russjcardiolРоссийский кардиологический журналRussian Journal of Cardiology1560-40712618-7620«SILICEA-POLIGRAF» LLCrussjcardiol-1440Research ArticleКЛИНИКА И ФАРМАКОТЕРАПИЯGUIDELINES FOR THE PRACTITIONERСРАВНИТЕЛЬНАЯ ФАРМАКОЭКОНОМИЧЕСКАЯ ОЦЕНКА ЭНОКСАПАРИНА И НЕФРАКЦИОНИРОВАННОГО ГЕПАРИНА ПРИ ОСТРОМ КОРОНАРНОМ СИНДРОМЕ БЕЗ ПОДЪЕМА СЕГМЕНТА STPHARMACO-ECONOMIC COMPARISON OF ENOXAPARIN AND UNFRACTIONATED HEPARIN IN ACUTE CORONARY SYNDROME WITHOUT ST SEGMENT ELEVATIONСыровА. В.SyrovA. V.

сотрудник

rsmu@rsmu.ruЗыряновС. К.ZyryanovS. K.

профессор кафедры

rsmu@rsmu.ruБелоусовЮ. Б.BelousovYu. B.

зав. кафедрой и курсом, член-корреспондент РАМН, профессор, д.м.н.

rsmu@rsmu.ruКлинический госпиталь МСЧ ГУВДRussian FederationРоссийский государственный медицинский университет, кафедра клинической фармакологии, МоскваRussian Federation201028042010025966Copyright © Сыров А.В., Зырянов С.К., Белоусов Ю.Б., 20102010Сыров А.В., Зырянов С.К., Белоусов Ю.Б.Syrov A.V., Zyryanov S.K., Belousov Y.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://russjcardiol.elpub.ru/jour/article/view/1440

Острый коронарный синдром (ОКС) – форма ишемической болезни, объединяющая острый инфаркт миокарда с подъемом сегмента ST (ОКС с подъемом сегмента ST), острый инфаркт миокарда без подъема сегмента ST и нестабильную стенокардию (ОКС без подъема сегмента ST). Эти состояния объединены в единый синдром в связи с высоким риском развития острого инфаркта миокарда и острой коронарной смерти у этой группы больных, что и определяет особую актуальность лечения ОКС. Применение антикоагулянтов, в частности, эноксапарина или нефракционированного гепарина является базисным компонентом медикаментозного лечения ОКС без подъема сегмента ST (ОКСбпST). Целью настоящего исследования являлось выявление антикоагулянта, обладающего клиническими и фармако-экономическими преимуществами при консервативном лечении ОКСбпST.

 

Acute coronary syndrome (ACS) is a form of coronary heart disease (CHD), combining acute myocardial infarction with ST segment elevation (STE ACS), acute myocardial infarction without ST segment elevation, and unstable angina (non-STE ACS). These clinical forms are considered as one syndrome, due to a high risk of acute myocardial infarction and sudden coronary death. Therefore, the problem of ACS treatment is particularly important. The management of non-STE ACS should always include anticoagulants – specifically, enoxaparin or unfractionated heparin. This study was aimed at identifying the anticoagulant with the best clinical and pharmaco-economic characteristics in conservative treatment of non-STE ACS.

острый коронарный синдромантикоагулянтызатраты на лечениесоотношение “затраты – эффективность”Acute coronary syndromeanticoagulantstherapy costscost-effectiveness ratioReferencesМ. В. Авксентьева, П. А. Воробьев, В. Б. Герасимов, С. Г. Горохова, С. А. Кобина Экономическая оценка эффективности лекарственной терапии (фармакоэкономический анализ). — С.: Ньюмедиамед, 2000.М. В. Авксентьева, П. А. Воробьев, В. Б. Герасимов, С. Г. Горохова, С. А. Кобина Экономическая оценка эффективности лекарственной терапии (фармакоэкономический анализ). — С.: Ньюмедиамед, 2000.С. А. Берестов, О. Е. Овчинникова, З. С. Баркаган Экономическая оценка использования гепарина и фраксипарина в отделении патологии беременных. Проблемы стандартизации в здравоохранении. 2000. № 4. С. 22—23.С. А. Берестов, О. Е. Овчинникова, З. С. Баркаган Экономическая оценка использования гепарина и фраксипарина в отделении патологии беременных. Проблемы стандартизации в здравоохранении. 2000. № 4. С. 22—23.Всероссийское научное общество кардиологов. Рекомендации по лечению острого коронарного синдрома без стойкого подъёма сегмента ST на ЭКГ. Кардиология. 2004. № 4 (приложение: 1—28).Всероссийское научное общество кардиологов. Рекомендации по лечению острого коронарного синдрома без стойкого подъёма сегмента ST на ЭКГ. Кардиология. 2004. № 4 (приложение: 1—28).ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non—ST-Elevation Myocardial Infarction. J Am Coll Cardiol, 2007; 50:652—726, doi:10.1016/j.jacc.2007.02.028 (Published online 6 August 2007).ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non—ST-Elevation Myocardial Infarction. J Am Coll Cardiol, 2007; 50:652—726, doi:10.1016/j.jacc.2007.02.028 (Published online 6 August 2007).Antman EM. Low molecular weight heparins for acute coronary syndrome: tackling the issues head-on. Am Heart J 2003;146:191—3.Antman EM. Low molecular weight heparins for acute coronary syndrome: tackling the issues head-on. Am Heart J 2003;146:191—3.Antman EM, Cohen M, Radley D, et al. Assessment of the treatment effect of enoxparin for unstable angina/non-Q-wave myocardial infarction: TIMI11B-ESSENCE meta-analysis. Circulation 1999;100:1602— 8.Antman EM, Cohen M, Radley D, et al. Assessment of the treatment effect of enoxparin for unstable angina/non-Q-wave myocardial infarction: TIMI11B-ESSENCE meta-analysis. Circulation 1999;100:1602— 8.Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the Thrombolysis In Myocar-dial Infarction (TIMI) 11B trial. Circulation 1999;100:1593— 601.Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the Thrombolysis In Myocar-dial Infarction (TIMI) 11B trial. Circulation 1999;100:1593— 601.Becker RC, Ball SP, Eisenberg P, et al. A randomized, multicenter trial of weight-adjusted intravenous heparin dose titration and pointof-care coagulation monitoring in hospitalized patients with active thromboembolic disease: Antithrombotic Therapy Consortium Investigators.Am Heart J 1999;137:59 —71.Becker RC, Ball SP, Eisenberg P, et al. A randomized, multicenter trial of weight-adjusted intravenous heparin dose titration and pointof-care coagulation monitoring in hospitalized patients with active thromboembolic disease: Antithrombotic Therapy Consortium Investigators.Am Heart J 1999;137:59 —71.Bertrand ME, Simoons ML, Fox KA, et al. Management of acute coronary syndromes: acute coronary syndromes without persistent ST segment elevation: recommendations of the Task Force of the European Society of Cardiology. Eur Heart J. 2000;21:1406—1432.Bertrand ME, Simoons ML, Fox KA, et al. Management of acute coronary syndromes: acute coronary syndromes without persistent ST segment elevation: recommendations of the Task Force of the European Society of Cardiology. Eur Heart J. 2000;21:1406—1432.Blazing MA, de Lemos JA, White HD, et al, for the A to Z Investigators. Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non—ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial. JAMA. 2004;292:55— 64.Blazing MA, de Lemos JA, White HD, et al, for the A to Z Investigators. Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non—ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial. JAMA. 2004;292:55— 64.Braunwald E. Unstable angina: an etiologic approach to management [editorial]. Circulation 1998;98:2219 —22.Braunwald E. Unstable angina: an etiologic approach to management [editorial]. Circulation 1998;98:2219 —22.Braunwald E. Unstable angina: a classification. Circulation 1989;80: 410—4.Braunwald E. Unstable angina: a classification. Circulation 1989;80: 410—4.Braunwald E, Antman EM, Beasely JW, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non—STsegment elevation myocardial infarction: summary article. Circulation. 2002;106:1893—1900.Braunwald E, Antman EM, Beasely JW, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non—STsegment elevation myocardial infarction: summary article. Circulation. 2002;106:1893—1900.Braunwald E, Mark DB, Jones RH, et al. Unstable Angina: Diagnosis and Management. 3—1-1994; AHCPR Publication No. 94—0602:1—154.Braunwald E, Mark DB, Jones RH, et al. Unstable Angina: Diagnosis and Management. 3—1-1994; AHCPR Publication No. 94—0602:1—154.Cohen M, Adams PC, Hawkins L, Bach M, Fuster V. Usefulness of antithrombotic therapy in resting angina pectoris or non- Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). Am J Cardiol 1990;66:1287—92.Cohen M, Adams PC, Hawkins L, Bach M, Fuster V. Usefulness of antithrombotic therapy in resting angina pectoris or non- Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group). Am J Cardiol 1990;66:1287—92.Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecularweight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997;337:447—452.Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecularweight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997;337:447—452.Cohen M, Theroux P, Borzak S, et al., for the ACUTE II Investigators. Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: the ACUTE II study. The Antithrombotic Combination Using Tirofiban and Enoxaparin. Am Heart J 2002;144:470 —7.Cohen M, Theroux P, Borzak S, et al., for the ACUTE II Investigators. Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: the ACUTE II study. The Antithrombotic Combination Using Tirofiban and Enoxaparin. Am Heart J 2002;144:470 —7.Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000;83:361- 6.Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000;83:361- 6.Diuguid DL. Choosing a Paranteral Anticoagulant Agent. N Engl J Med 2001;345:18, 1340—1341.Diuguid DL. Choosing a Paranteral Anticoagulant Agent. N Engl J Med 2001;345:18, 1340—1341.FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective random-ised multicentre study. Lancet 1999;354:701—7.FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective random-ised multicentre study. Lancet 1999;354:701—7.Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet 1996;347:561— 8.Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet 1996;347:561— 8.Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med 1999;130:719 —28.Garber AM, Solomon NA. Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease. Ann Intern Med 1999;130:719 —28.Gaspoz JM, Coxson PG, Goldman PA, et al. Cost effectiveness of aspirin, clopidogrel, or both for secondary prevention of coronary heart disease. N Engl J Med 2002;346:1800 —6.Gaspoz JM, Coxson PG, Goldman PA, et al. Cost effectiveness of aspirin, clopidogrel, or both for secondary prevention of coronary heart disease. N Engl J Med 2002;346:1800 —6.Gibbons RJ, Fuster V, Therapy for Patients with Acute Coronary Syndromes — New Opportunities. N Engl J Med 2006,354;1524—14.Gibbons RJ, Fuster V, Therapy for Patients with Acute Coronary Syndromes — New Opportunities. N Engl J Med 2006,354;1524—14.Goodman SG, Cohen M, Bigonzi F, et al. Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one-year results of the ESSENCE study. J Am Coll Cardiol. 2000;36:693—698.Goodman SG, Cohen M, Bigonzi F, et al. Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one-year results of the ESSENCE study. J Am Coll Cardiol. 2000;36:693—698.Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. The Task Force for the Diagnisis and Treatment of non-ST-segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. European Heart Jornal (2007) 28, 1598—1660 (Published online 14 June 2007).Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. The Task Force for the Diagnisis and Treatment of non-ST-segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. European Heart Jornal (2007) 28, 1598—1660 (Published online 14 June 2007).Gurfinkel EP, Manos EJ, Mejail RI, et al. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. J Am Coll Cardiol 1995;26:313— 8.Gurfinkel EP, Manos EJ, Mejail RI, et al. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. J Am Coll Cardiol 1995;26:313— 8.Hamm CW, Braunwald E. A classification of unstable angina revisited. Circulation 2000;102:118 —22.Hamm CW, Braunwald E. A classification of unstable angina revisited. Circulation 2000;102:118 —22.Hassan WM, Flaker GC, Feutz C, Petroski GF, Smith D. Improved anticoagulation with a weight-adjusted heparin nomogram in patients with acute coronary syndromes: a randomized trial. J Thromb Thrombolysis 1995;2:245—9.Hassan WM, Flaker GC, Feutz C, Petroski GF, Smith D. Improved anticoagulation with a weight-adjusted heparin nomogram in patients with acute coronary syndromes: a randomized trial. J Thromb Thrombolysis 1995;2:245—9.Hirsh J. Heparin. N Engl J Med 1991;324:1565—74.Hirsh J. Heparin. N Engl J Med 1991;324:1565—74.Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:188S—203S.Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:188S—203S.Hirsh J, Warkentin TE, Raschke R, Granger C, Ohman EM, Dalen JE. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998;114:489S—510S.Hirsh J, Warkentin TE, Raschke R, Granger C, Ohman EM, Dalen JE. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998;114:489S—510S.Holdright D, Patel D, Cunningham D, et al. Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. J Am Coll Cardiol 1994;24:39 —45.Holdright D, Patel D, Cunningham D, et al. Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. J Am Coll Cardiol 1994;24:39 —45.Hochman JS, Wali AU, Barvila D, et al. A new regimen for heparin use in acute coronary syndromes. Am Heart J 1999;138:313— 8.Hochman JS, Wali AU, Barvila D, et al. A new regimen for heparin use in acute coronary syndromes. Am Heart J 1999;138:313— 8.Klein W, Buchwald A, Hillis SE, et al. Comparison of low-molecularweight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC) (published erratum appears in Circulation 1998;97:413). Circulation 1997;96:61— 8.Klein W, Buchwald A, Hillis SE, et al. Comparison of low-molecularweight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC) (published erratum appears in Circulation 1998;97:413). Circulation 1997;96:61— 8.Kuntz KM, Fleischmann KE, Hunink MGM, Douglas PS. Costeffectiveness of diagnostic strategies for patients with chest pain. Ann Intern Med 1999;130:709 —18.Kuntz KM, Fleischmann KE, Hunink MGM, Douglas PS. Costeffectiveness of diagnostic strategies for patients with chest pain. Ann Intern Med 1999;130:709 —18.Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001;104:365—72.Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001;104:365—72.Mark DB, Cowper PA, Berkowitz SD, et al. Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events [unstable angina or non-Q-wave myocardial infarction]. Circulation 1998;97:1702—7.Mark DB, Cowper PA, Berkowitz SD, et al. Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events [unstable angina or non-Q-wave myocardial infarction]. Circulation 1998;97:1702—7.Mukherjee D, Fang J, Kline-Rogers E, Otten R, Eagle KA. Impact of combination evidence based medical treatment in patients with acute coronary syndromes in various TIMI risk groups. Heart 2005;91:381—2.Mukherjee D, Fang J, Kline-Rogers E, Otten R, Eagle KA. Impact of combination evidence based medical treatment in patients with acute coronary syndromes in various TIMI risk groups. Heart 2005;91:381—2.Neri SG, Gensini GF, Poggesi L, et al. Effect of heparin, aspirin, or alteplase in reduction of myocardial ischaemia in refractory unstable angina. Lancet 1990;335:615— 8.Neri SG, Gensini GF, Poggesi L, et al. Effect of heparin, aspirin, or alteplase in reduction of myocardial ischaemia in refractory unstable angina. Lancet 1990;335:615— 8.Oler A, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. JAMA 1996;276:811—5.51.Oler A, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. JAMA 1996;276:811—5.51.Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 2003;108:1682—7.Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 2003;108:1682—7.Petersen JL, Mahaffey KW, Hasselblad V, et al. Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview. JAMA 2004;292:89 —96.Petersen JL, Mahaffey KW, Hasselblad V, et al. Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview. JAMA 2004;292:89 —96.Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998;338:1498 —505.Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998;338:1498 —505.Schleinitz MD, Heidenreich PA. A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone. Ann Intern Med 2005;142:251—9.Schleinitz MD, Heidenreich PA. A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone. Ann Intern Med 2005;142:251—9.Shapiro SS. Treating Thrombosis in the 21st Century N Engl J Med 2003,349; 1762—1764 -18Shapiro SS. Treating Thrombosis in the 21st Century N Engl J Med 2003,349; 1762—1764 -18SYNERGY Executive Committee. The SYNERGY Trial: study design and rationale. Am Heart J. 2002;143:952—960.SYNERGY Executive Committee. The SYNERGY Trial: study design and rationale. Am Heart J. 2002;143:952—960.Telford AM, Wilson C. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome. Lancet 1981;1:1225— 8.Telford AM, Wilson C. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome. Lancet 1981;1:1225— 8.Theroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988;319:1105—11.Theroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988;319:1105—11.Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation 1998; 97:1195—206.Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation 1998; 97:1195—206.Theroux P, Waters D, Qiu S, McCans J, de Guise P, Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993;88:2045— 8.Theroux P, Waters D, Qiu S, McCans J, de Guise P, Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993;88:2045— 8.Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330 —5.Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330 —5.Williams DO, Kirby MG, McPherson K, Phear DN. Anticoagulant treatment of unstable angina. Br J Clin Pract 1986;40:114 —6.Williams DO, Kirby MG, McPherson K, Phear DN. Anticoagulant treatment of unstable angina. Br J Clin Pract 1986;40:114 —6.Yeghiazarians Y, Braunstein J B, Askari A, Stone P H. Unstable Angina Pectoris N Engl J Med 2007,342;101—111-Yeghiazarians Y, Braunstein J B, Askari A, Stone P H. Unstable Angina Pectoris N Engl J Med 2007,342;101—111-

The authors declare that there are no conflicts of interest present.