| Background:Acute Ischemic Stroke(AIS)is a common and frequently-occurring disease in the elderly.It results in hign disability in China and even in the whole world.The hign disability leads a serious threat to life and health and places heavy burden to the community and the family.When AIS happens,the decreased cerebral blood flow due to occlusion of cerebral arteries causes decreased brain tissue perfusion.Then the neuronal death of responsible vessels territory leads to local neurological deficits of patients and the quality of life of patients becomes worse.Stroke patients are increasing year by year,especially groups of atherosclerosis-based cerebrovascular disease with high risk.The diagnosis and treatment in the acute phase of AIS,especially restoring blood supply of ischemic penumbra,is crucial for prognosis.Clinicians combine personal experience with evidence-based medicine to develop different effective individualized therapeutic regimens in accordance with the clinical guidelines.Current treatments for AIS includes ultra-early thrombolytic therapy,anticoagulant therapy,antiplatelet therapy(dual antiplatelet therapy and mono antiplatelet therapy),defibrinogen therapy,intravascular therapy and neuroprotection therapy.Thrombolytic therapy can not be widely carried out due to constraints of therapeutic time window,hospital delivery delay,high risk of complications;Anticoagulant therapy is generally not recommended to improve the prognosis of stroke due to the risk of bleeding;The efficacy and safety of defibrinogen therapy remain unclear and lack of evidence from large-scale clinical trials;Intravascular therapy is generally used in the case of ineffective arterial thrombolytic therapy,and because of lack of large-scale clinical evidence it is not widely used.However,antiplatelet aggregation agents,aspirin and clopidogrel,etc.,effectively prevent the deterioration of the disease and improve the prognosis of stroke and currently are applied widely in the antithrombotic regimen of AIS.They act on different targets of antithrombotic pathways and play a important role in secondary prevention of AIS.The combined use of antiplatelet agents is based on the view that by inhibiting platelet activation in different ways,the antithrombotic effects are strengthened.Aspirin and clopidogrel have synergistic effects on antiplatelet aggregation.Moreover,aspirin or clopidogrel has drug resistance and their combination ensures the effect of antiplatelet aggregation a certain extent,but may also increase the risk of bleeding.Thus,dual antiplatelet therapy should be applied in the clinical treatment cautiously.For acute ischemic stroke patients,the efficacy and safety of dual antiplatelet therapy are still controvertial.The combined use of antiplatelet agents is based on the view that by inhibiting platelet activation in different ways,the antithrombotic effects strengthen.Aspirin and clopidogrel have synergistic effects on antiplatelet aggregation.Moreover,aspirin or clopidogrel has drug resistance and their combination ensures the effect of antiplatelet aggregation a certain extent,but may also increase the risk of bleeding.Thus,dual antiplatelet therapy should be applied in the clinical treatment cautiously.For acute ischemic stroke patients,the efficacy and safety of dual antiplatelet therapy are still controvertial.Antiplatelet agents can reduce the risk of atherosclerotic disease(ischemic stroke,myocardial infarction,and vascular death).At first aspirin was widely recommended for clinical use,reducing the risk of early recurrent risk and early mortality in acute ischemic stroke patients with unthrombolytic treatment.In the International Stroke Trial(IST),early prognosis of aspirin is better compared with anticoagulant treatmen[9].However,in a Swedish double-blind controlled study,Aspirin has been shown to be ineffective in patients with progressive stroke[10].early worsening of the disease after stroke is common and lead to ultimately residual disability.Aspirin reduces early recurrence and death rate but is also ineffective in patients with progressive stroke.In addition,aspirin has been shown to have a higher rate of relapse in stroke prevention[11,12].Thus,more effective and safe antiplatelet agents or other combination regimens has been a hot topic in clinical research at home and abroad.In a randomized,double-blind trial called CAPRIE in 1996,the efficacy of clopidogrel for atherosclerotic disease was superior to that of aspirin,confirming the effect of the ADP receptor antagonist pathway on antiplatelet aggregation[131.With the progress of researches,researches combined antiplatelet aggregation have gradually become hot but also controversial.In the MATCH trial in 2004[14],18 months aspirin and clopidogrel compared with clopidogrel were assigned to stroke patients and the result showed that dual antiplatelet therapy did not reduce the incidence of major vascular events,but increased the risk of bleeding events.However,this experiment has its limitations.First of all,patients are mainly in the non-acute phase and the medication time is too long.Moreover,there are not classification for stroke type and there is overpresentation with small vessel stroke.In the CARESS[3]trial in 2005 and the CLAIR in 2010[4],the subjects included symptomatic intracranial stenosis,aspirin and clopidogrel versus aspirin alone,dual antiplatelet therapy reduces nicroembolic signaling[3]and reduces the risk of recurrent stroke[3,4].However,there were results[15]consistent with MATCH results that dual antiplatelet therapy is not superior to mono antiplatelet therapy in reducing the incidence of major vascular events and would increase the incidence of adverse events.However,unlike MATCH experiment,Its mono antiplatelet therapy is aspirin.In CHARISMA the in 2011[16],aspirin vs dual antiplatelet therapy,the result also confirmed that the safety and efficacy of dual antiplatelet therapy is not superior than mono antiplatelet therapy.The result of a study in 2012[17]compared stenting with intensive medical therapy(dual antiplatelet therapy)showed that dual antiplatelet therapy is superior to stenting and reduces the risk of early stroke recurrence.The 2012 SPS3[18]experiment included subjects of lacunar cerebral infarction and found that there is no significant difference between two groups in the risk of stroke recurrence,but dual antiplatelet therapy did not increase the risk of bleeding.In addition to two experiments for patients of symptomatic intracranial arterial stenosis,other experiments did not find advantages of the effecacy and safety of dual antiplatelet therapy.However,a meta-analysis in 2012[5]showed that dual antiplatelet was superior to aspirin monotherapy,and there was no significant difference in bleeding risk.In a large multicenter clinical trial in 2013,CHANCE[6]study,5170 patients with high-risk TIA or minor stroke at age 40 or older were treated with mono antiplatelet therapy(aspirin 90 days)and dual antiplatelet therapy(clopidogrel 90 days+ aspirin 21 days)respectively.The results showed that dual antiplatelet therapy significantly reduced the relative risk of stroke recurrence at 90 days by 32%without increasing the risk of bleeding.The results of the 1-year follow-up are still confirmed dual antiplatelet therapy advantages[19].The CHANCE study is currently the first and only multicenter clinical study to demonstrate that dual antiplatelet therapy benefits patients with acute ischemic stroke.For acute ischemic stroke patients,the efficacy and safety of antiplatelet aggregation therapy are still controversial.The antithrombotic effect of acute ischemic stroke plays an important role in the prognosis of stroke,but other prognostic factors also play a role in prognosis.The clinical baseline data and history of patients are different and the effects they exert on the prognosis are also different.The intervention for prognosis factors is also essential.Hypertension is one of the risk factors for ischemic stroke.With systolic blood pressure Increasing by 10 mmHg,the stroke risk increases by 49%;with diastolic blood pressure increasing by 5 mmHg,the stroke risk increases by 46%[20]For patients with hypertension,secondary prevention of antihypertensive therapy should be accepted.High Cholesterol levels are another risk factor for ischemic stroke.SPARCL study results show that intensive cholesterol lowering treatment(80 mg daily)can reduce the risk of ischemic stroke by 16%[21].Stroke and transient ischemic attack secondary prevention guidelines recommend the use of enhanced lipid-lowering to reduce the risk of stroke events[22].Blood glucose has an impact on on micro vascular desease.The management of abnormal glucose should be paid great attention by clinicians.According to data from China National Stroke Registry(CNSR),diabetes is an independent risk factor of death or life dependence in patients with ischemic stroke within 6 months of onset[23].The early stage of diabetes mellitus is also an independent risk factor of death for ischemic stroke patients within 1 year[24].At present,the efficacy and safety of antiplatelet therapy are still controvertial.1.Dual antiplatelet therapy is mainly based on large multi-center clinical trials CHANCE study.However,this study is mainly aimed at TIA or minor stroke patients of non-disabled,high risk of recurrence and low risk of bleeding.Howevr,for the disabled patients,benefit is still lack of evidence and related studies are necessary.2.There are a number of studies before the CHANCE study trying to prove the benefit of dual antiplatelet therapy.Unfortunately,these studies ended in failure and showed that dual antiplatelet therapy is not superior to mono antiplatelet therapy.Dual antiplatelet therapy is mainly based on CHANCE study.However,whether this theoretical evidence-based basis is sufficient to support the application of dual antiplatelet therapy is controversial.First,the population of this study was 40 years old or older and non-disabled patients;Moreover,other studies trying to prove the benefit of dual antiplatelet therapy failed until a meta-analysis that did not include the CHANCE study showed that bebefit;Mono antiplatelet therapy was more focused on aspirin,but clopidogrel was also widely used clinically and its comparison with dual antiplatelet therapy is also very important;Application of dual antiplatelet therapy is not normative.No research has shown that after 24 hours of onset dual antiplatelet therapy can benefit patients.The duration of dual antiplatelet therapy is 3 weeks and load dose the first day is 300 mg,but due to various clinical experience of clinicians and individual treatment of patients,the application of treatment can not be so.3.The outcomes of previous studies are often the risk of the recurrence stroke and adverse events.However,whethe antiplatelet therapy can improve functional recovery is not clear.In the early stage of stroke,at least more than 1/3 of patients suffer early deterioration and progressive stroke.Progressive stroke eventually leads to disability;a double-blind controlled study in Sweden demonstrated that aspirin was ineffective for progressive stroke and did not reduce disability rate.Different antiplatelet aggregation regimens differ in antiplatelet aggregation function,reducing brain tissue damage,reducing early disease deterioration and early recurrence risk.So different antiplatelet aggregation regimes may benefit differently for patients in terms of functional recovery and disability levels.Another CHANCE study suggested that dual antiplatelet therapy is superior to mono antiplatelet therapy in terms of functional prognosis and reduces the poor prognosis by 1.7%(mRS 2-6).But this study included minor strokes and TIA populations and the mono antiplatelet therapy is aspirin.Another study "Triple Antiplatelets for Reducing Dependency After Ischaemic Stroke(TARDIS)" is in progress.Therefore,this article mainly included disabled population of AIS,to explore effect of antiplatelet therapy on functional prognosis and analyse different prognostic factors in different treatment groups.objective:In the acute phase of ischemic stroke,antiplatelet aggregation therapy has an important impact on prognosis and functional recovery for patients.Antiplatelet aggregation therapy is fundamental to secondary prevention of cerebrovascular disease.However,the efficacy and safety of dual antiplatelet therapy and mono antiplatelet therapy are still controversial at the present.Many of the previous outcomes were focused on assessing the risk of recurrent stroke after antiplatelet therapy,and the evaluation of patients’ functional outcomes as level of disability is less.This study was conducted to assess the efficacy of different antiplatelet aggregation regimens and the prognostic factors by retrospectively analyzing data from patients with acute ischemic stroke hospitalized at Zhujiang hospital of Southern Medical University from April to December 2016.Method:We retrospectively analyzed the data of patients with AIS who were hospitalized and followed up at the Zhujiang Hospital of Southern Medical University from April 2016 to December 2016.All the included patients were with administration of antiplatelet aggregation regimens.A total of 131 patients were included in this study.The interval between the onset of symptoms and the time arrived hospital is not more than 3 days.We first detailedly recorded and collated the relevant data:age,sex,admission time(interval from onset to hospital),therapeutic regimen,imaging information,systolic blood pressure,laboratory data on admission(K+,urea nitrogen,creatinine,blood glucose,urinary acid,cholesterol,triglyceride,low density lipoprotein,high density lipoprotein,r-glutamyltransferase(GGT),white blood cells,red blood cells,hemoglobin,fibrinogen,activated partial thromboplastin time(APTT)),hospitalization time,therapeutic regimen at discharge,previous history(history of hypertension,history of stroke,history of heart disease,smoking history),mRS score(on admission,at discharge,after 3 months).The group with combined use of two antiplatelet aggregation drugs(mainly aspirin and clopidogrel)was assigned to the dual antiplatelet group.And the group with one antiplatelet aggregation drug(mainly clopidogrel)was assigned to mono antiplatelet group.According to mRS score,the prognosis was divided into two groups:favorable prognosis mRS 0-2,poor prognosis mRS 3-6.Short-term outcomes:mRS score at discharge,mRS score difference at discharge(mRS score at discharge-mRS score at admission);Long-term outcomes:mRS score after 3 months,mRS score difference after 3 months(mRS score after 3 months-mRS score at admission).statistical method:categorical variables were presented as percentages and continuous variables as median.Chi-square test and t-test were performed for comparison of categorical variables and continuous variables between two groups.The logistic regression analysis was used to analyze the prognostic factors.Alpha boundary value is set to 0.05(bilateral)and statistical software is SPSS 20.0.Result:131 patients were followed up with complete data.1.After antiplatelet aggregation treatment,the overall rate of poor prognosis of the patients showed a downward trend;mRS score difference after 3 months is further improved than that at discharge.The effects of mono antiplatelet therapy and dual antiplatelet therapy on the recovery of functional prognosis(degree of disability and degree of change of disability)was not different(P>0.05).2.With antiplatelet aggregation treatment,the dual antiplatelet therapy and mono antiplatelet therapy group had not shown bleeding events after 3 months.The safety of the two groups has no difference.3.In addition to patients with heart disease,in the patients with positive history of diabetes,hypertension and stroke,the rate of favorable prognosis of the patients with dual antiplatelet therapy showed a higher trend than that with mono antiplatelet therapy(P>0.05).4.Prognosis on admission(mRS score)affects that at discharge(P<0.01,OR 8.391,95%CI 3.992-17.638)and after 3 months(P<0.01,OR 7.399,95%CI 3.067-17.849).The higher the mRS score on admission,the greater the risk of poor prognosis at discharged and 3 months.Conclusion:In summary,the overall prognosis of acute ischemic stroke patients with antiplatelet aggregation treatment has improved,but the effects of dual antiplatelet therapy and mono antiplatelet therapy on the recovery of functional prognosis(degree of disability and degree of change of disability)was not different.And the safety of the two groups has also no difference.Clinicians should strengthen the emphasis on the regular application of dual antiplatelet therapy.However,this study uses a single-center retrospective cohort study,it is necessary to get more evidence from large multicenter prospective study. |
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