Jeff Evans

WASHINGTON — Carotid artery stenting may provide a safe and effective means of restoring ocular blood circulation and improving the vision of patients with severe carotid stenosis, especially those with chronic ocular ischemic syndrome, Dr. Shoichiro Kawaguchi reported at the annual meeting of the American Association of Neurological Surgeons.

“It is well-known that severe internal carotid stenosis influences the flow dynamics of the ophthalmic artery in chronic ocular ischemic syndrome,” said Dr. Kawaguchi of the department of neurosurgery at Nara (Japan) Medical University.

Of the 38 patients in the study with internal carotid artery stenosis of 80% or more, 9 had experienced clinical symptoms of a transient ischemic attack and 29 had reversible ischemic neurologic deficits. Eight of those with reversible ischemic neurologic deficits had chronic ocular ischemic syndrome.

Before undergoing carotid artery stenting (CAS), 13 patients exhibited a reversed flow pattern on ophthalmic artery color Doppler flow imaging, whereas the other 25 patients showed an arch stenosis (antegrade) flow pattern. At 24 hours after CAS, all patients had an antegrade flow pattern and a significant rise in mean peak systolic flow velocity in the ophthalmic artery from −0.038 m/sec before CAS to 0.36 m/sec afterward. All CAS procedures were performed on patients under general anesthesia more than 4 weeks after their last neurologic event.

There was no difference in the degree of carotid stenosis among patients with or without chronic ocular ischemic syndrome, but those with the syndrome had significant improvement in peak systolic flow velocity in the ophthalmic artery.

Measurements did not change significantly from 1 week to 3 months after CAS. Seven of the eight patients with chronic ocular ischemic syndrome improved their visual acuity during the mean follow-up of 2.8 years.

WASHINGTON — Carotid artery stenting may provide a safe and effective means of restoring ocular blood circulation and improving the vision of patients with severe carotid stenosis, especially those with chronic ocular ischemic syndrome, Dr. Shoichiro Kawaguchi reported at the annual meeting of the American Association of Neurological Surgeons.

“It is well-known that severe internal carotid stenosis influences the flow dynamics of the ophthalmic artery in chronic ocular ischemic syndrome,” said Dr. Kawaguchi of the department of neurosurgery at Nara (Japan) Medical University.

Of the 38 patients in the study with internal carotid artery stenosis of 80% or more, 9 had experienced clinical symptoms of a transient ischemic attack and 29 had reversible ischemic neurologic deficits. Eight of those with reversible ischemic neurologic deficits had chronic ocular ischemic syndrome.

Before undergoing carotid artery stenting (CAS), 13 patients exhibited a reversed flow pattern on ophthalmic artery color Doppler flow imaging, whereas the other 25 patients showed an arch stenosis (antegrade) flow pattern. At 24 hours after CAS, all patients had an antegrade flow pattern and a significant rise in mean peak systolic flow velocity in the ophthalmic artery from −0.038 m/sec before CAS to 0.36 m/sec afterward. All CAS procedures were performed on patients under general anesthesia more than 4 weeks after their last neurologic event.

There was no difference in the degree of carotid stenosis among patients with or without chronic ocular ischemic syndrome, but those with the syndrome had significant improvement in peak systolic flow velocity in the ophthalmic artery.

Measurements did not change significantly from 1 week to 3 months after CAS. Seven of the eight patients with chronic ocular ischemic syndrome improved their visual acuity during the mean follow-up of 2.8 years.

WASHINGTON — Carotid artery stenting may provide a safe and effective means of restoring ocular blood circulation and improving the vision of patients with severe carotid stenosis, especially those with chronic ocular ischemic syndrome, Dr. Shoichiro Kawaguchi reported at the annual meeting of the American Association of Neurological Surgeons.

“It is well-known that severe internal carotid stenosis influences the flow dynamics of the ophthalmic artery in chronic ocular ischemic syndrome,” said Dr. Kawaguchi of the department of neurosurgery at Nara (Japan) Medical University.

Of the 38 patients in the study with internal carotid artery stenosis of 80% or more, 9 had experienced clinical symptoms of a transient ischemic attack and 29 had reversible ischemic neurologic deficits. Eight of those with reversible ischemic neurologic deficits had chronic ocular ischemic syndrome.

Before undergoing carotid artery stenting (CAS), 13 patients exhibited a reversed flow pattern on ophthalmic artery color Doppler flow imaging, whereas the other 25 patients showed an arch stenosis (antegrade) flow pattern. At 24 hours after CAS, all patients had an antegrade flow pattern and a significant rise in mean peak systolic flow velocity in the ophthalmic artery from −0.038 m/sec before CAS to 0.36 m/sec afterward. All CAS procedures were performed on patients under general anesthesia more than 4 weeks after their last neurologic event.

There was no difference in the degree of carotid stenosis among patients with or without chronic ocular ischemic syndrome, but those with the syndrome had significant improvement in peak systolic flow velocity in the ophthalmic artery.

Measurements did not change significantly from 1 week to 3 months after CAS. Seven of the eight patients with chronic ocular ischemic syndrome improved their visual acuity during the mean follow-up of 2.8 years.

WASHINGTON — Depressed or anxious patients who are referred to cardiac rehabilitation programs are significantly more likely to comply poorly or have a poorer outcome than are patients without the conditions, Angele McGrady, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Because of this, patients who are referred to cardiac rehabilitation programs “need to be quickly screened for depression and anxiety prior to entering rehabilitation, said Dr. McGrady, who is professor of psychiatry at the University of Toledo (Ohio).

Depression is a known risk factor for the development and worsening of coronary heart disease (Psychosom. Med. 2005;67 [suppl. 1]:S19-S25).

Anxiety also may be a risk factor for CHD. Recent research has associated high levels of phobic anxiety with an increased risk of a fatal cardiac event (Circulation 2005;111:480–7).

At the University of Toledo Medical Center, patients who have angina or chronic heart failure, or who have had a myocardial infarction or a coronary artery bypass graft (CABG), get referred to the cardiac rehabilitation program. Such programs are known to be effective in reducing mortality. But in order for patients to benefit, they must complete the full program of exercise, stress management, and nutritional counseling, Dr. McGrady said.

In the rehabilitation program, patients are first psychologically assessed using the Beck Depression Inventory, the Beck Anxiety Inventory, and the SF-36 quality of life measure. A week later, patients come back for a walk test (number of feet walked in a certain period of time).

Over the next 6 months, the patients attend 36 sessions that are largely exercise based; these sessions also include stress management, smoking cessation, and lifestyle counseling, such as nutritional assessment and recommendations for improving nutrition. At the end of 6 months, psychological and physical tests are repeated.

Of 380 consecutive patients who were referred to the medical center over a period of about 2 years, exactly half completed the full rehabilitation program. Other centers have reported dropout rates at cardiac rehabilitation centers ranging from 20% to 65%, she said.

The overall sample had an average age of 61 years; most patients were males (63%) and white (79%). Completers tended to have a higher average age (63 years vs. 59 years) and were more often male (67% vs. 60%) than were noncompleters.

On entry to the rehabilitation program, the 190 patients who completed the program had a significantly lower mean Beck Depression Inventory score than did the 190 noncompleters (8.6 vs. 11.7). The completers also reported a significantly higher initial quality of life than did noncompleters in physical (39.2 vs. 35.7) and mental health (47.6 vs. 43.4).

Beck Anxiety Inventory scores were significantly lower among the completers than in a group of 68 early dropout patients who did not come back at week 2 for the walk test and did not begin the program.

This means that the only chance to catch the nearly 20% of patients who dropped out early, before even starting the actual rehabilitation process, was at the time of the psychological assessment. Early interventions at this point could improve adherence to the program and subsequent outcomes, Dr. McGrady said.

According to the diagnostic category of patients, those who had myocardial infarction, angina, or heart failure had significantly higher anxiety scores than did patients who underwent CABG. Heart failure patients also had significantly higher depression scores than did those who underwent CABG.

No significant differences between patients in different diagnostic categories were found on walk tests or in the patients' perceptions of physical health.

WASHINGTON — Depressed or anxious patients who are referred to cardiac rehabilitation programs are significantly more likely to comply poorly or have a poorer outcome than are patients without the conditions, Angele McGrady, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Because of this, patients who are referred to cardiac rehabilitation programs “need to be quickly screened for depression and anxiety prior to entering rehabilitation, said Dr. McGrady, who is professor of psychiatry at the University of Toledo (Ohio).

Depression is a known risk factor for the development and worsening of coronary heart disease (Psychosom. Med. 2005;67 [suppl. 1]:S19-S25).

Anxiety also may be a risk factor for CHD. Recent research has associated high levels of phobic anxiety with an increased risk of a fatal cardiac event (Circulation 2005;111:480–7).

At the University of Toledo Medical Center, patients who have angina or chronic heart failure, or who have had a myocardial infarction or a coronary artery bypass graft (CABG), get referred to the cardiac rehabilitation program. Such programs are known to be effective in reducing mortality. But in order for patients to benefit, they must complete the full program of exercise, stress management, and nutritional counseling, Dr. McGrady said.

In the rehabilitation program, patients are first psychologically assessed using the Beck Depression Inventory, the Beck Anxiety Inventory, and the SF-36 quality of life measure. A week later, patients come back for a walk test (number of feet walked in a certain period of time).

Over the next 6 months, the patients attend 36 sessions that are largely exercise based; these sessions also include stress management, smoking cessation, and lifestyle counseling, such as nutritional assessment and recommendations for improving nutrition. At the end of 6 months, psychological and physical tests are repeated.

Of 380 consecutive patients who were referred to the medical center over a period of about 2 years, exactly half completed the full rehabilitation program. Other centers have reported dropout rates at cardiac rehabilitation centers ranging from 20% to 65%, she said.

The overall sample had an average age of 61 years; most patients were males (63%) and white (79%). Completers tended to have a higher average age (63 years vs. 59 years) and were more often male (67% vs. 60%) than were noncompleters.

On entry to the rehabilitation program, the 190 patients who completed the program had a significantly lower mean Beck Depression Inventory score than did the 190 noncompleters (8.6 vs. 11.7). The completers also reported a significantly higher initial quality of life than did noncompleters in physical (39.2 vs. 35.7) and mental health (47.6 vs. 43.4).

Beck Anxiety Inventory scores were significantly lower among the completers than in a group of 68 early dropout patients who did not come back at week 2 for the walk test and did not begin the program.

This means that the only chance to catch the nearly 20% of patients who dropped out early, before even starting the actual rehabilitation process, was at the time of the psychological assessment. Early interventions at this point could improve adherence to the program and subsequent outcomes, Dr. McGrady said.

According to the diagnostic category of patients, those who had myocardial infarction, angina, or heart failure had significantly higher anxiety scores than did patients who underwent CABG. Heart failure patients also had significantly higher depression scores than did those who underwent CABG.

No significant differences between patients in different diagnostic categories were found on walk tests or in the patients' perceptions of physical health.

WASHINGTON — Depressed or anxious patients who are referred to cardiac rehabilitation programs are significantly more likely to comply poorly or have a poorer outcome than are patients without the conditions, Angele McGrady, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Because of this, patients who are referred to cardiac rehabilitation programs “need to be quickly screened for depression and anxiety prior to entering rehabilitation, said Dr. McGrady, who is professor of psychiatry at the University of Toledo (Ohio).

Depression is a known risk factor for the development and worsening of coronary heart disease (Psychosom. Med. 2005;67 [suppl. 1]:S19-S25).

Anxiety also may be a risk factor for CHD. Recent research has associated high levels of phobic anxiety with an increased risk of a fatal cardiac event (Circulation 2005;111:480–7).

At the University of Toledo Medical Center, patients who have angina or chronic heart failure, or who have had a myocardial infarction or a coronary artery bypass graft (CABG), get referred to the cardiac rehabilitation program. Such programs are known to be effective in reducing mortality. But in order for patients to benefit, they must complete the full program of exercise, stress management, and nutritional counseling, Dr. McGrady said.

In the rehabilitation program, patients are first psychologically assessed using the Beck Depression Inventory, the Beck Anxiety Inventory, and the SF-36 quality of life measure. A week later, patients come back for a walk test (number of feet walked in a certain period of time).

Over the next 6 months, the patients attend 36 sessions that are largely exercise based; these sessions also include stress management, smoking cessation, and lifestyle counseling, such as nutritional assessment and recommendations for improving nutrition. At the end of 6 months, psychological and physical tests are repeated.

Of 380 consecutive patients who were referred to the medical center over a period of about 2 years, exactly half completed the full rehabilitation program. Other centers have reported dropout rates at cardiac rehabilitation centers ranging from 20% to 65%, she said.

The overall sample had an average age of 61 years; most patients were males (63%) and white (79%). Completers tended to have a higher average age (63 years vs. 59 years) and were more often male (67% vs. 60%) than were noncompleters.

On entry to the rehabilitation program, the 190 patients who completed the program had a significantly lower mean Beck Depression Inventory score than did the 190 noncompleters (8.6 vs. 11.7). The completers also reported a significantly higher initial quality of life than did noncompleters in physical (39.2 vs. 35.7) and mental health (47.6 vs. 43.4).

Beck Anxiety Inventory scores were significantly lower among the completers than in a group of 68 early dropout patients who did not come back at week 2 for the walk test and did not begin the program.

This means that the only chance to catch the nearly 20% of patients who dropped out early, before even starting the actual rehabilitation process, was at the time of the psychological assessment. Early interventions at this point could improve adherence to the program and subsequent outcomes, Dr. McGrady said.

According to the diagnostic category of patients, those who had myocardial infarction, angina, or heart failure had significantly higher anxiety scores than did patients who underwent CABG. Heart failure patients also had significantly higher depression scores than did those who underwent CABG.

No significant differences between patients in different diagnostic categories were found on walk tests or in the patients' perceptions of physical health.

Rosiglitazone may be associated with an increased risk of myocardial infarction, according to the results of a meta-analysis of 42 published and unpublished randomized trials.

Patients who received rosiglitazone (Avandia) were 43% more likely to have an MI than were patients who received an active comparator drug or a placebo during 24–52 weeks of treatment. This result was significant but had a wide confidence interval that placed the increase in risk between 3% and 98%. Rosiglitazone also was associated with a nonsignificant 64% increase in the odds of death from cardiovascular causes, reported Dr. Steven E. Nissen and Kathy Wolski of the Cleveland Clinic (N. Engl. J. Med. 2007 [Epub doi: 10.1056/NEJMoa072761]).

“Because exposure of such patients to rosiglitazone is widespread, the public health impact of an increase in cardiovascular risk could be substantial if our data are borne out by further analysis and the results of larger controlled trials,” they wrote.

In response to the current study, the manufacturer of rosiglitazone, GlaxoSmithKline, issued a statement saying that the company “strongly disagrees with the conclusions … which are based on incomplete evidence and a methodology that the author admits has significant limitations.”

The meta-analysis involved 5 studies that originally were submitted to the Food and Drug Administration for an advisory board hearing on the drug's approval, 35 clinical trials initially identified in GlaxoSmithKline's clinical-trial registry (9 published and 26 unpublished), and 2 large, recently published clinical trials (DREAM—Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication and ADOPT—A Diabetes Outcome Progression Trial). These trials included 15,560 patients who were randomized to receive regimens that included rosiglitazone and 12,283 assigned to control groups that received an active comparator or placebo.

The small number of MIs (86 with rosiglitazone and 72 with control) and deaths from cardiovascular causes (39 with rosiglitazone and 22 with control) make the results susceptible to small changes in the classification of events. The lack of a standard method for identifying or validating outcomes in the trials might have caused these events to be missed or misclassified, Dr. Bruce M. Psaty of the University of Washington, Seattle, and Dr. Curt D. Furberg of Wake Forest University, Winston-Salem, N.C., wrote in an accompanying editorial (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa072761]).

The investigators had access to only trial-level data and not to patient-level data, and thus could not determine the outcome of the composite of death or myocardial infarction. Time-to-event data for cardiovascular events were not available for these trials, so hazard ratios could not be calculated.

GlaxoSmithKline is conducting the randomized, open-label Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial. In a teleconference on May 21, Dr. Robert J. Meyer of the FDA's Center for Drug Evaluation and Research said an interim analysis of the safety data from RECORD was “reassuring.” In its statement, GlaxoSmithKline said it “has not found any safety risk that would interrupt” of the trial.

An unpublished reanalysis of the DREAM trial also provides “contradictory evidence about the risk in patients treated with Avandia,” compared with the current meta-analysis, Dr. Meyer said.

The FDA does not know if the potential increased risk of MI or heart-related death extends to other thiazolidinedione drugs, such as pioglitazone (Actos), he said.

Dr. Meyer said the FDA received a meta-analysis from GlaxoSmithKline in August 2006 that included 42 randomized, controlled trials (many of which are likely the same as those in the current study). The FDA is reanalyzing this study because of some issues with the way in which the company conducted its analysis. That meta-analysis also indicated an increased risk of MI and heart-related adverse events.

Dr. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, said, “I would not consider an analysis by the company to be useful here. We really have to focus on analyses done by independent people, and that includes perhaps the FDA and certainly outside physician-scientists,”

The rosiglitazone label was recently changed to include a warning about a potential increase in heart attacks and heart-related chest pain in some individuals. This warning was based on the result of a controlled clinical trial in patients with existing heart failure, according to the FDA.

In their editorial, Dr. Psaty and Dr. Furberg said that, “in view of the potential cardiovascular risks and in the absence of evidence of other health advantages, except for laboratory measures of glycemic control, the rationale for prescribing rosiglitazone at this time is unclear. Unless new data provide a different picture of the risk-benefit profile, regulatory action by the FDA is now warranted.”

According to Dr. Nissen, “the FDA needs to begin to think more clearly about these kinds of risky situations and act earlier.”

Dr. Meyer said that the FDA would not exclude any regulatory action at this point, and an advisory board committee meeting could take place in the next few months.

The investigators said their results led them to question “the appropriateness of the current regulatory pathways for the development of drugs to treat diabetes,” a sentiment that was echoed in the editorial.

“Rosiglitazone was approved on the basis of short-term studies of the surrogate end point of glycemic control,” Dr. Psaty and Dr. Furberg wrote.

But the underlying assumption that high levels of glycated hemoglobin increase risk and that a reduction in this measure will improve health outcomes “ignores the many actions of the genes activated by PPAR-γ agonists, only some of which are currently known. Many physicians did not require proof of health benefits as a criterion for selecting rosiglitazone as a therapy for type 2 diabetes,” they added.

Rosiglitazone potentially could contribute to the risk of MI by increasing LDL cholesterol levels or modestly reducing hemoglobin levels, which could provoke ischemic events in those with heart failure, the investigators said.

Dr. Richard Hellman, president of the American Association of Clinical Endocrinologists, noted that glitazones probably affect more than 100 human genes. “When an agent is so active at the gene level, postmarketing studies need to address the issue of special populations,” said Dr. Hellman, clinical professor of medicine, University of Missouri, Kansas City. The findings “provide more ammunition for increased caution” in prescribing rosiglitazone.

'The FDA needs to begin to think more clearly about these kinds of risky situations and act earlier.' DR. NISSEN

Rosiglitazone may be associated with an increased risk of myocardial infarction, according to the results of a meta-analysis of 42 published and unpublished randomized trials.

Patients who received rosiglitazone (Avandia) were 43% more likely to have an MI than were patients who received an active comparator drug or a placebo during 24–52 weeks of treatment. This result was significant but had a wide confidence interval that placed the increase in risk between 3% and 98%. Rosiglitazone also was associated with a nonsignificant 64% increase in the odds of death from cardiovascular causes, reported Dr. Steven E. Nissen and Kathy Wolski of the Cleveland Clinic (N. Engl. J. Med. 2007 [Epub doi: 10.1056/NEJMoa072761]).

“Because exposure of such patients to rosiglitazone is widespread, the public health impact of an increase in cardiovascular risk could be substantial if our data are borne out by further analysis and the results of larger controlled trials,” they wrote.

In response to the current study, the manufacturer of rosiglitazone, GlaxoSmithKline, issued a statement saying that the company “strongly disagrees with the conclusions … which are based on incomplete evidence and a methodology that the author admits has significant limitations.”

The meta-analysis involved 5 studies that originally were submitted to the Food and Drug Administration for an advisory board hearing on the drug's approval, 35 clinical trials initially identified in GlaxoSmithKline's clinical-trial registry (9 published and 26 unpublished), and 2 large, recently published clinical trials (DREAM—Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication and ADOPT—A Diabetes Outcome Progression Trial). These trials included 15,560 patients who were randomized to receive regimens that included rosiglitazone and 12,283 assigned to control groups that received an active comparator or placebo.

The small number of MIs (86 with rosiglitazone and 72 with control) and deaths from cardiovascular causes (39 with rosiglitazone and 22 with control) make the results susceptible to small changes in the classification of events. The lack of a standard method for identifying or validating outcomes in the trials might have caused these events to be missed or misclassified, Dr. Bruce M. Psaty of the University of Washington, Seattle, and Dr. Curt D. Furberg of Wake Forest University, Winston-Salem, N.C., wrote in an accompanying editorial (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa072761]).

The investigators had access to only trial-level data and not to patient-level data, and thus could not determine the outcome of the composite of death or myocardial infarction. Time-to-event data for cardiovascular events were not available for these trials, so hazard ratios could not be calculated.

GlaxoSmithKline is conducting the randomized, open-label Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial. In a teleconference on May 21, Dr. Robert J. Meyer of the FDA's Center for Drug Evaluation and Research said an interim analysis of the safety data from RECORD was “reassuring.” In its statement, GlaxoSmithKline said it “has not found any safety risk that would interrupt” of the trial.

An unpublished reanalysis of the DREAM trial also provides “contradictory evidence about the risk in patients treated with Avandia,” compared with the current meta-analysis, Dr. Meyer said.

The FDA does not know if the potential increased risk of MI or heart-related death extends to other thiazolidinedione drugs, such as pioglitazone (Actos), he said.

Dr. Meyer said the FDA received a meta-analysis from GlaxoSmithKline in August 2006 that included 42 randomized, controlled trials (many of which are likely the same as those in the current study). The FDA is reanalyzing this study because of some issues with the way in which the company conducted its analysis. That meta-analysis also indicated an increased risk of MI and heart-related adverse events.

Dr. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, said, “I would not consider an analysis by the company to be useful here. We really have to focus on analyses done by independent people, and that includes perhaps the FDA and certainly outside physician-scientists,”

The rosiglitazone label was recently changed to include a warning about a potential increase in heart attacks and heart-related chest pain in some individuals. This warning was based on the result of a controlled clinical trial in patients with existing heart failure, according to the FDA.

In their editorial, Dr. Psaty and Dr. Furberg said that, “in view of the potential cardiovascular risks and in the absence of evidence of other health advantages, except for laboratory measures of glycemic control, the rationale for prescribing rosiglitazone at this time is unclear. Unless new data provide a different picture of the risk-benefit profile, regulatory action by the FDA is now warranted.”

According to Dr. Nissen, “the FDA needs to begin to think more clearly about these kinds of risky situations and act earlier.”

Dr. Meyer said that the FDA would not exclude any regulatory action at this point, and an advisory board committee meeting could take place in the next few months.

The investigators said their results led them to question “the appropriateness of the current regulatory pathways for the development of drugs to treat diabetes,” a sentiment that was echoed in the editorial.

“Rosiglitazone was approved on the basis of short-term studies of the surrogate end point of glycemic control,” Dr. Psaty and Dr. Furberg wrote.

But the underlying assumption that high levels of glycated hemoglobin increase risk and that a reduction in this measure will improve health outcomes “ignores the many actions of the genes activated by PPAR-γ agonists, only some of which are currently known. Many physicians did not require proof of health benefits as a criterion for selecting rosiglitazone as a therapy for type 2 diabetes,” they added.

Rosiglitazone potentially could contribute to the risk of MI by increasing LDL cholesterol levels or modestly reducing hemoglobin levels, which could provoke ischemic events in those with heart failure, the investigators said.

Dr. Richard Hellman, president of the American Association of Clinical Endocrinologists, noted that glitazones probably affect more than 100 human genes. “When an agent is so active at the gene level, postmarketing studies need to address the issue of special populations,” said Dr. Hellman, clinical professor of medicine, University of Missouri, Kansas City. The findings “provide more ammunition for increased caution” in prescribing rosiglitazone.

'The FDA needs to begin to think more clearly about these kinds of risky situations and act earlier.' DR. NISSEN

Rosiglitazone may be associated with an increased risk of myocardial infarction, according to the results of a meta-analysis of 42 published and unpublished randomized trials.

Patients who received rosiglitazone (Avandia) were 43% more likely to have an MI than were patients who received an active comparator drug or a placebo during 24–52 weeks of treatment. This result was significant but had a wide confidence interval that placed the increase in risk between 3% and 98%. Rosiglitazone also was associated with a nonsignificant 64% increase in the odds of death from cardiovascular causes, reported Dr. Steven E. Nissen and Kathy Wolski of the Cleveland Clinic (N. Engl. J. Med. 2007 [Epub doi: 10.1056/NEJMoa072761]).

“Because exposure of such patients to rosiglitazone is widespread, the public health impact of an increase in cardiovascular risk could be substantial if our data are borne out by further analysis and the results of larger controlled trials,” they wrote.

In response to the current study, the manufacturer of rosiglitazone, GlaxoSmithKline, issued a statement saying that the company “strongly disagrees with the conclusions … which are based on incomplete evidence and a methodology that the author admits has significant limitations.”

The meta-analysis involved 5 studies that originally were submitted to the Food and Drug Administration for an advisory board hearing on the drug's approval, 35 clinical trials initially identified in GlaxoSmithKline's clinical-trial registry (9 published and 26 unpublished), and 2 large, recently published clinical trials (DREAM—Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication and ADOPT—A Diabetes Outcome Progression Trial). These trials included 15,560 patients who were randomized to receive regimens that included rosiglitazone and 12,283 assigned to control groups that received an active comparator or placebo.

The small number of MIs (86 with rosiglitazone and 72 with control) and deaths from cardiovascular causes (39 with rosiglitazone and 22 with control) make the results susceptible to small changes in the classification of events. The lack of a standard method for identifying or validating outcomes in the trials might have caused these events to be missed or misclassified, Dr. Bruce M. Psaty of the University of Washington, Seattle, and Dr. Curt D. Furberg of Wake Forest University, Winston-Salem, N.C., wrote in an accompanying editorial (N. Engl. J. Med. 2007 [Epub doi:10.1056/NEJMoa072761]).

The investigators had access to only trial-level data and not to patient-level data, and thus could not determine the outcome of the composite of death or myocardial infarction. Time-to-event data for cardiovascular events were not available for these trials, so hazard ratios could not be calculated.

GlaxoSmithKline is conducting the randomized, open-label Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial. In a teleconference on May 21, Dr. Robert J. Meyer of the FDA's Center for Drug Evaluation and Research said an interim analysis of the safety data from RECORD was “reassuring.” In its statement, GlaxoSmithKline said it “has not found any safety risk that would interrupt” of the trial.

An unpublished reanalysis of the DREAM trial also provides “contradictory evidence about the risk in patients treated with Avandia,” compared with the current meta-analysis, Dr. Meyer said.

The FDA does not know if the potential increased risk of MI or heart-related death extends to other thiazolidinedione drugs, such as pioglitazone (Actos), he said.

Dr. Meyer said the FDA received a meta-analysis from GlaxoSmithKline in August 2006 that included 42 randomized, controlled trials (many of which are likely the same as those in the current study). The FDA is reanalyzing this study because of some issues with the way in which the company conducted its analysis. That meta-analysis also indicated an increased risk of MI and heart-related adverse events.

Dr. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, said, “I would not consider an analysis by the company to be useful here. We really have to focus on analyses done by independent people, and that includes perhaps the FDA and certainly outside physician-scientists,”

The rosiglitazone label was recently changed to include a warning about a potential increase in heart attacks and heart-related chest pain in some individuals. This warning was based on the result of a controlled clinical trial in patients with existing heart failure, according to the FDA.

In their editorial, Dr. Psaty and Dr. Furberg said that, “in view of the potential cardiovascular risks and in the absence of evidence of other health advantages, except for laboratory measures of glycemic control, the rationale for prescribing rosiglitazone at this time is unclear. Unless new data provide a different picture of the risk-benefit profile, regulatory action by the FDA is now warranted.”

According to Dr. Nissen, “the FDA needs to begin to think more clearly about these kinds of risky situations and act earlier.”

Dr. Meyer said that the FDA would not exclude any regulatory action at this point, and an advisory board committee meeting could take place in the next few months.

The investigators said their results led them to question “the appropriateness of the current regulatory pathways for the development of drugs to treat diabetes,” a sentiment that was echoed in the editorial.

“Rosiglitazone was approved on the basis of short-term studies of the surrogate end point of glycemic control,” Dr. Psaty and Dr. Furberg wrote.

But the underlying assumption that high levels of glycated hemoglobin increase risk and that a reduction in this measure will improve health outcomes “ignores the many actions of the genes activated by PPAR-γ agonists, only some of which are currently known. Many physicians did not require proof of health benefits as a criterion for selecting rosiglitazone as a therapy for type 2 diabetes,” they added.

Rosiglitazone potentially could contribute to the risk of MI by increasing LDL cholesterol levels or modestly reducing hemoglobin levels, which could provoke ischemic events in those with heart failure, the investigators said.

Dr. Richard Hellman, president of the American Association of Clinical Endocrinologists, noted that glitazones probably affect more than 100 human genes. “When an agent is so active at the gene level, postmarketing studies need to address the issue of special populations,” said Dr. Hellman, clinical professor of medicine, University of Missouri, Kansas City. The findings “provide more ammunition for increased caution” in prescribing rosiglitazone.

'The FDA needs to begin to think more clearly about these kinds of risky situations and act earlier.' DR. NISSEN

Intravitreal injections of bevacizumab may stabilize or improve macular thickness and visual acuity after only 1 month in patients with diabetic macular edema, according to findings from a short-term, uncontrolled, retrospective study.

Dr. J. Fernando Arevalo of the Clinica Oftalmológica Centro Caracas (Venezuela) and colleagues reported the results of 6 months of follow-up after the treatment of 78 eyes in 64 diabetic macular edema patients with off-label bevacizumab (Avastin), which is a complete, full-length humanized antibody that binds to all subtypes of vascular endothelial growth factor (VEGF). VEGF is known to increase retinal vessel permeability, which occurs to an excessive degree in diabetic macular edema and results in the leakage of fluid and plasma constituents that thicken the retina as they pass into it.

Systemic therapy with bevacizumab is approved by the Food and Drug Administration for use in combination with other therapies for the treatment of metastatic colorectal carcinoma and recurrent or metastatic nonsquamous, non-small cell lung cancer.

The best-corrected visual acuity of the patients significantly improved from an average minimum angle of resolution of 7.4 minutes of arc to 4 minutes of arc 1 month after an injection of either 1.25 mg or 2.5 mg bevacizumab. The mean retinal thickness of the 1-mm central retina decreased from 387 mcm to 287.9 mcm after the first month, as measured by optical coherence tomography. Although these outcomes continued to improve slightly during the next 5 months of the study, neither outcome at the 6-month follow-up was significantly better than it had been at 1 month, according to the investigators.

There was no significant difference in either outcome between patients who had proliferative diabetic retinopathy and previous panretinal photocoagulation and those with nonproliferative diabetic retinopathy and macular edema (Ophthalmology 2007;114:743–50).

A majority of the 78 eyes improved by at least two lines of letters (based on the Early Treatment Diabetic Retinopathy Study) of best-corrected visual acuity (55%) or remained stable (41%) at the end of 6 months. Most of the eyes (81%) were initially treated with 2.5 mg bevacizumab, whereas others (19%) received 1.25 mg. About 20% of patients who received either initial dosage later needed one or two additional injections of the medication. Outcomes were similar between each dosage group.

No episodes of inflammation or severe losses of vision occurred immediately after injection, and no ocular or systemic adverse events were reported during the 6-month study.

“Our results indicate that intravitreal bevacizumab injections may have a beneficial effect on macular thickness and visual acuity, independent of the type of macular edema that is present (focal vs. diffuse). Therefore, in the future this new treatment modality could replace or complement focal/grid laser photocoagulation,” or perhaps laser photocoagulation could “consolidate the results obtained with one intravitreal bevacizumab injection and decrease the need for reinjections,” the researchers wrote.

Bevacizumab needs to be evaluated in a multicenter, randomized, controlled trial with longer follow-up before it is possible “to make any specific treatment recommendations,” the investigators advised.

Intravitreal injections of bevacizumab may stabilize or improve macular thickness and visual acuity after only 1 month in patients with diabetic macular edema, according to findings from a short-term, uncontrolled, retrospective study.

Dr. J. Fernando Arevalo of the Clinica Oftalmológica Centro Caracas (Venezuela) and colleagues reported the results of 6 months of follow-up after the treatment of 78 eyes in 64 diabetic macular edema patients with off-label bevacizumab (Avastin), which is a complete, full-length humanized antibody that binds to all subtypes of vascular endothelial growth factor (VEGF). VEGF is known to increase retinal vessel permeability, which occurs to an excessive degree in diabetic macular edema and results in the leakage of fluid and plasma constituents that thicken the retina as they pass into it.

Systemic therapy with bevacizumab is approved by the Food and Drug Administration for use in combination with other therapies for the treatment of metastatic colorectal carcinoma and recurrent or metastatic nonsquamous, non-small cell lung cancer.

The best-corrected visual acuity of the patients significantly improved from an average minimum angle of resolution of 7.4 minutes of arc to 4 minutes of arc 1 month after an injection of either 1.25 mg or 2.5 mg bevacizumab. The mean retinal thickness of the 1-mm central retina decreased from 387 mcm to 287.9 mcm after the first month, as measured by optical coherence tomography. Although these outcomes continued to improve slightly during the next 5 months of the study, neither outcome at the 6-month follow-up was significantly better than it had been at 1 month, according to the investigators.

There was no significant difference in either outcome between patients who had proliferative diabetic retinopathy and previous panretinal photocoagulation and those with nonproliferative diabetic retinopathy and macular edema (Ophthalmology 2007;114:743–50).

A majority of the 78 eyes improved by at least two lines of letters (based on the Early Treatment Diabetic Retinopathy Study) of best-corrected visual acuity (55%) or remained stable (41%) at the end of 6 months. Most of the eyes (81%) were initially treated with 2.5 mg bevacizumab, whereas others (19%) received 1.25 mg. About 20% of patients who received either initial dosage later needed one or two additional injections of the medication. Outcomes were similar between each dosage group.

No episodes of inflammation or severe losses of vision occurred immediately after injection, and no ocular or systemic adverse events were reported during the 6-month study.

“Our results indicate that intravitreal bevacizumab injections may have a beneficial effect on macular thickness and visual acuity, independent of the type of macular edema that is present (focal vs. diffuse). Therefore, in the future this new treatment modality could replace or complement focal/grid laser photocoagulation,” or perhaps laser photocoagulation could “consolidate the results obtained with one intravitreal bevacizumab injection and decrease the need for reinjections,” the researchers wrote.

Bevacizumab needs to be evaluated in a multicenter, randomized, controlled trial with longer follow-up before it is possible “to make any specific treatment recommendations,” the investigators advised.

Intravitreal injections of bevacizumab may stabilize or improve macular thickness and visual acuity after only 1 month in patients with diabetic macular edema, according to findings from a short-term, uncontrolled, retrospective study.

Dr. J. Fernando Arevalo of the Clinica Oftalmológica Centro Caracas (Venezuela) and colleagues reported the results of 6 months of follow-up after the treatment of 78 eyes in 64 diabetic macular edema patients with off-label bevacizumab (Avastin), which is a complete, full-length humanized antibody that binds to all subtypes of vascular endothelial growth factor (VEGF). VEGF is known to increase retinal vessel permeability, which occurs to an excessive degree in diabetic macular edema and results in the leakage of fluid and plasma constituents that thicken the retina as they pass into it.

Systemic therapy with bevacizumab is approved by the Food and Drug Administration for use in combination with other therapies for the treatment of metastatic colorectal carcinoma and recurrent or metastatic nonsquamous, non-small cell lung cancer.

The best-corrected visual acuity of the patients significantly improved from an average minimum angle of resolution of 7.4 minutes of arc to 4 minutes of arc 1 month after an injection of either 1.25 mg or 2.5 mg bevacizumab. The mean retinal thickness of the 1-mm central retina decreased from 387 mcm to 287.9 mcm after the first month, as measured by optical coherence tomography. Although these outcomes continued to improve slightly during the next 5 months of the study, neither outcome at the 6-month follow-up was significantly better than it had been at 1 month, according to the investigators.

There was no significant difference in either outcome between patients who had proliferative diabetic retinopathy and previous panretinal photocoagulation and those with nonproliferative diabetic retinopathy and macular edema (Ophthalmology 2007;114:743–50).

A majority of the 78 eyes improved by at least two lines of letters (based on the Early Treatment Diabetic Retinopathy Study) of best-corrected visual acuity (55%) or remained stable (41%) at the end of 6 months. Most of the eyes (81%) were initially treated with 2.5 mg bevacizumab, whereas others (19%) received 1.25 mg. About 20% of patients who received either initial dosage later needed one or two additional injections of the medication. Outcomes were similar between each dosage group.

No episodes of inflammation or severe losses of vision occurred immediately after injection, and no ocular or systemic adverse events were reported during the 6-month study.

“Our results indicate that intravitreal bevacizumab injections may have a beneficial effect on macular thickness and visual acuity, independent of the type of macular edema that is present (focal vs. diffuse). Therefore, in the future this new treatment modality could replace or complement focal/grid laser photocoagulation,” or perhaps laser photocoagulation could “consolidate the results obtained with one intravitreal bevacizumab injection and decrease the need for reinjections,” the researchers wrote.

Bevacizumab needs to be evaluated in a multicenter, randomized, controlled trial with longer follow-up before it is possible “to make any specific treatment recommendations,” the investigators advised.

WASHINGTON — Breast cancer patients who are at risk of developing chronic distress may be identified at diagnosis by their low quality of life and high level of negative affectivity, Steven C. Palmer, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Psychological distress appears in approximately 25%–35% of women with breast cancer and is generally predicted by younger age, lower optimism, increased pessimism, declining functional status, and greater illness burden.

Most patients lose the feeling of distress over time, but few studies have examined the subset of patients who remain chronically distressed.

Dr. Palmer and his colleagues at the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, are conducting an ongoing study of 154 patients with a mean age of about 53 years who had newly diagnosed ductal carcinoma in situ or breast cancer.

None of the patients had yet received chemotherapy. Most of the patients were white American (75%) and married (68%); 46% were college educated.

At diagnosis, 33% of the patients reported elevated distress on the Hopkins Symptom Checklist, but this decreased to 20% after 3 months and 21% after 6 months.

Most patients (58%) never reported feeling distressed, whereas 21% had a single episode of distress and another 21% had chronic distress (defined as two or more episodes).

Low baseline quality of life and high negative affectivity were independent predictors of chronic distress in a multivariate analysis. Together, they predicted 40% of the variance in chronicity of distress, according to Dr. Palmer.

The level of distress of women who experienced a single episode tended to decline to a nonclinically significant level by 3 months. These women also could not be differentiated from women with chronic distress, based on their baseline level of distress, which would make it difficult to conduct an interventional study on only chronically distressed women.

“You need another stratifier to be able to differentiate how these two” groups will respond to distress over time, Dr. Palmer said.

Women who were never distressed and those who had a single episode slowly improved throughout the 6-month period, whereas women with chronic distress remained at the same level of distress the whole period.

Overall, about 59% of women who were distressed at baseline recovered by 3 months.

“It's both significant and striking that women who have no distress have very high levels of baseline quality of life,” Dr. Palmer said.

Those women had a significantly higher quality of life at baseline than women with one episode of distress. Those with one episode also had significantly higher quality of life than chronically distressed women did.

By the end of 6 months, quality of life had increased slightly among women who were never distressed and had substantially increased in women who had one episode of distress.

Quality of life declined, however, among women with chronic distress even though they started with a low level, he said.

The amount of supportive services that were used by women in each group also seemed to increase with the level of distress.

The study is planned to continue for another 6 months of follow-up.

WASHINGTON — Breast cancer patients who are at risk of developing chronic distress may be identified at diagnosis by their low quality of life and high level of negative affectivity, Steven C. Palmer, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Psychological distress appears in approximately 25%–35% of women with breast cancer and is generally predicted by younger age, lower optimism, increased pessimism, declining functional status, and greater illness burden.

Most patients lose the feeling of distress over time, but few studies have examined the subset of patients who remain chronically distressed.

Dr. Palmer and his colleagues at the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, are conducting an ongoing study of 154 patients with a mean age of about 53 years who had newly diagnosed ductal carcinoma in situ or breast cancer.

None of the patients had yet received chemotherapy. Most of the patients were white American (75%) and married (68%); 46% were college educated.

At diagnosis, 33% of the patients reported elevated distress on the Hopkins Symptom Checklist, but this decreased to 20% after 3 months and 21% after 6 months.

Most patients (58%) never reported feeling distressed, whereas 21% had a single episode of distress and another 21% had chronic distress (defined as two or more episodes).

Low baseline quality of life and high negative affectivity were independent predictors of chronic distress in a multivariate analysis. Together, they predicted 40% of the variance in chronicity of distress, according to Dr. Palmer.

The level of distress of women who experienced a single episode tended to decline to a nonclinically significant level by 3 months. These women also could not be differentiated from women with chronic distress, based on their baseline level of distress, which would make it difficult to conduct an interventional study on only chronically distressed women.

“You need another stratifier to be able to differentiate how these two” groups will respond to distress over time, Dr. Palmer said.

Women who were never distressed and those who had a single episode slowly improved throughout the 6-month period, whereas women with chronic distress remained at the same level of distress the whole period.

Overall, about 59% of women who were distressed at baseline recovered by 3 months.

“It's both significant and striking that women who have no distress have very high levels of baseline quality of life,” Dr. Palmer said.

Those women had a significantly higher quality of life at baseline than women with one episode of distress. Those with one episode also had significantly higher quality of life than chronically distressed women did.

By the end of 6 months, quality of life had increased slightly among women who were never distressed and had substantially increased in women who had one episode of distress.

Quality of life declined, however, among women with chronic distress even though they started with a low level, he said.

The amount of supportive services that were used by women in each group also seemed to increase with the level of distress.

The study is planned to continue for another 6 months of follow-up.

WASHINGTON — Breast cancer patients who are at risk of developing chronic distress may be identified at diagnosis by their low quality of life and high level of negative affectivity, Steven C. Palmer, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Psychological distress appears in approximately 25%–35% of women with breast cancer and is generally predicted by younger age, lower optimism, increased pessimism, declining functional status, and greater illness burden.

Most patients lose the feeling of distress over time, but few studies have examined the subset of patients who remain chronically distressed.

Dr. Palmer and his colleagues at the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, are conducting an ongoing study of 154 patients with a mean age of about 53 years who had newly diagnosed ductal carcinoma in situ or breast cancer.

None of the patients had yet received chemotherapy. Most of the patients were white American (75%) and married (68%); 46% were college educated.

At diagnosis, 33% of the patients reported elevated distress on the Hopkins Symptom Checklist, but this decreased to 20% after 3 months and 21% after 6 months.

Most patients (58%) never reported feeling distressed, whereas 21% had a single episode of distress and another 21% had chronic distress (defined as two or more episodes).

Low baseline quality of life and high negative affectivity were independent predictors of chronic distress in a multivariate analysis. Together, they predicted 40% of the variance in chronicity of distress, according to Dr. Palmer.

The level of distress of women who experienced a single episode tended to decline to a nonclinically significant level by 3 months. These women also could not be differentiated from women with chronic distress, based on their baseline level of distress, which would make it difficult to conduct an interventional study on only chronically distressed women.

“You need another stratifier to be able to differentiate how these two” groups will respond to distress over time, Dr. Palmer said.

Women who were never distressed and those who had a single episode slowly improved throughout the 6-month period, whereas women with chronic distress remained at the same level of distress the whole period.

Overall, about 59% of women who were distressed at baseline recovered by 3 months.

“It's both significant and striking that women who have no distress have very high levels of baseline quality of life,” Dr. Palmer said.

Those women had a significantly higher quality of life at baseline than women with one episode of distress. Those with one episode also had significantly higher quality of life than chronically distressed women did.

By the end of 6 months, quality of life had increased slightly among women who were never distressed and had substantially increased in women who had one episode of distress.

Quality of life declined, however, among women with chronic distress even though they started with a low level, he said.

The amount of supportive services that were used by women in each group also seemed to increase with the level of distress.

The study is planned to continue for another 6 months of follow-up.

Emergency medical services can play a key role in assessing and routing acute ischemic stroke patients to intravenous thrombolytic therapy stroke centers, according to updated American Heart Association and American Stroke Association guidelines for the early management of adult patients with the condition.

“For the first time, we have included recommendations for emergency medical services” to use brief stroke identification algorithms—such as the Los Angeles Prehospital Stroke Screen or the Cincinnati Prehospital Stroke Scale—to begin stroke management in the field with established stroke protocols, and to take patients to centers where there are adequate treatment resources, Dr. Harold P. Adams Jr., chair of the 16-member writing panel, said in an interview.

“One of the things that we would like EMS to do … is to bypass those hospitals that do not have the resources to take care of a patient with stroke. This does not mean that [the patient] has to go to a big, tertiary, academic medical center. Our hope is that some of these patients can be successfully treated in community hospitals,” Dr. Adams said.

The panel strongly recommended the creation of primary stroke centers that have “the personnel, programs, expertise, and infrastructure to care for many patients with uncomplicated strokes, [use] many acute therapies (such as intravenous rtPA [recombinant tissue plasminogen activator]), and [admit] such patients into a stroke unit” (Stroke 2007;38:1655–711).

More specialized comprehensive stroke centers also could be developed “to care for patients with complicated types of strokes, patients with intracerebral hemorrhage or subarachnoid hemorrhage, and those requiring specific interventions ([such as] surgery or endovascular procedures) or an intensive care unit type of setting.”

Both types of centers could be certified by an external body, such as the Joint Commission on Accreditation of Healthcare Organizations, according to the panel.

The updated guidelines still strongly endorse the administration of IV rtPA within the first 3 hours of onset of stroke, which “remains the engine that's driving acute stroke care,” said Dr. Adams, professor of neurology and director of the division of cerebrovascular disorders at the University of Iowa, Iowa City.

The panelists expanded the eligibility of patients for rtPA in noting that it may be okay for patients who had a seizure at the onset of a stroke to receive the treatment “as long as the physician is convinced that residual impairments are secondary to stroke and not a postictal phenomenon.”

Other IV therapies were not recommended outside of a clinical trial.

Intra-arterial thrombolytics garnered support from the panel only in specific circumstances in patients who are not candidates for IV rtPA. Such agents should be administered only at “experienced stroke centers with immediate access to cerebral angiography and qualified interventionalists,” the guidelines noted.

Endovascular interventions with the Food and Drug Administration-approved Merci device were considered to be reasonable in the treatment of “carefully selected patients.” But it was noted that further study of the device in clinical trials is needed to define its role in the emergency management of stroke because its utility in “improving outcomes after stroke is unclear.”

Although the guidelines continue to recommend CT or MR imaging for diagnosis, the panelists advised physicians not to delay emergency treatment in order to obtain multimodal CT or MR imaging or vascular imaging in patients whose symptoms started fewer than 3 hours before and who have acute ischemic stroke. Chest x-rays also are not considered necessary for the initial evaluation of most stroke patients.

It is now advised that antihypertensive medications be restarted around 24 hours after the stroke in patients who have preexisting hypertension and are neurologically stable, unless there is a specific contraindication to doing so. Vasopressors may be used to improve cerebral blood flow in “exceptional cases,” but their usage requires close neurologic and cardiac monitoring.

The previous, “rather liberal” guidelines for controlling blood glucose levels have been changed to a lower minimum threshold for treatment, Dr. Adams pointed out.

Blood glucose concentrations of more than 140 mg/dL to 185 mg/dL “probably should trigger administration of insulin,” followed by “close monitoring of glucose concentrations with adjustment of insulin doses to avoid hypoglycemia,” according to the guidelines.

The panel also voiced concern about the need for palliative care in some patients. “There are some patients who are so devastated by stroke, even acutely, that we do not have much to offer. We do need to remember that there are some patients who warrant and deserve palliative care,” Dr. Adams said.

Emergency medical services can play a key role in assessing and routing acute ischemic stroke patients to intravenous thrombolytic therapy stroke centers, according to updated American Heart Association and American Stroke Association guidelines for the early management of adult patients with the condition.

“For the first time, we have included recommendations for emergency medical services” to use brief stroke identification algorithms—such as the Los Angeles Prehospital Stroke Screen or the Cincinnati Prehospital Stroke Scale—to begin stroke management in the field with established stroke protocols, and to take patients to centers where there are adequate treatment resources, Dr. Harold P. Adams Jr., chair of the 16-member writing panel, said in an interview.

“One of the things that we would like EMS to do … is to bypass those hospitals that do not have the resources to take care of a patient with stroke. This does not mean that [the patient] has to go to a big, tertiary, academic medical center. Our hope is that some of these patients can be successfully treated in community hospitals,” Dr. Adams said.

The panel strongly recommended the creation of primary stroke centers that have “the personnel, programs, expertise, and infrastructure to care for many patients with uncomplicated strokes, [use] many acute therapies (such as intravenous rtPA [recombinant tissue plasminogen activator]), and [admit] such patients into a stroke unit” (Stroke 2007;38:1655–711).

More specialized comprehensive stroke centers also could be developed “to care for patients with complicated types of strokes, patients with intracerebral hemorrhage or subarachnoid hemorrhage, and those requiring specific interventions ([such as] surgery or endovascular procedures) or an intensive care unit type of setting.”

Both types of centers could be certified by an external body, such as the Joint Commission on Accreditation of Healthcare Organizations, according to the panel.

The updated guidelines still strongly endorse the administration of IV rtPA within the first 3 hours of onset of stroke, which “remains the engine that's driving acute stroke care,” said Dr. Adams, professor of neurology and director of the division of cerebrovascular disorders at the University of Iowa, Iowa City.

The panelists expanded the eligibility of patients for rtPA in noting that it may be okay for patients who had a seizure at the onset of a stroke to receive the treatment “as long as the physician is convinced that residual impairments are secondary to stroke and not a postictal phenomenon.”

Other IV therapies were not recommended outside of a clinical trial.

Intra-arterial thrombolytics garnered support from the panel only in specific circumstances in patients who are not candidates for IV rtPA. Such agents should be administered only at “experienced stroke centers with immediate access to cerebral angiography and qualified interventionalists,” the guidelines noted.

Endovascular interventions with the Food and Drug Administration-approved Merci device were considered to be reasonable in the treatment of “carefully selected patients.” But it was noted that further study of the device in clinical trials is needed to define its role in the emergency management of stroke because its utility in “improving outcomes after stroke is unclear.”

Although the guidelines continue to recommend CT or MR imaging for diagnosis, the panelists advised physicians not to delay emergency treatment in order to obtain multimodal CT or MR imaging or vascular imaging in patients whose symptoms started fewer than 3 hours before and who have acute ischemic stroke. Chest x-rays also are not considered necessary for the initial evaluation of most stroke patients.

It is now advised that antihypertensive medications be restarted around 24 hours after the stroke in patients who have preexisting hypertension and are neurologically stable, unless there is a specific contraindication to doing so. Vasopressors may be used to improve cerebral blood flow in “exceptional cases,” but their usage requires close neurologic and cardiac monitoring.

The previous, “rather liberal” guidelines for controlling blood glucose levels have been changed to a lower minimum threshold for treatment, Dr. Adams pointed out.

Blood glucose concentrations of more than 140 mg/dL to 185 mg/dL “probably should trigger administration of insulin,” followed by “close monitoring of glucose concentrations with adjustment of insulin doses to avoid hypoglycemia,” according to the guidelines.

The panel also voiced concern about the need for palliative care in some patients. “There are some patients who are so devastated by stroke, even acutely, that we do not have much to offer. We do need to remember that there are some patients who warrant and deserve palliative care,” Dr. Adams said.

Emergency medical services can play a key role in assessing and routing acute ischemic stroke patients to intravenous thrombolytic therapy stroke centers, according to updated American Heart Association and American Stroke Association guidelines for the early management of adult patients with the condition.

“For the first time, we have included recommendations for emergency medical services” to use brief stroke identification algorithms—such as the Los Angeles Prehospital Stroke Screen or the Cincinnati Prehospital Stroke Scale—to begin stroke management in the field with established stroke protocols, and to take patients to centers where there are adequate treatment resources, Dr. Harold P. Adams Jr., chair of the 16-member writing panel, said in an interview.

“One of the things that we would like EMS to do … is to bypass those hospitals that do not have the resources to take care of a patient with stroke. This does not mean that [the patient] has to go to a big, tertiary, academic medical center. Our hope is that some of these patients can be successfully treated in community hospitals,” Dr. Adams said.

The panel strongly recommended the creation of primary stroke centers that have “the personnel, programs, expertise, and infrastructure to care for many patients with uncomplicated strokes, [use] many acute therapies (such as intravenous rtPA [recombinant tissue plasminogen activator]), and [admit] such patients into a stroke unit” (Stroke 2007;38:1655–711).

More specialized comprehensive stroke centers also could be developed “to care for patients with complicated types of strokes, patients with intracerebral hemorrhage or subarachnoid hemorrhage, and those requiring specific interventions ([such as] surgery or endovascular procedures) or an intensive care unit type of setting.”

Both types of centers could be certified by an external body, such as the Joint Commission on Accreditation of Healthcare Organizations, according to the panel.

The updated guidelines still strongly endorse the administration of IV rtPA within the first 3 hours of onset of stroke, which “remains the engine that's driving acute stroke care,” said Dr. Adams, professor of neurology and director of the division of cerebrovascular disorders at the University of Iowa, Iowa City.

The panelists expanded the eligibility of patients for rtPA in noting that it may be okay for patients who had a seizure at the onset of a stroke to receive the treatment “as long as the physician is convinced that residual impairments are secondary to stroke and not a postictal phenomenon.”

Other IV therapies were not recommended outside of a clinical trial.

Intra-arterial thrombolytics garnered support from the panel only in specific circumstances in patients who are not candidates for IV rtPA. Such agents should be administered only at “experienced stroke centers with immediate access to cerebral angiography and qualified interventionalists,” the guidelines noted.

Endovascular interventions with the Food and Drug Administration-approved Merci device were considered to be reasonable in the treatment of “carefully selected patients.” But it was noted that further study of the device in clinical trials is needed to define its role in the emergency management of stroke because its utility in “improving outcomes after stroke is unclear.”

Although the guidelines continue to recommend CT or MR imaging for diagnosis, the panelists advised physicians not to delay emergency treatment in order to obtain multimodal CT or MR imaging or vascular imaging in patients whose symptoms started fewer than 3 hours before and who have acute ischemic stroke. Chest x-rays also are not considered necessary for the initial evaluation of most stroke patients.

It is now advised that antihypertensive medications be restarted around 24 hours after the stroke in patients who have preexisting hypertension and are neurologically stable, unless there is a specific contraindication to doing so. Vasopressors may be used to improve cerebral blood flow in “exceptional cases,” but their usage requires close neurologic and cardiac monitoring.

The previous, “rather liberal” guidelines for controlling blood glucose levels have been changed to a lower minimum threshold for treatment, Dr. Adams pointed out.

Blood glucose concentrations of more than 140 mg/dL to 185 mg/dL “probably should trigger administration of insulin,” followed by “close monitoring of glucose concentrations with adjustment of insulin doses to avoid hypoglycemia,” according to the guidelines.

The panel also voiced concern about the need for palliative care in some patients. “There are some patients who are so devastated by stroke, even acutely, that we do not have much to offer. We do need to remember that there are some patients who warrant and deserve palliative care,” Dr. Adams said.

WASHINGTON — Psychosocial risk factors contribute a level of risk for cardiovascular events in clinically symptomatic women that is similar to the traditional major risk factors, Thomas Rutledge, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Dr. Rutledge and his associates prospectively studied the risk factors of smoking, hypertension, diabetes, dyslipidemia, inactivity, obesity, depression, and social isolation in a cohort of 734 women with clinical symptoms of myocardial ischemia. Each underwent coronary angiography and psychosocial testing. About 30% of the patients had one event (MI, heart failure, stroke, or death) during a follow-up of 6 years.

Although the women were clinically symptomatic, the rate of obstructive coronary artery disease was relatively low (39%). Risk factors tended to cluster, which was associated with about a threefold increase from the lowest group to the highest group in death and CVD rates. Those events occurred in 12% of women with none or one risk factor, 19% with two to three risk factors, and 30% with four to six risk factors. The magnitude of the effects for depression and social isolation were comparable with those for the major CVD risk factors. All significant risk factors increased the risk of death and CVD events by about 50%–100%.

WASHINGTON — Psychosocial risk factors contribute a level of risk for cardiovascular events in clinically symptomatic women that is similar to the traditional major risk factors, Thomas Rutledge, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Dr. Rutledge and his associates prospectively studied the risk factors of smoking, hypertension, diabetes, dyslipidemia, inactivity, obesity, depression, and social isolation in a cohort of 734 women with clinical symptoms of myocardial ischemia. Each underwent coronary angiography and psychosocial testing. About 30% of the patients had one event (MI, heart failure, stroke, or death) during a follow-up of 6 years.

Although the women were clinically symptomatic, the rate of obstructive coronary artery disease was relatively low (39%). Risk factors tended to cluster, which was associated with about a threefold increase from the lowest group to the highest group in death and CVD rates. Those events occurred in 12% of women with none or one risk factor, 19% with two to three risk factors, and 30% with four to six risk factors. The magnitude of the effects for depression and social isolation were comparable with those for the major CVD risk factors. All significant risk factors increased the risk of death and CVD events by about 50%–100%.

WASHINGTON — Psychosocial risk factors contribute a level of risk for cardiovascular events in clinically symptomatic women that is similar to the traditional major risk factors, Thomas Rutledge, Ph.D., reported at the annual meeting of the Society of Behavioral Medicine.

Dr. Rutledge and his associates prospectively studied the risk factors of smoking, hypertension, diabetes, dyslipidemia, inactivity, obesity, depression, and social isolation in a cohort of 734 women with clinical symptoms of myocardial ischemia. Each underwent coronary angiography and psychosocial testing. About 30% of the patients had one event (MI, heart failure, stroke, or death) during a follow-up of 6 years.

Although the women were clinically symptomatic, the rate of obstructive coronary artery disease was relatively low (39%). Risk factors tended to cluster, which was associated with about a threefold increase from the lowest group to the highest group in death and CVD rates. Those events occurred in 12% of women with none or one risk factor, 19% with two to three risk factors, and 30% with four to six risk factors. The magnitude of the effects for depression and social isolation were comparable with those for the major CVD risk factors. All significant risk factors increased the risk of death and CVD events by about 50%–100%.

WASHINGTON — Medicine and health are so often in the news that it may be worthwhile to be prepared to do interviews in a variety of media when the time comes, said Ms. Patricia A. Clark, a communications expert in media training, speech coaching, and message development from Ogden Dunes, Ind.

“The physician today cannot possibly get through his or her entire career professionally without talking to the media, so you better be ready,” Ms. Clark said at a meeting of the Society for Pediatric Dermatology.

Before one tries to get a particular message across during an interview, it is necessary to understand the medium through which the message is delivered (television, radio, print) and the messenger.

“If you don't understand the medium you're working with … and if you aren't an appealing messenger—and I don't mean handsome or beautiful, I mean eager, avid, happy to be here,” she said, then we will have 'remoted' you out before you get to the message.”

Stories on the evening news are packaged into preset lengths: a 90-second story, which normally provides 10–20 seconds for commentary from the physician; or a 110-second story, which could provide 30–40 seconds if the sound bite is good or just 10–20 seconds if it is not. When a person does not deliver a succinct message in those time frames, the media will pull out a piece of what was said when they are putting the story together, leaving the potential for misquotation.

The television camera diminishes appearance and does not catch subtlety, so it is necessary to restore what it takes away by increasing your smile, perk, and warmth. And on television, “every time you look away, you give away: You give away believability,” she said.

The media likes conflict and controversy, visuals, and emotion, which “for doctors means pulling patients out of your pocket … and putting a face on the complex issues” rather than drawing attention to yourself and your or your specialty's problems, she said.

Stories on the radio are not much different from television, but the lack of a visual element puts more focus on what is said.

Newspaper stories are now smaller than ever, and interview subjects may get only an inch or two of space—the media savvy will be higher in the story while those who are not end up at the bottom, according to Ms. Clark.

You are apt to be stuck at the bottom of a story if you are called at 9 a.m. to do an interview and the reporter's deadline is 3 p.m., but you decide to call the reporter back at 2:50 p.m. The story is blank at 9 a.m., but it's all ready to go at 2:50 p.m., and other sources have already weighed in with their interpretations of the issue. Your quote will be stuck at the bottom because it is too late to try to integrate it into the story, she said.

The concept of a “message box” can help physicians answer questions, but still return to the central message they want to get across. The message box consists of four points (more or less) around a box that you want to talk about or anticipate talking about during an interview. Each one leads back to the message that you want to convey, she said.

“No matter what question I ask you as a reporter, you answer my question, you acknowledge it, you neutralize it, and you use it as an opportunity to bridge back to one of these four sides,” she advised.

Points are scored only on offense. “When you're talking about what you want to talk about, that's offense. When you're answering my question, that's defense. So you want to take my question and use it as an opportunity to stay on message,” she said.

Not all questions have to be answered literally. A question might be an opening to deflect your answer to a point you want to make, Ms. Clark advised.

WASHINGTON — Medicine and health are so often in the news that it may be worthwhile to be prepared to do interviews in a variety of media when the time comes, said Ms. Patricia A. Clark, a communications expert in media training, speech coaching, and message development from Ogden Dunes, Ind.

“The physician today cannot possibly get through his or her entire career professionally without talking to the media, so you better be ready,” Ms. Clark said at a meeting of the Society for Pediatric Dermatology.

Before one tries to get a particular message across during an interview, it is necessary to understand the medium through which the message is delivered (television, radio, print) and the messenger.

“If you don't understand the medium you're working with … and if you aren't an appealing messenger—and I don't mean handsome or beautiful, I mean eager, avid, happy to be here,” she said, then we will have 'remoted' you out before you get to the message.”

Stories on the evening news are packaged into preset lengths: a 90-second story, which normally provides 10–20 seconds for commentary from the physician; or a 110-second story, which could provide 30–40 seconds if the sound bite is good or just 10–20 seconds if it is not. When a person does not deliver a succinct message in those time frames, the media will pull out a piece of what was said when they are putting the story together, leaving the potential for misquotation.

The television camera diminishes appearance and does not catch subtlety, so it is necessary to restore what it takes away by increasing your smile, perk, and warmth. And on television, “every time you look away, you give away: You give away believability,” she said.

The media likes conflict and controversy, visuals, and emotion, which “for doctors means pulling patients out of your pocket … and putting a face on the complex issues” rather than drawing attention to yourself and your or your specialty's problems, she said.

Stories on the radio are not much different from television, but the lack of a visual element puts more focus on what is said.

Newspaper stories are now smaller than ever, and interview subjects may get only an inch or two of space—the media savvy will be higher in the story while those who are not end up at the bottom, according to Ms. Clark.

You are apt to be stuck at the bottom of a story if you are called at 9 a.m. to do an interview and the reporter's deadline is 3 p.m., but you decide to call the reporter back at 2:50 p.m. The story is blank at 9 a.m., but it's all ready to go at 2:50 p.m., and other sources have already weighed in with their interpretations of the issue. Your quote will be stuck at the bottom because it is too late to try to integrate it into the story, she said.

The concept of a “message box” can help physicians answer questions, but still return to the central message they want to get across. The message box consists of four points (more or less) around a box that you want to talk about or anticipate talking about during an interview. Each one leads back to the message that you want to convey, she said.

“No matter what question I ask you as a reporter, you answer my question, you acknowledge it, you neutralize it, and you use it as an opportunity to bridge back to one of these four sides,” she advised.

Points are scored only on offense. “When you're talking about what you want to talk about, that's offense. When you're answering my question, that's defense. So you want to take my question and use it as an opportunity to stay on message,” she said.

Not all questions have to be answered literally. A question might be an opening to deflect your answer to a point you want to make, Ms. Clark advised.

WASHINGTON — Medicine and health are so often in the news that it may be worthwhile to be prepared to do interviews in a variety of media when the time comes, said Ms. Patricia A. Clark, a communications expert in media training, speech coaching, and message development from Ogden Dunes, Ind.

“The physician today cannot possibly get through his or her entire career professionally without talking to the media, so you better be ready,” Ms. Clark said at a meeting of the Society for Pediatric Dermatology.

Before one tries to get a particular message across during an interview, it is necessary to understand the medium through which the message is delivered (television, radio, print) and the messenger.

“If you don't understand the medium you're working with … and if you aren't an appealing messenger—and I don't mean handsome or beautiful, I mean eager, avid, happy to be here,” she said, then we will have 'remoted' you out before you get to the message.”

Stories on the evening news are packaged into preset lengths: a 90-second story, which normally provides 10–20 seconds for commentary from the physician; or a 110-second story, which could provide 30–40 seconds if the sound bite is good or just 10–20 seconds if it is not. When a person does not deliver a succinct message in those time frames, the media will pull out a piece of what was said when they are putting the story together, leaving the potential for misquotation.

The television camera diminishes appearance and does not catch subtlety, so it is necessary to restore what it takes away by increasing your smile, perk, and warmth. And on television, “every time you look away, you give away: You give away believability,” she said.

The media likes conflict and controversy, visuals, and emotion, which “for doctors means pulling patients out of your pocket … and putting a face on the complex issues” rather than drawing attention to yourself and your or your specialty's problems, she said.

Stories on the radio are not much different from television, but the lack of a visual element puts more focus on what is said.

Newspaper stories are now smaller than ever, and interview subjects may get only an inch or two of space—the media savvy will be higher in the story while those who are not end up at the bottom, according to Ms. Clark.

You are apt to be stuck at the bottom of a story if you are called at 9 a.m. to do an interview and the reporter's deadline is 3 p.m., but you decide to call the reporter back at 2:50 p.m. The story is blank at 9 a.m., but it's all ready to go at 2:50 p.m., and other sources have already weighed in with their interpretations of the issue. Your quote will be stuck at the bottom because it is too late to try to integrate it into the story, she said.

The concept of a “message box” can help physicians answer questions, but still return to the central message they want to get across. The message box consists of four points (more or less) around a box that you want to talk about or anticipate talking about during an interview. Each one leads back to the message that you want to convey, she said.

“No matter what question I ask you as a reporter, you answer my question, you acknowledge it, you neutralize it, and you use it as an opportunity to bridge back to one of these four sides,” she advised.

Points are scored only on offense. “When you're talking about what you want to talk about, that's offense. When you're answering my question, that's defense. So you want to take my question and use it as an opportunity to stay on message,” she said.

Not all questions have to be answered literally. A question might be an opening to deflect your answer to a point you want to make, Ms. Clark advised.

WASHINGTON — Angioplasty techniques that use new devices to prepare selected complex lesions in coronary arteries for drug-eluting stents may provide better acute outcomes and potentially result in less late stent thrombosis than balloon angioplasty, Dr. Charles A. Simonton said at a symposium jointly sponsored by the Washington Hospital Center and the Cardiovascular Research Institute.

The indications for drug-eluting stents have expanded to include more patients with multivessel disease and longer and more complex lesions—those who used to be sent for coronary artery bypass grafting—because of their lower restenosis rate. This, however, has led to increased stent thrombosis rates and perhaps other as yet unknown complications, said Dr. Simonton, director of clinical innovation and research at the Carolinas Heart Institute, Charlotte, N.C.

There are no data to support the use of plaque modification with these devices to reduce restenosis, but they can help facilitate stenting procedures, he said.

“The data here are rather shallow, so a lot of it has to do with actual practical experience as opposed to strong data to support these devices,” he said.

Interventional labs that take care of more complex cases “rely on these devices perhaps more than labs that do not do quite as much complex work.”

The results of a meta-analysis of 16 randomized trials that compared balloon angioplasty with coronary atherectomy, laser angioplasty, or cutting ballon atherectomy in 9,222 patients showed that these debulking devices may help interventionalists get through procedures, but they increase major adverse cardiac event rates and do not improve restenosis rates or revascularization rates up to 1 year after treatment (J. Am. Coll. Cardiol. 2004;43:936–42).

Thus, these adjunctive devices appear to provide discouraging results in unselected patients. However, they may be beneficial in selected patients, Dr. Simonton said.

“There has to be a good, strong motivational reason to use a debulking device for atheroablation in a procedure to help you get through it,” he advised.

A variety of devices may address problems related to plaque shifting, treating calcification in highly stenosed lesions, precisely dilating vessels, and reducing the risk of stent thrombosis by improving stent strut apposition and mechanical factors that may be associated with thrombosis.

▸ Directional coronary atherectomy (DCA). Dr. Simonton uses this procedure in ostial lesions, particularly true ostial stenosis of the left anterior descending coronary artery in which plaque shifting may compromise a small left circumflex artery.

Two-stent procedures should be avoided in that type of lesion.

Directional coronary atherectomy also can be used in ostial diagonal marginal branches and aorto-ostial lesions, occasionally in bifurcation lesions to help convert a two-step into a one-step procedure, in lesions near large side branches, and in some very eccentric bulky lesions.

The randomized AMIGO trial (Atherectomy Before Multilink Improves Lumen Gain and Clinical Outcomes), which compared directional coronary atherectomy followed by the multilink bare metal stent with the stent alone, showed no difference between groups in restenosis on angiography, except that restenosis was significantly lower in the subgroup of patients who had bifurcation lesions (Am. J. Cardiol. 2004;93:953–8).

▸ Rotational atherectomy. The Rotablator, a miniature, rotating, diamond-studded burr, is most effective on severely calcified lesions, which are associated with lower angiographic success and a higher rate of complications after many types of percutaneous coronary intervention.

Use of the Rotablator (Boston Scientific) before stenting in selected patients can help to avoid “stent regret” in which a lesion is covered by a partially deployed stent but is not dilatable.

This may make it difficult to get the balloon out and to get a high-pressure balloon into the stent to obtain adequate postdilatation, he said.

Small burr sizes on the Rotablator are currently preferred to alter the morphology and compliance of the plaque rather than to debulk and increase the size of the lumen.

▸ Cutting balloon. These devices provide focal dilatation by scoring and modifying the plaque without slipping from it. They work well on ostial lesions with or without calcification, lesions in small vessels, and highly resistant lesions.

▸ Excimer laser. The new technique of infusing saline while using the laser removes contrast medium and blood from the field to eliminate the large amount of bubbling that occurrs without the use of saline.

A new spatial configuration of the laser fibers also has increased the size of lumen that can be created by at least 22%.

But the laser is used more to facilitate a procedure in highly stenosed chronic total occlusions rather than to ablate a lesion.

Some of the other emerging coronary applications for the excimer laser include occluded saphenous vein grafts and in acute myocardial infarction to facilitate percutaneous coronary intervention.

WASHINGTON — Angioplasty techniques that use new devices to prepare selected complex lesions in coronary arteries for drug-eluting stents may provide better acute outcomes and potentially result in less late stent thrombosis than balloon angioplasty, Dr. Charles A. Simonton said at a symposium jointly sponsored by the Washington Hospital Center and the Cardiovascular Research Institute.

The indications for drug-eluting stents have expanded to include more patients with multivessel disease and longer and more complex lesions—those who used to be sent for coronary artery bypass grafting—because of their lower restenosis rate. This, however, has led to increased stent thrombosis rates and perhaps other as yet unknown complications, said Dr. Simonton, director of clinical innovation and research at the Carolinas Heart Institute, Charlotte, N.C.

There are no data to support the use of plaque modification with these devices to reduce restenosis, but they can help facilitate stenting procedures, he said.

“The data here are rather shallow, so a lot of it has to do with actual practical experience as opposed to strong data to support these devices,” he said.

Interventional labs that take care of more complex cases “rely on these devices perhaps more than labs that do not do quite as much complex work.”

The results of a meta-analysis of 16 randomized trials that compared balloon angioplasty with coronary atherectomy, laser angioplasty, or cutting ballon atherectomy in 9,222 patients showed that these debulking devices may help interventionalists get through procedures, but they increase major adverse cardiac event rates and do not improve restenosis rates or revascularization rates up to 1 year after treatment (J. Am. Coll. Cardiol. 2004;43:936–42).

Thus, these adjunctive devices appear to provide discouraging results in unselected patients. However, they may be beneficial in selected patients, Dr. Simonton said.

“There has to be a good, strong motivational reason to use a debulking device for atheroablation in a procedure to help you get through it,” he advised.

A variety of devices may address problems related to plaque shifting, treating calcification in highly stenosed lesions, precisely dilating vessels, and reducing the risk of stent thrombosis by improving stent strut apposition and mechanical factors that may be associated with thrombosis.

▸ Directional coronary atherectomy (DCA). Dr. Simonton uses this procedure in ostial lesions, particularly true ostial stenosis of the left anterior descending coronary artery in which plaque shifting may compromise a small left circumflex artery.

Two-stent procedures should be avoided in that type of lesion.

Directional coronary atherectomy also can be used in ostial diagonal marginal branches and aorto-ostial lesions, occasionally in bifurcation lesions to help convert a two-step into a one-step procedure, in lesions near large side branches, and in some very eccentric bulky lesions.

The randomized AMIGO trial (Atherectomy Before Multilink Improves Lumen Gain and Clinical Outcomes), which compared directional coronary atherectomy followed by the multilink bare metal stent with the stent alone, showed no difference between groups in restenosis on angiography, except that restenosis was significantly lower in the subgroup of patients who had bifurcation lesions (Am. J. Cardiol. 2004;93:953–8).

▸ Rotational atherectomy. The Rotablator, a miniature, rotating, diamond-studded burr, is most effective on severely calcified lesions, which are associated with lower angiographic success and a higher rate of complications after many types of percutaneous coronary intervention.

Use of the Rotablator (Boston Scientific) before stenting in selected patients can help to avoid “stent regret” in which a lesion is covered by a partially deployed stent but is not dilatable.

This may make it difficult to get the balloon out and to get a high-pressure balloon into the stent to obtain adequate postdilatation, he said.

Small burr sizes on the Rotablator are currently preferred to alter the morphology and compliance of the plaque rather than to debulk and increase the size of the lumen.

▸ Cutting balloon. These devices provide focal dilatation by scoring and modifying the plaque without slipping from it. They work well on ostial lesions with or without calcification, lesions in small vessels, and highly resistant lesions.

▸ Excimer laser. The new technique of infusing saline while using the laser removes contrast medium and blood from the field to eliminate the large amount of bubbling that occurrs without the use of saline.

A new spatial configuration of the laser fibers also has increased the size of lumen that can be created by at least 22%.

But the laser is used more to facilitate a procedure in highly stenosed chronic total occlusions rather than to ablate a lesion.

Some of the other emerging coronary applications for the excimer laser include occluded saphenous vein grafts and in acute myocardial infarction to facilitate percutaneous coronary intervention.

WASHINGTON — Angioplasty techniques that use new devices to prepare selected complex lesions in coronary arteries for drug-eluting stents may provide better acute outcomes and potentially result in less late stent thrombosis than balloon angioplasty, Dr. Charles A. Simonton said at a symposium jointly sponsored by the Washington Hospital Center and the Cardiovascular Research Institute.

The indications for drug-eluting stents have expanded to include more patients with multivessel disease and longer and more complex lesions—those who used to be sent for coronary artery bypass grafting—because of their lower restenosis rate. This, however, has led to increased stent thrombosis rates and perhaps other as yet unknown complications, said Dr. Simonton, director of clinical innovation and research at the Carolinas Heart Institute, Charlotte, N.C.

There are no data to support the use of plaque modification with these devices to reduce restenosis, but they can help facilitate stenting procedures, he said.

“The data here are rather shallow, so a lot of it has to do with actual practical experience as opposed to strong data to support these devices,” he said.

Interventional labs that take care of more complex cases “rely on these devices perhaps more than labs that do not do quite as much complex work.”

The results of a meta-analysis of 16 randomized trials that compared balloon angioplasty with coronary atherectomy, laser angioplasty, or cutting ballon atherectomy in 9,222 patients showed that these debulking devices may help interventionalists get through procedures, but they increase major adverse cardiac event rates and do not improve restenosis rates or revascularization rates up to 1 year after treatment (J. Am. Coll. Cardiol. 2004;43:936–42).

Thus, these adjunctive devices appear to provide discouraging results in unselected patients. However, they may be beneficial in selected patients, Dr. Simonton said.

“There has to be a good, strong motivational reason to use a debulking device for atheroablation in a procedure to help you get through it,” he advised.

A variety of devices may address problems related to plaque shifting, treating calcification in highly stenosed lesions, precisely dilating vessels, and reducing the risk of stent thrombosis by improving stent strut apposition and mechanical factors that may be associated with thrombosis.

▸ Directional coronary atherectomy (DCA). Dr. Simonton uses this procedure in ostial lesions, particularly true ostial stenosis of the left anterior descending coronary artery in which plaque shifting may compromise a small left circumflex artery.

Two-stent procedures should be avoided in that type of lesion.

Directional coronary atherectomy also can be used in ostial diagonal marginal branches and aorto-ostial lesions, occasionally in bifurcation lesions to help convert a two-step into a one-step procedure, in lesions near large side branches, and in some very eccentric bulky lesions.

The randomized AMIGO trial (Atherectomy Before Multilink Improves Lumen Gain and Clinical Outcomes), which compared directional coronary atherectomy followed by the multilink bare metal stent with the stent alone, showed no difference between groups in restenosis on angiography, except that restenosis was significantly lower in the subgroup of patients who had bifurcation lesions (Am. J. Cardiol. 2004;93:953–8).

▸ Rotational atherectomy. The Rotablator, a miniature, rotating, diamond-studded burr, is most effective on severely calcified lesions, which are associated with lower angiographic success and a higher rate of complications after many types of percutaneous coronary intervention.

Use of the Rotablator (Boston Scientific) before stenting in selected patients can help to avoid “stent regret” in which a lesion is covered by a partially deployed stent but is not dilatable.

This may make it difficult to get the balloon out and to get a high-pressure balloon into the stent to obtain adequate postdilatation, he said.

Small burr sizes on the Rotablator are currently preferred to alter the morphology and compliance of the plaque rather than to debulk and increase the size of the lumen.

▸ Cutting balloon. These devices provide focal dilatation by scoring and modifying the plaque without slipping from it. They work well on ostial lesions with or without calcification, lesions in small vessels, and highly resistant lesions.

▸ Excimer laser. The new technique of infusing saline while using the laser removes contrast medium and blood from the field to eliminate the large amount of bubbling that occurrs without the use of saline.

A new spatial configuration of the laser fibers also has increased the size of lumen that can be created by at least 22%.

But the laser is used more to facilitate a procedure in highly stenosed chronic total occlusions rather than to ablate a lesion.

Some of the other emerging coronary applications for the excimer laser include occluded saphenous vein grafts and in acute myocardial infarction to facilitate percutaneous coronary intervention.

WASHINGTON — Patients with juvenile-onset ankylosing spondylitis have functional outcomes similar to adult-onset disease, but more often have less severe lumbar degeneration and more hip involvement requiring total hip arthroplasty, Ms. Lianne S. Gensler said in a poster session at the annual meeting of the American College of Rheumatology.

Ms. Gensler and her associates compared the disease characteristics of a cohort of 53 patients with juvenile-onset ankylosing spondylitis (JoAS) and 349 patients with adult-onset AS (AoAS) in a multicenter, cross-sectional study.

Compared with AoAS patients, JoAS patients were significantly younger (average 50 vs. 56 years), had significantly longer duration of AS (37 vs. 31 years), and included significantly more women (40% vs. 23%), said Ms. Gensler of the University of California, San Francisco.

Although each group had similar functional outcomes, JoAS patients were 45% less likely to have severe lumbar disease than were AoAS patients. The comparison was adjusted for disease duration, gender, white race, having ever been a smoker, family history of AS, and occupational activity. But JoAS patients were more than twice as likely as AoAS patients to need total hip arthroplasty.

WASHINGTON — Patients with juvenile-onset ankylosing spondylitis have functional outcomes similar to adult-onset disease, but more often have less severe lumbar degeneration and more hip involvement requiring total hip arthroplasty, Ms. Lianne S. Gensler said in a poster session at the annual meeting of the American College of Rheumatology.

Ms. Gensler and her associates compared the disease characteristics of a cohort of 53 patients with juvenile-onset ankylosing spondylitis (JoAS) and 349 patients with adult-onset AS (AoAS) in a multicenter, cross-sectional study.

Compared with AoAS patients, JoAS patients were significantly younger (average 50 vs. 56 years), had significantly longer duration of AS (37 vs. 31 years), and included significantly more women (40% vs. 23%), said Ms. Gensler of the University of California, San Francisco.

Although each group had similar functional outcomes, JoAS patients were 45% less likely to have severe lumbar disease than were AoAS patients. The comparison was adjusted for disease duration, gender, white race, having ever been a smoker, family history of AS, and occupational activity. But JoAS patients were more than twice as likely as AoAS patients to need total hip arthroplasty.

WASHINGTON — Patients with juvenile-onset ankylosing spondylitis have functional outcomes similar to adult-onset disease, but more often have less severe lumbar degeneration and more hip involvement requiring total hip arthroplasty, Ms. Lianne S. Gensler said in a poster session at the annual meeting of the American College of Rheumatology.

Ms. Gensler and her associates compared the disease characteristics of a cohort of 53 patients with juvenile-onset ankylosing spondylitis (JoAS) and 349 patients with adult-onset AS (AoAS) in a multicenter, cross-sectional study.

Compared with AoAS patients, JoAS patients were significantly younger (average 50 vs. 56 years), had significantly longer duration of AS (37 vs. 31 years), and included significantly more women (40% vs. 23%), said Ms. Gensler of the University of California, San Francisco.

Although each group had similar functional outcomes, JoAS patients were 45% less likely to have severe lumbar disease than were AoAS patients. The comparison was adjusted for disease duration, gender, white race, having ever been a smoker, family history of AS, and occupational activity. But JoAS patients were more than twice as likely as AoAS patients to need total hip arthroplasty.