Effect of vitamin D on antiplatelet drug responsiveness in elderly patients with ischemic stroke

Objective To investigate the effect of vitamin D on platelet reactivity after combined treatment with aspirin and clopidogrel in elderly patients with ischemic stroke. Methods A total of 190 elderly patients with ischemic stroke treated with aspirin and clopidogrel in Beijing Bo′ai Hospital from June 2017 to August 2018 were enrolled in this study.Venous blood was collected for platelet aggregation rate, 25-hydroxyvitamin D[25(OH)D] and clinical biochemical indexes during 1~2 weeks.According to 25 (OH) D quartile, the patients were further divided into Q1(≤7.18 μg/L) group (n=50), Q2: (>7.18-≤9.39 μg/L) group (n=50), Q3: (>9.39-≤13.74 μg/L) group (50), Q4: (>13.74 μg/L) (n=40). In order to evaluate the effect of calcitriol on platelet aggregation, platelet rich plasma (PRP) in healthy group (15 cases) and clopidogrel resistance group (15 cases) were treated with calcitriol (10 nmol/L) and saline (37 ℃ pretreatment for 5 minutes), respectively, and to compare the difference of maximum platelet aggregation rate induced by ADP between the two treatments. Results There were significant differences in ADP-induced maximum platelet aggregation rate (MPAR) ((49.36±23.34)%, (48.80±20.90)%, (37.02±18.24)%, (36.02±14.46)%, F=3.426, P=0.018) and clopidogrel resistance (CR)/ clopidogrel sensitive (CS) ratio (30/20, 24/26, 15/35, 10/30, χ2=15.119, P=0.002) among the vitamin D quartiles (increasing). Moreover, the MPAR and CR showed a decreasing trend with the increase of vitamin D concentration.Logistic regression analysis showed that serum 25(OH)D level was an independent inhibited factor for clopidogrel resistance in elderly patients with ischemic stroke (Q4 vs Q1, OR=0.699, 95%CI 0.582~0.838, P<0.001; Q3 vs Q1, OR=0.848, 95%CI 0.755-0.953, P=0.006). In vitro, compared with physiological saline, the aggregation rates of platelet in healthy group and CR group decreased after calcitriol pretreatment, and the difference was statistically significant(healthy group: (69.8±12.7)% vs (58.6±11.5)%, t=12.13, P<0.001; CR group: (65.5±8.3)% vs (56.3±7.6)%, t=11.48, P<0.001). Conclusion Vitamin D reduces the high residual platelet reactivity after antiplatelet therapy.Further study is needed to determine whether vitamin D supplementation may improve the efficacy of clopidogrel. Key words: Ischemic stroke; Antiplatelet therapy; Vitamin D; Drug resistance