抗血小板方案对缺血性卒中的预防结论与参考文献

　　第 6 章 结 论

　　在综合考虑效果及出血风险时，西洛他唑表现出了优于其他抗血小板方案的结果。

　　除了西洛他唑外，阿司匹林加双嘧达莫及氯吡格雷也表现出了优于阿司匹林的效果，且与阿司匹林相比不增加出血风险。

　　噻氯匹定与氯吡格雷相比，预防复合血管事件发生的作用无显着差别，但噻氯匹定的耐受性更差。

　　三氟柳与阿司匹林、阿司匹林加双嘧达莫及氯吡格雷相比，效果无显着差别，但出血风险显着降低。

　　除了阿司匹林外，西洛他唑尚未与其他抗血小板方案进行系统的直接对比。

　　参考文献

　　[1] Writing Group M, Lloyd-Jones D, Adams RJ, et al. Heart disease and strokestatistics--2010 update: A report from the american heart association[J].Circulation, 2010, 121(7):e46-e215.

　　[2] Elkins JS, Johnston SC. Thirty-year projections for deaths from ischemicstroke in the united states[J]. Stroke, 2003, 34(9):2109-2112.

　　[3] Thijs V, Lemmens R, Fieuws S. Network meta-analysis: Simultaneousmeta-analysis of common antiplatelet regimens after transient ischaemicattack or stroke[J]. European heart journal, 2008, 29(9):1086-1092.

　　[4] Malloy RJ, Kanaan AO, Silva MA, et al. Evaluation of antiplatelet agents forsecondary prevention of stroke using mixed treatment comparisonmeta-analysis[J]. Clinical therapeutics, 2013, 35(10):1490-1500.

　　[5] Wang YJ, Zhang SM, Zhang L, et al. Chinese guidelines for the secondaryprevention of ischemic stroke and transient ischemic attack 2010[J]. CNSneuroscience & therapeutics, 2012, 18(2):93-101.

　　[6] Kim SK, Kang SW, Kim DH, et al. Matrix metalloproteinase-3 genepolymorphisms are associated with ischemic stroke[J]. Journal of interferon& cytokine research : the official journal of the International Society forInterferon and Cytokine Research, 2012, 32(2):81-86.

　　[7] Collaboration AT. Collaborative overview of randomised trials of antiplatelettherapy--i: Prevention of death, myocardial infarction, and stroke byprolonged antiplatelet therapy in various categories of patients[J]. BMJ, 1994,308(6921):81-106.

　　[8] Antithrombotic Trialists C. Collaborative meta-analysis of randomised trialsof antiplatelet therapy for prevention of death, myocardial infarction, andstroke in high risk patients[J]. BMJ, 2002, 324(7329):71-86.

　　[9] Vane JR, Botting RM. The mechanism of action of aspirin[J]. Thrombosisresearch, 2003, 110(5-6):255-258.

　　[10]Greer DM. Aspirin and antiplatelet agent resistance: Implications forprevention of secondary stroke[J]. CNS drugs, 2010, 24(12):1027-1040.

　　[11]Altman R, Luciardi HL, Muntaner J, et al. The antithrombotic profile ofaspirin. Aspirin resistance, or simply failure?[J]. Thrombosis journal, 2004,2(1):1.

　　[12]Antithrombotic Trialists C, Baigent C, Blackwell L, et al. Aspirin in theprimary and secondary prevention of vascular disease: Collaborativemeta-analysis of individual participant data from randomised trials[J]. Lancet,2009, 373(9678):1849-1860.

　　[13]De la Cruz JP, Mata JM, Sanchez de la Cuesta F. Triflusal vs aspirin on theinhibition of human platelet and vascular cyclooxygenase[J]. Generalpharmacology, 1992, 23(2):297-300.

　　[14]Garcia-Rafanell J, Ramis J, Gomez L, et al. Effect of triflusal and othersalicylic acid derivatives on cyclic amp levels in rat platelets[J]. Archivesinternationales de pharmacodynamie et de therapie, 1986, 284(1):155-165.

　　[15]Putz P, Buyse H, Delvaux D, et al. Triflusal versus acetylsalicylic acid: Adouble-blind study for the prophylaxis of deep vein thrombosis after hipsurgery[J]. Acta chirurgica Belgica, 1991, 91(6):269-276.

　　[16]European Stroke Organisation Executive C, Committee ESOW. Guidelinesfor management of ischaemic stroke and transient ischaemic attack 2008[J].Cerebrovascular diseases (Basel, Switzerland), 2008, 25(5):457-507.

　　[17]Acheson J, Danta G, Hutchinson EC. Controlled trial of dipyridamole incerebral vascular disease[J]. British medical journal, 1969, 1(5644):614-615.

　　[18]Diener HC, Cunha L, Forbes C, et al. European stroke prevention study. 2.Dipyridamole and acetylsalicylic acid in the secondary prevention ofstroke[J]. Journal of the neurological sciences, 1996, 143(1-2):1-13.

　　[19]Leonardi-Bee J, Bath PM, Bousser MG, et al. Dipyridamole for preventingrecurrent ischemic stroke and other vascular events: A meta-analysis ofindividual patient data from randomized controlled trials[J]. Stroke; a journalof cerebral circulation, 2005, 36(1):162-168.

　　[20]Verro P, Gorelick PB, Nguyen D. Aspirin plus dipyridamole versus aspirin forprevention of vascular events after stroke or tia: A meta-analysis[J]. Stroke; ajournal of cerebral circulation, 2008, 39(4):1358-1363.

　　[21]Committee CS. A randomised, blinded, trial of clopidogrel versus aspirin inpatients at risk of ischaemic events (CAPRIE)[J]. Lancet, 1996,348(9038):1329-1339.

　　[22]Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-releasedipyridamole versus clopidogrel for recurrent stroke[J]. The New Englandjournal of medicine, 2008, 359(12):1238-1251.

　　[23]Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrelcompared with clopidogrel alone after recent ischaemic stroke or transientischaemic attack in high-risk patients (MATCH): Randomised, double-blind,placebo-controlled trial[J]. Lancet, 2004, 364(9431):331-337.

　　[24]Sudo T, Tachibana K, Toga K, et al. Potent effects of novel anti-plateletaggregatory cilostamide analogues on recombinant cyclic nucleotidephosphodiesterase isozyme activity[J]. Biochemical pharmacology, 2000,59(4):347-356.

　　[25]Gotoh F, Tohgi H, Hirai S, et al. Cilostazol stroke prevention study: Aplacebo-controlled double-blind trial for secondary prevention of cerebralinfarction[J]. Journal of stroke and cerebrovascular diseases, 2000,9(4):147-157.

　　[26]Dinicolantonio JJ, Lavie CJ, Fares H, et al. Meta-analysis of cilostazol versusaspirin for the secondary prevention of stroke[J]. The American journal ofcardiology, 2013, 112(8):1230-1234.

　　[27]Fields WS, Lemak NA, Frankowski RF, et al. Controlled trial of aspirin incerebral ischemia[J]. Stroke, 1977, 8(3):301-314.

　　[28]The canadian cooperative study group. A randomized trial of aspirin andsulfinpyrazone in threatened stroke[J]. The New England journal of medicine,1978, 299(2):53-59.

　　[29]Guiraud-Chaumeil B, Rascol A, David J, et al. Prevention of recurrences ofcerebral ischemic vascular accidents by platelet antiaggregants. Results of a3-year controlled therapeutic trial[J]. Revue neurologique, 1982,138(5):367-385.

　　[30]Bousser MG, Eschwege E, Haguenau M, et al. "Aicla" controlled trial ofaspirin and dipyridamole in the secondary prevention of athero-thromboticcerebral ischemia[J]. Stroke, 1983, 14(1):5-14.

　　[31]Sorensen PS, Pedersen H, Marquardsen J, et al. Acetylsalicylic acid in theprevention of stroke in patients with reversible cerebral ischemic attacks. Adanish cooperative study[J]. Stroke, 1983, 14(1):15-22.

　　[32]Tohgi H. The effect of ticlopidine on tia compared with aspirin: Adouble-blind, twelve-month follow-up study[J]. Agents and actions.Supplements, 1984, 15):279-282.

　　[33]The american-canadian co-operative study group. Persantine aspirin trial incerebral ischemia. Part ii: Endpoint results. [J]. Stroke, 1985, 16(3):406-415.

　　[34]A swedish cooperative study. High-dose acetylsalicylic acid after cerebralinfarction.[J]. Stroke, 1987, 18(2):325-334.

　　[35]Gent M, Blakely JA, Easton JD, et al. The canadian american ticlopidinestudy (CATS) in thromboembolic stroke[J]. Lancet, 1989,1(8649):1215-1220.

　　[36]Hass WK, Easton JD, Adams HP, et al. A randomized trial comparingticlopidine hydrochloride with aspirin for the prevention of stroke inhigh-risk patients. Ticlopidine aspirin stroke study group[J]. The NewEngland journal of medicine, 1989, 321(8):501-507.

　　[37]ESPS group. European stroke prevention study[J]. Stroke, 1990,21(8):1122-1130.

　　[38]The salt collaborative group. Swedish aspirin low-dose trial (SALT) of 75 mgaspirin as secondary prophylaxis after cerebrovascular ischaemic events[J].Lancet, 1991, 338(8779):1345-1349.

　　[39]The dutch TIA trial study group. A comparison of two doses of aspirin (30 mgvs. 283 mg a day) in patients after a transient ischemic attack or minorischemic stroke[J]. The New England journal of medicine, 1991,325(18):1261-1266.

　　[40]Farrell B, Godwin J, Richards S, et al. The united kingdom transientischaemic attack (UK-TIA) aspirin trial: Final results[J]. Journal ofneurology, neurosurgery, and psychiatry, 1991, 54(12):1044-1054.

　　[41]Gorelick PB, Richardson D, Kelly M, et al. Aspirin and ticlopidine forprevention of recurrent stroke in black patients: A randomized trial[J].JAMA : the journal of the American Medical Association, 2003,289(22):2947-2957.

　　[42]Ito E, Takahashi A, Yamamoto H, et al. Ticlopidine alone versus ticlopidineplus aspirin for preventing recurrent stroke[J]. Internal medicine (Tokyo,Japan), 2003, 42(9):793-799.

　　[43]Matias-Guiu J, Ferro JM, Alvarez-Sabin J, et al. Comparison of triflusal andaspirin for prevention of vascular events in patients after cerebral infarction:The tacip study: A randomized, double-blind, multicenter trial[J]. Stroke,2003, 34(4):840-848.

　　[44]Culebras A, Rotta-Escalante R, Vila J, et al. Triflusal vs aspirin for preventionof cerebral infarction: A randomized stroke study[J]. Neurology, 2004,62(7):1073-1080.

　　[45]Kwon SU, Cho YJ, Koo JS, et al. Cilostazol prevents the progression of thesymptomatic intracranial arterial stenosis: The multicenter double-blindplacebo-controlled trial of cilostazol in symptomatic intracranial arterialstenosis[J]. Stroke, 2005, 36(4):782-786.

　　[46]Halkes PH, van Gijn J, Kappelle LJ, et al. Aspirin plus dipyridamole versusaspirin alone after cerebral ischaemia of arterial origin (ESPRIT):Randomised controlled trial[J]. Lancet, 2006, 367(9523):1665-1673.

　　[47]Kennedy J, Hill MD, Ryckborst KJ, et al. Fast assessment of stroke andtransient ischaemic attack to prevent early recurrence (FASTER): Arandomised controlled pilot trial[J]. Lancet neurology, 2007, 6(11):961-969.

　　[48]Fukuuchi Y, Tohgi H, Okudera T, et al. A randomized, double-blind studycomparing the safety and efficacy of clopidogrel versus ticlopidine injapanese patients with noncardioembolic cerebral infarction[J].Cerebrovascular diseases (Basel, Switzerland), 2008, 25(1-2):40-49.

　　[49]Huang Y, Cheng Y, Wu J, et al. Cilostazol as an alternative to aspirin afterischaemic stroke: A randomised, double-blind, pilot study[J]. Lancetneurology, 2008, 7(6):494-499.

    [50]Guo JJ, Xu E, Lin QY, et al. Effect of cilostazol on cerebral arteries insecondary prevention of ischemic stroke[J]. Neuroscience bulletin, 2009,25(6):383-390.

　　[51]Uchiyama S, Fukuuchi Y, Yamaguchi T. The safety and efficacy ofclopidogrel versus ticlopidine in japanese stroke patients: Combined resultsof two phase iii, multicenter, randomized clinical trials[J]. Journal ofneurology, 2009, 256(6):888-897.

　　[52]Shinohara Y, Katayama Y, Uchiyama S, et al. Cilostazol for prevention ofsecondary stroke (CSPS 2): An aspirin-controlled, double-blind, randomisednon-inferiority trial[J]. Lancet neurology, 2010, 9(10):959-968.

　　[53]Hankey GJ, Johnston SC, Easton JD, et al. Effect of clopidogrel plus asa vs.Asa early after tia and ischaemic stroke: A substudy of the charisma trial[J].International journal of stroke, 2011, 6(1):3-9.

　　[54]Kwon SU, Hong KS, Kang DW, et al. Efficacy and safety of combinationantiplatelet therapies in patients with symptomatic intracranial atheroscleroticstenosis[J]. Stroke, 2011, 42(10):2883-2890.

　　[55]Lee YS, Bae HJ, Kang DW, et al. Cilostazol in acute ischemic stroketreatment (CAIST trial): A randomized double-blind non-inferiority trial[J].Cerebrovascular diseases (Basel, Switzerland), 2011, 32(1):65-71.

　　[56]Uchiyama S, Ikeda Y, Urano Y, et al. The japanese aggrenox(extended-release dipyridamole plus aspirin) stroke prevention versus aspirinprogramme (JASAP) study: A randomized, double-blind, controlled trial[J].Cerebrovascular diseases (Basel, Switzerland), 2011, 31(6):601-613.

　　[57]Benavente OR, Hart RG, McClure LA, et al. Effects of clopidogrel added toaspirin in patients with recent lacunar stroke[J]. The New England journal ofmedicine, 2012, 367(9):817-825.

　　[58]Nakamura T, Tsuruta S, Uchiyama S. Cilostazol combined with aspirinprevents early neurological deterioration in patients with acute ischemicstroke: A pilot study[J]. Journal of the neurological sciences, 2012,313(1-2):22-26.

　　[59]Uchiyama S, Tanahashi N, Minematsu K. Clopidogrel two doses comparative1-year assessment of safety and efficacy (COMPASS) study in japanesepatients with ischemic stroke[J]. Cerebrovascular diseases (Basel,Switzerland), 2012, 34(3):229-239.

　　[60]Han SW, Lee SS, Kim SH, et al. Effect of cilostazol in acute lacunarinfarction based on pulsatility index of transcranial doppler (ECLIPSE): Amulticenter, randomized, double-blind, placebo-controlled trial[J]. Europeanneurology, 2013, 69(1):33-40.

　　[61]Reuther R DW, Loew D. The treatment of transitory ischemic attacks withacetylsalicylic acid: Results of a double-blind-study (author's transl)[J].Munchener medizinische Wochenschrift, 1980, 122:795-798.

　　[62]Matias Guiu J AJ, Galiano L, Codina A. The efficacy and safety of low-doseaspirin versus triflusal in the longterm outcome of young stroke patients[J].Neurology, 1994, 44(Suppl 2):288A (Abstract 636P).

　　[63]Smirne S F-SL, Cicinotta D, Zamboni M, Ambrosoli L, Poli A. Triflusal andprevention of cerebrovascular attacks: Double blind clinical study vs asa[J].Journal of neurology, 1994, 241(1):Abstract 53.

　　[64]Lam SK, Owen A. Is the finding of the profess study consistent withpredictions of network meta-analysis?[J]. European heart journal, 2008,29(20):2580.

　　[65]Hankey GJ, Sudlow CL, Dunbabin DW. Thienopyridines or aspirin to preventstroke and other serious vascular events in patients at high risk of vasculardisease? A systematic review of the evidence from randomized trials[J].Stroke, 2000, 31(7):1779-1784.

　　[66]Chi YW, Lavie CJ, Milani RV, et al. Safety and efficacy of cilostazol in themanagement of intermittent claudication[J]. Vascular health and riskmanagement, 2008, 4(6):1197-1203.

　　[67]Takahashi S, Oida K, Fujiwara R, et al. Effect of cilostazol, a cyclic ampphosphodiesterase inhibitor, on the proliferation of rat aortic smooth musclecells in culture[J]. Journal of cardiovascular pharmacology, 1992,20(6):900-906.

　　[68]Otsuki M, Saito H, Xu X, et al. Cilostazol represses vascular cell adhesionmolecule-1 gene transcription via inhibiting nf-kappab binding to itsrecognition sequence[J]. Atherosclerosis, 2001, 158(1):121-128.

　　[69]Nishio Y, Kashiwagi A, Takahara N, et al. Cilostazol, a campphosphodiesterase inhibitor, attenuates the production of monocytechemoattractant protein-1 in response to tumor necrosis factor-alpha invascular endothelial cells[J]. Hormone and metabolic research, 1997,29(10):491-495.

　　[70]Shinoda-Tagawa T, Yamasaki Y, Yoshida S, et al. A phosphodiesteraseinhibitor, cilostazol, prevents the onset of silent brain infarction in japanesesubjects with type ii diabetes[J]. Diabetologia, 2002, 45(2):188-194.

　　[71]Tamhane U, Meier P, Chetcuti S, et al. Efficacy of cilostazol in reducingrestenosis in patients undergoing contemporary stent based pci: Ameta-analysis of randomised controlled trials[J]. Euro Intervention, 2009,5(3):384-393.

　　[72]Soga Y, Yokoi H, Kawasaki T, et al. Efficacy of cilostazol after endovasculartherapy for femoropopliteal artery disease in patients with intermittentclaudication[J]. Journal of the American College of Cardiology, 2009,53(1):48-53.
 

　　致 谢

　　谨借此论文完成之际，向尊敬的导师杨弋教授表示衷心的感谢。难忘恩师的教诲、无微不至的关心和帮助！他广博的学问、严谨的治学态度和高尚的医德医风给我留下了深刻的印象，恩师儒雅的性格、精湛的医术、高尚的品格及宽以待人的生活态度是我毕生学习的榜样。

　　衷心地感谢吉林大学第一医院神经内科所有指导、帮助和关心过我的各位师长及同学，你们无私的帮助使我成长。感谢我的同门师兄弟、师姐妹和同学们对我的关心与鼓励！忘不了欢笑和泪水我们一起走过的日子，祝福我们的友谊！

　　感谢父母家人对我的默默支持与无私的爱，感谢我的朋友们一直以来无私的帮助和支持，你们永远是我坚实的后盾和前进的动力！

　　最后衷心的感谢参加本论文评审和答辩的各位专家教授在百忙中参加我的论文答辩，祝各位老师事业蒸蒸日上！