Bivalirudin called safe and effective in HIT

WASHINGTON – Bivalirudin is an attractive off-label option for the treatment of heparin-induced thrombocytopenia, Dr. Lee Joseph said at the annual meeting of the American College of Cardiology.

She presented what is believed to be the largest-ever case series of patients treated for heparin-induced thrombocytopenia (HIT) using bivalirudin (Angiomax): 641 patients treated over a 9-year period at the Cleveland Clinic, where bivalirudin has been the treatment of choice for HIT since 2002.

Roughly half of the bivalirudin-treated patients with confirmed or suspected HIT were medical patients, the other half surgical. One-quarter of the patients were in the intensive care unit. Chronic renal failure was present in 27% of patients, and 8% had chronic liver disease. Their average duration of heparin exposure was 7 days. At the time when HIT was diagnosed, 55% of the patients had a venous thromboembolism, and 10% had an arterial thromboembolic event.

The treatment outcomes were impressive, particularly when compared with studies involving the other anticoagulants used in treating HIT, Dr. Joseph said. There were no HIT-related amputations in bivalirudin-treated patients. The rate of new thrombosis was 4.6%. All-cause 30-day mortality was 14.5%, with a 0.2% incidence of death due to HIT-related thrombosis. The major bleeding rate was 7.6%, with a 2.4% rate of nonmajor bleeding. Fatal bleeding occurred in 1.5% of patients treated with the direct thrombin inhibitor.

Patients received bivalirudin for a median of 9 days. A therapeutic activated partial thromboplastin time was attained within a median of 12 hours.

A search for predictors of treatment outcome turned up three risk factors for major bleeding events and/or 30-day mortality on bivalirudin: dialysis dependence, being in the intensive care unit, and having a platelet count nadir below 60,000/uL, according to Dr. Joseph, who is now with the department of cardiovascular medicine at the University of Iowa in Iowa City.

The sole available agent approved in the United States for treatment of HIT is argatroban. Its use is problematic because of its very long half-life and resulting difficulty in transitioning to long-term anticoagulation with warfarin. Bivalirudin and fondaparinux (Arixtra), an indirect factor Xa inhibitor, are used off-label in treating HIT. Physicians at the Cleveland Clinic have used bivalirudin almost exclusively for more than a decade because of its short half-life of about 25 minutes, its low immunogenicity, the fact that only 20% of the medication is eliminated renally, the potential for rapid dose titration with no need for an initial bolus, and bivalirudin’s minimal interference with INR measurement. Plus cardiologists were already comfortable using bivalirudin in the cardiac catheterization lab, she explained.

In published studies of argatroban, fondaparinux, and lepirudin – an agent no longer available in the United States – HIT-related amputation rates of 5%-14% were reported, along with 30-day all-cause mortality rates of 7%-18% and major bleeding rates of 6%-15%.

Dr. Joseph said a prospective study comparing bivalirudin with other agents for HIT is in the planning stages.

An audience member noted that bivalirudin is an expensive drug and wondered about the possibility of using dabigatran, a less costly oral direct thrombin inhibitor, in treating HIT. Dr. Joseph replied that nearly all patients with HIT are hospitalized, and many are seriously ill, so an intravenously administered agent with a short half-life or rapid reversibility is the preferred strategy.

She reported having no financial conflicts with regard to this study, which was free of commercial support.

[email protected]

WASHINGTON – Bivalirudin is an attractive off-label option for the treatment of heparin-induced thrombocytopenia, Dr. Lee Joseph said at the annual meeting of the American College of Cardiology.

She presented what is believed to be the largest-ever case series of patients treated for heparin-induced thrombocytopenia (HIT) using bivalirudin (Angiomax): 641 patients treated over a 9-year period at the Cleveland Clinic, where bivalirudin has been the treatment of choice for HIT since 2002.

Roughly half of the bivalirudin-treated patients with confirmed or suspected HIT were medical patients, the other half surgical. One-quarter of the patients were in the intensive care unit. Chronic renal failure was present in 27% of patients, and 8% had chronic liver disease. Their average duration of heparin exposure was 7 days. At the time when HIT was diagnosed, 55% of the patients had a venous thromboembolism, and 10% had an arterial thromboembolic event.

The treatment outcomes were impressive, particularly when compared with studies involving the other anticoagulants used in treating HIT, Dr. Joseph said. There were no HIT-related amputations in bivalirudin-treated patients. The rate of new thrombosis was 4.6%. All-cause 30-day mortality was 14.5%, with a 0.2% incidence of death due to HIT-related thrombosis. The major bleeding rate was 7.6%, with a 2.4% rate of nonmajor bleeding. Fatal bleeding occurred in 1.5% of patients treated with the direct thrombin inhibitor.

Patients received bivalirudin for a median of 9 days. A therapeutic activated partial thromboplastin time was attained within a median of 12 hours.

A search for predictors of treatment outcome turned up three risk factors for major bleeding events and/or 30-day mortality on bivalirudin: dialysis dependence, being in the intensive care unit, and having a platelet count nadir below 60,000/uL, according to Dr. Joseph, who is now with the department of cardiovascular medicine at the University of Iowa in Iowa City.

The sole available agent approved in the United States for treatment of HIT is argatroban. Its use is problematic because of its very long half-life and resulting difficulty in transitioning to long-term anticoagulation with warfarin. Bivalirudin and fondaparinux (Arixtra), an indirect factor Xa inhibitor, are used off-label in treating HIT. Physicians at the Cleveland Clinic have used bivalirudin almost exclusively for more than a decade because of its short half-life of about 25 minutes, its low immunogenicity, the fact that only 20% of the medication is eliminated renally, the potential for rapid dose titration with no need for an initial bolus, and bivalirudin’s minimal interference with INR measurement. Plus cardiologists were already comfortable using bivalirudin in the cardiac catheterization lab, she explained.

In published studies of argatroban, fondaparinux, and lepirudin – an agent no longer available in the United States – HIT-related amputation rates of 5%-14% were reported, along with 30-day all-cause mortality rates of 7%-18% and major bleeding rates of 6%-15%.

Dr. Joseph said a prospective study comparing bivalirudin with other agents for HIT is in the planning stages.

An audience member noted that bivalirudin is an expensive drug and wondered about the possibility of using dabigatran, a less costly oral direct thrombin inhibitor, in treating HIT. Dr. Joseph replied that nearly all patients with HIT are hospitalized, and many are seriously ill, so an intravenously administered agent with a short half-life or rapid reversibility is the preferred strategy.

She reported having no financial conflicts with regard to this study, which was free of commercial support.

[email protected]

WASHINGTON – Bivalirudin is an attractive off-label option for the treatment of heparin-induced thrombocytopenia, Dr. Lee Joseph said at the annual meeting of the American College of Cardiology.

She presented what is believed to be the largest-ever case series of patients treated for heparin-induced thrombocytopenia (HIT) using bivalirudin (Angiomax): 641 patients treated over a 9-year period at the Cleveland Clinic, where bivalirudin has been the treatment of choice for HIT since 2002.

Roughly half of the bivalirudin-treated patients with confirmed or suspected HIT were medical patients, the other half surgical. One-quarter of the patients were in the intensive care unit. Chronic renal failure was present in 27% of patients, and 8% had chronic liver disease. Their average duration of heparin exposure was 7 days. At the time when HIT was diagnosed, 55% of the patients had a venous thromboembolism, and 10% had an arterial thromboembolic event.

The treatment outcomes were impressive, particularly when compared with studies involving the other anticoagulants used in treating HIT, Dr. Joseph said. There were no HIT-related amputations in bivalirudin-treated patients. The rate of new thrombosis was 4.6%. All-cause 30-day mortality was 14.5%, with a 0.2% incidence of death due to HIT-related thrombosis. The major bleeding rate was 7.6%, with a 2.4% rate of nonmajor bleeding. Fatal bleeding occurred in 1.5% of patients treated with the direct thrombin inhibitor.

Patients received bivalirudin for a median of 9 days. A therapeutic activated partial thromboplastin time was attained within a median of 12 hours.

A search for predictors of treatment outcome turned up three risk factors for major bleeding events and/or 30-day mortality on bivalirudin: dialysis dependence, being in the intensive care unit, and having a platelet count nadir below 60,000/uL, according to Dr. Joseph, who is now with the department of cardiovascular medicine at the University of Iowa in Iowa City.

The sole available agent approved in the United States for treatment of HIT is argatroban. Its use is problematic because of its very long half-life and resulting difficulty in transitioning to long-term anticoagulation with warfarin. Bivalirudin and fondaparinux (Arixtra), an indirect factor Xa inhibitor, are used off-label in treating HIT. Physicians at the Cleveland Clinic have used bivalirudin almost exclusively for more than a decade because of its short half-life of about 25 minutes, its low immunogenicity, the fact that only 20% of the medication is eliminated renally, the potential for rapid dose titration with no need for an initial bolus, and bivalirudin’s minimal interference with INR measurement. Plus cardiologists were already comfortable using bivalirudin in the cardiac catheterization lab, she explained.

In published studies of argatroban, fondaparinux, and lepirudin – an agent no longer available in the United States – HIT-related amputation rates of 5%-14% were reported, along with 30-day all-cause mortality rates of 7%-18% and major bleeding rates of 6%-15%.

Dr. Joseph said a prospective study comparing bivalirudin with other agents for HIT is in the planning stages.

An audience member noted that bivalirudin is an expensive drug and wondered about the possibility of using dabigatran, a less costly oral direct thrombin inhibitor, in treating HIT. Dr. Joseph replied that nearly all patients with HIT are hospitalized, and many are seriously ill, so an intravenously administered agent with a short half-life or rapid reversibility is the preferred strategy.

She reported having no financial conflicts with regard to this study, which was free of commercial support.

[email protected]