Anti-coagulation (AC) therapy with heparins followed by oral vitamin K-antagonists is recommended after deep venous thrombosis (DVT) and pulmonary embolism. The bleeding risk is related to the duration and intensity of AC therapy. A target INR of 2.0-3.0 is as effective as high-intensity AC therapy with target INR of 3.0-4.5 and causes less bleeding (1). This intensity of AC therapy is usually recommended after DVT or pulmonary embolism. Recommended duration of therapy is: 1) in patients with reversible or time-limited risk factors: 3 months of AC therapy, 2) first episode of idiopathic venous thrombo-embolism: at least 6 months 3) recurrent idiopathic venous thrombo-embolism or long-term risk factors: 12 months or life-long (2). In case persistent DVT and verified on a duplex scan after e.g. 6 months of therapy, one might consider prolonged AC therapy. Initiation of AC therapy with a loading dose is often used. However, this approach does not necessarily bring the therapy more quickly into the therapeutic range.
Recently, Ridker and co-workers assessed the effects of low intensity warfarin (target INR 1.5-2.0) in patients with idiopathic venous thrombo-embolism (3). The 508 patients were all treated with full-dose AC therapy for at least 6 months (median 6.5 month) and then randomised to low-intensity warfarin or placebo and followed for up to 4.3 years (median 2.1 years). In the placebo group, 37 developed recurrent venous thrombo-embolism (7.2 per 100 person-years) as compared with 14 in the low-intensity warfarin group (2.6 per 100 person-year) – a risk reduction of 64% (p<0.001). Major bleeding occurred in two patients in the placebo vs. five patients in the low intensity warfarin group (p=0.25). Low intensity warfarin was associated with a 48% reduction in the composite end point recurrent venous thrombo-embolism, major haemorrhage or death.
Preliminary data from Kearon et al shows that initial low-intensity warfarin (target INR 1.5-1.9) is significantly less effective than conventional-intensity warfarin (target INR 2.0-3.0) (4). Therefore, it seems appropriate to wait for the publication of more trials. While waiting for such trials initial therapy with target INR 2.0-3.0 for at least 6 months followed by low intensity AC therapy might be an option in some patients. Also, new drugs like oral thrombin inhibitors should be tested in this setting.
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