Self-Managed Long-Term Low-Molecular-Weight Heparin Compared with Usual-Care Anticoagulation for Patients with Proximal Venous Thrombosis: Harm Associated with Bleeding!.

Context: A substantial clinical need exists for an alternate to vitamin-K-antagonists for treating deep-vein thrombosis in many patients. Long-term low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and may be associated with less harm due to bleeding. Objective: Considerable evidence suggests that reporting of harms-related data* from randomized clinical trials needs improvement. In accordance with CONSORT* we present a harm analysis regarding hemorrhagic complications. Design: Randomized clinical trial using objective outcome measures. Setting: 30 centres across Canada. Participants: Acute symptomatic proximal-vein thrombosis patients. Intervention: Therapeutic tinzaparin subcutaneously once-daily, or usual-care intravenous unfractionated heparin/vitamin-K-antagonists for 3 months. Main Outcome Measures: Benefit was assessed by assessing the frequency of symptomatic objectively documented recurrent venous thromboembolism and harm by objectively documented hemorrhagic complications. Results: A broad-spectrum of patients was randomized. Of 737 patients, 18 of 369 receiving tinzaparin (4.9 percent) suffered recurrent venous thromboembolism at three months compared with 21 of 368 (5.7 percent) receiving usual-care; (absolute difference, −0.9 percent, 95 percent confidence interval −4.1 to 2.4). Hemorrhagic complications occurred less frequently in the low-molecular-weight heparin group; 48 of 369 patients, (13.0 percent) versus usual-care 73 of 368, (19.8 percent), (absolute difference −6.8 percent; p=0.011; risk ratio = 0.66). The prevalence of major bleeding according to the duration of study treatment favored low-molecular-weight heparin therapy. Major bleeding persisted throughout study treatment for patients in the usual-care group receiving warfarin but ceased early by day 23 in the low-molecular-weight heparin group (p=0.034). Twenty-five patients (6.8 percent) in the low-molecular-weight heparin group and 24 patients (6.5 percent) receiving usual-care died (absolute difference 0.3 percent, 95 percent confidence interval −3.4 to 3.9). Conclusion: Our findings are clinically relevant and important, offering the clinician an alternate therapy to vitamin-K-antagonist therapy which does not require anticoagulant monitoring in a wide range of patients with proximal venous thrombosis. Self-management with once-daily subcutaneous tinzaparin was at least as effective as usual-care and vitamin-K-antagonist therapy and offers a safety advantage with less harm due to bleeding.