Efficacy And Safety Of Butylphthalide In Secondary Prevention Of Stroke

【Background】Stroke is one of the diseases that seriously threaten human life and health,and has become the leading cause of death and disability in China,bringing heavy health and economic burden to the country.Among them,ischemic stroke accounts for 60% ~ 80%,with high incidence,high recurrence rate,high disability rate and high mortality.It is a group of clinical syndrome caused by various causes of disorder of blood supply,resulting in hypoxic ischemic necrosis,and then neurological dysfunction.The main clinical symptoms are weakness or numbness of one limb(or face),ataxia or difficulty understanding,and disturbance of consciousness.Currently,the drugs used for the secondary prevention of stroke mainly are antiplatelet drugs,hypotensive drugs,hypoglycemic drugs and other related drugs for underlying diseases.In recent years,butylphthalide(NBP)has been widely used in clinical practice,as recommended drugs in China Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2014(Grade Ⅱ recommendation,Grade B evidence),which can improve cerebral microcirculation and protect mitochondria through multi-stage and multi-target,so as to increase cerebral blood flow to alleviate ischemic stroke.However,previous studies tend to focus on the short-term therapeutic effect of stroke patients,and there are few studies on long-term use of butylphthalide as secondary prevention of stroke(especially in the real world),which requires further verification by large and high-quality clinical clinical researches.In recent years,with the continuous innovation and development of science and technology,telemedicine has made rapid progress in disease diagnosis and treatment.Standardized disease management and secondary prevention of stroke patients after discharge relying on the Internet can effectively reduce the recurrence of stroke patients and improve their quality of life.【Objectives】1.Case data of 1431 hospitalized patients with acute stroke in Shaanxi Province collected to analyze the epidemiological characteristics of hospitalized patients with ischemic stroke to provide clinical evidence for the prevention and treatment of stroke.2.The multi-center real world study conducted to observe whether NBP soft capsules could effectively reduce the recurrence of stroke and improve the quality of life of patients,and to analyze its efficacy and safety in secondary prevention of stroke to provide clinical basis for enriching the use of drugs for secondary prevention of stroke.【Research methods】Research 1: Epidemiological characteristics and risk factors of hospitalized ischemic stroke in Shaanxi ProvinceWe collected clinical case data of 1,431 inpatients with acute ischemic stroke admitted to the Department of Neurology of 108 hospitals in Shaanxi Province from April 2021 to April 2022.It included general information,clinical symptoms and signs(blurred consciousness,facial paralysis,paralysis,paresthesia,slurred speech,dysarticulation,blurred vision,ataxia,neglect,etc.),laboratory tests after admission(blood routine,urine routine,biochemistry,coagulation,etc.),Imaging examination data(CT or MRI),neurological scale(m RS,NIHSS)within 24 hours of admission,during hospitalization and at discharge,diagnosis and treatment information,etc.The epidemiological characteristics of inpatients with acute ischemic stroke in Shaanxi Province analyzed statistically by SPSS software,and the differences among subgroups such as gender,urban and rural areas,and degree of disability compared and analyzed.Research 2: Study on efficacy and safety of butylphthalide soft capsules in secondary prevention of strokeThe subjects of this study were 876 patients with acute ischemic stroke enrolled in the neurology department of 108 hospitals in Shaanxi Province from April2021 to April 2022.The case data and follow-up information of hospitalized patients with acute ischemic stroke collected.According to the actual situation of whether the patients took NBP as directed,they divided to NBP group(secondary prevention drugs + butylphthalide soft capsules for 3 months)and control group(secondary prevention drugs).Outcomes were as follows:(1)primary outcome: recurrence rate of stroke patients in 180 days;(2)secondary outcome: m RS,NIHSS and its changes at 30,90 and 180 days after stroke,proportion of patients with poor prognosis(m RS>2);(3)safety evaluation:frequency and severity of adverse events in the study,such as all-cause mortality,cardiovascular and cerebrovascular related adverse events,etc.SPSS software analyzes whether there was a statistical difference between the butylphthalide group and the control group at the end of the study.【Results】Research 1The 1431 inpatients with acute stroke were from April 2021 to April 2022 in Shaanxi Province.Age:(62.917±11.055)years old,male 947(66.2%)and female484(33.8%);There were 858(60.0%)urban residents and 573(40.0%)rural residents.The main occupations were farmers(731,51.1%)and retirees(307,21.5%).Educational background was primary school(487,34.0%)and middle school(402,28.1%).The medical insurance were rural cooperative medical insurance(569,39.8%),medical insurance for urban workers(492,34.4%)and medical insurance for urban residents(318,22.2%).The annual income of the family was 50,000 to 100,000 yuan(698,48.8%)and less than 50,000 yuan(514,35.9%).Patients who drink alcohol are 330(23.1%),and patients who smoke are52(36.5%);exercise habits: <2times/month(220,15.4%),2-5times/month(920,64.3%),>5times/month(291,20.3%);In terms of past medical history,the top three were hypertension(890,62.2%),diabetes(351,24.5%)and TIA(299,20.9%).The most common comorbidities were stroke + diabetes + hypertension(267,18.7%),stroke + hypertension +TIA(246,17.2%)and stroke + coronary heart disease + hypertension(107,7.5%).The main TOAST were LAA(554,38.7%)and SAA(684,47.8%).Internal carotid artery(361,25.2%)and middle cerebral artery(349,24.4%)were the main occluded blood vessels.The main treatment strategies were antiplatelet therapy(1345,94.0%),antihypertensive therapy(628,43.9%),lipid-lowering therapy(1163,81.3%),hypoglycemic therapy(295,20.6%),butylphthalide therapy(1121,78.3%)and thrombolysis therapy(107,7.5%).64.3% of the patients in the group could exercise occasionally,and 20.3% of the patients could exercise regularly.Among them,the rural population is better than the urban population in good exercise habit.36.7% of the patients in the group had smoking history,and 31.4% of the patients had been smoking for more than 10 years.The 23.1% of the patients in the group had drinking history,and14.4% of the patients had been drinking for more than 10 years.Urban,male,and people under the age of 60 had poor control of smoking and drinking.People with moderate and severe disabilities were higher than mild disabilities(3.3% vs.1.5%,P=0.019).Female were higher than male in high blood pressure(67.1% vs.59.7%,P=0.006)and atrial fibrillation(3.5% vs.1.4%,P=0.008).In terms of diabetes mellitus(28.0% vs.19.4%,p<0.001),the urban population was higher than the rural population in terms of diabetes.People over 60 years old were higher than under 60 years old in terms of TIA(22.8% vs.17.4%,P=0.016)and coronary heart disease(11.4% vs.4.8%,P<0.001).The main types of TOAST were SAO(684,47.8%)and LAA(554,38.7%).People with moderate and severe disabilities and men account for a high proportion of LAA.In terms of vascular occlusion,the internal carotid artery(361,25.2%)and middle cerebral artery(349,24.4%)were the main occlusion.The proportion of middle cerebral artery(34.8% vs.19.2%,P<0.001),anterior cerebral artery(13.0% vs.6.8%,P<0.001)and posterior cerebral artery type(13.8% vs.8.1%,P<0.001)in moderate and severe disability group was higher than that in mild disability group.The type of internal carotid artery(22.0% vs.26.8%,P<0.001)was lower than that in mild disability group.The vertebrobasilar artery type in urban population(14.7% vs.7.7%,P<0.001)was higher than that in rural population.The proportion of middle cerebral artery(22.1% vs.27.8%,P=0.016),anterior cerebral artery(4.7% vs.15.2%,P<0.001)and posterior cerebral artery(7.1% vs.14.3%,P<0.001)in urban population was lower than that in rural population.The type of anterior cerebral artery(13.3% vs.7.2%,P<0.001)and other blood vessels(36.6% vs.29.8%,P=0.011)in female population were higher than those in male population.The proportion of people over 60 years old in the type of internal carotid artery(27.8% vs.20.7%,P=0.003)was higher than that of people under 60 years old.The patients in the group were mainly treated with antiplatelet therapy(1345,94.0%),antihypertensive therapy(628,43.9%),lipid-lowering therapy(1163,81.3%),hypoglycemic therapy(295,20.6%),butylphthalide treatment(1121,78.3%),and thrombolytic therapy(107,7.5%).Among them,the proportion of moderate to severe disability group was higher than that of mild disability group in lipid lowering therapy(88.9% vs.77.5%,P<0.001)and thrombolytic therapy(13.4% vs.4.5%,P<0.001).The rate of antihypertensive therapy(39.8% vs.45.9%,P=0.029)was lower than that of mild disability group.The proportion of antihypertensive therapy(48.0% vs.37.7%,P<0.001)and hypoglycemic therapy(23.4% vs.16.4%,P=0.001)in urban population was higher than that in rural population,but lower in lipid lowering therapy(79.0% vs.84.6%,P=0.008)and butylphthalide therapy(76.2% vs.81.5%,P=0.018).Research 2:In this research,1431 patients with acute ischemic stroke were enrolled in the neurology department of 108 hospitals in Shaanxi Province from April 2021 to April 2022,excluding 497 patients with incomplete baseline information and 22 patients who were lost to follow-up(2.4% of patients lost to follow-up),and finally 876 patients were included for final analysis.Enrolled patients received standardized secondary prevention using the "stroke follow-up mini program".Patients devided according to whether they adhered to NBP.322 patients were classified into NBP group and 554 patients into control group.The basic information(such as height,weight,BMI,systolic blood pressure,diastolic blood pressure,heart rate),sex,age,marital status,occupation,tobacco and alcohol history,medical history,TOAST classification and clinical scores were similar between NBP group and control group,without significant statistical difference.The study endpoint showed that at 180 days after enrollment,two patients in the NBP group had recurrent stroke,while nine patients in the control group had recurrent stroke.Although there was no significant statistical difference,we could find that compared with the conventional secondary prevention group,patients receiving NBP for 3 months had a decreasing trend in the recurrence rate of stroke at 180 days.In terms of neurological scores,the proportion of m RS>2 points in NBP group at discharge,30 days,90 days and 180 days of enrollment was significantly lower than that in control group,and the improvement degree from baseline at discharge,30 days,90 days and 180 days of enrollment was better than that in control group,p<0.05.Multivariate logistic regression analysis indicated that diabetes history,TIA history,m RS and NIHSS on admission,and the use of NBP had statistical differences between the two groups(p<0.05),which could be used as a risk /protective factor affecting m RS at 180 days in stroke patients.In terms of safety outcome,there were no serious adverse events(2.2% vs.4.0%,P=0.152),180-day all-cause mortality(0.3% vs.1.3%,P=0.289),heart-brain related adverse events(1.6% vs.1.6%,P=0.935)and other adverse events(0.3% vs.1.1%,P=0.398)had no significant difference.[Conclusions]1.At present,the hospitalized patients with ischemic stroke in Shaanxi Province have a younger trend,and the proportion of male population is on the high side.In terms of behavior,smoking,drinking and exercise habit control are not ideal in cities,men and people under the age of 60.The prevalence rate of hypertension,diabetes,transient ischemic attack and other basic diseases in the group was higher,and the diagnosis and treatment after hospitalization were basically consistent with the guidelines,and different subgroups had their own epidemiological characteristics.2.NBP in secondary prevention of patients with ischemic stroke can significantly promote the recovery of neurological function,improve the prognosis,and reduce the tendency of stroke recurrence,which is safe and effective in the real world secondary prevention of stroke.3.Standardized management of patients with chronic diseases such as stroke by mhealth mode such as Internet can guide patients to use drugs rationally,improve medication compliance,promote them to develop healthy living habits,and reduce the recurrence rate of stroke,which is worthy of further verification.