The Efficacy Of Intermittent Administration Of Fibrinogen Depleting Agent On The Ischemic Stroke Recurrence And Carotid Plaque

The cumulative rate of stroke recurrence after acute ischemic stroke or transient ischemic attack(TIA)increased each year.Intervention of the vascular risk factors should be initiated as soon as possible.Elevated plasma fibrinogen level is an independent risk factor for ischemic stroke events and is closely related to the prognosis and recurrence after stroke.Plasma fibrinogen also plays an important role in the pathological process of atherosclerosis.We aim to observe the efficacy of the agent targeting at decreasing plasma fibrinogen level.There are two parts in our study:1)to investigate the efficacy of the intermittent fibrinogen depleting agent on the secondary prevention of ischemic stroke;2)to exam the efficacy of the intermittent fibrinogen depleting agent on carotid plaque;Part I:The efficacy of intermittent administration of fibrinogen depleting agent on the ischemic stroke recurrenceObjective:We aim to investigate the efficacy and safety of the intermittent fibrinogen-depleting agent in preventing the recurrence of ischemic stroke/TIA.Methods:We prospectively enrolled patients with ischemic stroke or TIA who were admitted to the department of Zhujiang Hospital of Southern Medical University from September 1,2015 to September 1,2016.Consecutive hospitalized stroke patients treated with intermittent administration of batroxobin at an interval of 3 months were defined as fibrinogen-depleting group.Consecutive stroke patients treated without batroxobin were enrolled into control group.The incidence of stroke recurrence,major adverse cardiovascular events and safety of the intermittent fibrinogen-depleting agent during 1-year follow-up were compared between the two groups.Results:A total of 98 participants were included into our study,with 48 patients in the fibrinogen-depleting group and 50 in the control group.During the 1-year follow-up,there were eight patients who suffered from the major adverse cardiovascular events,with three cases in the fibrinogen-depleting group(one case of lacunar infarction,two cases of angina),and five in control group(three cases of cerebral infarction,one case of TIA,one case of cerebral hemorrhage).Less recurrent ischemic stroke events were seen in fibrinogen-depleting group than in the control group,1 case(2.1%)v.s.4 cases(8.0%)respectively,but there were no statistically significance(P = 0.263).However,the incidence of the recurrent ischemic stroke in our study was much lower as compared with those reported in the literature(2.1 v.s.13.5%,respectively).The incidence of the major adverse cardiovascular events in fibrinogen-depleting group and control group were 3(6.3%)and 5(10.0%),respectively.The differences did not show statistical significance(RR=0.625,95%CI=0.184-3.309;P=0.715).The incidence of the adverse events was similar in both groups.Conclusion:(1)Intermittent fibrinogen-depleting therapy may help reduce the recurrence of ischemic stroke.(2)The repeated use of intermittent fibrinogen-depleting therapy will not affect its effect on decreasing the plasma fibrinogen level.(3)Intermittent fibrinogen-depleting therapy was safe and feasible,and did not increase bleeding events.Part Ⅱ:The efficacy of intermittent fibrinogen-depleting therapy on the carotid plaqueObjective:We aim to exam the efficacy of the intermittent fibrinogen-depleting therapy on carotid plaque.Methods:We prospectively enrolled patients with ischemic stroke or TIA who were admitted to the department of Zhujiang Hospital of Southern Medical University from September 1,2015 to September 1,2016.Carotid ultrasonography was performed in these patients in order to verify the existence of carotid plaques.Participants who had received the treatments of batroxobin were divided into fibrinogen-depleting group and those without batroxobin were the control group.The use of batroxobin or not and the frequency of fibrinogen-depleting agent was decided by the attending physician.Carotid ultrasonography was repeated in 12 months.The changes between baseline and follow-up carotid plaques were compared in the patients of fibrinogen-depleting group and the control group.Results:Sixty-four cases with follow-up carotid ultrasound examination were enrolled in our study,with 34 participants in fibrinogen-depleting group and 30 in control group.The baseline and follow-up carotid plaques thickness were 2.4±0.9 mm,and 2.3±1.0 mm,and the control group were 2.2±0.6mm,2.3±0.7mm.Carotid plaques thickness in fibrinogen-depleting groups tends to be stable.Carotid plaques thickness in control group was increased in 12 months.Change of carotid plaques thickness between the two groups showed statistically difference(P = 0.033).Baseline and follow-up carotid intima-media thickness,plaque number,gray scale median score had no differences between the two groups.Conclusion:The intermittent administration of fibrinogen-depleting agent may have an effect on stabilizing the carotid plaque thickness,but further studies with longer follow-up time are needed in order to confirm to efficacy of fibrinogen-depleting agent on carotid plaque.