NEW ORLEANS — Treatment with abciximab failed to improve the outcomes of patients with diabetes who underwent elective percutaneous coronary interventions in a randomized study with 701 patients.

All patients in the study received a loading dose of 600 mg of the antiplatelet drug clopidogrel at least 2 hours before their percutaneous coronary intervention (PCI), which suggested that clopidogrel treatment “may obviate the need for abciximab during elective PCI in patients at low to intermediate risk,” Julinda Mehilli, M.D., reported at the annual scientific sessions of the American Heart Association.

But the results from this German study, which was not sponsored by a pharmaceutical company, cannot be considered the last word on using a glycoprotein IIb/IIIa platelet inhibitor in patients with diabetes undergoing PCI, said some experts at the meeting.

One limitation is that the current study excluded patients with acute coronary syndrome, an acute myocardial infarction, or visible thrombus. “These patients have been the sweet spot for abciximab and other IIb/IIIa inhibitors,” commented Gregg W. Stone, M.D., director of cardiovascular research and education at the Cardiovascular Research Foundation of Lenox Hill Hospital in New York.

Other shortcomings of the study included its enrollment of a relatively small number of insulin-dependent diabetics, and the fact that it was underpowered to prove that patients did just as well without abciximab as they did with the drug, commented Eric R. Bates, M.D., a professor of medicine at the University of Michigan, Ann Arbor.

The study was designed as a superiority trial, to prove that abciximab-treated patients fared better than those who didn't get the drug. Dr. Bates was also skeptical that physicians who now use abciximab to treat diabetic patients undergoing elective PCI would be persuaded to change their practice based on the results of a single study.

The study was done at three German hospitals from January 2001 to October 2003. Patients were enrolled if they were on active treatment with either insulin or an oral hypoglycemic agent and were scheduled to undergo an elective PCI in a native coronary vessel. The study's primary end point was the incidence of death or MI during the first 12 months following the procedure.

All patients received a loading dose of clopidogrel plus 500 mg aspirin. Following randomization, patients in the abciximab group received a 0.25-mg/kg bolus followed by a 0.125-mcg/kg per minute infusion for 12 hours, along with 70 U/kg of unfractionated heparin.

Patients in the placebo group received a placebo bolus and infusion, along with a 140-U/kg bolus of heparin. Following their procedure, all patients received a 200-mg daily aspirin dosage that was continued indefinitely. Patients also received 75 mg clopidogrel b.i.d. until discharge or for a maximum of 3 days, and then continued on 75 mg clopidogrel daily for at least 6 months. Patients received other medications as indicated.

After 1 year of follow-up, the incidence of death or MI was essentially identical in the two groups: 8.3% among the 351 patients treated with abciximab, and 8.6% among those treated with placebo, reported Dr. Mehilli of the German Heart Center in Munich.

The secondary end point of the study was the incidence of angiographic restenosis at follow-up. By this criterion, the abciximab group did better: Angiographic restenosis occurred in 28.9% of the patients in the abciximab group, compared with 37.8% of placebo patients, a statistically significant difference.

But this result is already outdated because the study was done largely before the advent of drug-eluting stents. Only 10% of the patients received drug-eluting stents; in this small subgroup, treatment with abciximab conferred no significant advantage over placebo.

The edge in restenosis conferred by abciximab “would have been a very important finding 2 years ago, but now it's too little too late,” said Dr. Stone. “Drug-eluting stents are clearly the treatment of choice to reduce restenosis in patients with diabetes, and no drug has been shown to reduce restenosis when used on top of drug-eluting stents,” he said.

NEW ORLEANS — Treatment with abciximab failed to improve the outcomes of patients with diabetes who underwent elective percutaneous coronary interventions in a randomized study with 701 patients.

All patients in the study received a loading dose of 600 mg of the antiplatelet drug clopidogrel at least 2 hours before their percutaneous coronary intervention (PCI), which suggested that clopidogrel treatment “may obviate the need for abciximab during elective PCI in patients at low to intermediate risk,” Julinda Mehilli, M.D., reported at the annual scientific sessions of the American Heart Association.

But the results from this German study, which was not sponsored by a pharmaceutical company, cannot be considered the last word on using a glycoprotein IIb/IIIa platelet inhibitor in patients with diabetes undergoing PCI, said some experts at the meeting.

One limitation is that the current study excluded patients with acute coronary syndrome, an acute myocardial infarction, or visible thrombus. “These patients have been the sweet spot for abciximab and other IIb/IIIa inhibitors,” commented Gregg W. Stone, M.D., director of cardiovascular research and education at the Cardiovascular Research Foundation of Lenox Hill Hospital in New York.

Other shortcomings of the study included its enrollment of a relatively small number of insulin-dependent diabetics, and the fact that it was underpowered to prove that patients did just as well without abciximab as they did with the drug, commented Eric R. Bates, M.D., a professor of medicine at the University of Michigan, Ann Arbor.

The study was designed as a superiority trial, to prove that abciximab-treated patients fared better than those who didn't get the drug. Dr. Bates was also skeptical that physicians who now use abciximab to treat diabetic patients undergoing elective PCI would be persuaded to change their practice based on the results of a single study.

The study was done at three German hospitals from January 2001 to October 2003. Patients were enrolled if they were on active treatment with either insulin or an oral hypoglycemic agent and were scheduled to undergo an elective PCI in a native coronary vessel. The study's primary end point was the incidence of death or MI during the first 12 months following the procedure.

All patients received a loading dose of clopidogrel plus 500 mg aspirin. Following randomization, patients in the abciximab group received a 0.25-mg/kg bolus followed by a 0.125-mcg/kg per minute infusion for 12 hours, along with 70 U/kg of unfractionated heparin.

Patients in the placebo group received a placebo bolus and infusion, along with a 140-U/kg bolus of heparin. Following their procedure, all patients received a 200-mg daily aspirin dosage that was continued indefinitely. Patients also received 75 mg clopidogrel b.i.d. until discharge or for a maximum of 3 days, and then continued on 75 mg clopidogrel daily for at least 6 months. Patients received other medications as indicated.

After 1 year of follow-up, the incidence of death or MI was essentially identical in the two groups: 8.3% among the 351 patients treated with abciximab, and 8.6% among those treated with placebo, reported Dr. Mehilli of the German Heart Center in Munich.

The secondary end point of the study was the incidence of angiographic restenosis at follow-up. By this criterion, the abciximab group did better: Angiographic restenosis occurred in 28.9% of the patients in the abciximab group, compared with 37.8% of placebo patients, a statistically significant difference.

But this result is already outdated because the study was done largely before the advent of drug-eluting stents. Only 10% of the patients received drug-eluting stents; in this small subgroup, treatment with abciximab conferred no significant advantage over placebo.

The edge in restenosis conferred by abciximab “would have been a very important finding 2 years ago, but now it's too little too late,” said Dr. Stone. “Drug-eluting stents are clearly the treatment of choice to reduce restenosis in patients with diabetes, and no drug has been shown to reduce restenosis when used on top of drug-eluting stents,” he said.

NEW ORLEANS — Treatment with abciximab failed to improve the outcomes of patients with diabetes who underwent elective percutaneous coronary interventions in a randomized study with 701 patients.

All patients in the study received a loading dose of 600 mg of the antiplatelet drug clopidogrel at least 2 hours before their percutaneous coronary intervention (PCI), which suggested that clopidogrel treatment “may obviate the need for abciximab during elective PCI in patients at low to intermediate risk,” Julinda Mehilli, M.D., reported at the annual scientific sessions of the American Heart Association.

But the results from this German study, which was not sponsored by a pharmaceutical company, cannot be considered the last word on using a glycoprotein IIb/IIIa platelet inhibitor in patients with diabetes undergoing PCI, said some experts at the meeting.

One limitation is that the current study excluded patients with acute coronary syndrome, an acute myocardial infarction, or visible thrombus. “These patients have been the sweet spot for abciximab and other IIb/IIIa inhibitors,” commented Gregg W. Stone, M.D., director of cardiovascular research and education at the Cardiovascular Research Foundation of Lenox Hill Hospital in New York.

Other shortcomings of the study included its enrollment of a relatively small number of insulin-dependent diabetics, and the fact that it was underpowered to prove that patients did just as well without abciximab as they did with the drug, commented Eric R. Bates, M.D., a professor of medicine at the University of Michigan, Ann Arbor.

The study was designed as a superiority trial, to prove that abciximab-treated patients fared better than those who didn't get the drug. Dr. Bates was also skeptical that physicians who now use abciximab to treat diabetic patients undergoing elective PCI would be persuaded to change their practice based on the results of a single study.

The study was done at three German hospitals from January 2001 to October 2003. Patients were enrolled if they were on active treatment with either insulin or an oral hypoglycemic agent and were scheduled to undergo an elective PCI in a native coronary vessel. The study's primary end point was the incidence of death or MI during the first 12 months following the procedure.

All patients received a loading dose of clopidogrel plus 500 mg aspirin. Following randomization, patients in the abciximab group received a 0.25-mg/kg bolus followed by a 0.125-mcg/kg per minute infusion for 12 hours, along with 70 U/kg of unfractionated heparin.

Patients in the placebo group received a placebo bolus and infusion, along with a 140-U/kg bolus of heparin. Following their procedure, all patients received a 200-mg daily aspirin dosage that was continued indefinitely. Patients also received 75 mg clopidogrel b.i.d. until discharge or for a maximum of 3 days, and then continued on 75 mg clopidogrel daily for at least 6 months. Patients received other medications as indicated.

After 1 year of follow-up, the incidence of death or MI was essentially identical in the two groups: 8.3% among the 351 patients treated with abciximab, and 8.6% among those treated with placebo, reported Dr. Mehilli of the German Heart Center in Munich.

The secondary end point of the study was the incidence of angiographic restenosis at follow-up. By this criterion, the abciximab group did better: Angiographic restenosis occurred in 28.9% of the patients in the abciximab group, compared with 37.8% of placebo patients, a statistically significant difference.

But this result is already outdated because the study was done largely before the advent of drug-eluting stents. Only 10% of the patients received drug-eluting stents; in this small subgroup, treatment with abciximab conferred no significant advantage over placebo.

The edge in restenosis conferred by abciximab “would have been a very important finding 2 years ago, but now it's too little too late,” said Dr. Stone. “Drug-eluting stents are clearly the treatment of choice to reduce restenosis in patients with diabetes, and no drug has been shown to reduce restenosis when used on top of drug-eluting stents,” he said.

NEW ORLEANS — Routine use of an indwelling pulmonary artery catheter to guide medical therapy in patients hospitalized for decompensated heart failure can no longer be justified, according to the findings of a National Heart, Lung, and Blood Institute-sponsored randomized trial.

Use of a pulmonary artery catheter to titrate therapy aimed at lowering pulmonary capillary wedge pressure didn't affect the primary end points of mortality or days hospitalized during the next 6 months, compared with therapy guided solely by clinical assessment, in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), Lynne W. Stevenson, M.D., reported at the annual scientific sessions of the American Heart Association.

ESCAPE was a 26-site randomized trial involving 433 patients with decompensated severe heart failure in whom urgent pulmonary artery catheterization wasn't considered necessary.

A pulmonary artery catheter (PAC) is placed in roughly 40,000 heart failure (HF) patients per year. Controversy has surrounded the procedure since a 1996 study suggested PACs are associated with excessive risk and no proven benefit. ESCAPE was undertaken to answer the unresolved questions regarding PAC safety and efficacy.

Although use of a PAC had no effect on the primary end points in ESCAPE, at least it proved safe. Although PAC-related complications occurred in 4.2% of patients, 30-day mortality was 4.7% in the PAC group and 5.0% in controls, noted Dr. Stevenson, principal investigator in ESCAPE and codirector of the cardiomyopathy/HF program at Brigham and Women's Hospital, Boston.

However, 19% of patients in both arms were dead within 6 months. “This is higher mortality than most cancers, and we need to do better,” she said.

There was a consistent trend favoring the PAC group in terms of greater improvement in functional status and quality of life measures during 6 months of follow-up, which were secondary end points in ESCAPE.

The difference in one of these measures—time trade-off—reached statistical significance. Time trade-off is a measure in which patients are asked a difficult hypothetical question: if you had 24 months to live in your current state of health, how many of your remaining months would you be willing to trade in order spend your remaining time feeling better? The answer at baseline was a mean of 9 months.

“We found this astounding,” Dr. Stevenson said. “At the same time as we're designing trials to test survival, the patients are saying what matters to them most is not to live longer, but to live better.”

At 6 months' follow-up, PAC-managed patients were only willing to trade 3 of their remaining 24 months in order to feel better; the control group would trade 7.5 months.

Still being analyzed are echocardiographic data from ESCAPE. If therapy aimed at lowering pulmonary capillary wedge pressure can be titrated reasonably well using noninvasive echocardiographic measurements and the result is a patient perception of enhanced value of life, then echocardiography may provide a risk-free replacement for PAC.

Discussant Mariell L. Jessup, M.D., said the 19% mortality at 6 months in ESCAPE highlights the limitations of medical therapy with or without knowledge of hemodynamics.

Physicians and patients can look forward to better times with the coming shift from medical management to a wide array of nonpharmacologic therapies for advanced HF, including heart transplantation, second- and third-generation ventricular assist devices, cellular therapies, and passive ventricular restraint systems, said Dr. Jessup of the University of Pennsylvania, Philadelphia.

NEW ORLEANS — Routine use of an indwelling pulmonary artery catheter to guide medical therapy in patients hospitalized for decompensated heart failure can no longer be justified, according to the findings of a National Heart, Lung, and Blood Institute-sponsored randomized trial.

Use of a pulmonary artery catheter to titrate therapy aimed at lowering pulmonary capillary wedge pressure didn't affect the primary end points of mortality or days hospitalized during the next 6 months, compared with therapy guided solely by clinical assessment, in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), Lynne W. Stevenson, M.D., reported at the annual scientific sessions of the American Heart Association.

ESCAPE was a 26-site randomized trial involving 433 patients with decompensated severe heart failure in whom urgent pulmonary artery catheterization wasn't considered necessary.

A pulmonary artery catheter (PAC) is placed in roughly 40,000 heart failure (HF) patients per year. Controversy has surrounded the procedure since a 1996 study suggested PACs are associated with excessive risk and no proven benefit. ESCAPE was undertaken to answer the unresolved questions regarding PAC safety and efficacy.

Although use of a PAC had no effect on the primary end points in ESCAPE, at least it proved safe. Although PAC-related complications occurred in 4.2% of patients, 30-day mortality was 4.7% in the PAC group and 5.0% in controls, noted Dr. Stevenson, principal investigator in ESCAPE and codirector of the cardiomyopathy/HF program at Brigham and Women's Hospital, Boston.

However, 19% of patients in both arms were dead within 6 months. “This is higher mortality than most cancers, and we need to do better,” she said.

There was a consistent trend favoring the PAC group in terms of greater improvement in functional status and quality of life measures during 6 months of follow-up, which were secondary end points in ESCAPE.

The difference in one of these measures—time trade-off—reached statistical significance. Time trade-off is a measure in which patients are asked a difficult hypothetical question: if you had 24 months to live in your current state of health, how many of your remaining months would you be willing to trade in order spend your remaining time feeling better? The answer at baseline was a mean of 9 months.

“We found this astounding,” Dr. Stevenson said. “At the same time as we're designing trials to test survival, the patients are saying what matters to them most is not to live longer, but to live better.”

At 6 months' follow-up, PAC-managed patients were only willing to trade 3 of their remaining 24 months in order to feel better; the control group would trade 7.5 months.

Still being analyzed are echocardiographic data from ESCAPE. If therapy aimed at lowering pulmonary capillary wedge pressure can be titrated reasonably well using noninvasive echocardiographic measurements and the result is a patient perception of enhanced value of life, then echocardiography may provide a risk-free replacement for PAC.

Discussant Mariell L. Jessup, M.D., said the 19% mortality at 6 months in ESCAPE highlights the limitations of medical therapy with or without knowledge of hemodynamics.

Physicians and patients can look forward to better times with the coming shift from medical management to a wide array of nonpharmacologic therapies for advanced HF, including heart transplantation, second- and third-generation ventricular assist devices, cellular therapies, and passive ventricular restraint systems, said Dr. Jessup of the University of Pennsylvania, Philadelphia.

NEW ORLEANS — Routine use of an indwelling pulmonary artery catheter to guide medical therapy in patients hospitalized for decompensated heart failure can no longer be justified, according to the findings of a National Heart, Lung, and Blood Institute-sponsored randomized trial.

Use of a pulmonary artery catheter to titrate therapy aimed at lowering pulmonary capillary wedge pressure didn't affect the primary end points of mortality or days hospitalized during the next 6 months, compared with therapy guided solely by clinical assessment, in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), Lynne W. Stevenson, M.D., reported at the annual scientific sessions of the American Heart Association.

ESCAPE was a 26-site randomized trial involving 433 patients with decompensated severe heart failure in whom urgent pulmonary artery catheterization wasn't considered necessary.

A pulmonary artery catheter (PAC) is placed in roughly 40,000 heart failure (HF) patients per year. Controversy has surrounded the procedure since a 1996 study suggested PACs are associated with excessive risk and no proven benefit. ESCAPE was undertaken to answer the unresolved questions regarding PAC safety and efficacy.

Although use of a PAC had no effect on the primary end points in ESCAPE, at least it proved safe. Although PAC-related complications occurred in 4.2% of patients, 30-day mortality was 4.7% in the PAC group and 5.0% in controls, noted Dr. Stevenson, principal investigator in ESCAPE and codirector of the cardiomyopathy/HF program at Brigham and Women's Hospital, Boston.

However, 19% of patients in both arms were dead within 6 months. “This is higher mortality than most cancers, and we need to do better,” she said.

There was a consistent trend favoring the PAC group in terms of greater improvement in functional status and quality of life measures during 6 months of follow-up, which were secondary end points in ESCAPE.

The difference in one of these measures—time trade-off—reached statistical significance. Time trade-off is a measure in which patients are asked a difficult hypothetical question: if you had 24 months to live in your current state of health, how many of your remaining months would you be willing to trade in order spend your remaining time feeling better? The answer at baseline was a mean of 9 months.

“We found this astounding,” Dr. Stevenson said. “At the same time as we're designing trials to test survival, the patients are saying what matters to them most is not to live longer, but to live better.”

At 6 months' follow-up, PAC-managed patients were only willing to trade 3 of their remaining 24 months in order to feel better; the control group would trade 7.5 months.

Still being analyzed are echocardiographic data from ESCAPE. If therapy aimed at lowering pulmonary capillary wedge pressure can be titrated reasonably well using noninvasive echocardiographic measurements and the result is a patient perception of enhanced value of life, then echocardiography may provide a risk-free replacement for PAC.

Discussant Mariell L. Jessup, M.D., said the 19% mortality at 6 months in ESCAPE highlights the limitations of medical therapy with or without knowledge of hemodynamics.

Physicians and patients can look forward to better times with the coming shift from medical management to a wide array of nonpharmacologic therapies for advanced HF, including heart transplantation, second- and third-generation ventricular assist devices, cellular therapies, and passive ventricular restraint systems, said Dr. Jessup of the University of Pennsylvania, Philadelphia.

A coalition of neurovascular medical specialties has outlined a set of training and credentialing standards for performing carotid stenting that goes far beyond those released by interventional cardiologists and vascular surgeons.

The guidelines were developed by the American Academy of Neurology, the American Association of Neurological Surgeons, the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology, the Congress of Neurological Surgeons, and others. They were simultaneously published in several medical journals.

These standards come at a critical time, said Anthony Furlan, M.D., a neurologist who helped develop the guidelines, since the Food and Drug Administration recently approved the Guidant Rx ACCULINK carotid stent and issued conditional approval to Cordis Corp.'s PRECISE OTW Nitinol Self-Expanding Stent.

And officials at the Centers for Medicare and Medicaid Services are poised to allow coverage for carotid stenting outside of clinical trials in patients who would be high-risk candidates for endarterectomy and who have symptomatic carotid artery stenosis of at least 70%.

“Our role here is to provide guidance to credentialing committees,” said Dr. Furlan, who serves on the American Academy of Neurology's Stroke Systems Task Force and heads the section of stroke and neurologic intensive care at the Cleveland Clinic Foundation.

The new standards are also an attempt to combine the broad knowledge of the neurological communities, said John J. Connors III, M.D., director of interventional neuroradiology at Baptist Hospital of Miami. “With the potential for so many different specialties to be performing carotid stenting, these standards are an opportunity to provide quality assurance based on the collective knowledge of experts in the fields of the neurological sciences,” Dr. Connors said in an interview.

“Many physicians may be experts in one area, but with carotid stenting they need to have a basic fund of knowledge in addition to being masters of a variety of skills,” he said. Importantly, a basic knowledge of the brain is required, he said. The neurovascular guidelines call for any physician performing carotid stenting to have had a minimum of 6 months of formal training approved by the Accreditation Council for Graduate Medical Education (ACGME) in at least one of the neurosciences.

In addition, before beginning postgraduate training in cervicocerebral interventional procedures, physicians must be appropriately trained in and must competently complete at least 100 diagnostic cervicocerebral angiograms.

Under these standards, many physicians would need to engage in additional training in order to achieve competency in these procedures, Dr. Connors said. But he noted that even these guidelines are a low bar considering that the potential adverse outcomes in carotid stenting are stroke and death.

The Neurovascular Coalition guidelines are aimed at creating a minimal standard for training in these procedures, Dr. Connors said, but they aren't aimed at locking any specialties out of the field.

However, Dr. Connors said he is concerned that guidelines developed jointly by the Society for Cardiovascular Angiography and Interventions, the Society for Vascular Medicine and Biology, and the Society for Vascular Surgery (SCAI/SVMB/SVS) do not require sufficient training.

For example, the SCAI/SVMB/SVS guidelines released call for physicians to perform a minimum of 30 diagnostic carotid angiograms and 25 carotid-stenting procedures in order to attain competence in carotid stenting. “This is exactly one-tenth of the training required for coronary artery stenting,” Dr. Connors said.

But Dr. William A. Gray, M.D., director of endovascular care at the Swedish Heart Institute in Seattle and one of the authors of the SCAI/SVMB/SVS guidelines, does not agree that performing 100 angiograms is necessary to show proficiency. In fact, he sees that requirement as a bit excessive.

“We look at this as a potential barrier to entry for otherwise qualified operators,” Dr. Gray said in an interview. Instead, the threshold of 30 diagnostic angiograms is consistent with the experience of many cardiologists who have been working in the field for years, and with the experience of operators in the recently completed carotid stent trials.

Dr. Gray said he respects the work that went into the neurovascular document, but believes the guidelines developed by the interventional cardiologists and vascular surgeons are a better reflection of the reality of performing carotid stenting and its program development.

Another concern is the requirement for physicians to complete 100 angiograms could lead to some unnecessary procedures, said Kenneth Rosenfield, M.D., of Massachusetts General Hospital in Boston and an author of the SCAI guidelines.

With the need for diagnostic angiograms declining, some physicians might be inclined to perform the procedure just to satisfy the requirements for performing carotid artery stenting, he said.

“It should not be about setting barriers,” he said. “It should be about allowing patients access to these procedures,” Dr. Rosenfield said.

Comparing the Recommendations

A coalition of neurovascular medical specialties has outlined a set of training and credentialing standards for performing carotid stenting that goes far beyond those released by interventional cardiologists and vascular surgeons.

The guidelines were developed by the American Academy of Neurology, the American Association of Neurological Surgeons, the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology, the Congress of Neurological Surgeons, and others. They were simultaneously published in several medical journals.

These standards come at a critical time, said Anthony Furlan, M.D., a neurologist who helped develop the guidelines, since the Food and Drug Administration recently approved the Guidant Rx ACCULINK carotid stent and issued conditional approval to Cordis Corp.'s PRECISE OTW Nitinol Self-Expanding Stent.

And officials at the Centers for Medicare and Medicaid Services are poised to allow coverage for carotid stenting outside of clinical trials in patients who would be high-risk candidates for endarterectomy and who have symptomatic carotid artery stenosis of at least 70%.

“Our role here is to provide guidance to credentialing committees,” said Dr. Furlan, who serves on the American Academy of Neurology's Stroke Systems Task Force and heads the section of stroke and neurologic intensive care at the Cleveland Clinic Foundation.

The new standards are also an attempt to combine the broad knowledge of the neurological communities, said John J. Connors III, M.D., director of interventional neuroradiology at Baptist Hospital of Miami. “With the potential for so many different specialties to be performing carotid stenting, these standards are an opportunity to provide quality assurance based on the collective knowledge of experts in the fields of the neurological sciences,” Dr. Connors said in an interview.

“Many physicians may be experts in one area, but with carotid stenting they need to have a basic fund of knowledge in addition to being masters of a variety of skills,” he said. Importantly, a basic knowledge of the brain is required, he said. The neurovascular guidelines call for any physician performing carotid stenting to have had a minimum of 6 months of formal training approved by the Accreditation Council for Graduate Medical Education (ACGME) in at least one of the neurosciences.

In addition, before beginning postgraduate training in cervicocerebral interventional procedures, physicians must be appropriately trained in and must competently complete at least 100 diagnostic cervicocerebral angiograms.

Under these standards, many physicians would need to engage in additional training in order to achieve competency in these procedures, Dr. Connors said. But he noted that even these guidelines are a low bar considering that the potential adverse outcomes in carotid stenting are stroke and death.

The Neurovascular Coalition guidelines are aimed at creating a minimal standard for training in these procedures, Dr. Connors said, but they aren't aimed at locking any specialties out of the field.

However, Dr. Connors said he is concerned that guidelines developed jointly by the Society for Cardiovascular Angiography and Interventions, the Society for Vascular Medicine and Biology, and the Society for Vascular Surgery (SCAI/SVMB/SVS) do not require sufficient training.

For example, the SCAI/SVMB/SVS guidelines released call for physicians to perform a minimum of 30 diagnostic carotid angiograms and 25 carotid-stenting procedures in order to attain competence in carotid stenting. “This is exactly one-tenth of the training required for coronary artery stenting,” Dr. Connors said.

But Dr. William A. Gray, M.D., director of endovascular care at the Swedish Heart Institute in Seattle and one of the authors of the SCAI/SVMB/SVS guidelines, does not agree that performing 100 angiograms is necessary to show proficiency. In fact, he sees that requirement as a bit excessive.

“We look at this as a potential barrier to entry for otherwise qualified operators,” Dr. Gray said in an interview. Instead, the threshold of 30 diagnostic angiograms is consistent with the experience of many cardiologists who have been working in the field for years, and with the experience of operators in the recently completed carotid stent trials.

Dr. Gray said he respects the work that went into the neurovascular document, but believes the guidelines developed by the interventional cardiologists and vascular surgeons are a better reflection of the reality of performing carotid stenting and its program development.

Another concern is the requirement for physicians to complete 100 angiograms could lead to some unnecessary procedures, said Kenneth Rosenfield, M.D., of Massachusetts General Hospital in Boston and an author of the SCAI guidelines.

With the need for diagnostic angiograms declining, some physicians might be inclined to perform the procedure just to satisfy the requirements for performing carotid artery stenting, he said.

“It should not be about setting barriers,” he said. “It should be about allowing patients access to these procedures,” Dr. Rosenfield said.

Comparing the Recommendations

A coalition of neurovascular medical specialties has outlined a set of training and credentialing standards for performing carotid stenting that goes far beyond those released by interventional cardiologists and vascular surgeons.

The guidelines were developed by the American Academy of Neurology, the American Association of Neurological Surgeons, the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology, the Congress of Neurological Surgeons, and others. They were simultaneously published in several medical journals.

These standards come at a critical time, said Anthony Furlan, M.D., a neurologist who helped develop the guidelines, since the Food and Drug Administration recently approved the Guidant Rx ACCULINK carotid stent and issued conditional approval to Cordis Corp.'s PRECISE OTW Nitinol Self-Expanding Stent.

And officials at the Centers for Medicare and Medicaid Services are poised to allow coverage for carotid stenting outside of clinical trials in patients who would be high-risk candidates for endarterectomy and who have symptomatic carotid artery stenosis of at least 70%.

“Our role here is to provide guidance to credentialing committees,” said Dr. Furlan, who serves on the American Academy of Neurology's Stroke Systems Task Force and heads the section of stroke and neurologic intensive care at the Cleveland Clinic Foundation.

The new standards are also an attempt to combine the broad knowledge of the neurological communities, said John J. Connors III, M.D., director of interventional neuroradiology at Baptist Hospital of Miami. “With the potential for so many different specialties to be performing carotid stenting, these standards are an opportunity to provide quality assurance based on the collective knowledge of experts in the fields of the neurological sciences,” Dr. Connors said in an interview.

“Many physicians may be experts in one area, but with carotid stenting they need to have a basic fund of knowledge in addition to being masters of a variety of skills,” he said. Importantly, a basic knowledge of the brain is required, he said. The neurovascular guidelines call for any physician performing carotid stenting to have had a minimum of 6 months of formal training approved by the Accreditation Council for Graduate Medical Education (ACGME) in at least one of the neurosciences.

In addition, before beginning postgraduate training in cervicocerebral interventional procedures, physicians must be appropriately trained in and must competently complete at least 100 diagnostic cervicocerebral angiograms.

Under these standards, many physicians would need to engage in additional training in order to achieve competency in these procedures, Dr. Connors said. But he noted that even these guidelines are a low bar considering that the potential adverse outcomes in carotid stenting are stroke and death.

The Neurovascular Coalition guidelines are aimed at creating a minimal standard for training in these procedures, Dr. Connors said, but they aren't aimed at locking any specialties out of the field.

However, Dr. Connors said he is concerned that guidelines developed jointly by the Society for Cardiovascular Angiography and Interventions, the Society for Vascular Medicine and Biology, and the Society for Vascular Surgery (SCAI/SVMB/SVS) do not require sufficient training.

For example, the SCAI/SVMB/SVS guidelines released call for physicians to perform a minimum of 30 diagnostic carotid angiograms and 25 carotid-stenting procedures in order to attain competence in carotid stenting. “This is exactly one-tenth of the training required for coronary artery stenting,” Dr. Connors said.

But Dr. William A. Gray, M.D., director of endovascular care at the Swedish Heart Institute in Seattle and one of the authors of the SCAI/SVMB/SVS guidelines, does not agree that performing 100 angiograms is necessary to show proficiency. In fact, he sees that requirement as a bit excessive.

“We look at this as a potential barrier to entry for otherwise qualified operators,” Dr. Gray said in an interview. Instead, the threshold of 30 diagnostic angiograms is consistent with the experience of many cardiologists who have been working in the field for years, and with the experience of operators in the recently completed carotid stent trials.

Dr. Gray said he respects the work that went into the neurovascular document, but believes the guidelines developed by the interventional cardiologists and vascular surgeons are a better reflection of the reality of performing carotid stenting and its program development.

Another concern is the requirement for physicians to complete 100 angiograms could lead to some unnecessary procedures, said Kenneth Rosenfield, M.D., of Massachusetts General Hospital in Boston and an author of the SCAI guidelines.

With the need for diagnostic angiograms declining, some physicians might be inclined to perform the procedure just to satisfy the requirements for performing carotid artery stenting, he said.

“It should not be about setting barriers,” he said. “It should be about allowing patients access to these procedures,” Dr. Rosenfield said.

Comparing the Recommendations

Long abandoned as ineffective at secondary stroke prevention, carotid artery bypass surgery for complete atherosclerotic occlusion is getting a second look.

Known as extracranial/intracranial (EC/IC) bypass, the procedure involves surgical anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA). It is getting its second chance to prove its effectiveness in selected patients for complete carotid occlusion because technologic advances, such as refinement of PET, have made it possible to identify which patients are the best candidates for the procedure.

EC/IC bypass surgery has been shown in a series of small studies to normalize the oxygen extraction fraction (OEF), a marker of impaired cerebral blood flow in patients with carotid occlusion.

Whether that translates into a decreased stroke risk is the subject of the Carotid Occlusion Surgery Study (COSS), a $21-million, 7-year trial funded by the National Institutes of Health that is now underway in 28 U.S. centers.

Candidates for the trial must be patients with symptomatic carotid occlusion and increased OEF on PET. To date, 169 patients have enrolled, and 38 patients have been randomized to treatment.

Enrollment in the nonblinded, controlled clinical trial has been slow, in part because few neurologists knew the option of bypass surgery existed, said Colin Derdeyn, M.D., principal investigator for the Washington University site in St. Louis.

The First EC/IC Bypass Study

STA-MCA surgical anastomosis was developed in 1967 and routinely performed on patients with carotid occlusion throughout the 1970s and mid-1980s.

However, data from the EC/IC Bypass Study showed no benefit for the prevention of subsequent stroke among 808 patients with symptomatic carotid occlusion, despite restoring blood flow to the carotid artery in 96% of cases (N. Engl. J Med. 1985;313:1191-200).

The researchers were unable to assess whether the procedure was more appropriate for one or another group of patients based on their cerebral hemodynamics because at the time the technology necessary to understand and measure cerebral blood flow had not been developed, according to M. Gazi Yasargil, M.D., professor of neurosurgery at the University of Arkansas, Little Rock, the Swiss neurosurgeon who pioneered the surgical procedure. “The time is ripe to work out a perfect indication for bypass surgery,” he said.

Identifying Hemodynamics

PET has made it possible to measure OEF, a proven predictor of which patients have significantly decreased cerebral blood flow and are at increased stroke risk.

When there is unrestricted cerebral blood flow, the brain extracts about 40% of the oxygen delivered to it in the blood. Blood vessels dilate and constrict to maintain an equal OEF across the brain. When cerebral blood flow falls because of reduced perfusion pressure, the brain increases the fraction of oxygen extracted from the blood to 70% or 80% to support normal oxygen metabolism. This elevated OEF allows the brain to maintain normal function, but it puts patients at increased risk for stroke in the future.

Two prospective natural history studies, one conducted in the United States (JAMA 1998;280:1055-69) and the other in Japan (J. Nucl. Med. 1999;40:1992-8), have shown that having an increased OEF as measured by PET is an independent predictor of future stroke in medically treated patients with symptomatic carotid artery occlusion.

Depending on the precise clinical and PET criteria used, the 2-year ipsilateral stroke rates ranged from 26% to 57% in patients with an elevated OEF, compared with stroke rates of 5%-15% in patients with normal OEF, according to Dr. Derdeyn, coauthor of the U.S. study.

“The best information we have right now, as far as connecting an abnormality by physiologic imaging with a risk factor, is for increased oxygen extraction,” Dr. Derdeyn told INTERNAL MEDICINE NEWS. OEF is a powerful and independent predictor of stroke. “It identifies a high-risk subgroup, without question,” he said.

William J. Powers, M.D., principal investigator of COSS, agreed on the importance of identifying subsets of patients most likely to benefit from EC/IC. “It's absolutely clear that if [EC/IC bypass] is ever going to work, there has to be some more refined selection criteria to pick out the people, number one, who would be at particularly high risk if treated with medical therapy, and number two, in whom the subsequent risk of stroke seems to be related to a problem that the bypass would fix,” he told this newspaper.

COSS is based on the hypothesis that surgical anastomosis of the superficial temporal artery to the middle cerebral artery, when added to the best medical therapy, can reduce subsequent ipsilateral ischemic stroke by 40% at 2 years' follow-up in this highly select patient population, despite perioperative stroke and death.

Investigators anticipate that the stroke rate in COSS will turn out to be 40% in the medically treated group and 24% in the surgically treated group, even taking into account a 12% perioperative stroke and mortality rate, as reported in the original EC/IC trial, said Dr. Powers, codirector of the Stroke Center at Barnes-Jewish Hospital and the Washington University School of Medicine.

Even if these reduced stroke rates are borne out by the study, EC/IC bypass surgery is unlikely to become as common as coronary artery bypass; elevated OEF occurs in only 30% of patients with carotid occlusion. The study's $21-million price tag over the next 5-7 years may prove to be money well spent if it settles the question of patient selection once and for all. A similar trial, the Japanese EC/IC Trial (JET), is also working on the question of patient selection. A third trial, the Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON) study, was recently funded by NIH to examine the hotly debated question of whether carotid bypass surgery affects cognitive function.

Stroke is more likely in brains that respond to reduced perfusion (left) with higher OEF (right) in order to support normal oxygen metabolism (middle), some say. Courtesy Dr. Colin Derdeyn

Long abandoned as ineffective at secondary stroke prevention, carotid artery bypass surgery for complete atherosclerotic occlusion is getting a second look.

Known as extracranial/intracranial (EC/IC) bypass, the procedure involves surgical anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA). It is getting its second chance to prove its effectiveness in selected patients for complete carotid occlusion because technologic advances, such as refinement of PET, have made it possible to identify which patients are the best candidates for the procedure.

EC/IC bypass surgery has been shown in a series of small studies to normalize the oxygen extraction fraction (OEF), a marker of impaired cerebral blood flow in patients with carotid occlusion.

Whether that translates into a decreased stroke risk is the subject of the Carotid Occlusion Surgery Study (COSS), a $21-million, 7-year trial funded by the National Institutes of Health that is now underway in 28 U.S. centers.

Candidates for the trial must be patients with symptomatic carotid occlusion and increased OEF on PET. To date, 169 patients have enrolled, and 38 patients have been randomized to treatment.

Enrollment in the nonblinded, controlled clinical trial has been slow, in part because few neurologists knew the option of bypass surgery existed, said Colin Derdeyn, M.D., principal investigator for the Washington University site in St. Louis.

The First EC/IC Bypass Study

STA-MCA surgical anastomosis was developed in 1967 and routinely performed on patients with carotid occlusion throughout the 1970s and mid-1980s.

However, data from the EC/IC Bypass Study showed no benefit for the prevention of subsequent stroke among 808 patients with symptomatic carotid occlusion, despite restoring blood flow to the carotid artery in 96% of cases (N. Engl. J Med. 1985;313:1191-200).

The researchers were unable to assess whether the procedure was more appropriate for one or another group of patients based on their cerebral hemodynamics because at the time the technology necessary to understand and measure cerebral blood flow had not been developed, according to M. Gazi Yasargil, M.D., professor of neurosurgery at the University of Arkansas, Little Rock, the Swiss neurosurgeon who pioneered the surgical procedure. “The time is ripe to work out a perfect indication for bypass surgery,” he said.

Identifying Hemodynamics

PET has made it possible to measure OEF, a proven predictor of which patients have significantly decreased cerebral blood flow and are at increased stroke risk.

When there is unrestricted cerebral blood flow, the brain extracts about 40% of the oxygen delivered to it in the blood. Blood vessels dilate and constrict to maintain an equal OEF across the brain. When cerebral blood flow falls because of reduced perfusion pressure, the brain increases the fraction of oxygen extracted from the blood to 70% or 80% to support normal oxygen metabolism. This elevated OEF allows the brain to maintain normal function, but it puts patients at increased risk for stroke in the future.

Two prospective natural history studies, one conducted in the United States (JAMA 1998;280:1055-69) and the other in Japan (J. Nucl. Med. 1999;40:1992-8), have shown that having an increased OEF as measured by PET is an independent predictor of future stroke in medically treated patients with symptomatic carotid artery occlusion.

Depending on the precise clinical and PET criteria used, the 2-year ipsilateral stroke rates ranged from 26% to 57% in patients with an elevated OEF, compared with stroke rates of 5%-15% in patients with normal OEF, according to Dr. Derdeyn, coauthor of the U.S. study.

“The best information we have right now, as far as connecting an abnormality by physiologic imaging with a risk factor, is for increased oxygen extraction,” Dr. Derdeyn told INTERNAL MEDICINE NEWS. OEF is a powerful and independent predictor of stroke. “It identifies a high-risk subgroup, without question,” he said.

William J. Powers, M.D., principal investigator of COSS, agreed on the importance of identifying subsets of patients most likely to benefit from EC/IC. “It's absolutely clear that if [EC/IC bypass] is ever going to work, there has to be some more refined selection criteria to pick out the people, number one, who would be at particularly high risk if treated with medical therapy, and number two, in whom the subsequent risk of stroke seems to be related to a problem that the bypass would fix,” he told this newspaper.

COSS is based on the hypothesis that surgical anastomosis of the superficial temporal artery to the middle cerebral artery, when added to the best medical therapy, can reduce subsequent ipsilateral ischemic stroke by 40% at 2 years' follow-up in this highly select patient population, despite perioperative stroke and death.

Investigators anticipate that the stroke rate in COSS will turn out to be 40% in the medically treated group and 24% in the surgically treated group, even taking into account a 12% perioperative stroke and mortality rate, as reported in the original EC/IC trial, said Dr. Powers, codirector of the Stroke Center at Barnes-Jewish Hospital and the Washington University School of Medicine.

Even if these reduced stroke rates are borne out by the study, EC/IC bypass surgery is unlikely to become as common as coronary artery bypass; elevated OEF occurs in only 30% of patients with carotid occlusion. The study's $21-million price tag over the next 5-7 years may prove to be money well spent if it settles the question of patient selection once and for all. A similar trial, the Japanese EC/IC Trial (JET), is also working on the question of patient selection. A third trial, the Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON) study, was recently funded by NIH to examine the hotly debated question of whether carotid bypass surgery affects cognitive function.

Stroke is more likely in brains that respond to reduced perfusion (left) with higher OEF (right) in order to support normal oxygen metabolism (middle), some say. Courtesy Dr. Colin Derdeyn

Long abandoned as ineffective at secondary stroke prevention, carotid artery bypass surgery for complete atherosclerotic occlusion is getting a second look.

Known as extracranial/intracranial (EC/IC) bypass, the procedure involves surgical anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA). It is getting its second chance to prove its effectiveness in selected patients for complete carotid occlusion because technologic advances, such as refinement of PET, have made it possible to identify which patients are the best candidates for the procedure.

EC/IC bypass surgery has been shown in a series of small studies to normalize the oxygen extraction fraction (OEF), a marker of impaired cerebral blood flow in patients with carotid occlusion.

Whether that translates into a decreased stroke risk is the subject of the Carotid Occlusion Surgery Study (COSS), a $21-million, 7-year trial funded by the National Institutes of Health that is now underway in 28 U.S. centers.

Candidates for the trial must be patients with symptomatic carotid occlusion and increased OEF on PET. To date, 169 patients have enrolled, and 38 patients have been randomized to treatment.

Enrollment in the nonblinded, controlled clinical trial has been slow, in part because few neurologists knew the option of bypass surgery existed, said Colin Derdeyn, M.D., principal investigator for the Washington University site in St. Louis.

The First EC/IC Bypass Study

STA-MCA surgical anastomosis was developed in 1967 and routinely performed on patients with carotid occlusion throughout the 1970s and mid-1980s.

However, data from the EC/IC Bypass Study showed no benefit for the prevention of subsequent stroke among 808 patients with symptomatic carotid occlusion, despite restoring blood flow to the carotid artery in 96% of cases (N. Engl. J Med. 1985;313:1191-200).

The researchers were unable to assess whether the procedure was more appropriate for one or another group of patients based on their cerebral hemodynamics because at the time the technology necessary to understand and measure cerebral blood flow had not been developed, according to M. Gazi Yasargil, M.D., professor of neurosurgery at the University of Arkansas, Little Rock, the Swiss neurosurgeon who pioneered the surgical procedure. “The time is ripe to work out a perfect indication for bypass surgery,” he said.

Identifying Hemodynamics

PET has made it possible to measure OEF, a proven predictor of which patients have significantly decreased cerebral blood flow and are at increased stroke risk.

When there is unrestricted cerebral blood flow, the brain extracts about 40% of the oxygen delivered to it in the blood. Blood vessels dilate and constrict to maintain an equal OEF across the brain. When cerebral blood flow falls because of reduced perfusion pressure, the brain increases the fraction of oxygen extracted from the blood to 70% or 80% to support normal oxygen metabolism. This elevated OEF allows the brain to maintain normal function, but it puts patients at increased risk for stroke in the future.

Two prospective natural history studies, one conducted in the United States (JAMA 1998;280:1055-69) and the other in Japan (J. Nucl. Med. 1999;40:1992-8), have shown that having an increased OEF as measured by PET is an independent predictor of future stroke in medically treated patients with symptomatic carotid artery occlusion.

Depending on the precise clinical and PET criteria used, the 2-year ipsilateral stroke rates ranged from 26% to 57% in patients with an elevated OEF, compared with stroke rates of 5%-15% in patients with normal OEF, according to Dr. Derdeyn, coauthor of the U.S. study.

“The best information we have right now, as far as connecting an abnormality by physiologic imaging with a risk factor, is for increased oxygen extraction,” Dr. Derdeyn told INTERNAL MEDICINE NEWS. OEF is a powerful and independent predictor of stroke. “It identifies a high-risk subgroup, without question,” he said.

William J. Powers, M.D., principal investigator of COSS, agreed on the importance of identifying subsets of patients most likely to benefit from EC/IC. “It's absolutely clear that if [EC/IC bypass] is ever going to work, there has to be some more refined selection criteria to pick out the people, number one, who would be at particularly high risk if treated with medical therapy, and number two, in whom the subsequent risk of stroke seems to be related to a problem that the bypass would fix,” he told this newspaper.

COSS is based on the hypothesis that surgical anastomosis of the superficial temporal artery to the middle cerebral artery, when added to the best medical therapy, can reduce subsequent ipsilateral ischemic stroke by 40% at 2 years' follow-up in this highly select patient population, despite perioperative stroke and death.

Investigators anticipate that the stroke rate in COSS will turn out to be 40% in the medically treated group and 24% in the surgically treated group, even taking into account a 12% perioperative stroke and mortality rate, as reported in the original EC/IC trial, said Dr. Powers, codirector of the Stroke Center at Barnes-Jewish Hospital and the Washington University School of Medicine.

Even if these reduced stroke rates are borne out by the study, EC/IC bypass surgery is unlikely to become as common as coronary artery bypass; elevated OEF occurs in only 30% of patients with carotid occlusion. The study's $21-million price tag over the next 5-7 years may prove to be money well spent if it settles the question of patient selection once and for all. A similar trial, the Japanese EC/IC Trial (JET), is also working on the question of patient selection. A third trial, the Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON) study, was recently funded by NIH to examine the hotly debated question of whether carotid bypass surgery affects cognitive function.

Stroke is more likely in brains that respond to reduced perfusion (left) with higher OEF (right) in order to support normal oxygen metabolism (middle), some say. Courtesy Dr. Colin Derdeyn

NEW ORLEANS — Thrombolysis was safe and effective for treating acute ischemic stroke in patients who recently underwent cardiac catheterization in a review of 48 cases.

Many physicians have been reluctant to use thrombolysis in such patients because of the erroneous presumptions that the intracranial thrombus would not be dissolved by treatment and that postcatheterization patients are especially vulnerable to intracranial hemorrhage. But these concerns were not borne out by this case review, Pooja Khatri, M.D., said while presenting a poster at the 30th International Stroke Conference.

“This is a great population of patients to treat,” said Dr. Khatri, a neurologist at the University of Cincinnati.

Because these patients are still hospitalized when their strokes occur, they can be quickly diagnosed and treated, she explained.

Dr. Khatri and her associates collected case information on 48 consecutive, eligible patients who were treated at several U.S. academic centers since 2001. All patients had an ischemic stroke within 36 hours of cardiac catheterization. Of them, 10 were treated with tissue plasminogen activator (TPA), and the other 38 received only supportive care.

The median National Institutes of Health Stroke Scale (NIHSS) score at the time of diagnosis was 12 in the patients treated with TPA and 6 in those who did not receive thrombolytic therapy. The study's primary outcome was the median improvement in the NIHSS score at 24 hours after initial diagnosis. The median improvement in NIHSS score was 6 points in the patients who got TPA, compared with 0 points in those who did not, a statistically significant difference, reported Dr. Khatri at the conference, which was sponsored by the American Stroke Association.

By 7 days after diagnosis, scores had improved by a median of 6.5 points in those who got TPA and by a median of 2 points in those who did not, also a statistically significant difference.

Substantially better improvement was seen in patients treated with TPA even when the analysis excluded patients with mild strokes, defined as a NIHSS score of 5 or lower at the time of diagnosis. “This will hopefully lead to a substantial change in patient treatment,” she told CARDIOLOGY NEWS.

None of the 48 patients in the study had a symptomatic, intracranial hemorrhage. Six patients had minor, asymptomatic, intracranial hemorrhages, three in the group that received TPA and three in the group that did not get thrombolysis. A total of five patients had minor bleeding at their catheterization puncture sites; one of these patients had received TPA.

None of the patients in either group required a transfusion. No patient had a retroperitoneal hemorrhage, hemopericardium, or other sites of bleeding, Dr. Khatri said.

NEW ORLEANS — Thrombolysis was safe and effective for treating acute ischemic stroke in patients who recently underwent cardiac catheterization in a review of 48 cases.

Many physicians have been reluctant to use thrombolysis in such patients because of the erroneous presumptions that the intracranial thrombus would not be dissolved by treatment and that postcatheterization patients are especially vulnerable to intracranial hemorrhage. But these concerns were not borne out by this case review, Pooja Khatri, M.D., said while presenting a poster at the 30th International Stroke Conference.

“This is a great population of patients to treat,” said Dr. Khatri, a neurologist at the University of Cincinnati.

Because these patients are still hospitalized when their strokes occur, they can be quickly diagnosed and treated, she explained.

Dr. Khatri and her associates collected case information on 48 consecutive, eligible patients who were treated at several U.S. academic centers since 2001. All patients had an ischemic stroke within 36 hours of cardiac catheterization. Of them, 10 were treated with tissue plasminogen activator (TPA), and the other 38 received only supportive care.

The median National Institutes of Health Stroke Scale (NIHSS) score at the time of diagnosis was 12 in the patients treated with TPA and 6 in those who did not receive thrombolytic therapy. The study's primary outcome was the median improvement in the NIHSS score at 24 hours after initial diagnosis. The median improvement in NIHSS score was 6 points in the patients who got TPA, compared with 0 points in those who did not, a statistically significant difference, reported Dr. Khatri at the conference, which was sponsored by the American Stroke Association.

By 7 days after diagnosis, scores had improved by a median of 6.5 points in those who got TPA and by a median of 2 points in those who did not, also a statistically significant difference.

Substantially better improvement was seen in patients treated with TPA even when the analysis excluded patients with mild strokes, defined as a NIHSS score of 5 or lower at the time of diagnosis. “This will hopefully lead to a substantial change in patient treatment,” she told CARDIOLOGY NEWS.

None of the 48 patients in the study had a symptomatic, intracranial hemorrhage. Six patients had minor, asymptomatic, intracranial hemorrhages, three in the group that received TPA and three in the group that did not get thrombolysis. A total of five patients had minor bleeding at their catheterization puncture sites; one of these patients had received TPA.

None of the patients in either group required a transfusion. No patient had a retroperitoneal hemorrhage, hemopericardium, or other sites of bleeding, Dr. Khatri said.

NEW ORLEANS — Thrombolysis was safe and effective for treating acute ischemic stroke in patients who recently underwent cardiac catheterization in a review of 48 cases.

Many physicians have been reluctant to use thrombolysis in such patients because of the erroneous presumptions that the intracranial thrombus would not be dissolved by treatment and that postcatheterization patients are especially vulnerable to intracranial hemorrhage. But these concerns were not borne out by this case review, Pooja Khatri, M.D., said while presenting a poster at the 30th International Stroke Conference.

“This is a great population of patients to treat,” said Dr. Khatri, a neurologist at the University of Cincinnati.

Because these patients are still hospitalized when their strokes occur, they can be quickly diagnosed and treated, she explained.

Dr. Khatri and her associates collected case information on 48 consecutive, eligible patients who were treated at several U.S. academic centers since 2001. All patients had an ischemic stroke within 36 hours of cardiac catheterization. Of them, 10 were treated with tissue plasminogen activator (TPA), and the other 38 received only supportive care.

The median National Institutes of Health Stroke Scale (NIHSS) score at the time of diagnosis was 12 in the patients treated with TPA and 6 in those who did not receive thrombolytic therapy. The study's primary outcome was the median improvement in the NIHSS score at 24 hours after initial diagnosis. The median improvement in NIHSS score was 6 points in the patients who got TPA, compared with 0 points in those who did not, a statistically significant difference, reported Dr. Khatri at the conference, which was sponsored by the American Stroke Association.

By 7 days after diagnosis, scores had improved by a median of 6.5 points in those who got TPA and by a median of 2 points in those who did not, also a statistically significant difference.

Substantially better improvement was seen in patients treated with TPA even when the analysis excluded patients with mild strokes, defined as a NIHSS score of 5 or lower at the time of diagnosis. “This will hopefully lead to a substantial change in patient treatment,” she told CARDIOLOGY NEWS.

None of the 48 patients in the study had a symptomatic, intracranial hemorrhage. Six patients had minor, asymptomatic, intracranial hemorrhages, three in the group that received TPA and three in the group that did not get thrombolysis. A total of five patients had minor bleeding at their catheterization puncture sites; one of these patients had received TPA.

None of the patients in either group required a transfusion. No patient had a retroperitoneal hemorrhage, hemopericardium, or other sites of bleeding, Dr. Khatri said.

Patients with systemic lupus erythematosus who are under the age of 50 have a high rate of fragility fractures, osteoporosis, and poor bone mineral density, according to new research.

And as expected, steroid use was found to be significantly linked to reduced bone mineral density (BMD), reported C-S Yee of the University of Birmingham and colleagues (Ann. Rheum. Dis. 2005;64:111–113).

Although bisphosphonates are the only class of drugs that have shown efficacy in the treatment and prevention of corticosteroid-induced osteoporosis, their use in premenopausal women poses serious risks of birth defects in the event of an unplanned pregnancy, noted the authors.

The investigation included 242 participants with systemic lupus erythematosus (SLE), 231 (95%) of whom were female.

Study participants were asked to complete a questionnaire about risk factors for osteoporosis, including details about previous fractures and family history of fractures. There were also asked about drug use and in particular about the use of glucocorticoids, oral contraceptives, hormone therapy, calcium and vitamin D supplementation, and bisphosphonates.

Bone mineral densitometry screening was also performed.

Among the women, 126 (54%) were premenopausal, 39 (17%) had experienced premature menopause, and 64 (28%) had experienced normal menopause. The menopausal status of two patients was unknown because they did not fully complete the questionnaire.

A total of 123 patients (51%) had reduced BMD (T score less than −1.0), and 25 were in the osteoporotic range (T score less than −2.5).

Ten of the patients with reduced BMD and 3 in the osteoporotic range were taking bisphosphonates at the time of the scan.

There were 22 patients (9%) who had experienced fragility fractures since their diagnosis of SLE, all of whom were female. Of these, 2 (9%) had normal BMD, while the other 20 (91%) had reduced BMD, with 7 of these women were in the osteoporotic range.

Most of the patients with fragility fractures (82%) were menopausal, and only 3 were taking bisphosphonates at the time of the scan.

Non-Afro-Caribbean race and exposure to prednisolone (more than 10mg/day) were associated with reduced BMD, while age and menopause were associated with osteoporosis, according to the findings of a regression analysis.

Only low BMD and advanced age predicted fractures. Steroid exposure did not predict fracture rates, noted the authors. However, they noted that “it is likely that the effect of steroids on fractures is mediated predominantly by reduction in bone density in susceptible individuals.”

Despite a high prevalence of fractures in this cohort, the authors noted a low prevalence among the premenopausal women (3%).

Because the teratogenic risks of bisphosphonates are most relevant in premenopausal women, “we recommend bisphosphonates only in those premenopausal SLE patients with osteopenia or osteoporosis who require long-term, high-dose steroids. Bisphosphonates with the least evidence of persistence in the skeleton should be used,” they said.

Patients with systemic lupus erythematosus who are under the age of 50 have a high rate of fragility fractures, osteoporosis, and poor bone mineral density, according to new research.

And as expected, steroid use was found to be significantly linked to reduced bone mineral density (BMD), reported C-S Yee of the University of Birmingham and colleagues (Ann. Rheum. Dis. 2005;64:111–113).

Although bisphosphonates are the only class of drugs that have shown efficacy in the treatment and prevention of corticosteroid-induced osteoporosis, their use in premenopausal women poses serious risks of birth defects in the event of an unplanned pregnancy, noted the authors.

The investigation included 242 participants with systemic lupus erythematosus (SLE), 231 (95%) of whom were female.

Study participants were asked to complete a questionnaire about risk factors for osteoporosis, including details about previous fractures and family history of fractures. There were also asked about drug use and in particular about the use of glucocorticoids, oral contraceptives, hormone therapy, calcium and vitamin D supplementation, and bisphosphonates.

Bone mineral densitometry screening was also performed.

Among the women, 126 (54%) were premenopausal, 39 (17%) had experienced premature menopause, and 64 (28%) had experienced normal menopause. The menopausal status of two patients was unknown because they did not fully complete the questionnaire.

A total of 123 patients (51%) had reduced BMD (T score less than −1.0), and 25 were in the osteoporotic range (T score less than −2.5).

Ten of the patients with reduced BMD and 3 in the osteoporotic range were taking bisphosphonates at the time of the scan.

There were 22 patients (9%) who had experienced fragility fractures since their diagnosis of SLE, all of whom were female. Of these, 2 (9%) had normal BMD, while the other 20 (91%) had reduced BMD, with 7 of these women were in the osteoporotic range.

Most of the patients with fragility fractures (82%) were menopausal, and only 3 were taking bisphosphonates at the time of the scan.

Non-Afro-Caribbean race and exposure to prednisolone (more than 10mg/day) were associated with reduced BMD, while age and menopause were associated with osteoporosis, according to the findings of a regression analysis.

Only low BMD and advanced age predicted fractures. Steroid exposure did not predict fracture rates, noted the authors. However, they noted that “it is likely that the effect of steroids on fractures is mediated predominantly by reduction in bone density in susceptible individuals.”

Despite a high prevalence of fractures in this cohort, the authors noted a low prevalence among the premenopausal women (3%).

Because the teratogenic risks of bisphosphonates are most relevant in premenopausal women, “we recommend bisphosphonates only in those premenopausal SLE patients with osteopenia or osteoporosis who require long-term, high-dose steroids. Bisphosphonates with the least evidence of persistence in the skeleton should be used,” they said.

Patients with systemic lupus erythematosus who are under the age of 50 have a high rate of fragility fractures, osteoporosis, and poor bone mineral density, according to new research.

And as expected, steroid use was found to be significantly linked to reduced bone mineral density (BMD), reported C-S Yee of the University of Birmingham and colleagues (Ann. Rheum. Dis. 2005;64:111–113).

Although bisphosphonates are the only class of drugs that have shown efficacy in the treatment and prevention of corticosteroid-induced osteoporosis, their use in premenopausal women poses serious risks of birth defects in the event of an unplanned pregnancy, noted the authors.

The investigation included 242 participants with systemic lupus erythematosus (SLE), 231 (95%) of whom were female.

Study participants were asked to complete a questionnaire about risk factors for osteoporosis, including details about previous fractures and family history of fractures. There were also asked about drug use and in particular about the use of glucocorticoids, oral contraceptives, hormone therapy, calcium and vitamin D supplementation, and bisphosphonates.

Bone mineral densitometry screening was also performed.

Among the women, 126 (54%) were premenopausal, 39 (17%) had experienced premature menopause, and 64 (28%) had experienced normal menopause. The menopausal status of two patients was unknown because they did not fully complete the questionnaire.

A total of 123 patients (51%) had reduced BMD (T score less than −1.0), and 25 were in the osteoporotic range (T score less than −2.5).

Ten of the patients with reduced BMD and 3 in the osteoporotic range were taking bisphosphonates at the time of the scan.

There were 22 patients (9%) who had experienced fragility fractures since their diagnosis of SLE, all of whom were female. Of these, 2 (9%) had normal BMD, while the other 20 (91%) had reduced BMD, with 7 of these women were in the osteoporotic range.

Most of the patients with fragility fractures (82%) were menopausal, and only 3 were taking bisphosphonates at the time of the scan.

Non-Afro-Caribbean race and exposure to prednisolone (more than 10mg/day) were associated with reduced BMD, while age and menopause were associated with osteoporosis, according to the findings of a regression analysis.

Only low BMD and advanced age predicted fractures. Steroid exposure did not predict fracture rates, noted the authors. However, they noted that “it is likely that the effect of steroids on fractures is mediated predominantly by reduction in bone density in susceptible individuals.”

Despite a high prevalence of fractures in this cohort, the authors noted a low prevalence among the premenopausal women (3%).

Because the teratogenic risks of bisphosphonates are most relevant in premenopausal women, “we recommend bisphosphonates only in those premenopausal SLE patients with osteopenia or osteoporosis who require long-term, high-dose steroids. Bisphosphonates with the least evidence of persistence in the skeleton should be used,” they said.

The Food and Drug administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in a controlled study of patients with severe pulmonary hypertension. The randomized clinical trial leading to approval enrolled 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6–9 inhalations per day) was 19% vs. 4% for the placebo group. The rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost comes in single-use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Iloprost should not be inhaled more than once every 2 hours and is not effective in sleeping patients. Vital signs should be monitored when starting iloprost because of the risk of syncope.

Iloprost, not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, the drug's marketer in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA, in August 2004.

The Food and Drug administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in a controlled study of patients with severe pulmonary hypertension. The randomized clinical trial leading to approval enrolled 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6–9 inhalations per day) was 19% vs. 4% for the placebo group. The rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost comes in single-use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Iloprost should not be inhaled more than once every 2 hours and is not effective in sleeping patients. Vital signs should be monitored when starting iloprost because of the risk of syncope.

Iloprost, not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, the drug's marketer in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA, in August 2004.

The Food and Drug administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in a controlled study of patients with severe pulmonary hypertension. The randomized clinical trial leading to approval enrolled 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6–9 inhalations per day) was 19% vs. 4% for the placebo group. The rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost comes in single-use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Iloprost should not be inhaled more than once every 2 hours and is not effective in sleeping patients. Vital signs should be monitored when starting iloprost because of the risk of syncope.

Iloprost, not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, the drug's marketer in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA, in August 2004.