Letters to the Editor
Long-Term Standard-Dose Warfarin to Prevent Thrombosis
Am Fam Physician. 2005 Jul 1;72(01):36-41.
to the editor: I read with interest the two-part article “DVT and Pulmonary Embolism”1,2 in American Family Physician, but would like to make a couple of corrections. Drs. Ramzi and Leeper state that a heart rate of less than 100 beats per minute merits a risk score of 1.5 in their adaptation of the Wells Clinical Prediction Rule for pulmonary embolus.1 In fact, tachycardia warrants a risk score of 1.5 points according to the Wells’ Rule.3
In their discussion on the optimum International Normalized Ratio (INR) at which to anticoagulate post-thromboembolism patients, the authors recommend titrating warfarin (Coumadin) dosage to achieve an INR of 2.0 to 3.0 for a duration recommended by the American College of Chest Physicians.2 This recommended minimum duration of treatment varies from three to 12 months based on the risk of recurrence. Referencing two studies4,5 the authors then state: “Attempts have been made to maintain patients at an even lower INR (between 1.5 and 2.0), but results have been contradictory. Unless further data show otherwise, anticoagulation with a standard INR goal of 2.0 to 3.0 should be used.”2 This statement requires some clarification. The studies referenced4,5 do not contradict standard warfarin protocol or suggest an amendment to the initial long-term anticoagulation management of venous thromboembolism mentioned in the article. The patients in both studies had already completed at least three months of conventional-dose (INR = 2.0 to 3.0) anticoagulation before being randomized to their respective treatment arms.
Ridker and colleagues4 demonstrated in a placebo-controlled trial that long-term (mean duration 2.1 years) low-intensity (INR = 1.5 to 2.0) warfarin therapy resulted in a large and significant reduction in the risk of recurrent venous thromboembolism with little evidence of increased risk of major hemorrhage or stroke. They conclude that long-term low-intensity anticoagulation is a highly effective method of preventing recurrent venous thromboembolism. Thus, one might infer that continued low-intensity long-term anticoagulation after an initial period of full-dose anticoagulation is superior to full-dose anticoagulation that is halted after three to 12 months.
Kearon and colleagues5 demonstrated that long-term (mean duration 2.4 years) low-intensity warfarin was significantly less effective than conventional-dose warfarin for the prevention of recurrent venous thromboembolism, and that low-intensity warfarin does not reduce the risk of clinically significant bleeding. They conclude that the intensity of anticoagulation therapy should not be lowered after three months of treatment and that long-term conventional-intensity warfarin therapy is highly effective in prevention of recurrent thrombosis and is associated with a low frequency of bleeding.
Ridker4 and Kearon and colleagues5 therefore agree that warfarin therapy for at least two years in patients with a history of idiopathic venous thromboembolism reduces the rate of recurrence without significantly increasing the risk of major bleeding, with Kearon and colleagues finding greater efficacy and no added risk using the conventional dose.
1. Ramzi DM, Leeper KV. DVT and pulmonary embolism: part I. Diagnosis [published correction appears in Am Fam Physician 2004;70:1455]. Am Fam Physician. 2004;69:2829–36.
2. Ramzi DM, Leeper KV. DVT and pulmonary embolism: part II. Treatment and prevention. Am Fam Physician. 2004;69:2841–8.
3. Fdullo PF, Tapson VF. The evaluation of suspected pulmonary embolism. N Engl J Med. 2003;349:1247–56.
4. Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003;348:1425–34.
5. Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003;349:631–9.
editor’s note: This letter was sent to the authors of “DVT and Pulmonary Embolism: Part I. Diagnosis,” who declined to reply.
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