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(DMMSE à3) or vascular AD assessment scale cognitive subscale(DADAS-cog ! 4) at 6 months. Secondary outcomes included any distribution shift of DADAS-cog, DMMSE or cognitive improvement defined by DADAS-cog à2, or DMMSE ! 0. The primary outcome in the nimodipine group and placebo group were similar for DMMSE à3(4.18% and 7.22%, respectively, P = 0.15) and DADAS-cog ! 4(8.36% and 8.93% respectively,P = 0.88). The distribution shift of DADAS-cog and DMMSE 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 DADAS-cog à2(Odds Ratio, 1.54; 95% confidence interval[CI] 1.10–2.14, P < 0.01) or 84.0% and 74.6% respectively by DMMSE ! 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.

Analytical validation of GMEX rapid point- of care CYP2C19 genotyping system for the CHANCE-2 trial

Background and purpose Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events(HR-NICE).Conventional genetic testing methods used in CYP2C19 genotype-guided antiplatelet therapy for patients with HR-NICE did not satisfy the needs of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events(CHANCE)-2 trial.Therefore,we developed the rapid-genotyping GMEX(point-of care)system to meet the needs of the CHANCE-2 trial.Methods Healthy individuals and patients with history of cardiovascular diseases(n=408)were enrolled from six centres of the CHANCE-2 trial.We compared the laboratory-based genomic test results with Sanger sequencing test results for accuracy verification.Next,we demonstrated the accuracy,timeliness and clinical operability of the GMEX system compared with laboratory-based technology(YZY Kit)to verify whether the GMEX system satisfies the needs of the CHANCE-2 trial.Results Genotypes reported by the GMEX system showed 100%agreement with those determined by using the YZY Kit and Sanger sequencing for all three CYP2C19 alleles(*2,*3 and*17)tested.The average result’s turnaround times for the GMEX and YZY Kit methods were 85.0(IQR:85.0-86.0)and 1630.0(IQR:354.0-7594.0)min(p<0.001),respectively.Conclusions Our data suggest that the GMEX system is a reliable and feasible point-of care system for rapid CYP2C19 genotyping for the CHANCE-2 trial or related clinical and research applications.

Gastrointestinal bleeding during acute ischaemic stroke hospitalisation increases the risk of stroke recurrence

Objective Gastrointestinal(GI)bleeding in patients who had a stroke is strongly associated with a higher risk of death and loss of independence.However,it is unknown whether GI bleeding increases risk for recurrence of stroke.In this study,we assess the potential relationship between GI bleeding and stroke recurrence in patients within 12 months of an acute ischaemic stroke(AIS),using the China National Stroke Registry(CNSR).Methods This study included 22216 patients who had an ischaemic stroke included in the CNSR from 2007 to 2008.We analysed baseline patient characteristics,GI bleeding and outcomes of patients who had an AIS,specifically stroke recurrence at 3,6 and 12 months.We used multivariable logistic regression to evaluate a possible association between GI bleeding and stroke recurrence.results Of the 12415 patients included in our study,12.3%,15.5%and 17.7%had a stroke recurrence at 3,6 and 12 months,respectively.GI bleeding was an independent stroke recurrence risk factor in patients after ischaemic stroke at 3 months(adjusted OR 1.481,95%CI 1.118 to 1.962),6 months(adjusted OR 1.448,95%CI 1.106 to 1.896)and 12 months(adjusted OR 1.350;95%CI 1.034 to 1.763).Conclusion GI bleeding was associated with the increased risk of stroke recurrence after an AIS.