Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel.

Abstract

OBJECTIVES:

The purpose of this study was to determine the efficacy and safety of enoxaparin (ENOX) versus unfractionated heparin (UFH) in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy with and without clopidogrel.

BACKGROUND:

The efficacy and safety of ENOX and clopidogrel given together in STEMI remains to be defined.

METHODS:

We compared the rates of major adverse cardiovascular events (MACE) as well as the rates of bleeding in medically managed patients randomized to ENOX versus UFH in the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial, stratified by concomitant clopidogrel use.

RESULTS:

Enoxaparin significantly reduced the rate of the composite of death, recurrent myocardial infarction, myocardial ischemia, or stroke, compared with UFH, both in patients (n = 2,173) treated with clopidogrel (10.8% vs. 13.9%, adjusted odds ratio [OR(adj)] 0.70, p = 0.013) and in patients (n = 12,918) not treated with clopidogrel (13.3% vs. 15.3%, OR(adj) 0.85, p = 0.003) with no evidence of heterogeneity (p(interaction) = 0.21). The excess risk of TIMI major bleeding with ENOX versus UFH was numerically but not statistically significantly higher in patients treated with clopidogrel (2.7% vs. 1.0%) versus those who were not (2.1% vs. 1.2%) (p(interaction) = 0.61). Net clinical benefit (MACE and major bleeding) favored treatment with ENOX over UFH, either with concomitant clopidogrel (absolute risk reduction 2.4%, 95% confidence interval [CI] -0.5% to 5.3%) or without (absolute risk reduction 1.7%, 95% CI 0.5% to 3.0%) (p(interaction) = 0.61).

CONCLUSIONS:

In patients with STEMI receiving fibrinolytic therapy, the net benefit of ENOX is similar in patients who are and are not treated with clopidogrel. The totality of trial data suggest that the combination of a fibrinolytic, aspirin, clopidogrel, and ENOX offers an attractive pharmacologic reperfusion strategy in STEMI.

• Authors: Marc S Sabatine, David A Morrow, Anthony Dalby, Mathias Pfisterer, Tibor Duris, Jose Lopez-Sendon, Sabina A Murphy, Runlin Gao, Elliott M Antman, Eugene Braunwald, ExTRACT-TIMI 25 Investigators
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 49 Issue 23 Pg. 2256-63 (Jun 12 2007) ISSN: 1558-3597 [Electronic] United States
• PMID: 17560290 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Enoxaparin
• Fibrinolytic Agents
• Platelet Aggregation Inhibitors
• Heparin
• Clopidogrel
• Ticlopidine

Topics

• Aged
• Clopidogrel
• Double-Blind Method
• Drug Therapy, Combination
• Enoxaparin (adverse effects, therapeutic use)
• Female
• Fibrinolytic Agents (adverse effects, therapeutic use)
• Heparin (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Myocardial Infarction (drug therapy)
• Platelet Aggregation Inhibitors (therapeutic use)
• Thrombolytic Therapy
• Ticlopidine (analogs & derivatives, therapeutic use)
• Treatment Outcome