / Q000009:adverse effects* / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome
D009553:Nimodipine