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.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of hydroxychloroquine, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus.

Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy. In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

No unusual side effects occurred in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of hydroxychloroquine, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus.

Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy. In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

No unusual side effects occurred in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of hydroxychloroquine, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus.

Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy. In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

No unusual side effects occurred in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children.