The efficacy and safety of nimodipine in acute ischemic stroke patients with mild cognitive impairment: a double-blind, randomized, placebo-controlled trial.

Nimodipine might be effective in subcortical vascular dementia (VaD). Its benefit in preventing further cognitive decline in patients with acute ischemic stroke (AIS) and vascular mild cognitive impairment (VaMCI) remains to be established. In this multicenter, double-blind trial, we randomly assigned 654 eligible patients to nimodipine 30 mg three times a day or placebo. The primary outcome was any cognitive decline defined by the changes on the Mini-Mental State Examination (ΔMMSE ≤ -3) or vascular AD assessment scale cognitive subscale (ΔADAS-cog ≥ 4) at 6 months. Secondary outcomes included any distribution shift of ΔADAS-cog, ΔMMSE or cognitive improvement defined by ΔADAS-cog ≤ -2, or ΔMMSE ≥ 0. The primary outcome in the nimodipine group and placebo group were similar for ΔMMSE ≤ -3 (4.18% and 7.22%, respectively, P = 0.15) and ΔADAS-cog ≥ 4 (8.36% and 8.93% respectively, P = 0.88). The distribution shift of ΔADAS-cog and ΔMMSE differed significantly between the two groups (P = 0.03 and P = 0.05 respectively). Cognitive improvement occurred in 55.4% in the nimodipine group and 43.6% in the placebo group measured by ΔADAS-cog ≤ -2 (Odds Ratio, 1.54; 95% confidence interval [CI] 1.10-2.14, P < 0.01) or 84.0% and 74.6% respectively by ΔMMSE ≥ 0 (Odds Ratio, 1.79; 95% CI 1.18-2.70, P < 0.01). Nimodipine was associated with better cognitive function in the memory domain. The adverse events rate was similar in two groups. This study is registered with ClinicalTrials.gov, NCT01220622. Nimodipine did not show benefit to prevent cognitive decline in AIS patients with VaMCI, but improved cognition moderately, especially measured in the memory domain.