Self-managed long-term low-molecular-weight heparin therapy: the balance of benefits and harms.

PURPOSE: 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 (LMWH), body-weight adjusted, avoids anticoagulant monitoring and may be associated with less bleeding. We evaluated the effectiveness and safety of long-term LMWH compared with vitamin K antagonist therapy in a broad spectrum of patients with proximal vein thrombosis. METHODS: We performed a multicenter, randomized, open-label clinical trial using objective outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and 12 months. RESULTS: Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%) receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1-2.4). Hemorrhagic complications occurred less frequently in the LMWH group largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of 368 patients (19.8%) receiving usual-care anticoagulation (absolute difference -6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by day 23, P = .034) for patients receiving LMWH but persisted throughout the study treatment interval for patients receiving vitamin K antagonist therapy. No mortality advantage was shown for LMWH. CONCLUSION: Our study shows that LMWH is similar in effectiveness to the usual-care vitamin K antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians' therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.

Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer.

PURPOSE: A substantial clinical need exists for an alternative to vitamin K antagonists for treating deep-vein thrombosis in cancer patients who are at high risk of both recurrent venous thromboembolism and bleeding. Low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and has been shown to be more effective than vitamin-K-antagonist therapy. SUBJECTS AND METHODS: Subjects were patients with cancer and acute symptomatic proximal-vein thrombosis. We performed a multi-centre randomized, open-label clinical trial using objective outcome measures comparing long-term therapeutic tinzaparin subcutaneously once daily with usual-care long-term vitamin-K-antagonist therapy for 3 months. Outcomes were assessed at 3 and 12 months. RESULTS: Of 200 patients, 100 received tinzaparin and 100 received usual care. At 12 months, the usual-care group had an excess of recurrent venous thromboembolism; 16 of 100 (16%) versus 7 of 100 (7%) receiving low-molecular-weight heparin (P=.044; risk ratio=.44; absolute difference -9.0; 95% confidence interval [CI], -21.7 to -0.7). Bleeding, largely minor, occurred in 27 patients (27%) receiving tinzaparin and 24 patients (24%) receiving usual care (absolute difference -3.0; 95% CI, -9.1 to 15.1). In patients without additional risk factors for bleeding at the time of randomization, major bleeding occurred in 0 of 51 patients (0%) receiving tinzaparin and 1 of 48 patients (2.1%) receiving usual care. Mortality at 1 year was high, reflecting the severity of the cancers; 47% in each group died. CONCLUSION: Our findings confirm the limited but benchmark data in the literature that long-term low-molecular-weight heparin is more effective than vitamin-K-antagonist therapy for preventing recurrent venous thromboembolism in patients with cancer and proximal venous thrombosis.

Quantitative assessment of thrombus burden predicts the outcome of treatment for venous thrombosis: a systematic review.

PURPOSE: Clot-burden change in patients receiving anticoagulant therapy, by predicting subsequent recurrent venous thromboembolism, may provide a clinically relevant surrogate endpoint of prognostic importance. The validity of this objective measure is yet to be established. METHODS: A PubMed search was performed to retrieve articles published up to December 2003. We identified 11 randomized trials reported from 1990 to 2003 that met our study identification and selection criteria. Anticoagulant therapy subsequently approved by regulatory affairs was assessed by clot-burden change and the validated outcome measure, long-term venous thromboembolism. Two additional randomized trials, partly meeting the inclusion criteria, were included in the sensitivity analysis. RESULTS: Individual studies suggested a predictive relationship between clot-burden change and likelihood of recurrent venous thromboembolism irrespective of the particular anticoagulant. The summary treatment effects strongly favored the therapy under evaluation and were in harmony for improved clot-burden (relative risk 0.82; 95% CI, 0.76-0.88; P <0.001) and for recurrent venous thromboembolism (relative risk 0.56; 95% CI, 0.42-0.76; P <0.001). The aggregate data show a striking predictive correlation for clot-burden change and subsequent recurrent venous thromboembolism using meta-regression analysis; (correlation = 0.81, P = 0.005) validating quantitative clot-burden assessment. CONCLUSION: Clot-burden change predicts long-term outcome, providing clinically relevant, patient-specific prognostic findings that may guide duration of anticoagulant therapy as well as provide a valid surrogate endpoint for clinical trials of innovative antithrombotic therapy, allowing more efficient trials exposing far fewer patients to the hazards of ineffective therapy than is required for outcome studies. Noninvasive assessment (duplex ultrasonography) of clot-burden change is currently being deployed for use in clinical trials.