The Correlation Study Between Antiplatelet Drug Therapy And Cerebral Microbleeds In Acute Ischemic Stroke

Objective: There is no obvious clinical manifestation in patients with cerebral microbleeds(CMBs),and it can be found only in the iconography and autopsy.Its essence is the blood metabolism products which leak into the outside of the vessel wall and is decomposed by macrophages~[1].Studies have found that the number of CMBs is associated with the severity of the artery blood vessel~[2],so it can be used to predict the occurrence of cerebral hemorrhage in a certain extent~[3].However,these questions on the correlation of CMBs and ischemic stroke hemorrhagic transformation,thrombolysis,antiplatelet and anticoagulant therapy in bleeding risk are still controversial.Recent CHANCE(Clopidogrel and Aspirin versus Aspirin Alone for the Treatment of High~risk Patients with Acute Non~disabling Cerebrovascular Event)studies in China have made it clear that patients with non acute cardiac ischemic stroke(Large~artery atherosclerosis)and patients with TIA(transient ischemic attack)early accepting the treatment of dual antiplatelet drug therapy can reduce the incidence of stroke by 3 months,But the study did not carry out the classification of stroke etiology,or did not specify the effects of different antithrombotic treatment options on the CMBs status.Therefore,in this study,according to different medication program and cerebral vascular disease etiology classification,patients with ischemic stroke as the research object,will be divided into groups,to explore the effect of monoclonal or dual antiplatelet to the recent occurrence of CMBs,at the same time,to analyze the related risk factors of CMBs,the distribution characteristics of CMBs and the relationship between the characteristics of the white matter lesions on radiograph.1 Object of study and inclusion and exclusion criteria:This study was a prospective study involving 139 patients with acute ischemic stroke who were admitted continuously by the Third Hospital of Hebei Medical University from December 2013 to October 2015.Auxiliary examination results of all patients were recorded at baseline and after admission in detail.According to the classical TOAST etiological classification of stroke~[4],the patients with definite diagnosis were divided into two large groups: Large~artery atherosclerosis(LAA),and Small~artery occlusion(SAO),and the LAA group was divided into LAA dual anti group and LAA monoclonal antiplatelet group,that LAA dual antiplatelet group and LAA monoclonal antiplatelet group,at the same time,patients with TIA were included in the TIA group.Exclude the following patients:ischemic stroke in patients with cardiac stroke,unexplained or other causes;previous history of cerebral hemorrhage or other brain organic disease;allergic to antiplatelet drugs;Combined with blood coagulation disorders,atrial fibrillation and severe heart,liver and kidney dysfunction;patients with coma and the contraindication of magnetic examination;not completing the relevant brain magnetic imagings or other medical history information is not complete;patients receiving anticoagulant therapy during treatment;claustrophobic syndrome patients.2 Research treatment and inspection program:The antiplatelet treatment options for each subgroup of the study were in accordance with by the two prevention guidelines for ischemic stroke and TIA in China in 2014,and LAA and TIA patients who have no special circumstances are receiving dual antiplatelet therapy,SAO patients received monoclonal antiplatelet.Patients in the LAA group were treated with monoclonal antiplatelet under the following circumstances: the patients with the history of peptic ulcer and black stool recently;the number of platelets be lower than normal;allergic to aspirin or clopidogrel;frequent bleeding gums recently;moderate and severe liver injury;the patients worrying about bleeding risk voluntarily choose monoclonal antiplatelet therapy;the patients with Slight petechia and Methods: ecchymosis on skin mucous membrane;slight hemorrhagic transformation after infarction,etc.Antiplatelet therapy options:(1)the monoclonal antiplatelet therapy: aspirin(100mg/d)or clopidogrel(75mg/d,the first dose 75mg);(2)dual antiplatelet therapy:aspirin combined with clopidogrel,usage as above,the cycle of the dual antiplatelet therapy be for 21 days to 90 days,and the average period of dual antiplatelet therapy was 78.3±4.6 days.The Imaging diagnosis of CMBs was performed by SWI in all patients enrolled,and SWI imaging data were collected at baseline and at the end of the study in two different periods to analyze the difference of the incidence of CMBs and the recent rate of subgroups at baseline,to study the relationship between the different antiplatelet therapy options and the incidence of CMBs and to observe the safety of the dual antiplatelet therapy for short term.All magnetic resonance imaging examination results were interpreted by the neurologists and neuroradiologist who did not kown the patient’s history.3 Imaging diagnostic criteria of the CMBs~[5]: When using SWI to detect the CMBs,that are the low signal lesions found in the non cerebral sulcus and its diameter is 2mm~5mm.There is no edema zone but image floating effect around it.At the same time,vascular malformations,small vascular flow void signal,sponge hemangioma,gas,calcium and iron deposition in bilateral basal ganglia,traumatic axonal injury be excluded and so on.The number of CMBs more than 1 were considered positive.4 Follow~up and terminal events of the study: We keeped in touch with the follow~up patients through telephone,outpatient referral for a period of about 3 months(the median time was 97.3±6.1days),and then completed the imaging review.Terminal events included myocardial infarction,recurrence of cerebral infarction,cerebral hemorrhage,other surgical treatment,the whole cause and other events leading to death.when it happened,the follow~up was over.5 Data statistics analysis: Using SPSS19 version of statistical software to analyze the data,and using X~2 test to compare the incidence of CMBs among subgroups;using binary classification unconditioned Logistic regression to analyze the risk factors of CMBs;using Spearman rank correlation test to analyze the correlation between the number of CMBs and the severity of cerebral white matter lesions.Results: 1 There were 139 patients who met the inclusion criteria in this study,average age 64.23±10.37 years old(36~82 years old),and among them,male patients 85 cases(61.2%),average age 62.72 years old(36~82 years),female patients 54 cases(38.8%),average age 66.61 years old(42~80 years old).LAA group 83 cases(59.7%),LAA dual antiplatelet group 56 cases(40.3%),LAA monoclonal antiplatelet group 27 cases(19.4%),SAO group 31 cases(22.3%),TIA group 25 cases(18%).Incidence of SWI in each group at baseline: LAA group 46.99%,SAO group 48.39%,TIA group 32%,and there was no statistical significant difference in CMBs positive rate among the groups at baseline(X~2=1.568,P=0.456).2 Using the four case table chi square test to compare the difference about incidence of recently CMBs,and according to the standard of a=0.05,It was concluded that there was no statistical significant difference in the incidence of CMBs between the LAA group and the SAO group at baseline(PearsonX~2=0.669,P=0.413>0.05,SAO group was higher than LAA group,and there were bias in demographic characteristics),and there was no statistical significant difference in the incidence of CMBs among these subgroups,ie LAA dual antiplatelet group and LAA monoclonal antiplatelet group(Pearson X~2=0.005,P=0.942),LAA dual antiplatelet group and TIA group(PearsonX~2=0.053,P=0.819),LAA dual antiplatelet group and SAO group(Pearson X~2=0.768,P=0.381),LAA monoclonal antiplatelet group and SAO group(Pearson X~2=0.441,P=0.507).3 This study aimed to explore the risk factors of CMBs in patients with acute ischemic stroke at baseline,and regarded the occurrence of CMBs as a dependent variable,Cardiovascular risk factors such as smoking,drinking,hypertension,diabetes,and the history of long term antiplatelet drug usage were regarded as independent variables,then adjusting these factors such as age,sex,smoking and drinking,etc.and analyzing these data by single factor logistic regression analysis.The results show that diabetes,hypertension,the history of cerebral infarction,the history of antiplatelet drug usage,glycosylated hemoglobin and cerebral white matter lesions increased the risk of CMBs(the valunes of OR were respectively 3.087,3.845,2.493,4.715,1.988,2.364;the valunes of P were respectively 0.002,0.001,0.011,0.000,0.050,0.000,P<0.05),and then the statistically significant indicators above were regarded as the independent variables in the further analysis and the multiple factors logistic regression analysis was performed to draw the conclusion that diabetes(OR=3.951,95%CI :1.259~12.394,P=0.019),hypertension(OR=2.836,95%CI:1.051~7.654,P=0.040),cerebral white matter lesions(OR=2.212,95%CI:1.299~3.766,P=0.003)and the history of antiplatelet drug usage(OR=22.820,95%CI:3.814~136.549,P =0.001)were proved to be the risk factors for CMBs.Using single factor Logistic regression analysis to find the risk factors of of the newly emerging CMBs,and only that CMBs positive(OR=2.788,95%CI:1.165~6.669,P=0.021)and coronary heart disease(OR=2.704,95%CI :1.097~6.663,P=0.031)at baseline were found to have statistical significance,then using multiple factors logistic regression analysis to analyze the risk factor of the new CMBs,and the former was proved to be the risk factor of the new CMBs.3In addition,the study also found that there was a significant correlation between the number of CMBs and the severity of the deep white matter hyperintensity and periventricular hyperintensity(r=0.424,P =0.000;r=0.479,P=0.000,P<0.05).Conclusion:1 LAA dual antiplatelet group and TIA group received dual antiplatelet therapy in the short term did not obviously increase the incidence of CMBs,and it prompted the benefit of short term dual therapy is still higher than the potential bleeding risk.2 This study also found that diabetes,the history of antiplatelet drug usage,the severity of white matter lesions and the hypertension were all closely related to CMBs,and these risk factors controlled should be actively intervened in order to reduce the probability of bleeding in clinical treatment.It is also found that the ones with CMBS positive at baseline when receiving antiplatelet therapy had higher CMBS occurrence probability,therefore we need to weigh the advantages and disadvantages before treatment;3 There was a significant correlation between the number of CMBs and the severity of the deep white matter hyperintensity and periventricular hyperintensity,so the results suggest that white matter lesions can also predict the potential risk of CMBs.