The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and Safety of Tenecteplase in Combination With Enoxaparin, Abciximab, or Unfractionated Heparin: The ASSENT-3 Randomized Trial in Acute MI - ASSENT 3

Description:

The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 is a randomized trial that compared the efficacy and safety of tenecteplase plus enoxaparin or abciximab, with that of tenecteplase plus weight-adjusted unfractionated heparin (UFH) in patients with acute myocardial infarction (AMI).

Hypothesis:

Is the combination of tenecteplase plus enoxaparin or abciximab as safe and efficacious as tenecteplase plus weight-adjusted UFH in patients with AMI?

Study Design

Study Design:

Drug/Procedures Used:

Patients with AMI <6 hours (n=6,095) were randomly assigned to one of three regimens: full-dose tenecteplase and enoxaparin for a maximum of seven days (enoxaparin group, n=2,040), half-dose tenecteplase with weight-adjusted low-dose UFH and a 12-hour infusion of abciximab (abciximab group, n=2,017), or full-dose tenecteplase with weight-adjusted UFH for 48 hours (UFH group, n=2,038).

Principal Findings:

There were significantly fewer efficacy endpoints (composites of 30-day mortality, in-hospital reinfarction, or in-hospital refractory ischemia) in the enoxaparin and abciximab groups than in the UFH group: 233/2,037 (11.4%) vs. 315/2,038 (15.4%; relative risk 0.74 [95% confidence interval 0.63-0.87], p=0.0002) for enoxaparin and 223/2,017 (11.1%) vs. 315/2,038 (15.4%; 0.72 [0.61-0.84], p<0.0001) for abciximab. Similarly, the efficacy plus safety endpoint (in-hospital intracranial hemorrhage or in-hospital major bleeding complications) were significantly lower for the enoxaparin group, and trended to be lower in the abciximab group compared with the UFH group: 280/2,037 (13.7%) vs. 347/2,036 (17.0%; 0.81 [0.70-0.93], p=0.0146) for enoxaparin, and 287/2016 (14.2%) vs. 347/2036 (17.0%; 0.84 [0.72-0.96], p=0.057) for abciximab.

Among patients over the age of 75, the risk of the composite endpoint of efficacy and safety was worse in the abciximab group compared to the heparin group: 36.9% versus 28.0% (p=0.001), but not in the enoxaparin group (25.5%). Likewise, among diabetics, the risk of the composite endpoint of efficacy and safety was worse in the abciximab group relative to the heparin group: 22.3% versus 16.5%, p=0.0007, but not in the enoxaparin group (13.9%). The rates of major hemmorrhage were increased in the abciximab group relative to the heparin group (4.3% vs. 2.2%, p=0.0002), but were not increased significantly in the enoxaparin group (3.0%, p=NS vs. heparin). Thirty-day mortality was lowest in the enoxaparin group (5.4%), and is the lowest in a major thrombolytic trial reported to date.

The tenecteplase plus enoxaparin or abciximab regimens reduce the frequency of ischemic complications in AMI patients. Tenecteplase plus enoxaparin seems to be an attractive alternative reperfusion regimen because of the simplicity of administration, and warrants further study.

Interpretation:

The combination of the fibrin-specific agent tenecteplase with enoxaparin was more efficacious than tenecteplase with heparin, and there was no increase in the risk of bleeding or intracranial hemorrhage, even in the elderly patients over the age of 75.

In contrast, while efficacy was improved with the combination of tenecteplase plus abciximab, this was offset by a doubling in the rate of major hemorrhage, and a higher event rate in patients over the age of 75 and in diabetic patients. Tenecteplase plus enoxaparin is a viable alternative regimen to tenecteplase plus UFH for the treatment of ST elevation AMI.

References:

Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 2001;358:605-13.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism

Keywords: Risk, Myocardial Infarction, Hospital Mortality, Platelet Aggregation Inhibitors, Heparin, Immunoglobulin Fab Fragments, Fibrinolytic Agents, Intracranial Hemorrhages, Enoxaparin, Confidence Intervals, Tissue Plasminogen Activator, Fibrin, Diabetes Mellitus


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