A Clinical Study On PAS Corktails Therapy For The Large-artery Atherosclerosis Stroke Subtype Among Patients With Ischemic Stroke

ObjectiveTo explore the short-term and long-term efficacy of PAS corktails therapy, probucol, aspirin plus rosuvastatin for TOAST classification subtype Large-artery atherosclerosis in patients with ischemic stroke.MethodsAcute ischemic stroke patients were collected in The Stroke Unite of Tianjin Huanhu hospital from March2009to March2010and tested with blood examination such as Total cholesterol, Low-density lipoprotein, high-sensitivity C-reactive protein, liver and kidney function, coagulation, etc. Neurologic deficits were evaluated by National Institutes of Health Stroke Scale, Barthel index and modified Rankin Scale, whereas carotid ultrasound, magnetic resonance angiography or computed tomography angiography in order to define145ischemic stroke patients with Large-artery atherosclerosis(LAA) ischemic stroke subtype and70ischemic stroke patients with Small-artery occlusion(SAO) ischemic stroke subtype were performed in the trail. The LAA patients were randomly divided into AS group (aspirin plus rosuvastatin) and PAS group (probucol, aspirin plus rosuvastatin), whereas the SAO group was a control group. At2weeks, the observed objects were tested with blood examination, neurologic deficits and adverse reactions including bleeding, rash, myalgia, liver enzymes≥3times, kinase≥5times, allergies, long QT interval etc. At3months, the observed objects were tested with blood examination, carotid ultrasound, neurologic deficits and adverse reactions. At1year and3years, the observed objects were tested with blood examination, carotid ultrasound, neurologic deficits, adverse reactions and end point events including cerebrovasular diseases, coronary artery diseases, peripheral artery diseases induced by atherosclerosis and death.Results1Among the three groups, there were no differences of year (P=0.131), gender (P=0.933), hypertension (P=0.909), diabetes (P=0.946), smoking (P=0.843), using aspirin or statins or probucol ever (P=0.884) on admission.2Drug safety in the three groups:Among the three groups, at2weeks, there were no difference of liver enzymes≥3times (P=0.452), gastrointestinal discomfort (P=0.452). At3months, there were no difference of liver enzymes≥3times (P=0.809), gastrointestinal discomfort (P=0.902), rash (P=0.874). At1year, there were no difference of liver enzymes≥3times (P=0.307), gastrointestinal discomfort (P=0.906), rash (P=0.999).At3years, there were no difference of liver enzymes≥3times (P=0.495), gastrointestinal discomfort (P=0.671), rash (P=0.999).3Efficacy of drugs in the three groups:3.1End point events analysis:Among the three groups, at1year, there were significantly differences of total end events (P=0.014) and no differences of cerebrovacular events (P=0.349), coronary artery events (P=0.844), peripheral artery events induced by atherosclerosis (P=0.452),2types of artery events (P=0.222) and death (P=0.110). At3years, there were statistical differences of cerebrovascular events (P=0.003), coronary artery events (P=0.018), death (P=0.003) and total end point events (P<0.001) and no differences of peripheral artery events caused by atherosclerosis (P=0.246),2types of artery events.In AS group and PAS group, at1year, there were no differences of cerebrovacular events (P=0.263), coronary artery events (P=0.673), peripheral artery events induced by atherosclerosis (P=1.000),2types of artery events (P=0.197) and death (P=0.353) and the events in PAS group were less than those in AS group of total end point events (P=0.039). At3years, the events in PAS group were less than those in AS group, cerebrovascular events (P=0.011), coronary artery events (P=0.041) and total end point events (P<0.001) and no differences of peripheral artery events caused by atherosclerosis (P=0.610),2types of artery events (P=1.000) and death (P=0.055).3.2Neurological function evaluation in AS group and PAS group:At2weeks, there were statistical differences of NIHSS comparing with those on admission (AS group P＜0.001, PAS group P＜0.001) and no difference between the two groups (P=0.235). At3months, there were statistical differences of NIHSS comparing with those on admission (AS group P＜0.001, PAS group P<0.001) and no difference between the two groups (P=0.476). At1year, there were statistical differences of NIHSS comparing with those on admission (AS group P<0.001, PAS group P＜0.001) and no difference between the two groups (P=0.262).At3years, there were statistical differences of NIHSS comparing with those on admission (AS group P＜0.001, PAS group P＜0.001) and no difference between the two groups (P=0.207). The BI and mRS in the two groups had the same trend with NIHSS.3.3Changes of LDL and hsCRP in AS group and PAS group:At2weeks, the serum LDL were lower than those on admission (AS group P＜0.001, PAS group P＜0.001) and serum LDL in PAS group decreased more than those in AS group statistically (P＜0.001). At3months, the serum LDL were lower than those on admission(AS group P＜0.001, PAS group P＜0.001) and serum LDL in PAS group decreased more than those in AS group statistically (P＜0.001).At1year, the serum LDL were lower than those on admission (AS group P＜0.001, PAS group P＜0.001) and serum LDL in PAS group decreased more than those in AS group statistically (P＜0.001).At3years, the serum LDL were lower than those on admission (AS group P＜0.001, PAS group P＜0.001) and serum LDL in PAS group decreased more than those in AS group statistically (P＜0.001). The hsCRP in the two groups had the same trend with serum LDL.3.4Changes of plaque in carotid artery in AS group and PAS group:At1year, plaque in carotid artery comparing those on admission were smaller (AS group P＜0.001, PAS group P＜0.001) and those in PAS group comparing AS group were smaller (P＜0.001). At3years, plaque in carotid artery comparing those on admission were smaller (AS group P＜0.001, PAS group P＜0.001) and those in PAS group comparing AS group were smaller (P＜0.001).Conclusions1The PAS corktails therapy had proper drug safety on acute phase managements of LAA and its secondary prevention.2The PAS corktails not only reduced the cerebrovascular recurrence in patients with LAA, but also reduced coronary artery, peripheral artery events and death caused by atherosclerosis.3The PAS corktails therapy can improve neurological deficits and the recovery of neurological function, the abilities of daily living and make patients beneficial overall.4The PAS corktails therapy can reduce serum LDL and hsCRP, minimize the inflammation, reverse the progression of plaque and regress the atherosclerosis.