Treatment for DVT and PE has historically involved anticoagulation with intravenous unfractionated heparin initially, followed by long-term oral anticoagulation. The initial treatment has been revolutionized by the introduction of low-molecular-weight heparin (LMWH) preparations. For an excellent review of treatment modalities and duration of therapy, see The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy (16).

Adequate anticoagulation decreases the risk of recurrent venous thromboembolism by 80%, from a range of 29% to 47% untreated, to a range of 5% to 7% treated (17). During adequate anticoagulant therapy—at least 5 days of heparin and 3 months of oral anticoagulation (International Normalized Ratio, 2.0 to 4.5), LMWH, or adjusted-dose subcutaneous unfractionated heparin—the risk of fatal PE is low: 0.4% and 0.3% during and after treatment for DVT and 1.5% and 0 during and after treatment for PE (18). Anticoagulation with standard heparin must be achieved rapidly, and it has been shown that if therapeutic levels are reached in the first 24 hours, the recurrence rate is lower than if therapeutic levels are not reached in the first 24 hours (level I evidence) (19). Continuous intravenous unfractionated heparin is better than intermittent subcutaneous standard heparin for thromboembolism recurrence (level I evidence).

After heparin is begun, what are guidelines for its use? Heparin administration for 5 days has been compared with that for 10 days, and no difference in recurrent thrombosis has been found (7.1% vs. 7.0%, level I evidence) (20). Oral anticoagulants are begun at maintenance dosing, rather than loading dosing, to decrease the chances of warfarin-induced skin necrosis. Studies (all level I evidence) have evaluated the length of optimal oral anticoagulant therapy. In comparisons of 6 weeks to 6 months of warfarin (Coumadin), the recurrence rate was 18.1%
versus 9.5% in favor of longer treatment at 2-year follow-up (21). Another study compared 4 weeks with 3 months of treatment in medical patients; the recurrence rate for 4 weeks was 7.8%, in comparison with 4.0% with 3 months of treatment (22). A third study suggested that oral anticoagulants should be used for longer rather than shorter periods, especially with continuing risk factors (23). The usual recommendation is for a 3- to 6-month period of oral anticoagulation after a first DVT. For example, with reversible or time-limited risk factors and a first thromboembolic event, treatment for 3 to 6 months is recommended, whereas for an idiopathic cause and a first event, treatment for at least 6 months is recommended (24). Natural history studies suggest that after a first DVT, the risk of recurrent thrombosis is 17.5% at 2 years, 25% at 5 years, and 30% at 8 years (25). However, the prognosis after DVT is variable. If DVT is triggered by an isolated event (e.g., trauma or surgery), the risk of recurrence after an adequate course of anticoagulant therapy is low. If DVT occurs in the setting of persistent risk factors, the risk of recurrence is high.

The optimal duration of warfarin therapy after DVT depends on clinical circumstances (Table 32.4). In general, patients with a first episode of venous thrombosis should receive warfarin for 3 to 6 months. Patients with a second episode of venous thromboembolism have a significantly lower rate of recurrence if they receive warfarin indefinitely (2.6% risk during 4 years of follow-up) as opposed to 6 months (20.7% risk of recurrence). However, this therapy exposes the patient to a higher risk of bleeding complications (26). Prospective clinical trials addressing the optimal duration of warfarin therapy in patients with a first episode of DVT and an irreversible risk factor considered to place the patient at high risk of recurrence (e.g., malignancy, identifiable thrombophilia such as factor V Leiden) are lacking. Each patient must be considered individually, the duration of therapy depending on the relative bleeding and thrombotic risks.

Idiopathic DVT is an interesting problem. Most authorities believe that true idiopathic thrombosis requires more than 6 months of warfarin. A recent multicenter trial suggested that, after 6 months of therapy, low-dose warfarin at an INR of 1.5 to 2.0 should be used, based on a 64% risk reduction for recurrent DVT after the initial 6 months of standard warfarin therapy (level 1 evidence) (27). However, a second study in a similar group of patients found that full-dose warfarin at an INR 2.0 to 3.0 was superior to low-dose warfarin without a difference in bleeding (level 1 evidence) (28). Thus for idiopathic DVT, extended warfarin is indicated, the length still to be determined. Current guidelines suggest 6 to 12 months for idiopathic DVT (16).