抗血栓药物研究进展Research progress of antithrombotic agents
朱文婷
摘要(Abstract):
抗血栓药物包括抗血小板药物和抗凝药物2种。随着近几十年的发展,已经出现了多种药效良好并且应用广泛的抗血栓药物,这些药物可以减低患者血栓事件的发生,可是也会随之增加患者的出血风险。同时,患者的病理特征、个体差异以及药物间的相互作用,也会影响药物的药效以及导致不良反应的发生。因此了解血栓形成的分子机制以及抗血栓药物的靶点等特征,有助于临床合理用药。
关键词(KeyWords): 血栓;抗血栓药物;血小板;凝血
基金项目(Foundation):
作者(Author): 朱文婷
DOI: 10.19577/j.1007-4406.2018.05.020
参考文献(References):
- [1]BENJAMIN E J,BLAHA M J,CHIUVE S E,et al. Heart disease and stroke statistics-2017 update:a report from the American Heart Association[J]. Circulation,2017,135(10):e146.
- [2]MACKMAN N. Triggers,targets and treatments for thrombosis[J].Nature,2008,451(7181):914.
- [3]JOLLY S S,NATARAJAN M K. Atrial fibrillation and PCI-do we still need aspirin?[J]. N Engl J Med,2016,375(25):2490.
- [4]EIKELBOOM J W,CONNOLLY S J,BOSCH J,et al. Rivaroxaban with or without aspirin in stable cardiovascular disease[J]. N Engl J Med,2017,377(14):1319.
- [5]WANG Y,PAN Y,ZHAO X,et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack(CHANCE)trial:one-year outcomes[J]. Circulation,2015,132(1):40.
- [6] GREENE M F SOLOMON C G. Aspirin to prevent preeclampsia[J]. N Engl J Med,2017,377(7):690.
- [7]LI C,HIRSH J,XIE C,et al. Reversal of the anti-platelet effects of aspirin and clopidogrel[J]. J Thromb Haemost,2012,10(4):521.
- [8]LI L,GERAGHTY O C,MEHTA Z,et al. Age-specific risks,severity,time course,and outcome of bleeding on long-term antiplatelet treatment after vascular events:a population-based cohort study[J]. Lancet,2017,390(10093):490.
- [9] CONNOLLY S J,POGUE J,HART R G,et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation[J]. N Engl J Med,2009,360(20):2066.
- [10]LEVINE G N,BATES E R,BLANKENSHIP J C,et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention:a report of the American College of Cardiology Foundation/american Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions[J]. Catheter Cardiovasc Interv,2013,82(4):E266.
- [11]MONTALESCOT G,SECHTEM U,ACHENBACH S,et al. 2013ESC guidelines on the management of stable coronary artery disease:the task force on the management of stable coronary artery disease of the European Society of Cardiology[J]. Eur Heart J,2013,34(38):2949.
- [12]张维娟.氯吡格雷与阿司匹林治疗老年冠心病的临床疗效比较[J].中国处方药,2017,15(5):40.
- [13]WALLENTIN L,BECKER R C,BUDAJ A,et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes[J]. N Engl J Med,2009,361(11):1045.
- [14]彭凌云,丁怀胜,李原,等.氯吡格雷低反应的高危冠心病患者改用替格瑞洛抗血栓治疗效果观察[J].河北医科大学学报,2016,37(12):1370.
- [15]HIATT W R,FOWKES F G,HEIZER G,et al. Ticagrelor versus clopidogrel in symptomatic peripheral artery disease[J]. N Engl J Med,2017,376(1):32.
- [16] MONTALESCOT G,van’t HOF AW,LAPOSTOLLE F,et al.Prehospital ticagrelor in ST-segment elevation myocardial infarction[J]. N Engl J Med,2014,371(11):1016.
- [17]CATTANEO M,SCHULZ R,NYLANDER S. Adenosine-mediated effects of ticagrelor:evidence and potential clinical relevance[J].J Am Coll Cardiol,2014,63(23):2503.
- [18]TILLEY S L,COFFMAN T M,KOLLER B H. Mixed messages:modulation of inflammation and immune responses by prostaglandins and thromboxanes[J]. J Clin Invest,2001,108(1):15.
- [19]HALKES P H,van GIJN J,KAPPELLE L J,et al. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin(ESPRIT):randomised controlled trial[J]. Lancet,2006,367(9523):1665.
- [20]O’DONOGHUE M L,BHATT D L,WIVIOTT S D,et al. Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes:the lessons from antagonizing the cellular effects of Thrombin-Acute Coronary Syndromes Trial[J]. Circulation,2011,123(17):1843.
- [21] WIVIOTT S D,FLATHER M D,O’DONOGHUE ML,et al.Randomized trial of atopaxar in the treatment of patients with coronary artery disease:the lessons from antagonizing the cellular effect of Thrombin-Coronary Artery Disease Trial[J]. Circulation,2011,123(17):1854.
- [22]CAVENDER M A,SCIRICA B M,BONACA M P,et al. Vorapaxar in patients with diabetes mellitus and previous myocardial infarction:findings from the thrombin receptor antagonist in secondary prevention of atherothrombotic ischemic events-TIMI 50 trial[J]. Circulation,2015,131(12):1047.
- [23]TRICOCI P,HUANG Z,HELD C,et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes[J]. N Engl J Med,2012. 366(1):20.
- [24]MORROW D A,BRAUNWALD E,BONACA M P,et al. Vorapaxar in the secondary prevention of atherothrombotic events[J]. N Engl J Med,2012,366(15):1404.
- [25]AISIKU O,PETERS CG,De CEUNYNCK K,et al. Parmodulins inhibit thrombus formation without inducing endothelial injury caused by vorapaxar[J]. Blood,2015,125(12):1976.
- [26]De CEUNYNCK K,PETERS CG,JAIN A,et al. PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury[J]. Proc Natl Acad Sci U S A,2018,115(5):E982.
- [27] TELLO-MONTOLIU A,JOVER E,RIVERA J,et al. New perspectives in antiplatelet therapy[J]. Curr Med Chem,2012,19(3):406.
- [28]李盼,乔建林,徐开林.血小板受体GPVI作为抗血栓靶点的研究进展[J].中国实验血液学杂志,2017,25(1):264.
- [29]WANG Y,GAO H,SHI C,et al. Leukocyte integrin Mac-1 regulates thrombosis via interaction with platelet GPIbalpha[J]. Nat Commun,2017,8:15559.
- [30]CROWTHER MA,JULIAN J,Mc CARTY D,et al. Treatment of warfarin-associated coagulopathy with oral vitamin K:a randomised controlled trial[J]. Lancet,2000,356(9241):1551.
- [31]MEGA JL,WALKER JR,RUFF CT,et al. Genetics and the clinical response to warfarin and edoxaban:findings from the randomised,double-blind ENGAGE AF-TIMI 48 trial[J]. Lancet,2015,385(9984):2280.
- [32]PIRMOHAMED M,BURNSIDE G,ERIKSSON N,et al. A randomized trial of genotype-guided dosing of warfarin[J]. N Engl J Med,2013,369(24):2294.
- [33]CROWTHER M A,AGENO W,GARCIA D,et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin:a randomized trial[J]. Ann Intern Med,2009,150(5):293.
- [34]LUBETSKY A,YONATH H,OLCHOVSKY D,et al. Comparison of oral vs intravenous phytonadione(vitamin K1)in patients with excessive anticoagulation:a prospective randomized controlled study[J]. Arch Intern Med,2003,163(20):2469.
- [35]GOLDSTEIN J N,REFAAI M A,MILLING T J,et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions:a phase 3b,open-label,non-inferiority,randomised trial[J]. Lancet,2015,385(9982):2077.
- [36]PARRY-JONES A R,DI NAPOLI M,GOLDSTEIN J N,et al.Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage[J]. Ann Neurol,2015,78(1):54.
- [37]Furie B,. Furie BC. Mechanisms of thrombus formation[J]. N Engl J Med,2008. 359(9):938.
- [38] ERLINGE D,OMEROVIC E,FRBERT O,et al. Bivalirudin versus heparin monotherapy in myocardial infarction[J]. N Engl J Med,2017,377(12):1132.
- [39]ERLINGE D,OMEROVIC E,FROBERT O,et al. Clinically significant bleeding with low-dose rivaroxaban versus aspirin,in addition to P2Y12 inhibition,in acute coronary syndromes(GEMINIACS-1):a double-blind,multicentre,randomised trial[J]. Lancet,2017,389(10081):1799.
- [40]WEITZ J I,LENSING AWA,PRINS M H,et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism[J]. N Engl J Med,2017,376(13):1211.
- [41]ERIKSSON B I,BORRIS L C,FRIEDMAN R J,et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty[J]. N Engl J Med,2008,358(26):2765.
- [42]LASSEN M R,AGENO W,BORRIS L C,et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty[J]. N Engl J Med,2008,358(26):2776.
- [43]路丹,刘艳霞,王妍,等.利伐沙班治疗老年恶性肿瘤并发下肢深静脉血栓的疗效及安全性评估[J].中国医药指南,2017,15(9):125.
- [44]AGNELLI G,BULLER H R,COHEN A,et al. Apixaban for extended treatment of venous thromboembolism[J]. N Engl J Med,2013,368(8):699.
- [45] GRANGER C B,ALEXANDER J H,MCMURRAY J J,et al.Apixaban versus warfarin in patients with atrial fibrillation[J]. N Engl J Med,2011,365(11):981.
- [46] LASSEN M R,RASKOB G E,GALLUS A,et al. Apixaban or enoxaparin for thromboprophylaxis after knee replacement[J]. N Engl J Med,2009,361(6):594.
- [47]LASSEN M R,RASKOB G E,GALLUS A,et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement(ADVANCE-2):a randomised double-blind trial[J]. Lancet,2010,375(9717):807.
- [48]BARRETT Y C,WANG Z,FROST C,et al. Clinical laboratory measurement of direct factor Xa inhibitors:anti-Xa assay is preferable to prothrombin time assay[J]. Thromb Haemost,2010,104(6):1263.
- [49]GERNER S T,KURAMATSU J B,SEMBILL J A,et al. Association of prothrombin complex concentrates administration and hematoma enlargement in NOAC-related intracerebral hemorrhage[J].Ann Neurol,2018,83(1):186
- [50]CONNOLLY S J,MILLING T J,Jr,EIKELBOOM J W,et al.Andexanet Alfa for acute major bleeding associated with factor Xa inhibitors[J]. N Engl J Med,2016,375(12):1131.
- [51]CONNORS J M. Antidote for factor Xa anticoagulants[J]. N Engl J Med,2015,373(25):2471.
- [52]Di NISIO M,MIDDELDORP S,BULLER H R. Direct thrombin inhibitors[J]. N Engl J Med,2005,353(10):1028.
- [53]BARRETO A D,FORD G A,SHEN L,et al. Randomized,multicenter trial of ARTSS-2(argatroban with recombinant tissue plasminogen activator for acute stroke)[J]. Stroke,2017,48(6):1608.
- [54] SCHULMAN S,KEARON C,KAKKAR A K,et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism[J]. N Engl J Med,2009,361(24):2342.
- [55]CONNOLLY S J,EZEKOWITZ M D,YUSUF S,et al. Dabigatran versus warfarin in patients with atrial fibrillation[J]. N Engl J Med,2009,361(12):1139.
- [56]CALKINS H,WILLEMS S,GERSTENFELD E P,et al. Uninterrupted dabigatran versus warfarin for ablation in atrial fibrillation[J]. N Engl J Med,2017,376(17):1627.
- [57]WOLZT M,LEVI M,SARICH T C,et al. Effect of recombinant factor VIIa on melagatran-induced inhibition of thrombin generation and platelet activation in healthy volunteers[J]. Thromb Haemost,2004,91(6):1090.
- [58]EERENBERG E S,KAMPHUISEN P W,SIJPKENS M K,et al.Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate:a randomized,placebo-controlled,crossover study in healthy subjects[J]. Circulation,2011,124(14):1573.
- [59] RUFF,C T,GIUGLIANO R P,ANTMAN EM. Management of bleeding with non-vitamin K antagonist oral anticoagulants in the era of specific reversal agents[J]. Circulation,2016,134(3):248.
- [60]POLLACK C V,REILLY P A,EIKELBOOM J,et al. Idarucizumab for dabigatran reversal[J]. N Engl J Med,2015,373(6):511.
- [61]POLLACK C V,REILLY P A,van RYN J,et al. Idarucizumab for dabigatran reversal-full cohort analysis[J]. N Engl J Med,2017,377(5):431.
- [62] GOB E,REYMANN S,LANGHAUSER F,et al. Blocking of plasma kallikrein ameliorates stroke by reducing thromboinflammation[J]. Ann Neurol,2015,77(5):784.
- [63] KLEINSCHNITZ C,STOLL G,BENDSZUS M,et al. Targeting coagulation factorⅫprovides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis[J]. J Exp Med,2006,203(3):513.
- [64]Gailani D,Gruber A. FactorⅪas a therapeutic target[J]. Arterioscler Thromb Vasc Biol,2016,36(7):1316.
- [65]BULLER H R,BETHUNE C,BHANOT S,et al. FactorⅪantisense oligonucleotide for prevention of venous thrombosis[J]. N Engl J Med,2015,372(3):232.
- [66]MEIJERS J C,TEKELENBURG W L,BOUMA B N,et al. High levels of coagulation factorⅪas a risk factor for venous thrombosis[J]. N Engl J Med,2000,342(10):696.