I. The development of antiplatelet therapy for cerebral artery stenosis Cerebral artery stenosis is an important risk factor for the development of ischemic cerebrovascular disease. In the treatment and prevention of ischemic cerebrovascular, the use of antiplatelet drugs is its basic approach. Endovascular stenting for cerebral artery stenosis is currently considered one of the most effective measures. However, intraoperative and postoperative occlusion and restenosis of stenotic lesions are possible, and the use of antiplatelet drugs is an effective method to prevent occlusion and restenosis. Shi Jin, Department of Neurology, Air Force General Hospital II. Classification and pharmacological mechanism of platelet drugs Anti-platelet drugs can be divided into: ① cyclooxygenase inhibitors: aspirin, ibuprofen, indobufen, thiopiridone, trifluralin; ② phosphodiesterase inhibitors: pansentin; ③ platelet calcium channel inhibitors: sulodexide; ④ thromboxane synthase inhibitors: picotamide; 5ADP receptor antagonists: ticlopidine and clopidogrel. Currently, aspirin, pansentin, clopidogrel or ticlopidine are used more frequently. 1. Aspirin (Aspirin) The mechanism of action of aspirin is to inhibit the production of thromboxane A2 by inactivating the acetylation of serine at position 529 of the active site of cyclooxygenase in the arachidonic acid metabolic pathway of platelets, thus preventing platelet aggregation and release reaction. 2. Clopidogrel and ticlopidine are a class of thienopyridine derivatives that selectively and irreversibly bind to an ADP receptor (P2YAC) on the platelet membrane surface through their active metabolites, blocking the inhibitory effect of ADP on adenylate cyclase and thereby promoting the production of cyclic adenosine monophosphate (cAMP)-dependent diastolic substances. cAMP)-dependent phosphorylation of vasodilator stimulated phosphoprotein (VASP), which inhibits ADP-mediated activation of GPIIb-IIIa receptors and thus platelet aggregation. Due to the side effects of ticlopidine, its use has been gradually reduced. Dipyridamole inhibits platelet release by inhibiting the activity of phosphodiesterase in platelets, or by enhancing endogenous PGI2. It is ineffective when PGI2 is deficient or when excessive doses of aspirin are applied. III. Clinical basis for the use of antiplatelet agents in endovascular stenting Because of the late development of cerebrovascular interventions, there is a lack of important international evidence-based support for the use of antiplatelet agents in the prevention and treatment of cerebrovascular stenosis, especially for the antiplatelet therapy before and after stenting. The current antiplatelet therapy regimen is still based on the experience of the use of drugs before and after cardiovascular interventional procedures. The latest AHA/ASA guidelines for secondary prevention of cerebral infarction/TIA, published in Stroke in February 2006, recommend aspirin, aspirin and extended-release pansentine, and clopidogrel as acceptable options for antithrombotic therapy in noncardiogenic ischemic stroke, with similar safety profiles, and state that aspirin is the most evidence-based of the antiplatelet agents. The available evidence supports aspirin at 75-150 mg/day. Available evidence supports the use of 75-150 mg/d of aspirin for long-term prevention of serious vascular events in high-risk patients, and authoritative guidelines in several countries generally recommend that 100 mg/d of aspirin be used for long-term primary and secondary prevention of cardiovascular disease [1]. In recent years, a series of large clinical trials have been conducted on clopidogrel, with the result that clopidogrel may be superior to aspirin, but the additional clinical benefit it provides is statistically uncertain and the adjusted authoritative guidelines do not agree on its efficacy over aspirin. However, in certain hypercoagulable states, such as patients undergoing PCI (percutaneous coronary intervention), who are at high risk of intracoronary thrombosis, the combination of the two drugs may provide greater benefit. However, other trials have drawn conclusions that are worth noting: the PCI-CUREE study confirmed that the combination of aspirin and clopidogrel was more effective than aspirin alone in patients undergoing PCI. In contrast, the results published in the CHARISMA study, which compared the effectiveness and safety of long-term combination antiplatelet therapy with monotherapy, included 15,603 patients over 45 years of age, randomized into 2 groups: aspirin (75 to 162 mg/d) + placebo group and aspirin (75 to 162 mg/d) + clopidogrel (75 mg/d) group. The results showed that for primary and secondary prevention of cardiovascular events, there was no significant difference in the primary efficacy endpoints (myocardial infarction, stroke, and vascular death) between the aspirin monotherapy group and the clopidogrel combination group (P=0.22). However, the incidence of bleeding was slightly higher in the clopidogrel-aspirin combination group, with moderate bleeding reaching statistical significance (P<0.001) [2]. The MATCH study also confirmed that the combination of antiplatelet agents for secondary prevention of cerebral infarction not only did not increase the efficacy but also increased the risk of bleeding. Therefore, combined antiplatelet therapy is currently not recommended in Germany and is only considered in certain special cases. The European Society of Cardiology (ESC) 2004 annual meeting clearly pointed out that resistance to antiplatelet agents is widespread, including the new drug clopidogrel, and the incidence of various drug resistance may be similar, and some patients may be ineffective with antiplatelet agents, but antiplatelet drug therapy should not be abandoned on the grounds of possible drug resistance alone [3]. IV. Timing, duration, and type of antiplatelet agents before and after cerebrovascular stenting The American College of Cardiology/American Heart Association/Cardiovascular Angiography and Interventions Consortium (ACC/AHA/SCAI) published an update of PCI guidelines in 2005 recommending that patients on long-term aspirin should receive 75-325 mg orally prior to PCI. For patients not on long-term aspirin, 300-325 mg of oral aspirin should be given at least 2 hours prior to PCI or preferably within 24 hours. Postoperatively, for patients without aspirin resistance, allergy and increased risk of bleeding, aspirin 325mg/day should be given for at least one month, followed by long-term oral aspirin 75 to 162mg/day. As for clobigrel, a loading dose of 300 mg at least 6 hours before surgery is considered optimal, and 75 mg/day orally for at least one month after surgery. Based on the results of the CREDO and PCI-CURE studies, clopidogrel should be recommended for all PCI patients for 9 to 12 months after treatment. However, it has been pointed out that in the CREDO and PCI-CURE studies, only patients taking clopidogrel preoperatively received long-term clopidogrel therapy, whereas earlier studies have shown that preoperative clopidogrel administration reduces major ischemic events. Therefore, it is not certain that long-term clopidogrel use provides additional clinical benefit. The benefit of long-term clopidogrel therapy could only be determined if both groups of patients received clopidogrel preoperatively or if both groups were re-randomized at 1 month postoperatively. Therefore, the debate will continue as to how long clopidogrel needs to be maintained as treatment after PCI. 1. The application of antiplatelet drugs before and after stenting of cerebral artery stenosis in some foreign hospitals In the course of cerebrovascular intervention, the famous Wallstent trial had described antiplatelet therapy before and after cerebral artery stenting, requiring patients undergoing stenting to take 325 mg of oral aspirin and 250 mg of reserpine before surgery, both 2/day for four weeks, but the postoperative The treatment was not described in detail [4]. Also well-known is the CAVATAS trial, also this is a randomized treatment study comparing stenting versus stripping for carotid and vertebral artery stenosis, including 22 medical centers in Europe, Australia, and Canada, but the application of antiplatelet drug therapy in the trial is described as aspirin minimum dose of 150 mg/day should be given at least 24 hours before endovascular treatment, or other antiplatelet drugs , postoperative antiplatelet therapy was administered throughout the follow-up phase, while the trial had a follow-up of 3 years [5]. The results of the study published by Nadim Al-Mubarak in Stroke describe in more detail the use of preoperative antiplatelet agents for stenting. Patients were asked to take preoperative clobigrel 75 mg/d as well as aspirin 325 mg, 2/d for at least 7 days, or aspirin 650 mg plus clobigrel 450 mg within 24 hours before the procedure.Postoperatively, patients were asked to continue oral clobigrel 75 mg/d as well as aspirin 325 mg, 2/d, and after 4 weeks change to long-term single dose aspirin 325 mg/d [6 ]. In his article published in Canada, M.D. Hill suggested that in the treatment of carotid stents, the use of antiplatelet agents could follow a "conventional" regimen: oral aspirin 75 mg/d plus ticlopidine (at a loading dose of 1000 mg, 250 mg, 2/day) before the procedure; or aspirin 75 mg/d plus clopidogrel (at a loading dose of 300 mg, 75 mg/day) and continued postoperatively with aspirin at a minimum dose of 75 mg /d plus ticlopidine 250 mg ,2/d or clopidogrel 75 mg/d [7]. In their joint study, the University of Pittsburgh and the University of Michigan Medical Center stated that all patients who will undergo carotid stenting without prior conventional antiplatelet therapy should receive oral aspirin and a loading dose of clopidogrel (300 mg) the night before treatment. And aspirin 81-325 mg/d and clobigrel 75 mg/d should be taken for at least 3 months after treatment at the University of Pittsburgh and for 6 months at the University of Michigan [8]. In the newly published multicenter, single-objective study of the Wingspan stent for intracranial artery stenosis, patients took aspirin 300 to 325 mg/day plus clopidogrel 75 mg/day preoperatively or aspirin 300 to 650 mg plus clopidogrel 225 mg/day on the day of surgery and clopidogrel 75 mg/day for 30 days postoperatively, and aspirin 300 to 325 mg/day for life [9]. Linz Hospital in Australia is taking aspirin 100 mg/d, clopidogrel 75 mg/d or ticlopidine 500 mg/d for 2 days preoperatively, and aspirin 100 mg/d long-term postoperatively, and clopidogrel 75 mg/d or ticlopidine is for 1 month [10]. 2. The current situation of some domestic hospitals in the application of antiplatelet drugs before and after stenting for cerebral artery stenosis There is also no unified scheme in the treatment of antiplatelet drugs in China, and the use of some representative hospitals in China is described by the following list: Unit Preoperative Postoperative Aspirin Clopidogrel Ticlopidine Aspirin Clopidogrel Ticlopidine Tiantan Hospital [11] 3-7 days, 300mg/d 3-7 days, 75mg/d 300mg/d,.3 months 75mg/d, 1 month Xuanwu Hospital [12] 3-5 days, 300mg/d 3-5 days, 250mg/d Same as before for another 9 weeks PLA General Hospital [13] 7-10 days, 100-150mg/d 7-10 days, 75mg/d for 3 months, followed by aspirin alone Liaoning Provincial People's Hospital [14] 3-7 days, 75mg, 2/d 300mg/d, June Started after 3 days, 75mg/d,January Xinqiao Hospital [15] 3 days, 100-150mg/d 3 days,75mg/d 100-150mg /d, 1 year 75mg/d, March Drum Tower Hospital [16] 3 days, 300mg/d 3 days 75mg/d 300mg/d, January 75mg/d,June-September Tongren Hospital [17] 3 days, 100mg/d 3 to 5 days, 75mg/d 100mg long term 75mg/d, June Southwest Hospital [18] 3 to 5 days, 300mg/d 3 to 5 days, 75mg/d 300mg/d, June 75mg/d, June Hunan Provincial People's Hospital [19] 3 days, 300mg/d 3 days 75mg/d 300mg/d, long term Clofibrate 300mg/d, 7 days, 75mg/d, March Heilongjiang Provincial Hospital [20] 3 to 5 days, 300mg/d 250mg,1/d, 3 to 5 days Aspirin 300mg/d, 6 to 8 weeks, followed by 150mg/d, June 250mg/d, 6 to 8 weeks Chaoyang Hospital [21] 3 days. 300mg, 2/d 3 days, 75mg/d 300mg/d, long term 75mg/d, 4 weeks For antiplatelet agents when using cerebral artery stenting at home and abroad, there are no large-scale clinical trials to illustrate the relationship with clinical endpoint events, but there is still some common understanding of some basic points, and the above information suggests that The perioperative period of cerebral artery stenting requires intensive antiplatelet therapy in the perioperative period of cerebral artery stenting. 2. Aspirin and clobigrel are currently the most commonly used drugs. 3. Preoperative preparation with antiplatelet therapy is generally required for 3-5 days, and the dose of aspirin is generally 300 mg/day, combined with clobigrel 75 mg/day. 4. The oral dose of aspirin after surgery is 300mg/day for more than 1 to 3 months, and the combined dose of clobigrel 75mg/day for more than 1 month. 5. Patients need long-term use of antiplatelet drugs. 6. The dosage of antiplatelet drugs acted by foreign literature is larger than that in China. However, there is still no objective theoretical and clinical trial evidence as to why antiplatelet drugs should be used in combination and in larger doses to intensify treatment during intracerebral artery stenting, and what is the duration of use after surgery.