High-risk Acute Coronary Syndrome Patients with Non-ST-Elevation Myocardial Infarction: Definition and Treatment

Article

Abstract

Introduction

Early risk stratification of patients with acute coronary syndromes (ACS), unstable angina, or non-ST-elevation myocardial infarction ensures patients receive appropriate care.

Materials and methods

Many risk-stratification models have been developed to identify high-risk ACS patients who would benefit most from an early invasive strategy and to determine patients at greater risk for bleeding complications. Although high-risk patients seem to benefit most from a combination of aggressive antithrombotic and early invasive therapies, stratification for risk of bleeding also helps in the choice and dosing of appropriate medical therapy.

Results

The effective use of glycoprotein IIb/IIIa inhibitors, in particular, is dependent on accurate risk assessment, whereas the risk-to-benefit ratio of direct thrombin inhibitors in high-risk versus low-risk patients as part of an initial therapy plan requires clarification. Nevertheless, use of the same anticoagulant throughout the care pathway may reduce the rates of death or recurrent myocardial infarction, and bleeding complications.

Key words

Acute coronary syndromes Glycoprotein Anticoagulation Enoxaparin 

References

  1. 1.
    Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, et al.; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction); American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association of Cardiovascular and Pulmonary Rehabilitation; Society for Academic Emergency Medicine. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 2007;116:e148–304.Google Scholar
  2. 2.
    Morrow DA, Cannon CP, Rifai N, Frey MJ, Vicari R, Lakkis N, et al.; TACTICS-TIMI 18 Investigators. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. JAMA 2001;286:2405–12.PubMedCrossRefGoogle Scholar
  3. 3.
    Lagerqvist B, Diderholm E, Lindahl B, Husted S, Kontny F, Ståhle E, et al. FRISC score for selection of patients for an early invasive treatment strategy in unstable coronary artery disease. Heart 2005;91:1047–52.PubMedCrossRefGoogle Scholar
  4. 4.
    Sulmasy DP. Cancer care, money, and the value of life: whose justice? Which rationality? J Clin Oncol 2007;25:217–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Froehlich JB, Karavite D, Russman PL, Erdem N, Wise C, Zelenock G, et al.; American College of Cardiology; American Heart Association. American College of Cardiology/American Heart Association preoperative assessment guidelines reduce resource utilization before aortic surgery. J Vasc Surg 2002;36:758–63.PubMedCrossRefGoogle Scholar
  6. 6.
    Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation 2000;101:2557–67.PubMedGoogle Scholar
  7. 7.
    Ferguson JJ, Califf RM, Antman EM, Cohen M, Grines CL, Goodman S, et al.; SYNERGY Trial Investigators. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 2004;292:45–54.PubMedCrossRefGoogle Scholar
  8. 8.
    Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, et al.; ACUITY Investigators. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;355:2203–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 2000;284:835–42.PubMedCrossRefGoogle Scholar
  10. 10.
    Yan AT, Yan RT, Tan M, Fung A, Cohen EA, Fitchett DH, et al.; Canadian Acute Coronary Syndromes 1 and 2 Registry Investigators. Management patterns in relation to risk stratification among patients with non-ST elevation acute coronary syndromes. Arch Intern Med 2007;167:1009–16.PubMedCrossRefGoogle Scholar
  11. 11.
    Cohen D, Maresh K, Nassif D, Jeremias A, Kleinman N, Berger P, et al. The frequency of elevated troponins among unselected patients undergoing percutaneous coronary intervention and its relationship to in-hospital outcomes: Results from the EVENT Registry. Presented at: The Transcatheter Cardiovascular Therapeutics Meeting; October 22–27, 2006; Washington, DC, USA. Abstract 398.Google Scholar
  12. 12.
    Nathan S, Amin A, Vassallo P, Kumar A, Calvin J. Patterns of resource utilization and early mortality in non-ST segment elevation acute coronary syndromes as functions of cardiac troponin positivity—insights from the TRACS Registry. Presented at: The Transcatheter Cardiovacular Therapeutics Meeting; October 22–27, 2006; Washington, DC, USA. Abstract 196.Google Scholar
  13. 13.
    de Servi S, Cavallini C, Dellavalle A, Santoro GM, Bonizzoni E, Marzocchi A, et al.; ROSAI-2 Investigators. Non-ST-elevation acute coronary syndrome in the elderly: treatment strategies and 30-day outcome. Am Heart J 2004;147:830–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Gomberg-Maitland M, Murphy SA, Moliterno DJ, Cannon CP. Are we appropriately triaging patients with unstable angina? Am Heart J 2005;149:613–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, et al.; GRACE Investigators. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 2004;291:2727–33.PubMedCrossRefGoogle Scholar
  16. 16.
    Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, et al.; Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 2003;163:2345–53.PubMedCrossRefGoogle Scholar
  17. 17.
    Steyerberg EW, Borsboom GJ, van Houwelingen HC, Eijkemans MJ, Habbema JD. Validation and updating of predictive logistic regression models: a study on sample size and shrinkage. Stat Med 2004;23:2567–86.PubMedCrossRefGoogle Scholar
  18. 18.
    Bradshaw PJ, Ko DT, Newman AM, Donovan LR, Tu JV. Validation of the Thrombolysis In Myocardial Infarction (TIMI) risk index for predicting early mortality in a population-based cohort of STEMI and non-STEMI patients. Can J Cardiol 2007;23:51–6.PubMedGoogle Scholar
  19. 19.
    Chase M, Robey JL, Zogby KE, Sease KL, Shofer FS, Hollander JE. Prospective validation of the Thrombolysis In Myocardial Infarction risk score in the emergency department chest pain population. Ann Emerg Med 2006;48:252–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Morrow DA, Antman EM, Snapinn SM, McCabe CH, Theroux P, Braunwald E. An integrated clinical approach to predicting the benefit of tirofiban in non-ST elevation acute coronary syndromes. Application of the TIMI Risk Score for UA/NSTEMI in PRISM-PLUS. Eur Heart J 2002;23:223–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F, et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ 2006;333:1091.PubMedCrossRefGoogle Scholar
  22. 22.
    Alter DA, Venkatesh V, Chong A, SESAMI study group. Evaluating the performance of the Global Registry of Acute Coronary Events risk-adjustment index across socioeconomic strata among patients discharged from the hospital after acute myocardial infarction. Am Heart J 2006;151:323–31.PubMedCrossRefGoogle Scholar
  23. 23.
    Bradshaw PJ, Ko DT, Newman AM, Donovan LR, Tu JV. Validity of the GRACE (Global Registry of Acute Coronary Events) acute coronary syndrome prediction model for six month post-discharge death in an independent data set. Heart 2006;92:905–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Yan AT, Jong P, Yan RT, Tan M, Fitchett D, Chow CM, et al.; Canadian Acute Coronary Syndromes registry investigators. Clinical trial-derived risk model may not generalize to real-world patients with acute coronary syndrome. Am Heart J 2004;148:1020–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Almeda FQ, Hendel RC, Nathan S, Meyer PM, Calvin JE, Klein LW. Improved in-hospital outcomes in acute coronary syndromes (unstable angina/non-ST segment elevation myocardial infarction) despite similar TIMI risk scores. J Invasive Cardiol 2003;15:502–6.PubMedGoogle Scholar
  26. 26.
    James SK, Lindahl B, Siegbahn A, Stridsberg M, Venge P, Armstrong P, et al. N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy. Circulation 2003;108:275–81.PubMedCrossRefGoogle Scholar
  27. 27.
    Manoukian SV, Feit F, Mehran R, Voeltz MD, Ebrahimi R, Hamon M, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes: an analysis from the ACUITY Trial. J Am Coll Cardiol 2007;49:1362–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Collet JP, Montalescot G, Agnelli G, Van de Werf F, Gurfinkel EP, López-Sendón J, et al.; GRACE Investigators. Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events. Eur Heart J 2005;26:2285–93.PubMedCrossRefGoogle Scholar
  29. 29.
    Masoudi FA, Plomondon ME, Magid DJ, Sales A, Rumsfeld JS. Renal insufficiency and mortality from acute coronary syndromes. Am Heart J 2004;147:623–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Yan AT, Yan RT, Tan M, Constance C, Lauzon C, Zaltzman J, et al.; Canadian Acute Coronary Syndromes (ACS) Registry Investigators. Treatment and one-year outcome of patients with renal dysfunction across the broad spectrum of acute coronary syndromes. Can J Cardiol 2006;22:115–20.PubMedGoogle Scholar
  31. 31.
    Fox KA, Antman EM, Montalescot G, Agewall S, SomaRaju B, Verheugt FW, et al. The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial. J Am Coll Cardiol 2007;49:2249–55.PubMedCrossRefGoogle Scholar
  32. 32.
    Voeltz MD, Patel AD, Feit F, Fazel R, Lincoff AM, Manoukian SV. Effect of anemia on hemorrhagic complications and mortality following percutaneous coronary intervention. Am J Cardiol 2007;99:1513–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Rao SV, Jollis JG, Harrington RA, Granger CB, Newby LK, Armstrong PW, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA 2004;292:1555–62.PubMedCrossRefGoogle Scholar
  34. 34.
    Yang X, Alexander KP, Chen AY, Roe MT, Brindis RG, Rao SV, et al.; CRUSADE Investigators. The implications of blood transfusions for patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE National Quality Improvement Initiative. J Am Coll Cardiol 2005;46:1490–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Montalescot G, White HD, Gallo R, Cohen M, Steg PG, Aylward PE, et al.; STEEPLE Investigators. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med 2006;355:1006–17.PubMedCrossRefGoogle Scholar
  36. 36.
    Steinhubl SR, Kastrati A, Berger PB. Variation in the definitions of bleeding in clinical trials of patients with acute coronary syndromes and undergoing percutaneous coronary interventions, and its impact on the apparent safety of antithrombotic drugs. Am Heart J 2007;154:3–11.PubMedCrossRefGoogle Scholar
  37. 37.
    Cohen M, Alexander KP, Rao SV. Bleeding after antithrombotic therapy in patients with acute ischemic heart disease. Is it the drugs or how we use them? J Thromb Thrombolysis 2007; doi: 10.1007/s11239-007-0182-x.
  38. 38.
    Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology, Bassand JP, Hamm CW, Ardissino D, Boersma E, Budaj A, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology. Eur Heart J. 2007;28:1598–660.PubMedCrossRefGoogle Scholar
  39. 39.
    Smith SC Jr, Feldman TE, Hirshfeld JW Jr, Jacobs AK, Kern MJ, King SB 3rd, et al.; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions Writting Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention. ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). Circulation 2006;113:156–75.PubMedCrossRefGoogle Scholar
  40. 40.
    Diderholm E, Andrén B, Frostfeldt G, Genberg M, Jernberg T, Lagerqvist B, et al.; Fast Revascularisation during InStability in Coronary artery disease (FRISC II) Investigators. The prognostic and therapeutic implications of increased troponin T levels and ST depression in unstable coronary artery disease: the FRISC II invasive troponin T electrocardiogram substudy. Am Heart J 2002;143:760–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Kastrati A, Mehilli J, Neumann FJ, Dotzer F, ten Berg J, Bollwein H, et al.; Intracoronary Stenting and Antithrombotic Regimen In: Rapid Early Action for Coronary Treatment 2 (ISAR-REACT 2) Trial Investigators. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006;295:1531–8.PubMedCrossRefGoogle Scholar
  42. 42.
    de Winter RJ, Windhausen F, Cornel JH, Dunselman PH, Janus CL, Bendermacher PE, et al.; Invasive versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) Investigators. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005;353:1095–104.PubMedCrossRefGoogle Scholar
  43. 43.
    Cannon CP, Weintraub WS, Demopoulos LA, Vicari R, Frey MJ, Lakkis N, et al.; TACTICS (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy)—Thrombolysis in Myocardial Infarction 18 Investigators. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001;344:1879–87.PubMedCrossRefGoogle Scholar
  44. 44.
    Fox KA, Poole-Wilson PA, Henderson RA, Clayton TC, Chamberlain DA, Shaw TR, et al.; Randomized Intervention Trial of unstable Angina Investigators. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet 2002;360:743–51.PubMedCrossRefGoogle Scholar
  45. 45.
    Spinler SA, Inverso SM, Cohen M, Goodman SG, Stringer KA, Antman EM, ESSENCE and TIMI 11B Investigators. Safety and efficacy of unfractionated heparin versus enoxaparin in patients who are obese and patients with severe renal impairment: analysis from the ESSENCE and TIMI 11B studies. Am Heart J 2003;146:33–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Thorevska N, Amoateng-Adjepong Y, Sabahi R, Schiopescu I, Salloum A, Muralidharan V, et al. Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin. Chest 2004;125:856–63.PubMedCrossRefGoogle Scholar
  47. 47.
    Antman EM, Morrow DA, McCabe CH, Murphy SA, Ruda M, Sadowski Z, et al.; ExTRACT-TIMI 25 Investigators. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med 2006;354:1477–88.PubMedCrossRefGoogle Scholar
  48. 48.
    White HD, Braunwald E, Murphy SA, Jacob AJ, Gotcheva N, Polonetsky L, et al. Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25. Eur Heart J 2007;28:1066–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Petersen JL, Mahaffey KW, Hasselblad V, Antman EM, Cohen M, Goodman SG, 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.PubMedCrossRefGoogle Scholar
  50. 50.
    sanofi-aventis US LLC. Lovenox® (enoxaparin sodium injection) prescribing information, 2007. http://products.sanofi-aventis.us/lovenox/lovenox.html. Accessed April 10, 2008.
  51. 51.
    Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:188S–203S.PubMedCrossRefGoogle Scholar
  52. 52.
    White HD, Kleiman NS, Mahaffey KW, Lokhnygina Y, Pieper KS, Chiswell K, et al. Efficacy and safety of enoxaparin compared with unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention in the Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial. Am Heart J 2006;152:1042–50.PubMedCrossRefGoogle Scholar
  53. 53.
    Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006;354:1464–76.PubMedCrossRefGoogle Scholar
  54. 54.
    Cohen M, Mahaffey KW, Pieper K, Pollack CV Jr, Antman EM, Hoekstra J, et al.; SYNERGY Trial Investigators. A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol 2006;48:1346–54.PubMedCrossRefGoogle Scholar
  55. 55.
    Boersma E, Harrington RA, Moliterno DJ, White H, Théroux P, Van de Werf F, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002;359:189–98.PubMedCrossRefGoogle Scholar
  56. 56.
    Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al.; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001–15.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Cardiac Catheterization LaboratoryNewark Beth Israel Medical CenterNewarkUSA

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