| Background and objective:Stroke is a leading cause of death and disability in China.Ischemic stroke,a most common type of stroke,accounts for about 80% of all stroke cases.Statins can effectively prevent stroke occurrence and reduce stroke recurrence,and hence serve as the cornerstone for the primary and secondary prevention of ischemic stroke.Studies focusing on statin medication for secondary prevention of ischemic stroke show that high-dose statins can improve the functional prognosis of patients with ischemic stroke.Therefore,the guidelines recommend high-dose statins for secondary prevention of stroke.However,in clinical practice in China,low-dose statins are commonly used in patients with ischemic stroke considering the patients’ lifestyle,the low-density lipoprotein level and ethnicity.Yet whether low-dose statins can improve the functional prognosis of patients with ischemic stroke is unknown.Studies among the Asian populations have found that low-dose statins can effectively reduce the risk of future adverse cardiovascular events and the recurrence of such events.And our previous study has shown that low-dose statins for primary prevention can lower the severity of stroke and improve the prognosis of patients.However,there is no research on the correlation between the low-dose statins for secondary prevention and the functional prognosis of patients with ischemic stroke.This study aims to analyze the correlation between the use of low-dose statins before admission and the prognosis of patients with recurrent ischemic stroke.Considering the insufficient primary prevention and high bleeding risk of reperfusion therapy,this study also focuses on the impact of low-dose statin therapy initiated immediately after admission on the prognosis of patients with first-episode ischemic stroke after vascular reperfusion therapy,and analyzes the first-episode acute stroke cases after thrombolysis and thrombectomy without statins as primary prevention to investigate the clinical characteristics and functional outcomes of patients with ischemic stroke.Methods:The three parts of the study were all designed as prospective cohort ones.The subjects were recruited from the Neurology Department of West China Hospital,Sichuan University.Low-dose statins were defined as atorvastatin less than 20 mg daily,or simvastatin and rosuvastatin less than 10 mg daily.The first part focuses on the patients with recurrent acute ischemic stroke.The patients recruited from November 1,2018 to May 31,2019 were divided into the statin group and the control group according to whether low dose statins were used for secondary prevention before recurrence.The demographic data,baseline data,medical history,laboratory examination data at admission were collected.The main outcome indicators were NIHSS(National Institutes of Health Stroke Scale)score at admission and 7 days after admission,and MRs(Modified Rankin Scale)score at 90 days after onset.The secondary outcome was all-cause death within three months of onset.The baseline and final data were compared using t-test,chi square test and non-parametric test.The correlation analysis of the outcome events and risk factors was conducted using single factor and multi factor logistic analysis.The subgroup analysis was performed using single factor logistic analysis.The second part focused on the patients with first-episode acute ischemic stroke who received the first-class thrombolysis therapy.The patients recruited from November 1,2018 to July 31,2020 were divided into the statin group and the control group according to whether they received statin treatment immediately after admission.The demographic data,baseline data,past history,medication history,laboratory examination data at admission and data of thrombolysis were collected.The effective outcomes included the improvement of NIHSS score at 7days of admission,and a good functional outcome at 90 days.The safety outcomes included the occurrence of cerebral and gastrointestinal hemorrhage during hospitalization and the occurrence of death events in 2 years.The baseline and final data were compared using t-test,chi square test and non-parametric test.The correlation analysis of the outcome events and risk factors was performed using single factor and multi factor logistic analysis.The single factor and multi factor Cox analysis and K-M curve were used in the survival analysis of death events.The subgroup analysis was performed using single factor logistic analysis and Cox analysis.The third part enrolled the first-episode acute ischemic stroke patients who did not receive statins for primary prevention before the onset of the treatment.Patients recruited from November 1,2018 to July 31,2020 were divided into the statin group and the control group according to whether statin treatment was started immediately after admission.The demographic data,baseline data,past history,medication history,laboratory examination data at admission and data of thrombus were collected.The outcome indexes and statistical methods were the same as those in the second study.Results:The first part finally included 219 eligible patients(mean age: 65.41±11.58years),and 69(31.5%)of them were female.We found that the statin group had lower NIHSS scores both at admission(p<0.001)and at discharge(p=0.001),and a lower m RS score at 90 days(p<0.001)than the control group.The statin group had milder neurological deficit at discharge(p=0.008)and a higher rate of FFO(Favorable Functional Outcome)(p<0.001)at 90 days than the control group,and the difference was statistically significant.Logistic regression analysis revealed that the use of low-dose statins(OR=0.098,P=0.049)was inversely associated with a higher m RS score(>1)at 90 days.The second part recruited 222 patients(mean age: 70.77±12.475 years),and113(50.9%)were female.We found that the statin group had a higher NIHSS score at 7 days(p<0.001)and a higher FFO rate at 90 days than the control group.Multivariable logistic regression analysis showed that statin medication(OR=2.291,P=0.014)was related to a higher NIHSS score at 7 days after admission.The statin group had lower rates of intracerebral haemorrhage and gastrointestinal haemorrhage during hospitalization,and less death events within 2years.Statin medication was negatively related to intracerebral haemorrhage(OR=0.379,P=0.008)and gastrointestinal haemorrhage(OR=0.027,P=0.023)during hospitalization and death events over 2 years.The third part recruited 275 patients(mean age: 66.62±13.397 years),and121(44.0%)of them were female.We found that the statin group had a higher NIHSS score(P<0.001)at 7 days,a higher FFO rate(P<0.001)at 90 days than the control group.Multivariable logistic regression analysis showed that statin medication(P=0.028,OR=1.773(1.064-2.952))was positively associated with a higher NIHSS score at 7 days and a higher FFO rate(P<0.001,OR=2.962(1.624-5.400))at 90 days.The statin group had lower rates of intracerebral haemorrhage(P=0.062)and gastrointestinal haemorrhage(P=0.027)during hospitalization and a lower rate of death events(P<0.001)within 2 years than the control group.Statin medication was not related to the rates of intracerebral haemorrhage and gastrointestinal haemorrhage events during hospitalization.Statin medication was negatively related to the occurrence of death events within 2years(P=0.041,OR=0.435(0.196-0.966)).Conclusion:In the first part,we found low-dose statin pretreatment was positively correlated to favorable functional outcomes of recurrent ischemic stroke patients.The patients with persistent statin use had milder neurological deficit and better functional outcomes.In the second part,immediate initiation of low-dose statin medication at admission was related to higher NIHSS scores of the first-episode acute ischemic stroke patients with thrombolysis after 7 days of admission,lower incidences of cerebral hemorrhage and gastrointestinal hemorrhage during hospitalization,and a lower rate of death events within 2 years.But it was not related to a higher FFO rate at 90 days.In the third part,immediate initiation of low-dose statin medication at admission was related to higher NIHSS scores of the first-episode acute ischemic stroke patients with thromboembolism after 7 days of admission,a higher FFO rate at 90 days and a low rate of death events within 2 years.But it was not related to the occurrence of cerebral hemorrhage and gastrointestinal hemorrhage during hospitalization. |
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