Self-Testing Helps Stabilize Warfarin Therapeutic Range

CHICAGO ? The new oral anticoagulants for stroke prevention in atrial fibrillation may be garnering all the buzz, but don?t count out the old standby warfarin yet.

"It?s not just a knee-jerk reaction that all patients should be switched to the new agents. It?s dependent upon how well you as a physician are managing your patients on warfarin," Dr. Jack E. Ansell asserted at the annual meeting of the American College of Cardiology.

"Warfarin therapy is all about management. If it?s not managed well, you can compare it to anything, and anything is going to be better. And if it?s managed very well, then it?s very difficult to beat warfarin therapy," said Dr. Ansell, who is the chairman of the department of medicine at Lenox Hill Hospital in New York.

A growing body of evidence indicates that the new standard in high-quality management of warfarin therapy involves patient self-testing of International Normalized Ratios (INR) at home using a fingerstick blood sample and a portable point-of-care device.

As a case in point: Dr. Ansell presented highlights of the new STABLE study, in which he and his coinvestigators conducted a retrospective analysis of the real-world experience of more than 29,000 warfarin-treated patients enrolled in a national commercial comprehensive self-test support service. The study was reported in JACC 2012 March 27 [doi: 10.1016/S0735-1097(12)61865-8]).

Patients who performed frequent self-testing ? meaning more than 80% of their self-testing was done on a weekly basis ? had a mean time spent in the therapeutic INR range (TTR) of 74%. That?s unprecedented, he said.

By comparison, in the pivotal RE-LY randomized trial for dabigatran (Pradaxa), the control group on warfarin had a TTR of 64% (N. Engl. J. Med. 2009;361:1139-51). In the ROCKET-AF trial of rivaroxaban (Xarelto), warfarin controls had a TTR of 55% (N. Engl. J. Med. 2011;365:883-91). And in the ARISTOTLE study of apixaban (Eliquis), an agent expected to soon receive Food and Drug Administration marketing approval, the warfarin control group had a TTR of 62% (N. Engl. J. Med. 2011;365:981-92).

In all these major randomized trials involving the novel oral anticoagulants, patients assigned to warfarin were closely managed, but in traditional fashion ? home self-testing wasn?t involved.

In contrast, in the STABLE study, the overall TTR, including those patients who self-tested variably and inconsistently, was still 69.7%.

"This is important because the cost-effectiveness analyses done with dabigatran and the other new anticoagulants suggest that when you get up to a TTR above 70% with warfarin, the cost-effectiveness of the new agents diminishes and warfarin actually becomes more cost-effective," according to Dr. Ansell.

A particularly impressive finding in STABLE was that patients who did weekly self-testing had a 2.3% incidence of critical value INR results, defined as an INR below 1.5 or greater than 5.0. "This is really a phenomenally low result," he commented. It represented a 48% reduction from the 4.4% incidence in patients with variable self-testing frequency.

Participants in the STABLE study tested themselves at home, but their warfarin dosing was managed by their referring physicians or anticoagulation clinics. Thus, an individual?s TTR reflected the warfarin management expertise of the referral source.

There are several reasons why home monitoring achieves better TTRs and ? as shown in other studies ? lower major bleeding and thrombotic event rates than with usual care or anticoagulation clinics not utilizing patient self-monitoring, Dr. Ansell said.

Home testing is more frequent, timely, and consistent, and the immediate feedback regarding INR results is likely to promote adherence.

A variant of patient self-testing starting to catch on in the United States is patient self-management. This entails teaching patients how to manage their own warfarin dose on the basis of their home INR measurements.

The most recent American College of Chest Physicians clinical practice guidelines on antithrombotic therapy for atrial fibrillation give patient self-management of warfarin therapy a class 2B recommendation, stating, "For patients treated with vitamin K antagonists who are motivated and can demonstrate competency in self-management strategies, including the self-testing equipment, we suggest patient self-management rather than the usual outpatient INR monitoring" (CHEST 2012;141: 2 suppl. e531S-e575S [doi: 10.1378/chest.11-2304]).

Session cochair Dr. Samuel Z. Goldhaber agreed with Dr. Ansell that warfarin still has a place in anticoagulation therapy. The fact that it costs as little as $4 per month while dabigatran, for example, retails for 60 times that amount, is not to be shrugged off in an era of runaway health care spending, he said.

Plus, warfarin, for all its drawbacks, is a known quantity backed by more than a half century of clinical experience.

"Even though warfarin can cause horrible complications, there are no more surprises left about what warfarin can do," observed Dr. Goldhaber, who is a professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women?s Hospital, Boston.

A potential game changer for warfarin is the possibility that rapid pharmacogenetic testing will enable physicians to improve upon the current method of warfarin dosing.

One advantage warfarin has is that bleeding episodes can be reversed by administration of vitamin K. In contrast, there is as yet no reliable means of reversing major bleeding in patients on the novel anticoagulants. But Dr. Lars Wallentin said this limitation of the new agents is outweighed by the consistent finding that they have lower rates of intracranial hemorrhage than those of warfarin.

"There is no antidote to warfarin that has proven to have any effect in patients with ICH. And there is no evidence as far as I can see that however you control INR you can reach as low a level of ICH as with these new agents. I think this is a specific downside of warfarin that we can?t get away from," said Dr. Wallentin, who is a professor of cardiology at Uppsala (Sweden) University.

The STABLE study was funded by Alere Home Monitoring, Inc. Dr. Ansell is a consultant to the company.

Dr. Goldhaber has served as a consultant to numerous pharmaceutical companies developing cardiovascular medications.

Dr. Wallentin was principal investigator in the ARISTOTLE study of apixaban, funded by Pfizer and Bristol Myers Squibb, and has served as a consultant to those and other pharmaceutical companies.

CHICAGO ? The new oral anticoagulants for stroke prevention in atrial fibrillation may be garnering all the buzz, but don?t count out the old standby warfarin yet.

"It?s not just a knee-jerk reaction that all patients should be switched to the new agents. It?s dependent upon how well you as a physician are managing your patients on warfarin," Dr. Jack E. Ansell asserted at the annual meeting of the American College of Cardiology.

"Warfarin therapy is all about management. If it?s not managed well, you can compare it to anything, and anything is going to be better. And if it?s managed very well, then it?s very difficult to beat warfarin therapy," said Dr. Ansell, who is the chairman of the department of medicine at Lenox Hill Hospital in New York.

A growing body of evidence indicates that the new standard in high-quality management of warfarin therapy involves patient self-testing of International Normalized Ratios (INR) at home using a fingerstick blood sample and a portable point-of-care device.

As a case in point: Dr. Ansell presented highlights of the new STABLE study, in which he and his coinvestigators conducted a retrospective analysis of the real-world experience of more than 29,000 warfarin-treated patients enrolled in a national commercial comprehensive self-test support service. The study was reported in JACC 2012 March 27 [doi: 10.1016/S0735-1097(12)61865-8]).

Patients who performed frequent self-testing ? meaning more than 80% of their self-testing was done on a weekly basis ? had a mean time spent in the therapeutic INR range (TTR) of 74%. That?s unprecedented, he said.

By comparison, in the pivotal RE-LY randomized trial for dabigatran (Pradaxa), the control group on warfarin had a TTR of 64% (N. Engl. J. Med. 2009;361:1139-51). In the ROCKET-AF trial of rivaroxaban (Xarelto), warfarin controls had a TTR of 55% (N. Engl. J. Med. 2011;365:883-91). And in the ARISTOTLE study of apixaban (Eliquis), an agent expected to soon receive Food and Drug Administration marketing approval, the warfarin control group had a TTR of 62% (N. Engl. J. Med. 2011;365:981-92).

In all these major randomized trials involving the novel oral anticoagulants, patients assigned to warfarin were closely managed, but in traditional fashion ? home self-testing wasn?t involved.

In contrast, in the STABLE study, the overall TTR, including those patients who self-tested variably and inconsistently, was still 69.7%.

"This is important because the cost-effectiveness analyses done with dabigatran and the other new anticoagulants suggest that when you get up to a TTR above 70% with warfarin, the cost-effectiveness of the new agents diminishes and warfarin actually becomes more cost-effective," according to Dr. Ansell.

A particularly impressive finding in STABLE was that patients who did weekly self-testing had a 2.3% incidence of critical value INR results, defined as an INR below 1.5 or greater than 5.0. "This is really a phenomenally low result," he commented. It represented a 48% reduction from the 4.4% incidence in patients with variable self-testing frequency.

Participants in the STABLE study tested themselves at home, but their warfarin dosing was managed by their referring physicians or anticoagulation clinics. Thus, an individual?s TTR reflected the warfarin management expertise of the referral source.

There are several reasons why home monitoring achieves better TTRs and ? as shown in other studies ? lower major bleeding and thrombotic event rates than with usual care or anticoagulation clinics not utilizing patient self-monitoring, Dr. Ansell said.

Home testing is more frequent, timely, and consistent, and the immediate feedback regarding INR results is likely to promote adherence.

A variant of patient self-testing starting to catch on in the United States is patient self-management. This entails teaching patients how to manage their own warfarin dose on the basis of their home INR measurements.

The most recent American College of Chest Physicians clinical practice guidelines on antithrombotic therapy for atrial fibrillation give patient self-management of warfarin therapy a class 2B recommendation, stating, "For patients treated with vitamin K antagonists who are motivated and can demonstrate competency in self-management strategies, including the self-testing equipment, we suggest patient self-management rather than the usual outpatient INR monitoring" (CHEST 2012;141: 2 suppl. e531S-e575S [doi: 10.1378/chest.11-2304]).

Session cochair Dr. Samuel Z. Goldhaber agreed with Dr. Ansell that warfarin still has a place in anticoagulation therapy. The fact that it costs as little as $4 per month while dabigatran, for example, retails for 60 times that amount, is not to be shrugged off in an era of runaway health care spending, he said.

Plus, warfarin, for all its drawbacks, is a known quantity backed by more than a half century of clinical experience.

"Even though warfarin can cause horrible complications, there are no more surprises left about what warfarin can do," observed Dr. Goldhaber, who is a professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women?s Hospital, Boston.

A potential game changer for warfarin is the possibility that rapid pharmacogenetic testing will enable physicians to improve upon the current method of warfarin dosing.

One advantage warfarin has is that bleeding episodes can be reversed by administration of vitamin K. In contrast, there is as yet no reliable means of reversing major bleeding in patients on the novel anticoagulants. But Dr. Lars Wallentin said this limitation of the new agents is outweighed by the consistent finding that they have lower rates of intracranial hemorrhage than those of warfarin.

"There is no antidote to warfarin that has proven to have any effect in patients with ICH. And there is no evidence as far as I can see that however you control INR you can reach as low a level of ICH as with these new agents. I think this is a specific downside of warfarin that we can?t get away from," said Dr. Wallentin, who is a professor of cardiology at Uppsala (Sweden) University.

The STABLE study was funded by Alere Home Monitoring, Inc. Dr. Ansell is a consultant to the company.

Dr. Goldhaber has served as a consultant to numerous pharmaceutical companies developing cardiovascular medications.

Dr. Wallentin was principal investigator in the ARISTOTLE study of apixaban, funded by Pfizer and Bristol Myers Squibb, and has served as a consultant to those and other pharmaceutical companies.

CHICAGO ? The new oral anticoagulants for stroke prevention in atrial fibrillation may be garnering all the buzz, but don?t count out the old standby warfarin yet.

"It?s not just a knee-jerk reaction that all patients should be switched to the new agents. It?s dependent upon how well you as a physician are managing your patients on warfarin," Dr. Jack E. Ansell asserted at the annual meeting of the American College of Cardiology.

"Warfarin therapy is all about management. If it?s not managed well, you can compare it to anything, and anything is going to be better. And if it?s managed very well, then it?s very difficult to beat warfarin therapy," said Dr. Ansell, who is the chairman of the department of medicine at Lenox Hill Hospital in New York.

A growing body of evidence indicates that the new standard in high-quality management of warfarin therapy involves patient self-testing of International Normalized Ratios (INR) at home using a fingerstick blood sample and a portable point-of-care device.

As a case in point: Dr. Ansell presented highlights of the new STABLE study, in which he and his coinvestigators conducted a retrospective analysis of the real-world experience of more than 29,000 warfarin-treated patients enrolled in a national commercial comprehensive self-test support service. The study was reported in JACC 2012 March 27 [doi: 10.1016/S0735-1097(12)61865-8]).

Patients who performed frequent self-testing ? meaning more than 80% of their self-testing was done on a weekly basis ? had a mean time spent in the therapeutic INR range (TTR) of 74%. That?s unprecedented, he said.

By comparison, in the pivotal RE-LY randomized trial for dabigatran (Pradaxa), the control group on warfarin had a TTR of 64% (N. Engl. J. Med. 2009;361:1139-51). In the ROCKET-AF trial of rivaroxaban (Xarelto), warfarin controls had a TTR of 55% (N. Engl. J. Med. 2011;365:883-91). And in the ARISTOTLE study of apixaban (Eliquis), an agent expected to soon receive Food and Drug Administration marketing approval, the warfarin control group had a TTR of 62% (N. Engl. J. Med. 2011;365:981-92).

In all these major randomized trials involving the novel oral anticoagulants, patients assigned to warfarin were closely managed, but in traditional fashion ? home self-testing wasn?t involved.

In contrast, in the STABLE study, the overall TTR, including those patients who self-tested variably and inconsistently, was still 69.7%.

"This is important because the cost-effectiveness analyses done with dabigatran and the other new anticoagulants suggest that when you get up to a TTR above 70% with warfarin, the cost-effectiveness of the new agents diminishes and warfarin actually becomes more cost-effective," according to Dr. Ansell.

A particularly impressive finding in STABLE was that patients who did weekly self-testing had a 2.3% incidence of critical value INR results, defined as an INR below 1.5 or greater than 5.0. "This is really a phenomenally low result," he commented. It represented a 48% reduction from the 4.4% incidence in patients with variable self-testing frequency.

Participants in the STABLE study tested themselves at home, but their warfarin dosing was managed by their referring physicians or anticoagulation clinics. Thus, an individual?s TTR reflected the warfarin management expertise of the referral source.

There are several reasons why home monitoring achieves better TTRs and ? as shown in other studies ? lower major bleeding and thrombotic event rates than with usual care or anticoagulation clinics not utilizing patient self-monitoring, Dr. Ansell said.

Home testing is more frequent, timely, and consistent, and the immediate feedback regarding INR results is likely to promote adherence.

A variant of patient self-testing starting to catch on in the United States is patient self-management. This entails teaching patients how to manage their own warfarin dose on the basis of their home INR measurements.

The most recent American College of Chest Physicians clinical practice guidelines on antithrombotic therapy for atrial fibrillation give patient self-management of warfarin therapy a class 2B recommendation, stating, "For patients treated with vitamin K antagonists who are motivated and can demonstrate competency in self-management strategies, including the self-testing equipment, we suggest patient self-management rather than the usual outpatient INR monitoring" (CHEST 2012;141: 2 suppl. e531S-e575S [doi: 10.1378/chest.11-2304]).

Session cochair Dr. Samuel Z. Goldhaber agreed with Dr. Ansell that warfarin still has a place in anticoagulation therapy. The fact that it costs as little as $4 per month while dabigatran, for example, retails for 60 times that amount, is not to be shrugged off in an era of runaway health care spending, he said.

Plus, warfarin, for all its drawbacks, is a known quantity backed by more than a half century of clinical experience.

"Even though warfarin can cause horrible complications, there are no more surprises left about what warfarin can do," observed Dr. Goldhaber, who is a professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women?s Hospital, Boston.

A potential game changer for warfarin is the possibility that rapid pharmacogenetic testing will enable physicians to improve upon the current method of warfarin dosing.

One advantage warfarin has is that bleeding episodes can be reversed by administration of vitamin K. In contrast, there is as yet no reliable means of reversing major bleeding in patients on the novel anticoagulants. But Dr. Lars Wallentin said this limitation of the new agents is outweighed by the consistent finding that they have lower rates of intracranial hemorrhage than those of warfarin.

"There is no antidote to warfarin that has proven to have any effect in patients with ICH. And there is no evidence as far as I can see that however you control INR you can reach as low a level of ICH as with these new agents. I think this is a specific downside of warfarin that we can?t get away from," said Dr. Wallentin, who is a professor of cardiology at Uppsala (Sweden) University.

The STABLE study was funded by Alere Home Monitoring, Inc. Dr. Ansell is a consultant to the company.

Dr. Goldhaber has served as a consultant to numerous pharmaceutical companies developing cardiovascular medications.

Dr. Wallentin was principal investigator in the ARISTOTLE study of apixaban, funded by Pfizer and Bristol Myers Squibb, and has served as a consultant to those and other pharmaceutical companies.