Low molecular weight heparin in the treatment of patients with venous thromboembolism - COLUMBUS
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).
Fixed-dose, subcutaneous LMWH is at least as efficacious as intravenous (IV), adjusted-dose unfractionated heparin (UFH) in patients with symptomatic VTE.
Patients Screened: 1,745
Patients Enrolled: 1,021
NYHA Class: NA
Mean Follow Up: 12 weeks
Mean Patient Age: >17 years
Mean Ejection Fraction: NA
Patients with acute, symptomatic DVT, PE, or both who required anticoagulation
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
Objectively confirmed symptomatic deep-vein thrombosis (DVT) or PE and major bleeding within 12 weeks of randomization
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.
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
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).
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.
The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997;337:657-62.
Clinical Topics: Anticoagulation Management, Dyslipidemia, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, Lipid Metabolism, Statins
Keywords: Pyrroles, Heparin, Low-Molecular-Weight, Thromboplastin, Pulmonary Embolism, Partial Thromboplastin Time, Warfarin, Heparin, Venous Thromboembolism, Heptanoic Acids, Nomograms
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