American Heart Journal
Volume 148, Issue 5 , Pages 764-775 , November 2004

Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial: Study design and rationale

  • Gregg W. Stone, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • Corresponding Author InformationReprint requests: Gregg W. Stone, MD, The Cardiovascular Research Foundation, 55 E 59th St, 6th Floor, New York City, New York 10022, USA.
    • ,
  • Michel Bertrand, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • Antonio Colombo, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • George Dangas, MD, PhD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • Michael E. Farkouh, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • Frederick Feit, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • Alexandra J. Lansky, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • A.Michael Lincoff, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • Roxana Mehran, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • Jeffrey W. Moses, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • Magnus Ohman, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA
    • ,
  • Harvey D. White, MD

      Affiliations

    • Columbia University Medical Center Cardiovascular Research Foundation, New York, NY, USA

Received 25 January 2004 ,Accepted 27 April 2004.

References 

  1. Cannon CP, Weintraub WS, Demopoulos LA, et al.  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;344:1879–1887
  2. FRISC II Investigators . Invasive compared with non-invasive treatment in unstable coronary-artery disease. Lancet. 1999;354:708–715
  3. Fox KA, Poole-Wilson PA, Henderson RA, et al.  Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction. Lancet. 2002;360:743–751
  4. McKay RG. “Ischemia-guided” versus “early invasive” strategies in the management of acute coronary syndrome/non–ST-segment elevation myocardial infarction: the interventionalist's perspective. J Am Coll Cardiol. 2003;41:96S–102S
  5. Boden W. “Routine invasive” versus “selective invasive” approaches to non–ST-segment elevation acute coronary syndromes management in the post-stent/platelet inhibition era. J Am Coll Cardiol. 2003;41:113S–122S
  6. Braunwald E, Antman EM, Beasley JW, et al.  ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2000;36:970–1062
  7. Yusuf S, Zhao F, Mehta SR, et al.  Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502
  8. Mehta SR, Yusuf S, Peters RJ, et al.  Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention. Lancet. 2001;358:527–533
  9. Steinhubl SR, Berger PB, Mann JT, et al.  Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411–2420
  10. PRISM-PLUS Study Investigators . Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non–Q-wave myocardial infarction. N Engl J Med. 1998;338:1488–1497
  11. PURSUIT Trial Investigators . Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med. 1998;339:436–443
  12. Boersma E, Harrington RA, Moliterno DJ, et al.  Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet. 2002;359:189–198
  13. Cohen M, Demers C, Gurfinkel EP, et al.  A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997;337:447–452
  14. Antman EM, McCabe CH, Gurfinkel EP, et al.  Enoxaparin prevents death and cardiac ischemic events in unstable angina/non–Q-wave myocardial infarction. Circulation. 1999;100:1593–1601
  15. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST segment elevation myocardial infarction. http://www.acc.org/clinical/guidelines/unstable/update_explantext.htm
  16. Braunwald E, Antman EM, Beasley JW, et al.  ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction —2002: summary article. Circulation. 2002;106:1893–1900
  17. Wood AJ. When increased therapeutic benefit comes at increased cost. N Engl J Med. 2002;346:1819–1821
  18. Mahoney EM, Jurkovitz CT, Chu H, et al.  Cost and cost-effectiveness of an early invasive vs conservative strategy for the treatment of unstable angina and non-ST-segment elevation myocardial infarction. JAMA. 2002;288:1851–1858
  19. Aguirre FV, Gill JB. Increasing benefit, reducing risk: focusing on hemorrhagic complications in percutaneous coronary intervention. J Invasive Cardiol. 2002;14(suppl B):48B–54B
  20. Milkovich G, Gibson G. Economic impact of bleeding complications and the role of antithrombotic therapies in percutaneous coronary intervention. Am J Health Syst Pharm. 2003;60(suppl 3):S15–21
  21. Hirsh J, Warkentin TE, Shaughnessy SG, et al.  Heparin and low molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest. 2001;119:64S–94S
  22. Hirsh J. Heparin. N Engl J Med. 1991;324:1565–1574
  23. Warkentin TE, Kelton JG. Heparin and platelets. Hematol Oncol Clin North Am. 1990;4:243–264
  24. Naqvi TZ, Shah PK, Ivey PA, et al.  Therapeutic concentrations of heparin augment platelet activation at the time of coronary angiography. J Cardiovasc Pharmacol Ther. 1998;3:91–102
  25. Chong BF, Ismail F. The mechanism of heparin-induced platelet aggregation. Eur J Haematol. 1989;43:245–251
  26. Storck J, Hollger N, Zimmermann RE. The influence of heparin and protamine sulfate on platelet ADP and platelet factor-4 release and the expression of glycoprotein IIb/IIIa. Haemostasis. 1994;24:358–363
  27. Xiao Z, Theroux P. Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor. Circulation. 1998;97:251–256
  28. Sobel M. Heparin modulates integrin function in human platelets. J Vasc Surg. 2001;33:587–594
  29. Kabbani SS, Watkins MW, Ashikaga T, et al.  Platelet reactivity characterized prospectively: a determinant of outcome 90 days after percutaneous coronary intervention. Circulation. 2001;104:181–186
  30. Weitz JI, Hudoba M, Massel D, et al.  Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin-III: independent inhibitors. J Clin Invest. 1990;86:385–391
  31. Weitz JI, Leslie B, Hudoba M. Thrombin binds to soluble fibrin degradation products where it is protected from inhibition by heparin-antithrombin but susceptible to inactivation by antithrombin-independent inhibitors. Circulation. 1998;97:544–552
  32. Becker DL, Fredenburgh JC, Stafford AR, Weitz JI. Exosites 1 and 2 are essential for protection of fibrin-bound thrombin from heparin-catalyzed inhibition by antithrombin and heparin cofactor II. J Biol Chem. 1999;274:6226–6233
  33. Barzu T, Molho P, Tobelem G, et al.  Binding and endocytosis of heparin by human endothelial cells in culture. Biochim Biophys Acta. 1985;845:196–203
  34. Young E, Prins M, Levine MN, Hirsh J. Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb Haemost. 1992;67:639–643
  35. Fuster V, Badimon L, Badimon JJ, et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 1992;326:242–250
  36. Mutch NJ, Robbie LA, Booth NA. Human thrombi contain an abundance of active thrombin. Thromb Haemost. 2001;86:1028–1034
  37. White CJ, Ramee SR, Collins TJ, et al.  Coronary thrombi increase PTCA risk. Circulation. 1996;93:253–258
  38. Anand SS, Yusuf S, Pogue P, et al.  Relationship of activated partial thromboplastin time to coronary events and bleeding in patients with acute coronary syndromes who receive heparin. Circulation. 2003;107:2884–2888
  39. Cohen M. The role of low-molecular-weight heparin in the management of acute coronary syndromes. J Am Coll Cardiol. 2003;41(4 suppl S):55S–61S
  40. Eikelboom J, White H, Yusuf S. The evolving role of direct thrombin inhibitors in acute coronary syndromes. J Am Coll Cardiol. 2003;41(4 suppl S):70S–78S
  41. Kleiman NS, Weitz JI. Putting heparin into perspective: its history and the evolution of its use during percutaneous coronary interventions. J Invasive Cardiol. 2000;12(suppl F):20F–26F
  42. Cornelli U, Fareed J. Human pharmacokinetics of low molecular weight heparins. Semin Thromb Hemost 1999;(suppl 3):57–61
  43. Harenberg J. Pharmacology of low molecular weight heparins. Semin Thromb Hemost 1990;(suppl 16):12–8
  44. Brufatto N, Ward A, Nesheim ME. Factor Xa is highly protected from antithrombin-fondaparinux and antithrombin-enoxaparin when incorporated into the prothrombinase complex. J Thromb Haemost. 2003;1:1258–1263
  45. Moliterno DJ, Hermiller JB, Kereiakes DJ, et al.  A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention. J Am Coll Cardiol. 2003;42:1132–1139
  46. Cohen M, Theroux P, Borzak S, et al.  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. Am Heart J. 2002;144:470–477
  47. Goodman SG, Fitchett D, Armstrong PW, et al.  Randomized evaluation of the safety and efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non–ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Circulation. 2003;107:238–244
  48. Ferguson JJ, Antman EM, Bates ER, et al.  Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes. Am Heart J. 2003;146:628–634
  49. Blazing MA, de Lemos JA, Dyke CK, et al.  The A-to-Z Trial: methods and rationale for a single trial investigating combined use of low-molecular weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy. Am Heart J. 2001;142:211–217
  50. Blazing MA, de Lemos JA, White HD, et al. Safety and efficacy of enoxaparin vs unfractured 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
  51. Young JJ, Kereiakes DJ, Grines CL, et al.  Low-molecular-weight heparin therapy in percutaneous coronary intervention. J Invasive Cardiol. 2000;12(suppl E):E14–18
  52. Collet JP, Montalescot G, Lison L, et al.  Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris. Circulation. 2001;103:658–663
  53. Kereiakes DJ, Montalescot G, Antman EM, et al.  Low-molecular-weight heparin therapy for non-ST-elevation acute coronary syndromes and during percutaneous coronary intervention: an expert consensus. Am Heart J. 2002;144:615–624
  54. Ferguson JJ, Califf RM, Antman EM, et al.  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
  55. Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost. 1999;82:165–174
  56. Brummel KE, Paradis SG, Butenas S, Mann KG. Thrombin functions during tissue factor–induced blood coagulation release and factor XIII activation. Blood. 2002;100:148–152
  57. Ashby CR, Daniel JL, Kunapuli SP, Smith JB. Platelet stimulatory and inhibitory receptors. In:  Colman RW editors. Hemostasis and Thrombosis. 4th edition. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001;p. 505–520
  58. Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol. 2002;22:1381–1389
  59. Colman R, Clowes A, James G. Overview of hemostasis. In:  Colman RW editors. Hemostasis and Thrombosis. 4th edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2001;p. 3–16
  60. Bittl JA, Chaitman BR, Feit F, et al.  Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina. Am Heart J. 2001;142:952–959
  61. Lincoff AM, Bittl JA, Harrington RA, et al.  Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention. JAMA. 2003;289:853–863
  62. Weitz JI, Bates ER. Direct thrombin inhibitors in cardiac disease. Cardiovasc Toxicol. 2003;3:13–25
  63. Maraganore JM, Adelman BA. Hirulog: a direct thrombin inhibitor for management of acute coronary syndromes. Coron Artery Dis. 1996;7:438–448
  64. Henry TD. Overcoming heparin limitations in high-risk percutaneous coronary intervention: the alternative strategy: replacing heparin with bivalirudin. J Invasive Cardiol 2002;(14 suppl B):19B–29B
  65. Bittl JA, Strony J, Brinker JA, et al.  Treatment with bivalirudin (hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. N Engl J Med. 1995;333:764–769
  66. Bittl JA, Feit F. A randomized comparison of bivalirudin and heparin in patients undergoing coronary angioplasty for postinfarction angina. Am J Cardiol. 1998;82:43P–49P
  67. Fuchs J, Cannon C. Hirulog in the treatment of unstable angina. Circulation. 1995;92:727–733
  68. Antman EM, McCabe CH, Braunwald E. Bivalirudin as a replacement for unfractionated heparin in unstable angina/non-ST-elevation myocardial infarction. Am Heart J. 2002;143:229–234
  69. Kong DF, Topol EJ, Bittl JA, et al.  Clinical outcomes of bivalirudin for ischemic heart disease. Circulation. 1999;100:2049–2053
  70. Roe MT, Christenson RH, Ohman EM, et al.  A randomized, placebo-controlled trial of early eptifibatide for non-ST-segment elevation acute coronary syndromes. Am Heart J. 2003;146:993–998
  71. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995;57:289–300
  72. Antman EM, Cohen M, Bernink PJ, et al.  The TIMI risk score for unstable angina/non-ST elevation MI. JAMA. 2000;284:835–842

PII: S0002-8703(04)00281-9

doi: 10.1016/j.ahj.2004.04.036

American Heart Journal
Volume 148, Issue 5 , Pages 764-775 , November 2004

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