Argatroban for Acute Myocardial Infarction - ARGAMI-2

Description:

Argatroban with thrombolytic therapy for acute myocardial infarction.

Hypothesis:

To evaluate thrombolytic therapy with argatroban for acute myocardial infarction.

Study Design

Study Design:

Patients Screened: 1,200
Patients Enrolled: 1,001

Patient Populations:

Adult patients

Within 6 hours of onset of chest pain > 30 min

ECG showing ST-segment elevation in 2 or more leads.

Exclusions:

CNS events

Chronic illness

Elevated creatinine

Patients at risk for bleeding events.

Primary Endpoints:

30-day total cardiovascular events.

Drug/Procedures Used:

Two doses of argatroban (60 µg + 2 µg /kg/min or 120 µg + 4 µg /kg/min for 72 hours) vs. heparin (5000 IU + 1000 IU/hour for 72 hours) with dose adjustment to achieve target aPTT of 55-85 seconds.

Concomitant Medications:

Simultaneous tPA (≤100 mg accelerated 90 minute regimen) or streptokinase (1.5 million units for 1 hour). All patients received 200 mg/day aspirin unless contraindicated.

Principal Findings:

Patients enrolled in the low-dose argatroban arm (n=199) were withdrawn from the study. The final analysis included 494 patients receiving high-dose argatroban and 507 patients on heparin. These 2 groups were well-matched at baseline.

At 30 days, both regimens were equally effective with no statistically significant difference in total cardiovascular events, mortality, recurrent MI, heart failure/cardiogenic shock, need for revascularization, or stroke. The incidence of major bleeding, intracranial hemorrhage, and stroke was less in the argatroban group.

Target aPTT was more frequently achieved in the high dose argatroban group (p<0.05).

Maintaining aPTT was easier with argatroban; only 35% of argatroban patients had an aPTT value below 55 seconds at 24 hours compared to 68% in the heparin group.

Interpretation:

Argatroban is a new fast-acting synthetic thrombin inhibitor derived from arginine (Coron Art Dis 1996;7:455-58). The safety profile, as revealed in the original ARGAMI trial, suggests argatroban may have some advantages over heparin in select patients following myocardial infarction (MI). Although no statistically significant differences were detected between the argatroban and heparin groups, the trial was not designed to test for equivalence. Direct thrombin inhibitors may possess meaningful safety advantages over unfractionated heparin. Whether these potential advantages are cost-effective will require further clinical trials.

References:

1. Circulation 1998;98(Suppl I):I-453-4. Final results

Clinical Topics: Anticoagulation Management, Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Novel Agents, Acute Heart Failure

Keywords: Thrombolytic Therapy, Myocardial Infarction, Stroke, Thrombin, Heparin, Coronary Disease, Shock, Cardiogenic, Pipecolic Acids, Intracranial Hemorrhages, Chest Pain, Heart Failure, Partial Thromboplastin Time


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