Abstract
Various therapies have been utilized for the treatment of unstable angina and non‐ST‐elevation myocardial infarction (NSTEMI). Each therapy has both advantages and disadvantages with regard to clinical outcomes and an increased risk of bleeding. One emerging primary therapy is low‐molecular‐weight heparin (LMWH). Concerns have emerged, however, over the use of LMWH in patients going to the catheterization laboratory or who receive platelet glycoprotein IIb/IIIa inhibitors. Available trial data point to the safety and efficacy of LMWH in these patients. Eventually, LMWH will probably replace unfractionated heparin (UFH) for the majority of patients with acute coronary syndromes (ACS). At present, however, practitioners need to consider individually how comfortable they are with the available data.
Keywords: acute coronary syndrome, aspirin, platelet glyco‐protein IIb/IIIa inhibitors, pentasaccharide, thienopyridines, thrombin inhibitors, unfractionated heparin
Full Text
The Full Text of this article is available as a PDF (80.1 KB).
References
- 1. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE III, Steward DE, Théroux P: ACC/AHA guideline update for the management of patients with unstable angina and non‐ST‐segment elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). Available at: http://www.acc.org/clinical/guidelines/unstable/unstable.pdf., 2002. [DOI] [PubMed]
- 2. Lewis HD Jr, Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE III, Schnaper HW, LeWinter MM, Linares E, Pouget JM, Sabharwal SC, Chester E, DeMots H: Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina: Results of a Veterans Administration Cooperative Study. N Engl J Med 1983; 309: 396–403 [DOI] [PubMed] [Google Scholar]
- 3. Cairns JA, Gent M, Singer J, Finnie KJ, Froggatt GM, Holder DA, Jablonsky G, Kostuk WJ, Melendez LJ, Myers MG: Aspirin, sulfinpyrazone, or both in unstable angina: Results of a Canadian multicenter trial. N Engl J Med 1985; 313: 1369–1375 [DOI] [PubMed] [Google Scholar]
- 4. Théroux P, Ouimet H, McCans J, Latour JG, Joly P, Levy G, Pelletier E, Juneau M, Stasiak J, deGuise P: Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988; 319: 1105–1111 [DOI] [PubMed] [Google Scholar]
- 5. RISC Group : Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet 1990; 336: 827–830 [PubMed] [Google Scholar]
- 6. Cohen M, Adams PC, Parry G, Xiong J, Chamberlain D, Wieczorck I, Fox KA, Chesebro J II, Strain J, Keller C, for the Antithrombotic Therapy in Acute Coronary Syndromes Research Group : Combination antithrombotic therapy in unstable rest angina and non‐Q wave infarction in nonprior aspirin users: Primary end points analysis from the ATACS trial. Circulation 1994; 89: 81–88 [DOI] [PubMed] [Google Scholar]
- 7. Gurfinkel EP, Manos EJ, Mejail RI, Cerda MA, Duronto EA, Garcia CN, Daroca AM, Mautner B: Low‐molecular‐weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. J Am Coll Cardiol 1995; 26: 313–318 [DOI] [PubMed] [Google Scholar]
- 8. Klein W, Buchwald A, Hillis SE, Monrad S, Sanz G, Turpie AG, van der Meer J, Olaisson E, Undeland S, Ludwig K: Comparison of low‐molecular‐weight 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). Circulation 1997; 96: 61–68 [DOI] [PubMed] [Google Scholar]
- 9. Comparison of two treatment durations (6 days and 14 days) of a low‐molecular‐weight heparin with a 6‐day treatment of unfrac‐tionated heparin in the initial management of unstable angina or non‐Q wave myocardial infarction : FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). Eur Heart J 1999; 20: 1553–1562 [DOI] [PubMed] [Google Scholar]
- 10. Cohen M, Demers C, Gurfinkel EP, Turpie AG, Fromell GJ, Goodman S, Langer A, Califf RM, Fox KA, Premmereur J, Bigonzi F: A comparison of low‐molecular‐weight 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 [DOI] [PubMed] [Google Scholar]
- 11. Antman EM, McCabe CH, Gurfinkel EP, Turpie AG, Bernink PJ, Salein D, Bayes De Luna A, Fox K, Lablanche JM, Radley D, Premmereur J, Braunwald E: Enoxaparin prevents death and cardiac ischemic events in unstable angina/non‐Q‐wave myocardial infarction. Results of the Thrombolysis In Myocardial Infarction (TIMI) 11B trial. Circulation 1999; 100: 1593–1601 [DOI] [PubMed] [Google Scholar]
- 12. Antman EM, Cohen M, Radley D, McCabe C, Rush J, Premmereur J, Braunwald E: Assessment of the treatment effect of enoxaparin for unstable angina/non‐Q‐wave myocardial infarction. TIMI 11B‐ESSENCE meta‐analysis. Circulation 1999; 100: 1602–1608 [DOI] [PubMed] [Google Scholar]
- 13. Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group : Low‐molecular‐weight heparin during instability in coronary artery disease. Lancet 1996; 347: 561–568 [PubMed] [Google Scholar]
- 14. FRagmin and Fast Revascularization during InStability in Coronary artery disease Investigators : Long‐term low‐molecular‐mass heparin in unstable coronary artery disease: FRISC II prospective randomized multicenter study. Lancet 1999; 354: 701–707 [PubMed] [Google Scholar]
- 15. Papamichael ND, Michalis LK, Katsouras CS, Adamidis K, Souria E, Sioros L, Papalambrakakoupoulos A, Goudevenos JA, Sideris DA, Novas J: Enoxaparin versus tinzaparin in unstable coronary syndromes. A head‐to‐head comparison (EVET trial) (abstr). Eur Heart J 2001; 22: 664 [Google Scholar]
- 16. Cohen M, Théroux P, Weber S, Laramee P, Huynh T, Borzak S, Diodati JG, Squire IB, Deckelbaum LI, Thornton AR, Harris KE, Sax FL, Lo MW, White HD: Combinations therapy with tirofiban and enoxaparin in acute coronary syndromes. Int J Cardiol 1999; 71: 273–281 [DOI] [PubMed] [Google Scholar]
- 17. Cohen M, Théroux P, Frey MJ, White HD, Borzak S, Weber S, Senatore F, Espenshade M, Mukherjee R, Thornton A, Bigonzi F, Sax FL: Anti‐thrombotic combination using tirofiban and enoxaparin: The ACUTE II Study (abstr). Circulation 2000; 102: II‐826 [Google Scholar]
- 18. Kaul S, Shah PK: Low‐molecular‐weight heparin in acute coronary syndrome: Evidence for superior or equivalent efficacy compared with unfractionated heparin? J Am Coll Cardiol 2000; 35: 1699–1712 [DOI] [PubMed] [Google Scholar]
- 19. Eikelboom JW, Anand SS, Malmberg K, Weitz JI, Ginsberg JS, Yusuf S: Unfractionated heparin and low‐molecular‐weight heparin in acute coronary syndrome without ST elevation: A meta‐analysis. Lancet 2000; 355: 1936–1942 [DOI] [PubMed] [Google Scholar]
- 20. The 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 [DOI] [PubMed] [Google Scholar]
- 21. PRISM‐PLUS study Investigators : Inhibition of the platelet glyco‐protein IIb/IIIa receptor with tirofiban in unstable angina and non‐Q wave myocardial infarction. N Engl J Med 1998; 338: 1488–1497 [DOI] [PubMed] [Google Scholar]
- 22. The CAPTURE Investigators : Randomised placebo‐controlled trial of abciximab before and during coronary intervention in refractory unstable angina: The CAPTURE study. Lancet 1997; 349: 2429–2435 [PubMed] [Google Scholar]
- 23. GUSTO IV‐ACS Investigators : Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularization: The GUSTO IV‐ACS randomized trial. Lancet 2001; 357: 1915–1924 [DOI] [PubMed] [Google Scholar]
- 24. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK: 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 [DOI] [PubMed] [Google Scholar]
- 25. Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, Copland I, Fox KA: Effects of pretreatment with clopidogrel and aspirin followed by long‐term therapy in patients undergoing percutaneous coronary intervention: The PCI‐CURE study. Lancet 2001; 358: 527–533 [DOI] [PubMed] [Google Scholar]
- 26. OASIS Investigators : Comparison of the effects of two doses of re‐combinant hirudin compared with heparin in patients with acute myocardial ischemia with ST elevation: A pilot study. Circulation 1997; 96: 769–777 [DOI] [PubMed] [Google Scholar]
- 27. OASIS Investigators : Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularization procedures in patients with acute myocardial ischemia without ST elevation: A randomized trial. Lancet 1999; 353: 429–438 [PubMed] [Google Scholar]
- 28. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIa Investigators : Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 1994; 90: 1631–1637 [DOI] [PubMed] [Google Scholar]
- 29. The GUSTO Investigators : A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes: The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb Investigators. N Engl J Med 1996; 335: 775–782 [DOI] [PubMed] [Google Scholar]
- 30. The Direct Thombin Inhibitor Trialists' Collaborative Group : Direct thrombin inhibitors in acute coronary syndromes: Principal results of a meta‐analysis based on individual patients' data. Lancet 2002; 359: 294–302 [DOI] [PubMed] [Google Scholar]
- 31. Simoons ML: Hot Line Session Oral Presentation, AHA; 2001. [Google Scholar]
- 32. Faxon DP, Spiro TE, Minor S, Coté G, Douglas J, Gottlieb R, Califf R, Dorosti K, Topol E, Gordon JB: Low‐molecular‐weight heparin in prevention of restenosis after angioplasty. Results of Enoxaparin Restenosis (ERA) Trial. Circulation 1994; 90: 908–914 [DOI] [PubMed] [Google Scholar]
- 33. Karsch KR, Preisack MB, Baildon R, Eschenfelder V, Foley D, Garcia EJ, Kaltenbach M, Meisner C, Selbmann HK, Serruys PW, Shiu MF, Sujatta M, Bonan R: Low‐molecular‐weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double‐blind, unfractionated heparin and placebo‐controlled, multicenter trial (REDUCE trial). Reduction of restenosis after PTCA, Early Administration of Reviparin in a Double‐Blind Unfractionated Heparin and Placebo‐Controlled Evaluation. J Am Coll Cardiol 1996; 28: 1437–1443 [DOI] [PubMed] [Google Scholar]
- 34. Kereiakes DJ, Grines C, Fry E, Esente P, Hoppensteadt D, Midei M, Barr L, Matthai W, Todd M. Broderick T, Rubinstein R, Fareed J, Santoian E, Neiderman A, Brodie B, Zidar J, Ferguson JJ, Cohen M: Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention. J Invas Cardiol 2001; 13: 272–278 [PubMed] [Google Scholar]
- 35. Ferguson JJ: Combining low‐molecular‐weight heparin and glyco‐protein IIb/IIIa antagonists for the treatment of acute coronary syndromes: The NICE 3 story. National Investigators Collaborating on Enoxaparin. J Invas Cardiol 2000; 12: E10–13 [PubMed] [Google Scholar]
- 36. Ferguson JJ, Antman EM, Bates ER, Cohen M, Every NR, Harrington RA, Pepine CJ, Théroux P, the Nice 3 Investigators: The use of enoxaparin and IIb/IIIa antagonists in acute coronary syndromes, including PCI: Final results of the NICE 3 study (abstr). J Am Coll Cardiol 2001; 37: Suppl A: 1A–648A 11153722 [Google Scholar]
- 37. Galeote G, Hussein M, Sobrino N, Calvo L, Yunda H, Sánchez‐Recalde A, Sobrino JA: Combination abciximab and enoxaparin or unfractionated heparin during percutaneous coronary intervention: A randomized study (abstr). Eur Heart J 2001; 22: 663 11286523 [Google Scholar]
- 38. Bhatt DL, Lincoff AM: Combined use of eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention: The results of the CRUISE trial. Circulation 2001; 104: II‐384–385 [Google Scholar]
- 39. Antman EM, Louwerenburg HW, Baars HF, Wesdorp JC, Hamer B, Bassand JP, Bigonzi F, Pisapia G, Gibson CM, Heidbuchel H, Braunwald E, Van de Werf F: Enoxaparin as adjunctive antithrombin therapy for ST‐elevation myocardial infarction: Results of the ENTIRE – Thrombolysis in Myocardial Infarction (TIMI) 23 trial. Circulation 2002; 105: 1642–1649 [DOI] [PubMed] [Google Scholar]
- 40. Goodman SG: Hot Line Session Oral Presentation, ACC; 2002. [Google Scholar]
- 41. Collet JP, Montalescot G, Lison L, Choussat R, Ankri A, Drobinski G, Sotirov I, Thomas D: Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris. Circulation 2001; 103: 658–663 [DOI] [PubMed] [Google Scholar]
- 42. Martin JL, Fry ETA, Serano A, Atherley TH, Ozoux MI, Gulmart C, Chevalier P, Bigonzi F, Pensyl C, Sanderink GJ: Pharmacokinetic study of enoxaparin in patients undergoing coronary intervention after treatment with subcutaneous enoxaparin in acute coronary syndromes: The PEPCI study (abstr). Eur Heart J 2001; 22: 14 11133204 [Google Scholar]
