Efficacy and Safety of Tenecteplase in Combination With the Low-Molecular-Weight Heparin Enoxaparin or Unfractionated Heparin in the Prehospital Setting

Abstract

Background-The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial infarction. Methods and Results-In the prehospital setting, 1639 patients with ST-elevation myocardial infarction were randomly assigned to treatment with tenecteplase and either (1) intravenous bolus of 30 mg enoxaparin (ENOX) followed by 1 mg/kg subcutaneously BID for a maximum of 7 days or (2) weight-adjusted unfractionated heparin (UFH) for 48 hours. The median treatment delay was 115 minutes after symptom onset (53% within 2 hours). ENOX tended to reduce the composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia to 14.2% versus 17.4% for UFH (Pϭ0.080), although there was no difference for this composite end point plus in-hospital intracranial hemorrhage or major bleeding (18.3% versus 20.3%, Pϭ0.30). Correspondingly, there were reductions in in-hospital reinfarction (3.5% versus 5.8%, Pϭ0.028) and refractory ischemia (4.4% versus 6.5%, Pϭ0.067) but increases in total stroke (2.9% versus 1.3%, Pϭ0.026) and intracranial hemorrhage (2.20% versus 0.97%, Pϭ0.047). The increase in intracranial hemorrhage was seen in patients Ͼ75 years of age. Conclusions-Prehospital fibrinolysis allows 53% of patients to receive reperfusion treatment within 2 hours after symptom onset. The combination of tenecteplase with ENOX reduces early ischemic events, but lower doses of ENOX need to be tested in elderly patients. At present, therefore, tenecteplase and UFH are recommended as the routine pharmacological reperfusion treatment in the prehospital setting.

Low-Molecular-Weight Heparins in Conjunction with Thrombolysis for ST-Elevation Acute Myocardial Infarction

“…Significant bleeding was comparable in the two treatment groups (3 vs. 4%). In the ASSENT-3 PLUS study [30,] a comparable effect of enoxaparin or UFH on the same efficacy and safety end-points as in ASSENT-3 trial was shown. By analyzing the individual components of the end points, a reduction of in-hospital reinfarction (4 vs. 6%; p = 0.03) and refractory ischemia (4 vs. 7%; p = 0.07) rates was observed, at the cost however of an increase in total stroke (3 vs. 2%; p = 0.03) and intracranial hemorrhage (2 vs. 1%; p = 0.05) with enoxaparin.…”

“…Of all the studies identified, 12 fulfilled criteria for analysis, including 26,831 patients overall [21,22,23,24,25,26,27,28,29,30,31,32]. LMWH evaluated in these studies were dalteparin, enoxaparin and reviparin.…”

“…Out of the eight trials (9,945 patients) evaluating enoxaparin [24,25,26,27,28,29,30,31], thrombolysis was carried out with streptokinase in three [24, 29, 31], with tenecteplase in another three [26, 27, 30], with alteplase in one [25], and with tenecteplase or streptokinase or anistreplase in another one [28]. In a single study, no anti-platelet therapy with aspirin was given until day 4 [28].…”

“…In general, however, a favorable effect with LMWH is observed. Relative to the clinical efficacy end-points, a trend towards a positive effect of dalteparin, enoxaparin and reviparin is apparent, not only in comparison to placebo [21, 22, 24, 29, 32], but also to UFH [23,26,27,28, 30, 31]. More in detail, mortality rates were not significantly affected by the treatment with LMWH (although it has to be noted that none of the studies was neither designed nor sized to detect such a difference), while the occurrence of reinfarction and recurrent ischemia/angina was, in general, favorably influenced.…”

The evolution of recombinant thrombolytics: Current status and future directions

“…90 Owing to its slow clearance rate, a single bolus regimen can be administered simplifying its application outside of a hospital setting. 91 The third point mutation with alanine, from residues 296-299, provides 80-fold higher resistance against inhibition by PAI-1. The molecule also possesses 14-fold enhanced fibrin specificity than t-PA but comparable fibrin-binding affinity and plasma clot lysis activity in vivo.…”