Using Enoxaparin as Adjunctive Antithrombin Therapy Reduces Death and MI
Using Enoxaparin as Adjunctive Antithrombin Therapy Reduces Death and MI
Aims: To determine the relationship between a strategy of enoxaparin (ENOX), early ST-segment resolution (STRes), and clinical outcomes on patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolysis.
Methods and results: Baseline and 180 min ECGs were analysed in 3208 of the 20 479 patients in the ExTRACT-TIMI 25 trial, which randomifzed patients with STEMI to ENOX vs. unfractionated heparin (UFH) as adjunctive therapy. STRes was defined as complete (70%), partial (30-70%), or none (<30%). There was no evidence for a difference in STRes between the groups assigned to the ENOX or UFH (median 69.4 vs. 67.2%; P = 0.13). Among patients with complete STRes (n = 1100), ENOX significantly reduced death or non-fatal recurrent MI at 30 days when compared with UFH (4.4 vs. 9.9%; ORadj 0.39; P < 0.001), whereas there was no difference in patients with only partial or no STRes [14.2 vs. 12.5%; ORadj 1.0; P = 0.98 (n = 368) and 16.2 vs. 15.9%; ORadj 1.0; P = 0.97 (n = 830), P for interaction = 0.008].
Conclusion: When compared with UFH, a strategy of ENOX significantly reduces death or non-fatal recurrent MI in patients who achieved complete STRes, but not in patients with less STRes. These data suggest that a strategy of ENOX improves outcomes by preventing re-occlusion in patients achieving initial successful reperfusion after fibrinolytic therapy rather than by facilitating initial reperfusion.
Treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI) centers on achieving early coronary reperfusion and maintaining arterial patency. The resolution of ST-segment elevation (STRes) on serial ECGs is a simple non-invasive surrogate for epicardial and myocardial reperfusion. Patients who achieve complete STRes have an improved short- and long-term prognosis. Fibrinolysis, the most frequently utilized reperfusion strategy world-wide, achieves reperfusion as detected by angiography and complete STRes on ECG in more than half of the patients. Re-occlusion of the infarct artery after initial successful reperfusion, leading to a recurrent myocardial infarction (MI), is associated with an almost three-fold increase in mortality. Therefore, maintaining patency of the infarct-related artery after fibrinolysis may be expected to reduce adverse clinical outcomes, in particular, among patients who achieved early patency.
In the ExTRACT-TIMI 25 trial, patients with STEMI were treated with fibrinolysis. An antithrombin strategy of enoxaparin (ENOX) administered for the duration of hospitalization resulted in an improved net clinical benefit (death, non-fatal recurrent MI, or major bleeding) when compared with the standard strategy of unfractionated heparin (UFH) administered for 48 h. This benefit may have been mediated by two potential mechanisms. First, as suggested by smaller studies, the combined anti-Xa and anti-IIa activity of ENOX may facilitate fibrinolysis and improve the rate of early reperfusion. Alternatively, a strategy of ENOX may not improve initial fibrinolysis, but over the ensuing days may maintain patency in arteries that were initially reperfused. The ExTRACT-TIMI 25 ECG study was carried out in order to explore the mechanisms using early STRes as a marker of reperfusion after fibrinolysis and examining the clinical outcomes of enhanced antithrombotic treatment according to reperfusion status.
Abstract and Introduction
Abstract
Aims: To determine the relationship between a strategy of enoxaparin (ENOX), early ST-segment resolution (STRes), and clinical outcomes on patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolysis.
Methods and results: Baseline and 180 min ECGs were analysed in 3208 of the 20 479 patients in the ExTRACT-TIMI 25 trial, which randomifzed patients with STEMI to ENOX vs. unfractionated heparin (UFH) as adjunctive therapy. STRes was defined as complete (70%), partial (30-70%), or none (<30%). There was no evidence for a difference in STRes between the groups assigned to the ENOX or UFH (median 69.4 vs. 67.2%; P = 0.13). Among patients with complete STRes (n = 1100), ENOX significantly reduced death or non-fatal recurrent MI at 30 days when compared with UFH (4.4 vs. 9.9%; ORadj 0.39; P < 0.001), whereas there was no difference in patients with only partial or no STRes [14.2 vs. 12.5%; ORadj 1.0; P = 0.98 (n = 368) and 16.2 vs. 15.9%; ORadj 1.0; P = 0.97 (n = 830), P for interaction = 0.008].
Conclusion: When compared with UFH, a strategy of ENOX significantly reduces death or non-fatal recurrent MI in patients who achieved complete STRes, but not in patients with less STRes. These data suggest that a strategy of ENOX improves outcomes by preventing re-occlusion in patients achieving initial successful reperfusion after fibrinolytic therapy rather than by facilitating initial reperfusion.
Introduction
Treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI) centers on achieving early coronary reperfusion and maintaining arterial patency. The resolution of ST-segment elevation (STRes) on serial ECGs is a simple non-invasive surrogate for epicardial and myocardial reperfusion. Patients who achieve complete STRes have an improved short- and long-term prognosis. Fibrinolysis, the most frequently utilized reperfusion strategy world-wide, achieves reperfusion as detected by angiography and complete STRes on ECG in more than half of the patients. Re-occlusion of the infarct artery after initial successful reperfusion, leading to a recurrent myocardial infarction (MI), is associated with an almost three-fold increase in mortality. Therefore, maintaining patency of the infarct-related artery after fibrinolysis may be expected to reduce adverse clinical outcomes, in particular, among patients who achieved early patency.
In the ExTRACT-TIMI 25 trial, patients with STEMI were treated with fibrinolysis. An antithrombin strategy of enoxaparin (ENOX) administered for the duration of hospitalization resulted in an improved net clinical benefit (death, non-fatal recurrent MI, or major bleeding) when compared with the standard strategy of unfractionated heparin (UFH) administered for 48 h. This benefit may have been mediated by two potential mechanisms. First, as suggested by smaller studies, the combined anti-Xa and anti-IIa activity of ENOX may facilitate fibrinolysis and improve the rate of early reperfusion. Alternatively, a strategy of ENOX may not improve initial fibrinolysis, but over the ensuing days may maintain patency in arteries that were initially reperfused. The ExTRACT-TIMI 25 ECG study was carried out in order to explore the mechanisms using early STRes as a marker of reperfusion after fibrinolysis and examining the clinical outcomes of enhanced antithrombotic treatment according to reperfusion status.
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