Randomized Trial of Low Molecular Weight Heparin (Dalteparin) in Prevention of Left Ventricular Thrombus Formation and Arterial Embolism After Acute Anterior Myocardial Infarction: The Fragmin in Acute Myocardial Infarction (FRAMI) Study - FRAMI

Description:

The goal of this study was to assess the safety and efficacy of dalteparin in the prevention of left ventricular (LV) thrombus formation and arterial embolism among patients with acute anterior myocardial infarction (MI).

Hypothesis:

Dalteparin, a low molecular weight heparin, would be associated with a reduction of LV thrombus formation and arterial embolism when administered to patients following an acute anterior MI.

Study Design

Study Design:

Patients Enrolled: 776
Mean Follow Up: 9 ± 2 days
Female: 27

Patient Populations:

History and electrocardiographic changes consistent with an evolving anterior ST-segment elevation MI (i.e., Q waves or ST-segment elevation ≥1 mm in leads I and aVL or ≥2 mm in any two or more contiguous precordial leads)

Exclusions:

Previous anterior MI, infarct site other than anterior, time from onset of symptoms to start of study treatment >15 hours, ongoing treatment with or indication for heparin or warfarin, systolic blood pressure >210 mm Hg, diastolic blood pressure >115 mm Hg, cerebrovascular events within the previous two months, known allergy to dalteparin, peptic ulcer, known bleeding disorders, serious liver or renal failure, pregnancy, neoplastic or concomitant life-threatening diseases, alcohol abuse, and simultaneous participation in another clinical trial

Primary Endpoints:

The primary endpoint of the FRAMI study was the composite of LV thrombus and arterial embolus on day 9 ± 2 after acute anterior MI.

Secondary Endpoints:

Secondary endpoints were LV thrombus, arterial embolism, reinfarction, total mortality, cardiovascular mortality, major hemorrhage (i.e., cerebrovascular or any bleeding requiring transfusion or surgical intervention), minor hemorrhage, allergic reactions, and thrombocytopenia.

Drug/Procedures Used:

Eligible patients were randomized to receive dalteparin (150 IU/kg total body weight every 12 hours injected subcutaneously in the abdominal area) or placebo. The scheduled treatment period was 9 ± 2 days. The treatment was started eight hours after thrombolytic therapy. In patients who did not receive thrombolytics, the study treatment was started immediately after randomization.

Concomitant Medications:

In patients with no contraindications and symptoms for ≤6 hours, streptokinase (1.5 x 106 IU/h) was administered. Soluble aspirin (300 mg) was given orally on admission and 160 mg/day subsequently.

During the study period, no other antithrombotic agents were allowed by protocol. After the study period, patients deemed to be at high risk for thromboembolic events were initiated on warfarin therapy.

Principal Findings:

The combined primary endpoint of LV thrombus and arterial embolism occurred more frequently in the placebo group than the dalteparin group (21.9% vs. 14.2%, p=0.003). The incidence of LV thrombus was higher in the placebo group than the dalteparin group (21.9% vs. 13.8%, p=0.22). There was not a significant difference between placebo and dalteparin in the observed incidence of ischemic stroke (1.3% vs. 1.0%, p=NS).

Major hemorrhage was more common in patients treated with dalteparin than placebo (2.9% vs. 0.3%, p=0.006), as was minor hemorrhage (13.4% vs. 2.1%, P<0.001). The mortality rates in the two groups were identical (5.9%). Additionally, there was no significant difference between placebo and dalteparin in reinfarction rates (2.1% vs. 1.6%, p=NS).

Interpretation:

Among patients with acute anterior MI, dalteparin was associated with a reduction in LV thrombus formation compared to placebo. Dalteparin was associated with a significant increase in both major and minor bleeding complications. There was not a significant difference between patients treated with dalteparin and placebo in the occurrence of arterial embolic events, reinfarction rates, or mortality.

These findings suggest that dalteparin therapy significantly reduces the incidence of LV thrombus formation in patients with acute anterior MI, but is also associated with a significant increase in both major and minor bleeding complications.

References:

Kontny F, Dale J, Abildgaard U, Pedersen TR. Randomized trial of low molecular weight heparin (dalteparin) in prevention of left ventricular thrombus formation and arterial embolism after acute anterior myocardial infarction: the Fragmin in Acute Myocardial Infarction (FRAMI) Study. J Am Coll Cardiol 1997;30:962-9.

Clinical Topics: Anticoagulation Management

Keywords: Thrombolytic Therapy, Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Streptokinase, Thrombosis, Body Weight, Dalteparin, Embolism


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