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Will the arrival of new oral anticoagulants such as dabigatran and rivaroxaban cause a rapid phase-out of the use of warfarin?
Yes.
In the next few years, there will be a shift from warfarin to the new anticoagulants.
In the countries where dabigatran and rivaroxaban are approved for orthopedic surgery prophylaxis, it is already having an effect. The big advantage is that it is currently recommended to extend prophylaxis beyond the standard 14-day period, up to 35 days and beyond, if there are continuing risk factors. The practicality of the administration of oral drugs that do not require monitoring is a big clinical advantage.
Where we see the most dramatic results, though, is in atrial fibrillation. In the RE-LY study, with 18,000 patients, two doses of dabigatran were compared with warfarin. The higher dose of 150 mg twice daily showed superiority in comparison with warfarin for stroke and systemic embolism, with the same bleeding rate.
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The lower dose showed equivalence, with less bleeding. Both the doses showed a reduction in the risk of intracranial bleeding, which is an important observation in that setting.
Patients and health professionals alike have all been seeking an alternative to warfarin. Although warfarin is an effective drug, it does have limitations, and from a practical point of view, it is difficult to use.
If you survey patients in anticoagulant clinics, they are all eagerly awaiting the new drugs. They appreciate that the new drugs are likely to be much more practical, without the requirement of monitoring.
If I were to predict what would happen, I think that patients who are currently stable on warfarin for long-term indications, such as atrial fibrillation, will continue warfarin. However, some patients will request the use of the new drugs because they are fed up with the monitoring and all the other restrictions associated with warfarin use — the limitations with other drug usage, and food, for example.
I think that in new patients starting long-term anticoagulants, doctors will, in fact, prescribe the new drugs if there is not a cost limitation.
Alexander G. Turpie, MD, is a Professor Emeritus at McMaster University in Hamilton, Ontario, Canada.
No.
I am hopeful that the development of novel anticoagulant agents will mean that patients at risk for thromboembolic disease will be able to take medicines that are more effective, safer or less burdensome than vitamin K antagonists. Data from phase-3 clinical trials are promising, and I would guess that at least one of these new oral agents will be available in the United States within the next 12 to 18 months. That notwithstanding, I do not expect warfarin to disappear quickly.
As one tries to imagine the transition from warfarin to newer anticoagulant agents, it is worth remembering that vitamin K antagonists are inexpensive, highly effective and time-tested. Indeed, agents such as warfarin have been used in clinical practice for longer than 50 years. In addition, I would contend that, during the last 15 to 20 years, vitamin K antagonists have been rendered safer and more user-friendly. The development and widespread implementation of the international normalized ratio, the proliferation of anticoagulation management services (or “clinics”) and the use of low-dose oral vitamin K have undoubtedly reduced the number of warfarin-treated patients who experience major bleeding. The arrival of point-of-care machines, which permit patients to monitor their international normalized ratio level more frequently, regardless of whether they are at home or traveling, has substantially mitigated the inconvenience traditionally associated with warfarin therapy.
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I do not expect that most patients who have been taking a stable dose of warfarin for a long time will switch to a new anticoagulant immediately after it hits the market. Instead, I see the greatest potential benefit of these agents in two populations: those who are on warfarin but have erratic international normalized ratio values and those who would benefit from anticoagulation but choose not to take it because the necessary international normalized ratio monitoring is not feasible for some reason.
Assuming the cost is not prohibitive, I suspect that most patients who are starting anticoagulant therapy de novo will choose one of the new agents rather than warfarin. On the other hand, warfarin will remain the only acceptable strategy for patients with mechanical heart valves for the foreseeable future. Furthermore, whether these novel agents will be safe and effective in special populations (eg, obese patients, patients with cancer or significant renal insufficiency) remains to be seen. Finally, it is difficult to predict how clinicians will respond to an agent that has no evidence-based reversal strategy and for which no standardized monitoring technique is available.
David A. Garcia, MD, is an Associate Professor, Division of Hematology/Oncology, University of New Mexico Health Sciences Center in Albuquerque.