Treatment Of Proximal Venous Thrombosis Research Articles

Fixed-dose, Body Weight-independent Subcutaneous LMW Heparin versus Adjusted Dose Unfractionated Intravenous Heparin in the Initial Treatment of Proximal Venous Thrombosis

Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism. Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee. The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02). Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis.

Treatment of Venous Thromboembolism with Low-Molecular-Weight Heparin.

There is now ample evidence to indicate that certain low-molecular-weight heparins given subcutaneously can replace continuous intravenous unfractionated heparin for the initial treatment of venous thromboembolism. The low-molecular-weight heparins have a predictably high absorption rate when given subcutaneously and a prolonged duration of action, permitting them to be given by a once or twice daily injection for the prevention or treatment of venous thrombosis. Furthermore, treatment does not require laboratory monitoring, thus eliminating the need for continuous IV infusion and permitting the early discharge of patients with venous thromboembolism. This should eventually lead to the outpatient treatment of venous thromboembolism. Studies to date indicate that low-molecular-weight heparin is more cost-effective than unfractionated heparin in the treatment of venous thromboembolism and the cost effectiveness will be increased by out-of-hospital treatment. At the present time, the findings associated with any individual low-molecular-weight heparin preparation cannot be extrapolated to different low-molecular-weight heparins, and therefore each must be evaluated in separate clinical trials. The information to date is that low-molecular-weight heparin is safer and more effective than continuous intravenous unfractionated heparin in the treatment of proximal venous thrombosis. The decreased mortality rate seen in two clinical trials, particularly in patients with metastatic cancer, was quite unexpected. This requires further confirmation in larger prospective randomized trials.

Low molecular weight heparin treatment of venous thromboembolism

T HE ACCEPTED standard treatment for acute deep vein thrombosis (DVT) is initial continuous intravenous heparin~,2, 3 followed by long-term oral anticoagulant therapy. 4-s It has been possible to perform a series of randomized clinical trials to evaluate the various approaches to treatment of venous thrombosis, because accurate objective tests have become available to detect venous thromboembolism (VTE) 9-13 and the methodology for clinical trials has improved. Almost all of the uncertainties confronted by clinicians in the selection of an appropriate course of anticoagulant therapy have been resolved by these clinical trials, vs It has become common clinical practice to adjust the heparin dose to maintain the activated partial thromboplastin time (APT]?) within a defined therapeutic range, ie, between 1.5 and 2.5 times control. To prevent unacceptably high rates of recurrent VTE, adequate initial hepatin treatment, as judged by the APTT response, is required, a,5 The use of an APTT ratio of 1.5 as the lower limit of the therapeutic range is supported by data from clinical trials. ~,~4 The relative risk for recurrence of VTE was 15 to 1 for patients receiving inadequate initial heparin treatment (APTT ratio, < 1.5). 1 These findings were strongly supported by a more recent randomized trial comparing intravenous heparin and oral anticoagulants with oral anticoagulants alone for the initial treatment of proximal venous thrombosis. ~5 Recurrent VTE occurred in 20% of patients treated with oral anticoagulants alone compared with 6% for those who received initial intravenous heparin adjusted to maintain the APTT above 1.5 times control. Most of the symptomatic recurrences occurred after the first month of treatment. In contrast to the strong association between the subtherapeutic APTT response and recurrent VTE, evidence supporting the use of an upper limit of the therapeutic range is weak. The use of a heparin protocol assures that virtually all patients (98% to 99%) will achieve the therapeutic range for the APTT, thereby decreasing the likelihood of recurrent VTE. Using this protocol, many patients will have APTT values greater than 2.5 times control during their course of therapy. Review of the bleeding complications associated with this trial indicated that major bleeding occurred most frequently in patients because of the presence of underlying causes for bleeding (eg, recent surgery, peptic ulcer disease, and cancer) rather than as a result of an elevated APTT) 4 These findings show a lack of an association between the supratherapeutic APTT result (ratio, 2.5 or more) and the risk of clinically important bleeding complications. Recently, trials have shown that the duration of initial heparin therapy can be shortened from 10 to 14 days to approximately 5 days. 7,8 In an era of fiscal constraint, short-course heparin allows effective treatment without detracting from patient care and, by shortening the inhospital stay, offers a substantial financial bene fit. 16 If an approach for the initial treatment of proximal vein thrombosis is developed that can be administered on an outpatient basis and does not require laboratory monitoring, it would markedly simplify treatment and improve costeffectiveness. A conservative estimate of the number of hospital days that would be saved by an outpatient approach to initial therapy is 5 to 6 days. It has been estimated that such a decrease in the duration of hospitalization would result in savings to the health care system of at least 500 million dollars annually in the United States alone. 16 A number of randomized trials have compared the effectiveness and safety of heparin administered by the subcutaneous and continu-

Low-molecular-weight heparins for the treatment of venous thromboembolism.

Recent studies have indicated that certain low-molecular-weight heparins given subcutaneously may replace continuous intravenous unfractionated heparin for the treatment of venous thromboembolism. Low-molecular-weight heparins have a predictably high absorption rate when given subcutaneously and they do not require laboratory monitoring. These characteristics of low-molecular-weight heparin therapy raise the possibility of treating uncomplicated patients with deep venous thrombosis or pulmonary embolism in the outpatient setting. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient low-molecular-weight heparin will likely prove to be highly cost-effective. At the present time, the finding associated with an individual low-molecular-weight heparin preparation cannot be extrapolated to different low-molecular-weight heparins and each must be evaluated in separate clinical trials. Recent randomized clinical trials indicate that low-molecular-weight heparin may be safer and more effective than continuous intravenous unfractionated heparin in the treatment of proximal venous thrombosis. A decreased mortality rate, which was particularly striking in patients with metastatic carcinoma, was unexpected and requires confirmation in further prospective randomized trials.

Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis: Hull RD, Raskob GE, Rosenbloom D, et al N Engl J Med 322:1260–1264 May 1990

Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis: Hull RD, Raskob GE, Rosenbloom D, et al N Engl J Med 322:1260–1264 May 1990

Heparin for 5 Days as Compared with 10 Days in the Initial Treatment of Proximal Venous Thrombosis

It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin, with warfarin added on day 5 to 10 and continued for several months. We performed a randomized, double-blind trial comparing a shorter course of continuous intravenous heparin (5 days, with warfarin sodium begun on the first day) with the conventional 10-day course of heparin (with warfarin sodium begun on the fifth day) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography. The frequency of objectively documented recurrent venous thromboembolism was low and essentially the same in the two groups (7.1 percent in the short-course group vs. 7.0 percent in the long-course group). Because the observed difference between the groups was 0.1 percent in favor of the long-course group, it is unlikely (P less than 0.05) that a true difference in favor of this group would be greater than 7.5 percent; the difference could be as much as 7.3 percent in favor of the short-course group. Major bleeding episodes were infrequent, and the rate was similar in both groups. We conclude that a five-day course of heparin is as effective as a 10-day course in treating deep venous thrombosis. Furthermore, using the shorter course would permit earlier discharge from the hospital and thus offer substantial cost savings.

A cost-effectiveness analysis of alternative approaches for long-term treatment of proximal venous thrombosis

A cost-effectiveness analysis of alternative approaches for long-term treatment of proximal venous thrombosis

A Cost-effectiveness Analysis of Alternative Approaches for Long-term Treatment of Proximal Venous Thrombosis

Recent data from randomized trials have provided a clear understanding of the effectiveness and safety of differing long-term anticoagulant therapies for proximal vein thrombosis. An issue that has not been addressed is their cost-effectiveness. We have performed a cost-effectiveness analysis to rank alternative approaches for long-term therapy. Less intense oral anticoagulant therapy using warfarin sodium is the most cost-effective approach and is preferred in the majority of patients.