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In Reply: We thank Dr. Jandali for his thoughtful comments on our article. We acknowledge that there may be a small subset of patients in whom low-intensity warfarin may be worth trying—such as patients with a history of idiopathic or recurrent venous thromboembolism in whom problematic (but not life-threatening) bleeding recurs—but only when the international normalized ratio (INR) is at the high end of the therapeutic range or slightly above it. However, when attempting to apply the results from PREVENT1 and ELATE2 to clinical practice and the management of anticoagulation after hemorrhage, it is important to note that in ELATE there was a higher incidence of recurrent thromboembolism in patients on lower-intensity anticoagulation than in those on conventional treatment, and no significant difference in major bleeding was noted between the high- and low-intensity groups.
We acknowledge, though, that the rates of major bleeding were surprisingly low in the high-intensity group in this study relative to historical controls and so may not apply to all patients.
It is also important to recognize that several studies have evaluated low-intensity dosing for stroke prophylaxis in atrial fibrillation with generally disappointing results, and at present, expert opinion continues to support a therapeutic INR goal of 2.0 to 3.0.3
Therefore, we believe that low-intensity warfarin treatment is only appropriate to try in a very small subset of carefully selected patients with a history of venous thromboembolism who have proven that they cannot tolerate full-dose warfarin and in whom a trial of low-dose warfarin treatment carries acceptable risk.
- Ridker PM, Goldhaber SZ, Danielson E, et al; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348:1425–1434.
- Kearon C, Ginsberg JS, Kovacs MJ, et al; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349:631–639.
- Holbrook A, Schulman S, Witt DM, et al; American College of Chest Physicians. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(suppl 2):e152S–e184S.
In Reply: We thank Dr. Jandali for his thoughtful comments on our article. We acknowledge that there may be a small subset of patients in whom low-intensity warfarin may be worth trying—such as patients with a history of idiopathic or recurrent venous thromboembolism in whom problematic (but not life-threatening) bleeding recurs—but only when the international normalized ratio (INR) is at the high end of the therapeutic range or slightly above it. However, when attempting to apply the results from PREVENT1 and ELATE2 to clinical practice and the management of anticoagulation after hemorrhage, it is important to note that in ELATE there was a higher incidence of recurrent thromboembolism in patients on lower-intensity anticoagulation than in those on conventional treatment, and no significant difference in major bleeding was noted between the high- and low-intensity groups.
We acknowledge, though, that the rates of major bleeding were surprisingly low in the high-intensity group in this study relative to historical controls and so may not apply to all patients.
It is also important to recognize that several studies have evaluated low-intensity dosing for stroke prophylaxis in atrial fibrillation with generally disappointing results, and at present, expert opinion continues to support a therapeutic INR goal of 2.0 to 3.0.3
Therefore, we believe that low-intensity warfarin treatment is only appropriate to try in a very small subset of carefully selected patients with a history of venous thromboembolism who have proven that they cannot tolerate full-dose warfarin and in whom a trial of low-dose warfarin treatment carries acceptable risk.
In Reply: We thank Dr. Jandali for his thoughtful comments on our article. We acknowledge that there may be a small subset of patients in whom low-intensity warfarin may be worth trying—such as patients with a history of idiopathic or recurrent venous thromboembolism in whom problematic (but not life-threatening) bleeding recurs—but only when the international normalized ratio (INR) is at the high end of the therapeutic range or slightly above it. However, when attempting to apply the results from PREVENT1 and ELATE2 to clinical practice and the management of anticoagulation after hemorrhage, it is important to note that in ELATE there was a higher incidence of recurrent thromboembolism in patients on lower-intensity anticoagulation than in those on conventional treatment, and no significant difference in major bleeding was noted between the high- and low-intensity groups.
We acknowledge, though, that the rates of major bleeding were surprisingly low in the high-intensity group in this study relative to historical controls and so may not apply to all patients.
It is also important to recognize that several studies have evaluated low-intensity dosing for stroke prophylaxis in atrial fibrillation with generally disappointing results, and at present, expert opinion continues to support a therapeutic INR goal of 2.0 to 3.0.3
Therefore, we believe that low-intensity warfarin treatment is only appropriate to try in a very small subset of carefully selected patients with a history of venous thromboembolism who have proven that they cannot tolerate full-dose warfarin and in whom a trial of low-dose warfarin treatment carries acceptable risk.
- Ridker PM, Goldhaber SZ, Danielson E, et al; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348:1425–1434.
- Kearon C, Ginsberg JS, Kovacs MJ, et al; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349:631–639.
- Holbrook A, Schulman S, Witt DM, et al; American College of Chest Physicians. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(suppl 2):e152S–e184S.
- Ridker PM, Goldhaber SZ, Danielson E, et al; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348:1425–1434.
- Kearon C, Ginsberg JS, Kovacs MJ, et al; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349:631–639.
- Holbrook A, Schulman S, Witt DM, et al; American College of Chest Physicians. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(suppl 2):e152S–e184S.