Low molecular weight heparin in the treatment of patients with venous thromboembolism - COLUMBUS

Nov 17, 2003
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Date Published:
01/01/1997
Date Updated:
11/17/2003
Original Posted Date:
11/17/2003
References

Description:

The goal of this study was to assess the safety and efficacy of low molecular weight heparin (LMWH) among patients with recurrent venous thromboembolism (VTE) or pulmonary embolism (PE).

Hypothesis:

Fixed-dose, subcutaneous LMWH is at least as efficacious as intravenous (IV), adjusted-dose unfractionated heparin (UFH) in patients with symptomatic VTE.

Study Design

Study Design:

Patients Screened: 1,745
Patients Enrolled: 1,021
NYHA Class: NA
Mean Follow Up: 12 weeks
Mean Patient Age: >17 years
Female: 51%
Mean Ejection Fraction: NA

Patient Populations:

Patients with acute, symptomatic DVT, PE, or both who required anticoagulation

Exclusions:

Patients who received therapeutic doses of LMWH, UFH, or oral anticoagulant therapy for more than 24 hours; contraindications to oral anticoagulation therapy; planned thrombolytic therapy; gastrointestinal bleeding in the preceding 14 days; surgery requiring anesthesia within the previous three days; stroke in the preceding 10 days; platelet count <100,000 per cubic millimeter; weight <35 kg; age <18 years; documented pregnancy or childbearing potential, but not using adequate contraception; or living in a location that made follow-up difficult

Primary Endpoints:

Objectively confirmed symptomatic deep-vein thrombosis (DVT) or PE and major bleeding within 12 weeks of randomization

Secondary Endpoints:

Mortality

Drug/Procedures Used:

Patients were randomized to either fixed-dose, subcutaneous LMWH or IV, adjusted-dose UFH. Those in the LMWH arm received reviparin subcutaneously in fixed doses of: 6300 U twice daily for patients weighing more than 60 kg, 4200 U twice daily for those weighing 46-60 kg, and 3500 U twice daily for those weighing 35-45 kg.

Patients randomized to receive UFH received an IV bolus of 5000 IU followed by an infusion dose of 1250 IU per hour, which was adjusted by a nomogram to achieve an activated partial-thromboplastin time of 60-80 seconds or 1.5-2.5 times a control value. The study medications were continued until the patient was at a therapeutic dose of oral anticoagulation for two consecutive days, and the patient had received the study drug for at least five days.

Concomitant Medications:

Oral anticoagulation with a coumarin derivative, which was continued for a total of 12 weeks and titrated to an international normalized ratio of 2.0-3.0

Principal Findings:

The rates of recurrent thromboembolic events were equivalent between the two groups (5.3% for LMWH and 4.9% for UFH) based on the predetermined definition of equivalence (i.e., <2.7% difference between the two groups).

Additionally, there was no significant difference between LMWH and UFH in rates of major bleeding (3.1% vs. 2.3%, p=0.63) or mortality (7.1% vs. 7.6%, p=0.89).

Interpretation:

Among patients with VTE, fixed-dose subcutaneous LMWH was as effective as IV UFH in the initial treatment of VTE without a significant increase in the rate of major bleeding or mortality.

References:

The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997;337:657-62.

Keywords: Pyrroles, Heparin, Low-Molecular-Weight, Thromboplastin, Pulmonary Embolism, Partial Thromboplastin Time, Warfarin, Heparin, Venous Thromboembolism, Heptanoic Acids, Nomograms


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