Efficacy and safety of enoxaparin in unselected patients with ST-segment elevation myocardial infarction

Summary

In randomized clinical trials the low-molecular-weight heparin enoxaparin has been shown to reduce ischemic complications in patients with acute ST elevation myocardial infarction (STEMI) treated with fibrinolysis. Little is known about the use and efficacy of enoxaparin in unselected patients with STEMI in clinical practice. In a retrospective analysis of the prospective ACOS registry we compared the outcomes of patients with STEMI treated with enoxaparin or unfractionated heparin. A total of 6,299 patients with STEMI < 12 hours were included in this analysis, 609 (10%) were treated with enoxaparin and 5,690 (90%) with unfractionated heparin. In the multivariable propensity score analysis enoxaparin was associated with a reduction in the combined endpoint of death and non-fatal reinfarction in the entire group (odds ratio 0.59; 95% CI 0.43–0.80) and the subgroups of patients treated without early reperfusion (odds ratio 0.65, 95% CI 0.43–0.97), fibrinolysis (odds ratio 0.64; 95% CI 0.33–1.26) and primary percutaneous coronary intervention (odds ratio 0.33;95% CI 0.15–0.72).There was no significant increase in severe bleeding complications with enoxaparin (6.5% versus 5.5%, p=0.4). In clinical practice in unselected patients with STEMI treated with or without early reperfusion therapy early treatment with enoxaparin compared to unfractionated heparin is associated with a significant reduction of the combined endpoint of inhospital death and reinfarction without a significant increase in severe bleeding complications.

Keywords

Acute myocardial infarction - thrombolysis / thrombolytic agents - clinical trials - heparins / LMWH

• References

• 1 Van de Werf F, Ardissino D, Betriu A. et al. Task Force on theManagement of Acute Myocardial Infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on theManagement of Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 2003; 24: 28-66.
• 2 Antman EM, Anbe DT, Armstrong PW. et al. American College of Cardiology; American Heart AssociationTask Force on Practice Guidelines; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of theAmerican College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients withAcute Myocardial Infarction). Circulation 2004; 110: e82-292.
• 3 Hirsh J. Heparin. N Engl J Med 1991; 324: 1565-1574.
• 4 Hirsh J, Warketin TE, Slaughnessy Sg. et al. Heparin and low molecular weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy and safety. Chest 2001; 119: 64S-94S.
• 5 Baird SH, Menown IB, McBride SJ. et al. Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. Eur Heart J 2002; 23: 627-632.
• 6 Ross AM, Molhoek P, Lundergan C. et al. Randomized comparison of enoxaparin, a low-molecularweight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin andAspirin Reperfusion Therapy (HART II). Circulation 2001; 104: 648-652.
• 7 The ASSENT-3 Investigators.. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: theASSENT-3 randomised trial in acute myocardial infarction. Lancet 2001; 358: 605-613.
• 8 Wallentin L, Goldstein P, Armstrong PW. et al. Efficacy and safety of tenecteplase in combinationwith the low-molecular-weight heparin enoxaparin in the prehospital setting. The ASSENT-3 PLUS randomized trial in acute myocardial infarction. Circulation 2003; 108: 135-142.
• 9 Eikelboom JW, Quinlan DJ, Metha SR. et al. Unfractionated and low-molecular-weight heparin as adjuncts to thrombolysis in aspirin-treated patients with ST-elevation acute myocardial infarction: a metaanalysis of the randomized trials. Circulation 2005; 112: 3855-3867.
• 10 Antman EM, Morrow DA, McCabe CH. et al. Enoxaparin versus unfractionated heparin as antithrombin therapy in patients receiving fibrinolysis for ST-elevation myocardial infarction. Design and rationale for the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25). Am Heart J 2005; 149: 217-226.
• 11 Antman EM, Morrow DA, McCabe CH. et al. Enoxaparin versus unfractionated heparin with thrombolysis for ST-elevation myocardial infarction. N Engl J Med 2006; 354: 1477-1488.
• 12 Zeymer U, Senges J. Qualitätsregister in der Kardiologie. Bundesgesundheitsbl-Gesundheitsforsch- Gesundheitsschutz 2004; 47: 533-539.
• 13 Morrow DA, Antman EM, Charlesworth A. et al. TIMI Risk Score for ST-elevation myocardial infarction: A convenient, bedside, clinical score for risk assessment at presentation. Circulation 2000; 102: 2031.
• 14 Welsh RC, Gordon P, Westerhout CM. et al. Anovel enoxaparin regimen for ST-elevation myocardial infarctionpatients undergoing primary percutaneous coronary intervention: intravenous but not subcutaneous enoxaparin achieves adequate anti-Xa levels. JAmColl Cardiol 2006; 47 A 228A (Abstract).
• 15 The ADVANCE MI Investigators.. Facilitated percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: results from the prematurely terminated Adressing the Value of facilitated Angioplasty after combination therapy or Eptifibatide monotherapy in acute Myocardial infarction trial (ADVANCE MI) trial. Am Heart J 2005; 150: 116-122.
• 16 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.
• 17 Montelascot G, White HD, Gallo R. et al. Enoxaparin versus unfractionated heparin in elecetive percutaneous coronary intervention. NEnglJMed 2006; 355: 1006-1017.