Sherry Boschert

SAN FRANCISCO - Long before she entered medical school or started her psychiatry residency, Dr. Emily Gray grew up enmeshed in online social media. Something that seemed like a routine part of her life now presents professional problems she hadn’t expected.

"I’ve always been in an Internet age," said Dr. Gray, who co-led a group discussion about the Internet and social networking at the annual meeting of the American College of Psychiatrists. When she attends meetings of the American Academy of Child and Adolescent Psychiatry, the peers she meets there simply ask if she’s on Facebook as a way of staying in touch. As a young, single woman, she has even tried online dating sites, said Dr. Gray, a chief resident in psychiatry at the University of California, San Diego.

Her peers aren’t the only ones who are online, however. So are her patients. And people who seek her out because they saw her profile online.

Social media began to produce problems with transference. She stopped Internet dating. She is considering creating separate Facebook accounts – one personal, one professional. "Psychiatrists need to be aware that public information that they enter online for dating or networking may be accessible to patients," she said.

While there are some steps that psychiatrists can and should take online to maintain boundaries, the best course of action is not always clear, and some things are beyond psychiatrists’ control, said Dr. Glen O. Gabbard, who co-led the discussion. Patients can comment online about psychiatrists, rate them, blog about them, find personal information about them, and even download a satellite image of a psychiatrist’s house if they want to.

"Privacy has become radically redefined," said Dr. Gabbard, chair of psychoanalysis and professor of psychiatry at Baylor College of Medicine, Houston. Plenary sessions at the college’s 2012 meeting will address some of these issues, he said.

In a show of hands, nearly all the psychiatrists in the room indicated that they had received e-mails from patients, but only a few said they participated in social networking sites. There are both advantages and disadvantages to using e-mail, websites, and social media that psychiatrists need to think through even as the ways in which these tools are used continue to change, he said.

"Ten years ago, I would have said, ‘Don’t respond to e-mails from patients.’ Now, patients expect you to e-mail and text them. It’s a moving target," Dr. Gabbard said. Unfortunately, state licensing boards tend to think in absolute, black-and-white terms about "boundary violations" in ways that might be lagging trends in technology use, he added.

Some legal precedents suggest that responding to a patient’s e-mail message establishes some form of a doctor-patient relationship, but not responding to an e-mail does not let a psychiatrist off the hook. Any e-mail that’s received becomes part of a patient’s record whether the psychiatrist responds to it, another session participant warned. One participant who does a lot of forensic psychiatry work urged her colleagues to "never forget that every word of that e-mail that you get can be put in front of a jury in court."

Some psychiatrists said they tell patients that they will not accept e-mails, or have patients sign an agreement to limit e-mails to making appointments, and explain that this is because they value the interpersonal, face-to-face therapeutic relationship. When asked to be friends on Facebook, they explain that they have friendly feelings toward patients, but are not friends.

Others said it’s naive to think that patients will respect these boundaries. Some patients will text about suicidal thoughts, send lengthy e-mail diaries about their status, or ask for advice.

Electronic media are not always a problem; sometimes they help in psychiatrists’ work. Some participants said a few patients cannot tolerate in-person sessions and electronic media help them connect with therapy. One psychiatrist said she finds patients’ e-mailed journals helpful. Another uses the unwanted e-mail to explore why the patient felt comfortable writing it but not talking about its contents in person.

A psychiatry resident has used online chat rooms to do family counseling with family members on computers in different rooms, which changes the dynamics compared with having everyone in the same room, Dr. Gray said.

Several psychiatrists said Skype is a helpful means of doing telepsychiatry. One suggested using Skype for visual contact but turning off the computer’s audio and speaking to the patient simultaneously by phone to maintain privacy.

Published reports have described the usefulness of computer programs in treating patients with eating disorders, Dr. Sandra M. DeJong of Harvard Medical School, Boston, said in an interview after the session. Various kinds of electronic media are being used to remind patients with chronic mental illness when to take their medications. Online programs are available to treat adolescent depression or childhood anxiety.

"I’m a child psychiatrist. We tend to have a lot of folks involved in the care of any individual patient. The efficiency with which we’re able as a treatment team to stay in touch with each other is much enhanced by the use of e-mail," she said.

She said she asks adolescent patients to show her their Facebook sites as part of the therapeutic session, or talk about what might be found if someone searched online for the patient’s name.

In many ways, boundary issues raised by e-mail are similar to boundary issues related to use of the telephone; they’re just in a different form, several participants noted. Psychiatrists have little control over Internet searches and the information they turn up, except for setting search engine alerts to be notified whenever their name is mentioned and perhaps hiring a company to scour erroneous information from the Web.

It’s the use of social networking sites like Facebook, LinkedIn, and others that seems to create the greatest ambiguity, some said. One doctor noted that even if you set the highest privacy settings and refuse to "friend" patients on Facebook, nonfriends can "see" you in other ways. "I have to caution family members about posting photos" that include him, he said.

New curricula are available from the American Association of Directors of Psychiatry Residency Training to inform trainees about the ramifications of electronic and social media.

One participant summed it up by saying, "We have to accept that this is the digital age."

Dr. Gray, Dr. Gabbard, and Dr. DeJong said they have no relevant financial disclosures. Dr. DeJong is a paid contributor to a nonprofit website, Children’s Emotional Health Link.

SAN FRANCISCO - Long before she entered medical school or started her psychiatry residency, Dr. Emily Gray grew up enmeshed in online social media. Something that seemed like a routine part of her life now presents professional problems she hadn’t expected.

"I’ve always been in an Internet age," said Dr. Gray, who co-led a group discussion about the Internet and social networking at the annual meeting of the American College of Psychiatrists. When she attends meetings of the American Academy of Child and Adolescent Psychiatry, the peers she meets there simply ask if she’s on Facebook as a way of staying in touch. As a young, single woman, she has even tried online dating sites, said Dr. Gray, a chief resident in psychiatry at the University of California, San Diego.

Her peers aren’t the only ones who are online, however. So are her patients. And people who seek her out because they saw her profile online.

Social media began to produce problems with transference. She stopped Internet dating. She is considering creating separate Facebook accounts – one personal, one professional. "Psychiatrists need to be aware that public information that they enter online for dating or networking may be accessible to patients," she said.

While there are some steps that psychiatrists can and should take online to maintain boundaries, the best course of action is not always clear, and some things are beyond psychiatrists’ control, said Dr. Glen O. Gabbard, who co-led the discussion. Patients can comment online about psychiatrists, rate them, blog about them, find personal information about them, and even download a satellite image of a psychiatrist’s house if they want to.

"Privacy has become radically redefined," said Dr. Gabbard, chair of psychoanalysis and professor of psychiatry at Baylor College of Medicine, Houston. Plenary sessions at the college’s 2012 meeting will address some of these issues, he said.

In a show of hands, nearly all the psychiatrists in the room indicated that they had received e-mails from patients, but only a few said they participated in social networking sites. There are both advantages and disadvantages to using e-mail, websites, and social media that psychiatrists need to think through even as the ways in which these tools are used continue to change, he said.

"Ten years ago, I would have said, ‘Don’t respond to e-mails from patients.’ Now, patients expect you to e-mail and text them. It’s a moving target," Dr. Gabbard said. Unfortunately, state licensing boards tend to think in absolute, black-and-white terms about "boundary violations" in ways that might be lagging trends in technology use, he added.

Some legal precedents suggest that responding to a patient’s e-mail message establishes some form of a doctor-patient relationship, but not responding to an e-mail does not let a psychiatrist off the hook. Any e-mail that’s received becomes part of a patient’s record whether the psychiatrist responds to it, another session participant warned. One participant who does a lot of forensic psychiatry work urged her colleagues to "never forget that every word of that e-mail that you get can be put in front of a jury in court."

Some psychiatrists said they tell patients that they will not accept e-mails, or have patients sign an agreement to limit e-mails to making appointments, and explain that this is because they value the interpersonal, face-to-face therapeutic relationship. When asked to be friends on Facebook, they explain that they have friendly feelings toward patients, but are not friends.

Others said it’s naive to think that patients will respect these boundaries. Some patients will text about suicidal thoughts, send lengthy e-mail diaries about their status, or ask for advice.

Electronic media are not always a problem; sometimes they help in psychiatrists’ work. Some participants said a few patients cannot tolerate in-person sessions and electronic media help them connect with therapy. One psychiatrist said she finds patients’ e-mailed journals helpful. Another uses the unwanted e-mail to explore why the patient felt comfortable writing it but not talking about its contents in person.

A psychiatry resident has used online chat rooms to do family counseling with family members on computers in different rooms, which changes the dynamics compared with having everyone in the same room, Dr. Gray said.

Several psychiatrists said Skype is a helpful means of doing telepsychiatry. One suggested using Skype for visual contact but turning off the computer’s audio and speaking to the patient simultaneously by phone to maintain privacy.

Published reports have described the usefulness of computer programs in treating patients with eating disorders, Dr. Sandra M. DeJong of Harvard Medical School, Boston, said in an interview after the session. Various kinds of electronic media are being used to remind patients with chronic mental illness when to take their medications. Online programs are available to treat adolescent depression or childhood anxiety.

"I’m a child psychiatrist. We tend to have a lot of folks involved in the care of any individual patient. The efficiency with which we’re able as a treatment team to stay in touch with each other is much enhanced by the use of e-mail," she said.

She said she asks adolescent patients to show her their Facebook sites as part of the therapeutic session, or talk about what might be found if someone searched online for the patient’s name.

In many ways, boundary issues raised by e-mail are similar to boundary issues related to use of the telephone; they’re just in a different form, several participants noted. Psychiatrists have little control over Internet searches and the information they turn up, except for setting search engine alerts to be notified whenever their name is mentioned and perhaps hiring a company to scour erroneous information from the Web.

It’s the use of social networking sites like Facebook, LinkedIn, and others that seems to create the greatest ambiguity, some said. One doctor noted that even if you set the highest privacy settings and refuse to "friend" patients on Facebook, nonfriends can "see" you in other ways. "I have to caution family members about posting photos" that include him, he said.

New curricula are available from the American Association of Directors of Psychiatry Residency Training to inform trainees about the ramifications of electronic and social media.

One participant summed it up by saying, "We have to accept that this is the digital age."

Dr. Gray, Dr. Gabbard, and Dr. DeJong said they have no relevant financial disclosures. Dr. DeJong is a paid contributor to a nonprofit website, Children’s Emotional Health Link.

SAN FRANCISCO - Long before she entered medical school or started her psychiatry residency, Dr. Emily Gray grew up enmeshed in online social media. Something that seemed like a routine part of her life now presents professional problems she hadn’t expected.

"I’ve always been in an Internet age," said Dr. Gray, who co-led a group discussion about the Internet and social networking at the annual meeting of the American College of Psychiatrists. When she attends meetings of the American Academy of Child and Adolescent Psychiatry, the peers she meets there simply ask if she’s on Facebook as a way of staying in touch. As a young, single woman, she has even tried online dating sites, said Dr. Gray, a chief resident in psychiatry at the University of California, San Diego.

Her peers aren’t the only ones who are online, however. So are her patients. And people who seek her out because they saw her profile online.

Social media began to produce problems with transference. She stopped Internet dating. She is considering creating separate Facebook accounts – one personal, one professional. "Psychiatrists need to be aware that public information that they enter online for dating or networking may be accessible to patients," she said.

While there are some steps that psychiatrists can and should take online to maintain boundaries, the best course of action is not always clear, and some things are beyond psychiatrists’ control, said Dr. Glen O. Gabbard, who co-led the discussion. Patients can comment online about psychiatrists, rate them, blog about them, find personal information about them, and even download a satellite image of a psychiatrist’s house if they want to.

"Privacy has become radically redefined," said Dr. Gabbard, chair of psychoanalysis and professor of psychiatry at Baylor College of Medicine, Houston. Plenary sessions at the college’s 2012 meeting will address some of these issues, he said.

In a show of hands, nearly all the psychiatrists in the room indicated that they had received e-mails from patients, but only a few said they participated in social networking sites. There are both advantages and disadvantages to using e-mail, websites, and social media that psychiatrists need to think through even as the ways in which these tools are used continue to change, he said.

"Ten years ago, I would have said, ‘Don’t respond to e-mails from patients.’ Now, patients expect you to e-mail and text them. It’s a moving target," Dr. Gabbard said. Unfortunately, state licensing boards tend to think in absolute, black-and-white terms about "boundary violations" in ways that might be lagging trends in technology use, he added.

Some legal precedents suggest that responding to a patient’s e-mail message establishes some form of a doctor-patient relationship, but not responding to an e-mail does not let a psychiatrist off the hook. Any e-mail that’s received becomes part of a patient’s record whether the psychiatrist responds to it, another session participant warned. One participant who does a lot of forensic psychiatry work urged her colleagues to "never forget that every word of that e-mail that you get can be put in front of a jury in court."

Some psychiatrists said they tell patients that they will not accept e-mails, or have patients sign an agreement to limit e-mails to making appointments, and explain that this is because they value the interpersonal, face-to-face therapeutic relationship. When asked to be friends on Facebook, they explain that they have friendly feelings toward patients, but are not friends.

Others said it’s naive to think that patients will respect these boundaries. Some patients will text about suicidal thoughts, send lengthy e-mail diaries about their status, or ask for advice.

Electronic media are not always a problem; sometimes they help in psychiatrists’ work. Some participants said a few patients cannot tolerate in-person sessions and electronic media help them connect with therapy. One psychiatrist said she finds patients’ e-mailed journals helpful. Another uses the unwanted e-mail to explore why the patient felt comfortable writing it but not talking about its contents in person.

A psychiatry resident has used online chat rooms to do family counseling with family members on computers in different rooms, which changes the dynamics compared with having everyone in the same room, Dr. Gray said.

Several psychiatrists said Skype is a helpful means of doing telepsychiatry. One suggested using Skype for visual contact but turning off the computer’s audio and speaking to the patient simultaneously by phone to maintain privacy.

Published reports have described the usefulness of computer programs in treating patients with eating disorders, Dr. Sandra M. DeJong of Harvard Medical School, Boston, said in an interview after the session. Various kinds of electronic media are being used to remind patients with chronic mental illness when to take their medications. Online programs are available to treat adolescent depression or childhood anxiety.

"I’m a child psychiatrist. We tend to have a lot of folks involved in the care of any individual patient. The efficiency with which we’re able as a treatment team to stay in touch with each other is much enhanced by the use of e-mail," she said.

She said she asks adolescent patients to show her their Facebook sites as part of the therapeutic session, or talk about what might be found if someone searched online for the patient’s name.

In many ways, boundary issues raised by e-mail are similar to boundary issues related to use of the telephone; they’re just in a different form, several participants noted. Psychiatrists have little control over Internet searches and the information they turn up, except for setting search engine alerts to be notified whenever their name is mentioned and perhaps hiring a company to scour erroneous information from the Web.

It’s the use of social networking sites like Facebook, LinkedIn, and others that seems to create the greatest ambiguity, some said. One doctor noted that even if you set the highest privacy settings and refuse to "friend" patients on Facebook, nonfriends can "see" you in other ways. "I have to caution family members about posting photos" that include him, he said.

New curricula are available from the American Association of Directors of Psychiatry Residency Training to inform trainees about the ramifications of electronic and social media.

One participant summed it up by saying, "We have to accept that this is the digital age."

Dr. Gray, Dr. Gabbard, and Dr. DeJong said they have no relevant financial disclosures. Dr. DeJong is a paid contributor to a nonprofit website, Children’s Emotional Health Link.

LOS ANGELES – Acute anemic events were associated with significantly increased risk for "silent" strokes not only in children with sickle cell disease but also in children with acute anemia due to other causes, a controlled study of 52 patients found.

Prospective screening of all children who were admitted to one hospital during a 30-month period found that 398 were having acute anemic events – accounting for nearly 1% of all admissions and 12% of children admitted with sickle cell disease. Diffusion-weighted MRI in 52 of these children showed evidence of acute silent infarction in 4 (18%) of 22 patients with sickle cell disease and in 2 (7%) of 30 patients without sickle cell disease, Dr. Michael M. Dowling and his associates reported at the International Stroke Conference.

"I didn’t initially plan a controlled study," but funders insisted, and the comparison yielded unexpected information, said Dr. Dowling, a pediatric neurologist at the University of Texas Southwestern Medical Center, Dallas. "I didn’t think these children [without sickle cell disease] would be having silent infarctions." The Children’s Medical Center of Dallas funded the study.

In addition, three patients with sickle cell disease showed evidence of what looked like remote silent infarctions on MRI (14%). Dr. Dowling said he was "fascinated" to also find evidence of remote silent infarctions in seven of the control patients (23%).

"These are not children with sickle cell disease. I’m worried that a lot of these children with acute anemic events were prone to recurrent anemic events from dysfunctional uterine bleeding, cancer, or repeat GI bleeds. I’m worried that at previous admissions they may have had an acute silent infarction in the setting of an acute anemic event that was missed," he said at the conference, which was sponsored by the American Heart Association.

Overall, 31% of all MRIs were abnormal, including both acute and remote silent infarctions.

"I think we can’t simply look at a severely anemic child in an emergency room and say he’s hemodynamically stable, because I think these kids are losing brain cells. We need to respond to them more quickly," he said.

He hopes that a future study will monitor these kinds of children at home via a pulse oximeter so that when their hemoglobin level falls, they can be brought in sooner for transfusion. "I think we can prevent injury," he said.

Previous studies suggest that approximately 10% of children with sickle cell disease will have a clinically evident stroke unless they get prophylactic therapy, and up to 35% will have silent infarctions.

"It’s a bad term because they’re not silent," Dr. Dowling said. "They cause significant cognitive impairment," educational delays, and increased risk for new or progressive silent infarctions and overt stroke.

His working definition of silent infarction is an MRI lesion consistent with infarction without a focal deficit lasting more than 24 hours. The study defined an acute anemic event as either a hemoglobin level no higher than 5.5 g/dL or, for children with sickle cell anemia whose "normal" hemoglobin level may be 6 g/dL, a decline of at least 30% from baseline hemoglobin level.

Follow-up imaging in four patients with acute silent infarctions showed signals consistent with permanent brain injury in three of them, but not in the fourth. "Some of these might be reversible," Dr. Dowling said.

He estimated that the incidence of acute silent infarction during acute anemic events is 633 per 100 patient-years in children with sickle cell disease, and 243 per 100 patient-years in children without sickle cell disease, based on the study’s findings. His estimates are much larger than are those from the SIT (Silent Infarct Transfusion) study, which suggested an incidence of 43 per 100 patient-years in children with sickle cell disease as a whole, he said.

"We have identified unsuspected silent infarctions occurring during acute anemic events in 18% of children with sickle cell disease and 7% of controls. I think these events may be telling us" that children with acute anemia may need closer observation, he said.

The etiologies of acute anemia were a bit surprising in both the sickle cell and control groups. There were more oncology patients than anticipated among the 294 children who were admitted without sickle cell disease. Aplastic or hemolytic anemias were the leading etiology. Others included GI bleed or liver problems, leukemias, lymphomas, and other cancers. Among patients with sickle cell disease and acute anemia, fewer than expected had acute chest syndrome, aplastic crisis, or splenic sequestration, although these still accounted for the majority. Some simply had infection, GI bleed, or other problems.

Dr. Dowling said he had no relevant conflicts of interest. He has received research support from First American Real Estate Services Inc.

LOS ANGELES – Acute anemic events were associated with significantly increased risk for "silent" strokes not only in children with sickle cell disease but also in children with acute anemia due to other causes, a controlled study of 52 patients found.

Prospective screening of all children who were admitted to one hospital during a 30-month period found that 398 were having acute anemic events – accounting for nearly 1% of all admissions and 12% of children admitted with sickle cell disease. Diffusion-weighted MRI in 52 of these children showed evidence of acute silent infarction in 4 (18%) of 22 patients with sickle cell disease and in 2 (7%) of 30 patients without sickle cell disease, Dr. Michael M. Dowling and his associates reported at the International Stroke Conference.

"I didn’t initially plan a controlled study," but funders insisted, and the comparison yielded unexpected information, said Dr. Dowling, a pediatric neurologist at the University of Texas Southwestern Medical Center, Dallas. "I didn’t think these children [without sickle cell disease] would be having silent infarctions." The Children’s Medical Center of Dallas funded the study.

In addition, three patients with sickle cell disease showed evidence of what looked like remote silent infarctions on MRI (14%). Dr. Dowling said he was "fascinated" to also find evidence of remote silent infarctions in seven of the control patients (23%).

"These are not children with sickle cell disease. I’m worried that a lot of these children with acute anemic events were prone to recurrent anemic events from dysfunctional uterine bleeding, cancer, or repeat GI bleeds. I’m worried that at previous admissions they may have had an acute silent infarction in the setting of an acute anemic event that was missed," he said at the conference, which was sponsored by the American Heart Association.

Overall, 31% of all MRIs were abnormal, including both acute and remote silent infarctions.

"I think we can’t simply look at a severely anemic child in an emergency room and say he’s hemodynamically stable, because I think these kids are losing brain cells. We need to respond to them more quickly," he said.

He hopes that a future study will monitor these kinds of children at home via a pulse oximeter so that when their hemoglobin level falls, they can be brought in sooner for transfusion. "I think we can prevent injury," he said.

Previous studies suggest that approximately 10% of children with sickle cell disease will have a clinically evident stroke unless they get prophylactic therapy, and up to 35% will have silent infarctions.

"It’s a bad term because they’re not silent," Dr. Dowling said. "They cause significant cognitive impairment," educational delays, and increased risk for new or progressive silent infarctions and overt stroke.

His working definition of silent infarction is an MRI lesion consistent with infarction without a focal deficit lasting more than 24 hours. The study defined an acute anemic event as either a hemoglobin level no higher than 5.5 g/dL or, for children with sickle cell anemia whose "normal" hemoglobin level may be 6 g/dL, a decline of at least 30% from baseline hemoglobin level.

Follow-up imaging in four patients with acute silent infarctions showed signals consistent with permanent brain injury in three of them, but not in the fourth. "Some of these might be reversible," Dr. Dowling said.

He estimated that the incidence of acute silent infarction during acute anemic events is 633 per 100 patient-years in children with sickle cell disease, and 243 per 100 patient-years in children without sickle cell disease, based on the study’s findings. His estimates are much larger than are those from the SIT (Silent Infarct Transfusion) study, which suggested an incidence of 43 per 100 patient-years in children with sickle cell disease as a whole, he said.

"We have identified unsuspected silent infarctions occurring during acute anemic events in 18% of children with sickle cell disease and 7% of controls. I think these events may be telling us" that children with acute anemia may need closer observation, he said.

The etiologies of acute anemia were a bit surprising in both the sickle cell and control groups. There were more oncology patients than anticipated among the 294 children who were admitted without sickle cell disease. Aplastic or hemolytic anemias were the leading etiology. Others included GI bleed or liver problems, leukemias, lymphomas, and other cancers. Among patients with sickle cell disease and acute anemia, fewer than expected had acute chest syndrome, aplastic crisis, or splenic sequestration, although these still accounted for the majority. Some simply had infection, GI bleed, or other problems.

Dr. Dowling said he had no relevant conflicts of interest. He has received research support from First American Real Estate Services Inc.

LOS ANGELES – Acute anemic events were associated with significantly increased risk for "silent" strokes not only in children with sickle cell disease but also in children with acute anemia due to other causes, a controlled study of 52 patients found.

Prospective screening of all children who were admitted to one hospital during a 30-month period found that 398 were having acute anemic events – accounting for nearly 1% of all admissions and 12% of children admitted with sickle cell disease. Diffusion-weighted MRI in 52 of these children showed evidence of acute silent infarction in 4 (18%) of 22 patients with sickle cell disease and in 2 (7%) of 30 patients without sickle cell disease, Dr. Michael M. Dowling and his associates reported at the International Stroke Conference.

"I didn’t initially plan a controlled study," but funders insisted, and the comparison yielded unexpected information, said Dr. Dowling, a pediatric neurologist at the University of Texas Southwestern Medical Center, Dallas. "I didn’t think these children [without sickle cell disease] would be having silent infarctions." The Children’s Medical Center of Dallas funded the study.

In addition, three patients with sickle cell disease showed evidence of what looked like remote silent infarctions on MRI (14%). Dr. Dowling said he was "fascinated" to also find evidence of remote silent infarctions in seven of the control patients (23%).

"These are not children with sickle cell disease. I’m worried that a lot of these children with acute anemic events were prone to recurrent anemic events from dysfunctional uterine bleeding, cancer, or repeat GI bleeds. I’m worried that at previous admissions they may have had an acute silent infarction in the setting of an acute anemic event that was missed," he said at the conference, which was sponsored by the American Heart Association.

Overall, 31% of all MRIs were abnormal, including both acute and remote silent infarctions.

"I think we can’t simply look at a severely anemic child in an emergency room and say he’s hemodynamically stable, because I think these kids are losing brain cells. We need to respond to them more quickly," he said.

He hopes that a future study will monitor these kinds of children at home via a pulse oximeter so that when their hemoglobin level falls, they can be brought in sooner for transfusion. "I think we can prevent injury," he said.

Previous studies suggest that approximately 10% of children with sickle cell disease will have a clinically evident stroke unless they get prophylactic therapy, and up to 35% will have silent infarctions.

"It’s a bad term because they’re not silent," Dr. Dowling said. "They cause significant cognitive impairment," educational delays, and increased risk for new or progressive silent infarctions and overt stroke.

His working definition of silent infarction is an MRI lesion consistent with infarction without a focal deficit lasting more than 24 hours. The study defined an acute anemic event as either a hemoglobin level no higher than 5.5 g/dL or, for children with sickle cell anemia whose "normal" hemoglobin level may be 6 g/dL, a decline of at least 30% from baseline hemoglobin level.

Follow-up imaging in four patients with acute silent infarctions showed signals consistent with permanent brain injury in three of them, but not in the fourth. "Some of these might be reversible," Dr. Dowling said.

He estimated that the incidence of acute silent infarction during acute anemic events is 633 per 100 patient-years in children with sickle cell disease, and 243 per 100 patient-years in children without sickle cell disease, based on the study’s findings. His estimates are much larger than are those from the SIT (Silent Infarct Transfusion) study, which suggested an incidence of 43 per 100 patient-years in children with sickle cell disease as a whole, he said.

"We have identified unsuspected silent infarctions occurring during acute anemic events in 18% of children with sickle cell disease and 7% of controls. I think these events may be telling us" that children with acute anemia may need closer observation, he said.

The etiologies of acute anemia were a bit surprising in both the sickle cell and control groups. There were more oncology patients than anticipated among the 294 children who were admitted without sickle cell disease. Aplastic or hemolytic anemias were the leading etiology. Others included GI bleed or liver problems, leukemias, lymphomas, and other cancers. Among patients with sickle cell disease and acute anemia, fewer than expected had acute chest syndrome, aplastic crisis, or splenic sequestration, although these still accounted for the majority. Some simply had infection, GI bleed, or other problems.

Dr. Dowling said he had no relevant conflicts of interest. He has received research support from First American Real Estate Services Inc.

LOS ANGELES – Acute anemic events were associated with significantly increased risk for "silent" strokes not only in children with sickle cell disease but also in children with acute anemia due to other causes, a controlled study of 52 patients found.

Prospective screening of all children who were admitted to one hospital during a 30-month period found that 398 were having acute anemic events – accounting for nearly 1% of all admissions and 12% of children admitted with sickle cell disease. Diffusion-weighted MRI in 52 of these children showed evidence of acute silent infarction in 4 (18%) of 22 patients with sickle cell disease and in 2 (7%) of 30 patients without sickle cell disease, Dr. Michael M. Dowling and his associates reported at the International Stroke Conference.

"I didn’t initially plan a controlled study," but funders insisted, and the comparison yielded unexpected information, said Dr. Dowling, a pediatric neurologist at the University of Texas Southwestern Medical Center, Dallas. "I didn’t think these children [without sickle cell disease] would be having silent infarctions." The Children’s Medical Center of Dallas funded the study.

In addition, three patients with sickle cell disease showed evidence of what looked like remote silent infarctions on MRI (14%). Dr. Dowling said he was "fascinated" to also find evidence of remote silent infarctions in seven of the control patients (23%).

"These are not children with sickle cell disease. I’m worried that a lot of these children with acute anemic events were prone to recurrent anemic events from dysfunctional uterine bleeding, cancer, or repeat GI bleeds. I’m worried that at previous admissions they may have had an acute silent infarction in the setting of an acute anemic event that was missed," he said at the conference, which was sponsored by the American Heart Association.

Overall, 31% of all MRIs were abnormal, including both acute and remote silent infarctions.

"I think we can’t simply look at a severely anemic child in an emergency room and say he’s hemodynamically stable, because I think these kids are losing brain cells. We need to respond to them more quickly," he said.

He hopes that a future study will monitor these kinds of children at home via a pulse oximeter so that when their hemoglobin level falls, they can be brought in sooner for transfusion. "I think we can prevent injury," he said.

Previous studies suggest that approximately 10% of children with sickle cell disease will have a clinically evident stroke unless they get prophylactic therapy, and up to 35% will have silent infarctions.

"It’s a bad term because they’re not silent," Dr. Dowling said. "They cause significant cognitive impairment," educational delays, and increased risk for new or progressive silent infarctions and overt stroke.

His working definition of silent infarction is an MRI lesion consistent with infarction without a focal deficit lasting more than 24 hours. The study defined an acute anemic event as either a hemoglobin level no higher than 5.5 g/dL or, for children with sickle cell anemia whose "normal" hemoglobin level may be 6 g/dL, a decline of at least 30% from baseline hemoglobin level.

Follow-up imaging in four patients with acute silent infarctions showed signals consistent with permanent brain injury in three of them, but not in the fourth. "Some of these might be reversible," Dr. Dowling said.

He estimated that the incidence of acute silent infarction during acute anemic events is 633 per 100 patient-years in children with sickle cell disease, and 243 per 100 patient-years in children without sickle cell disease, based on the study’s findings. His estimates are much larger than are those from the SIT (Silent Infarct Transfusion) study, which suggested an incidence of 43 per 100 patient-years in children with sickle cell disease as a whole, he said.

"We have identified unsuspected silent infarctions occurring during acute anemic events in 18% of children with sickle cell disease and 7% of controls. I think these events may be telling us" that children with acute anemia may need closer observation, he said.

The etiologies of acute anemia were a bit surprising in both the sickle cell and control groups. There were more oncology patients than anticipated among the 294 children who were admitted without sickle cell disease. Aplastic or hemolytic anemias were the leading etiology. Others included GI bleed or liver problems, leukemias, lymphomas, and other cancers. Among patients with sickle cell disease and acute anemia, fewer than expected had acute chest syndrome, aplastic crisis, or splenic sequestration, although these still accounted for the majority. Some simply had infection, GI bleed, or other problems.

Dr. Dowling said he had no relevant conflicts of interest. He has received research support from First American Real Estate Services Inc.

LOS ANGELES – Acute anemic events were associated with significantly increased risk for "silent" strokes not only in children with sickle cell disease but also in children with acute anemia due to other causes, a controlled study of 52 patients found.

Prospective screening of all children who were admitted to one hospital during a 30-month period found that 398 were having acute anemic events – accounting for nearly 1% of all admissions and 12% of children admitted with sickle cell disease. Diffusion-weighted MRI in 52 of these children showed evidence of acute silent infarction in 4 (18%) of 22 patients with sickle cell disease and in 2 (7%) of 30 patients without sickle cell disease, Dr. Michael M. Dowling and his associates reported at the International Stroke Conference.

"I didn’t initially plan a controlled study," but funders insisted, and the comparison yielded unexpected information, said Dr. Dowling, a pediatric neurologist at the University of Texas Southwestern Medical Center, Dallas. "I didn’t think these children [without sickle cell disease] would be having silent infarctions." The Children’s Medical Center of Dallas funded the study.

In addition, three patients with sickle cell disease showed evidence of what looked like remote silent infarctions on MRI (14%). Dr. Dowling said he was "fascinated" to also find evidence of remote silent infarctions in seven of the control patients (23%).

"These are not children with sickle cell disease. I’m worried that a lot of these children with acute anemic events were prone to recurrent anemic events from dysfunctional uterine bleeding, cancer, or repeat GI bleeds. I’m worried that at previous admissions they may have had an acute silent infarction in the setting of an acute anemic event that was missed," he said at the conference, which was sponsored by the American Heart Association.

Overall, 31% of all MRIs were abnormal, including both acute and remote silent infarctions.

"I think we can’t simply look at a severely anemic child in an emergency room and say he’s hemodynamically stable, because I think these kids are losing brain cells. We need to respond to them more quickly," he said.

He hopes that a future study will monitor these kinds of children at home via a pulse oximeter so that when their hemoglobin level falls, they can be brought in sooner for transfusion. "I think we can prevent injury," he said.

Previous studies suggest that approximately 10% of children with sickle cell disease will have a clinically evident stroke unless they get prophylactic therapy, and up to 35% will have silent infarctions.

"It’s a bad term because they’re not silent," Dr. Dowling said. "They cause significant cognitive impairment," educational delays, and increased risk for new or progressive silent infarctions and overt stroke.

His working definition of silent infarction is an MRI lesion consistent with infarction without a focal deficit lasting more than 24 hours. The study defined an acute anemic event as either a hemoglobin level no higher than 5.5 g/dL or, for children with sickle cell anemia whose "normal" hemoglobin level may be 6 g/dL, a decline of at least 30% from baseline hemoglobin level.

Follow-up imaging in four patients with acute silent infarctions showed signals consistent with permanent brain injury in three of them, but not in the fourth. "Some of these might be reversible," Dr. Dowling said.

He estimated that the incidence of acute silent infarction during acute anemic events is 633 per 100 patient-years in children with sickle cell disease, and 243 per 100 patient-years in children without sickle cell disease, based on the study’s findings. His estimates are much larger than are those from the SIT (Silent Infarct Transfusion) study, which suggested an incidence of 43 per 100 patient-years in children with sickle cell disease as a whole, he said.

"We have identified unsuspected silent infarctions occurring during acute anemic events in 18% of children with sickle cell disease and 7% of controls. I think these events may be telling us" that children with acute anemia may need closer observation, he said.

The etiologies of acute anemia were a bit surprising in both the sickle cell and control groups. There were more oncology patients than anticipated among the 294 children who were admitted without sickle cell disease. Aplastic or hemolytic anemias were the leading etiology. Others included GI bleed or liver problems, leukemias, lymphomas, and other cancers. Among patients with sickle cell disease and acute anemia, fewer than expected had acute chest syndrome, aplastic crisis, or splenic sequestration, although these still accounted for the majority. Some simply had infection, GI bleed, or other problems.

Dr. Dowling said he had no relevant conflicts of interest. He has received research support from First American Real Estate Services Inc.

LOS ANGELES – Acute anemic events were associated with significantly increased risk for "silent" strokes not only in children with sickle cell disease but also in children with acute anemia due to other causes, a controlled study of 52 patients found.

Prospective screening of all children who were admitted to one hospital during a 30-month period found that 398 were having acute anemic events – accounting for nearly 1% of all admissions and 12% of children admitted with sickle cell disease. Diffusion-weighted MRI in 52 of these children showed evidence of acute silent infarction in 4 (18%) of 22 patients with sickle cell disease and in 2 (7%) of 30 patients without sickle cell disease, Dr. Michael M. Dowling and his associates reported at the International Stroke Conference.

"I didn’t initially plan a controlled study," but funders insisted, and the comparison yielded unexpected information, said Dr. Dowling, a pediatric neurologist at the University of Texas Southwestern Medical Center, Dallas. "I didn’t think these children [without sickle cell disease] would be having silent infarctions." The Children’s Medical Center of Dallas funded the study.

In addition, three patients with sickle cell disease showed evidence of what looked like remote silent infarctions on MRI (14%). Dr. Dowling said he was "fascinated" to also find evidence of remote silent infarctions in seven of the control patients (23%).

"These are not children with sickle cell disease. I’m worried that a lot of these children with acute anemic events were prone to recurrent anemic events from dysfunctional uterine bleeding, cancer, or repeat GI bleeds. I’m worried that at previous admissions they may have had an acute silent infarction in the setting of an acute anemic event that was missed," he said at the conference, which was sponsored by the American Heart Association.

Overall, 31% of all MRIs were abnormal, including both acute and remote silent infarctions.

"I think we can’t simply look at a severely anemic child in an emergency room and say he’s hemodynamically stable, because I think these kids are losing brain cells. We need to respond to them more quickly," he said.

He hopes that a future study will monitor these kinds of children at home via a pulse oximeter so that when their hemoglobin level falls, they can be brought in sooner for transfusion. "I think we can prevent injury," he said.

Previous studies suggest that approximately 10% of children with sickle cell disease will have a clinically evident stroke unless they get prophylactic therapy, and up to 35% will have silent infarctions.

"It’s a bad term because they’re not silent," Dr. Dowling said. "They cause significant cognitive impairment," educational delays, and increased risk for new or progressive silent infarctions and overt stroke.

His working definition of silent infarction is an MRI lesion consistent with infarction without a focal deficit lasting more than 24 hours. The study defined an acute anemic event as either a hemoglobin level no higher than 5.5 g/dL or, for children with sickle cell anemia whose "normal" hemoglobin level may be 6 g/dL, a decline of at least 30% from baseline hemoglobin level.

Follow-up imaging in four patients with acute silent infarctions showed signals consistent with permanent brain injury in three of them, but not in the fourth. "Some of these might be reversible," Dr. Dowling said.

He estimated that the incidence of acute silent infarction during acute anemic events is 633 per 100 patient-years in children with sickle cell disease, and 243 per 100 patient-years in children without sickle cell disease, based on the study’s findings. His estimates are much larger than are those from the SIT (Silent Infarct Transfusion) study, which suggested an incidence of 43 per 100 patient-years in children with sickle cell disease as a whole, he said.

"We have identified unsuspected silent infarctions occurring during acute anemic events in 18% of children with sickle cell disease and 7% of controls. I think these events may be telling us" that children with acute anemia may need closer observation, he said.

The etiologies of acute anemia were a bit surprising in both the sickle cell and control groups. There were more oncology patients than anticipated among the 294 children who were admitted without sickle cell disease. Aplastic or hemolytic anemias were the leading etiology. Others included GI bleed or liver problems, leukemias, lymphomas, and other cancers. Among patients with sickle cell disease and acute anemia, fewer than expected had acute chest syndrome, aplastic crisis, or splenic sequestration, although these still accounted for the majority. Some simply had infection, GI bleed, or other problems.

Dr. Dowling said he had no relevant conflicts of interest. He has received research support from First American Real Estate Services Inc.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – Older adults with late-stage, age-related macular degeneration may have a significantly higher risk for hemorrhagic stroke than do individuals without the eye disease, a prospective, population-based study suggests.

There may be a common underlying process contributing to both age-related macular degeneration (AMD) and bleeding strokes, but more research will be needed to determine if that’s the case, Dr. Renske G. Wieberdink said in a press briefing at the International Stroke Conference.

"We don’t think there’s a causal relationship between AMD and stroke," said Dr. Wieberdink, an epidemiologist at Erasmus Medical Center, Rotterdam, the Netherlands.

During 1990-2007, data on 6,207 adults aged 55 years or older in the Rotterdam Study showed that 30% had early-stage (stage 1-3) AMD and 1.5% had late-stage (stage 4) AMD at baseline. Participants underwent physical examination, blood sampling, and full eye examinations every 3-4 years. During a median of nearly 14 years of follow-up, 726 participants developed a stroke, including 59 intracerebral hemorrhages, 397 cerebral infarctions, and 270 unspecified strokes.

Researchers found that the risk for any stroke was 56% higher in participants with late-stage AMD than in individuals without AMD after they controlled for the effects of age, sex, diabetes, blood pressure, use of antihypertensives, smoking, cholesterol levels, carotid artery plaques, body mass index, alcohol intake, and C-reactive protein levels.

Participants with late-stage AMD (either the wet or dry forms) had sixfold higher risk for intracerebral hemorrhage than did cohort members without AMD (hazard ratio, 6.11; 95% confidence interval, 2.34-15.98).

"This is a remarkable finding" that has not been reported before, Dr. Wieberdink said at the meeting, which was sponsored by the American Heart Association. "However, we should be cautious when interpreting the results. Although we reported a strong association, it is important to realize that our results are based on quite small numbers of late AMD and brain hemorrhage." The findings need to be replicated in other cohorts, she said.

Dr. Wieberdink is right to caution about overinterpreting the results of this small study without confirmation from additional studies, said Dr. Stephen Greenberg, who moderated the press briefing. But if the findings are replicated, patients will want to know if this should affect their decisions on whether or not to use blood-thinning agents such as aspirin or warfarin, said Dr. Greenberg, professor of neurology at Harvard Medical School and director of hemorrhagic stroke research at the Massachusetts General Hospital, both in Boston.

No significant association was seen between late-stage AMD and intracerebral infarction. Early-stage AMD was not associated with increased risk for any kind of stroke.

If there is a common mechanism underlying late-stage AMD and intracerebral hemorrhage, it’s unclear what it might be. "In the AMD field, AMD is not considered a vascular disorder, but that should be investigated further," she said.

"For bleeding strokes, we’re always looking for more etiologic factors," she added. "Maybe AMD provides more clues, but AMD is a disorder in which there is little knowledge of the pathway that leads to AMD."

Some previous studies have suggested that new agents to treat AMD may increase the risk of stroke. That’s unlikely to be a factor in the current study because the 1990-2007 study period came before those new agents became available, Dr. Wieberdink said.

The Rotterdam Study is a prospective, population-based cohort study of neurologic, ophthalmologic, cardiovascular, endocrinologic, and psychiatric diseases in older people.

The investigators reported having no relevant conflicts of interest.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – An endothelin receptor antagonist that showed promise in phase II clinical trials did not significantly reduce vasospasm-related morbidity and mortality in a phase III study of 1,147 patients treated with surgical clipping for aneurysmal subarachnoid hemorrhage.

Six weeks after randomization in the international, multicenter trial, 21% of 764 patients on the investigational drug clazosentan died or had vasospasm-related complications, compared with 25% of 383 patients on placebo, a nonsignificant difference, Dr. Robert Loch Macdonald reported at the International Stroke Conference.

The primary measure was a composite outcome of death from any cause within 6 weeks (5% in each group died), new cerebral infarct (in 12% on clazosentan and 13% on placebo), vasospasm-related neurological deterioration (in 15% and 18%, respectively), and the need for rescue therapy (in 11% and 16%, respectively).

Functional outcomes at 12 weeks also appeared to be no better in the clazosentan group than in the placebo group in the CONSCIOUS-2 trial (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage). In the treated group, 29% had a Glasgow Outcome Scale score of 4 or lower (indicating poor outcome), compared with 25% of the placebo group, a statistically insignificant difference, said Dr. Macdonald, head of neurosurgery at the University of Toronto.

Rates of adverse events were higher in the clazosentan group than with placebo, but investigators did not analyze these differences for statistical significance, he said at the conference, sponsored by the American Heart Association.

Lung complications occurred in 34% on clazosentan and 18% on placebo. In the clazosentan group, 13% had lung complications related to pulmonary edema, 22% developed anemia, 20% had hepatobiliary events, 12% developed hypotension, and 4% had a cerebral hemorrhage. In the placebo group, lung complications related to pulmonary edema were seen in 7%, 15% developed anemia, 17% had hepatobiliary events, 4% developed hypotension, and 3% had a cerebral hemorrhage.

A subgroup analysis suggested that patients who were sicker or who had more bleeding from the aneurysm may have benefited from the drug more than other patients, Dr. Macdonald said.

A separate CONSCIOUS-3 trial of clazosentan versus placebo in patients after treatment with endovascular coiling of aneurysmal subarachnoid hemorrhage was stopped once the CONSCIOUS-2 results were known. The results of CONSCIOUS-3 should be available in a few months. "Then we’ll decide whether to pursue the drug for those subgroups I mentioned, try to manage those side effects, or not develop the drug further," Dr. Macdonald said.

Previous optimism about clazosentan from the phase II clinical trial, CONSCIOUS-1, came from a significant reduction in vasospasm in the drug-treated group compared with placebo, not from measures of patient outcomes (Stroke 2008;39:3015-21).

It may be that CONSCIOUS-2 was too small, or didn’t measure the right outcomes, or the outcomes were affected by the adverse events, he said. "My other hypothesis at this point is that the angiographic vasospasm is only part of the phenomenon that causes stroke. If you get rid of the vasospasm, you don’t get rid of all of the things that cause stroke, and since you don’t do that, the person doesn’t get better."

Other strategies in trials to reduce vasospasm-related problems after treatment of aneurysmal subarachnoid hemorrhage include statin therapy or higher doses of nimodipine to avoid hypotension. "Those might be the way to go instead of drugs that only target dilating arteries," he said.

In a press briefing, Dr. Ralph Sacco, president of the American Heart Association, said that clazosentan is not the first investigational drug to show promise in phase II clinical testing and then be disappointing in a phase III trial.

"Subarachnoid hemorrhage is a very important, devastating type of stroke. We are still hopeful that we will have other medications in the future that will be helpful for delaying vasospasm and reducing morbidity with subarachnoid hemorrhage" besides currently available nimodipine, said Dr. Sacco, who also is professor of neurology and chair of neurological diseases at the University of Miami.

Vasospasm generally is more of a problem after surgical clipping than after endovascular coiling of aneurysms in patients with subarachnoid hemorrhage, so it’s possible that the CONSCIOUS-3 results differ somewhat from those of CONSCIOUS-2, Dr. Sacco said in a separate interview. "Coiling is also becoming much more frequently used among patients, both internationally and in the United States, for treatment of aneurysms."

Actelion Pharmaceuticals, which is developing clazosentan, funded the study and has provided research support to Dr. Macdonald. He also has been a consultant to the company and has ownership in Edge Therapeutics, a company that is developing drugs for subarachnoid hemorrhage. Dr. Sacco said he has no relevant conflicts of interest and was not involved in the CONSCIOUS-2 study.

LOS ANGELES – For the first time, a pediatric stroke severity scale has been validated in a prospective clinical trial.

The study in 15 North American medical centers showed excellent interrater reliability when neurologists used a pediatric version of the National Institutes of Health Stroke Scale for adults to examine children aged 2-18 years with acute arterial ischemic stroke.

The neurologists used the Pediatric NIH Stroke Scale (PedNIHSS) on 113 patients who were examined daily from admission to discharge, or through day 7 of hospitalization. Interrater reliability was tested in a subset of 25 patients who underwent simultaneous examinations by two pediatric neurologists. Characteristics of the subgroup were similar to those of the entire cohort, Dr. Rebecca N. Ichord reported at the International Stroke Conference.

The simultaneous raters’ scores were identical in 60% of ratings and were within a 1-point difference in 84% of ratings (Stroke 2011;42:613-7).

Research into potential ways of preventing or treating childhood stroke has been stymied in the past by the lack of a validated and reliable pediatric stroke scale. The PedNIHSS provides a way to index the severity of a child’s stroke, to make comparisons across treatment groups, and to get a baseline for predicting outcome, said Dr. Ichord, director of the pediatric stroke program at the Children’s Hospital of Philadelphia.

Clinicians, too, have been hungering for such a scale. "I have been asked over and over again [for a pediatric stroke scale] by clinicians who want to have a method of describing the severity of a child’s stroke," she said at the meeting, which was sponsored by the American Heart Association. "It helps them with clinical decision making. It helps them to prepare parents and counsel parents. It helps to guide them as to how quickly and how urgently the child’s care should move forward. It’s absolutely needed and wanted right now by clinicians on the front line."

Characteristics of the patients and the strokes in the study were similar to those reported in previous pediatric stroke cohort studies, which suggests the current findings are generalizable and the PedNIHSS should be applicable in other settings. Because all of the raters in the current study were pediatric neurologists or trainees, a separate study is needed to assess the PedNIHSS in the hands of other specialists, Dr. Ichord said.

The interrater reliability in the study compared favorably with that seen in studies of the adult NIHSS. The pediatric version also found good interrater reliability for facial weakness, dysarthria, and ataxia, which was not seen with the adult stroke scale. The reasons for this difference are unclear.

The PedNIHSS was drafted by a consensus panel of pediatric and adult stroke experts. They limited the use of the pediatric scale to ages 2-18 years because younger children have limited language abilities, which are needed for use of the PedNIHSS. Neonates and children younger than 2 years of age with acute ischemic stroke also frequently present without focal deficits, and so may require a scale with less emphasis on focal sensorimotor deficits, the investigators suggested.

A study is underway to compare PedNIHSS scores with infarct volume and with functional outcomes at 3 and 12 months.

Ischemic stroke is one of the top 10 causes of death among children, affecting 1.2-7.9 per 100,000 children aged 1 month to 18 years in North America and Europe, the investigators noted. Some 40%-60% of survivors are left with long-term motor and cognitive deficits that interfere with function.

Dr. Ichord and one of her associates in the study are on the clinical event committee for the Berlin Heart Trial for pediatric ventricular assist devices.

LOS ANGELES – For the first time, a pediatric stroke severity scale has been validated in a prospective clinical trial.

The study in 15 North American medical centers showed excellent interrater reliability when neurologists used a pediatric version of the National Institutes of Health Stroke Scale for adults to examine children aged 2-18 years with acute arterial ischemic stroke.

The neurologists used the Pediatric NIH Stroke Scale (PedNIHSS) on 113 patients who were examined daily from admission to discharge, or through day 7 of hospitalization. Interrater reliability was tested in a subset of 25 patients who underwent simultaneous examinations by two pediatric neurologists. Characteristics of the subgroup were similar to those of the entire cohort, Dr. Rebecca N. Ichord reported at the International Stroke Conference.

The simultaneous raters’ scores were identical in 60% of ratings and were within a 1-point difference in 84% of ratings (Stroke 2011;42:613-7).

Research into potential ways of preventing or treating childhood stroke has been stymied in the past by the lack of a validated and reliable pediatric stroke scale. The PedNIHSS provides a way to index the severity of a child’s stroke, to make comparisons across treatment groups, and to get a baseline for predicting outcome, said Dr. Ichord, director of the pediatric stroke program at the Children’s Hospital of Philadelphia.

Clinicians, too, have been hungering for such a scale. "I have been asked over and over again [for a pediatric stroke scale] by clinicians who want to have a method of describing the severity of a child’s stroke," she said at the meeting, which was sponsored by the American Heart Association. "It helps them with clinical decision making. It helps them to prepare parents and counsel parents. It helps to guide them as to how quickly and how urgently the child’s care should move forward. It’s absolutely needed and wanted right now by clinicians on the front line."

Characteristics of the patients and the strokes in the study were similar to those reported in previous pediatric stroke cohort studies, which suggests the current findings are generalizable and the PedNIHSS should be applicable in other settings. Because all of the raters in the current study were pediatric neurologists or trainees, a separate study is needed to assess the PedNIHSS in the hands of other specialists, Dr. Ichord said.

The interrater reliability in the study compared favorably with that seen in studies of the adult NIHSS. The pediatric version also found good interrater reliability for facial weakness, dysarthria, and ataxia, which was not seen with the adult stroke scale. The reasons for this difference are unclear.

The PedNIHSS was drafted by a consensus panel of pediatric and adult stroke experts. They limited the use of the pediatric scale to ages 2-18 years because younger children have limited language abilities, which are needed for use of the PedNIHSS. Neonates and children younger than 2 years of age with acute ischemic stroke also frequently present without focal deficits, and so may require a scale with less emphasis on focal sensorimotor deficits, the investigators suggested.

A study is underway to compare PedNIHSS scores with infarct volume and with functional outcomes at 3 and 12 months.

Ischemic stroke is one of the top 10 causes of death among children, affecting 1.2-7.9 per 100,000 children aged 1 month to 18 years in North America and Europe, the investigators noted. Some 40%-60% of survivors are left with long-term motor and cognitive deficits that interfere with function.

Dr. Ichord and one of her associates in the study are on the clinical event committee for the Berlin Heart Trial for pediatric ventricular assist devices.

LOS ANGELES – For the first time, a pediatric stroke severity scale has been validated in a prospective clinical trial.

The study in 15 North American medical centers showed excellent interrater reliability when neurologists used a pediatric version of the National Institutes of Health Stroke Scale for adults to examine children aged 2-18 years with acute arterial ischemic stroke.

The neurologists used the Pediatric NIH Stroke Scale (PedNIHSS) on 113 patients who were examined daily from admission to discharge, or through day 7 of hospitalization. Interrater reliability was tested in a subset of 25 patients who underwent simultaneous examinations by two pediatric neurologists. Characteristics of the subgroup were similar to those of the entire cohort, Dr. Rebecca N. Ichord reported at the International Stroke Conference.

The simultaneous raters’ scores were identical in 60% of ratings and were within a 1-point difference in 84% of ratings (Stroke 2011;42:613-7).

Research into potential ways of preventing or treating childhood stroke has been stymied in the past by the lack of a validated and reliable pediatric stroke scale. The PedNIHSS provides a way to index the severity of a child’s stroke, to make comparisons across treatment groups, and to get a baseline for predicting outcome, said Dr. Ichord, director of the pediatric stroke program at the Children’s Hospital of Philadelphia.

Clinicians, too, have been hungering for such a scale. "I have been asked over and over again [for a pediatric stroke scale] by clinicians who want to have a method of describing the severity of a child’s stroke," she said at the meeting, which was sponsored by the American Heart Association. "It helps them with clinical decision making. It helps them to prepare parents and counsel parents. It helps to guide them as to how quickly and how urgently the child’s care should move forward. It’s absolutely needed and wanted right now by clinicians on the front line."

Characteristics of the patients and the strokes in the study were similar to those reported in previous pediatric stroke cohort studies, which suggests the current findings are generalizable and the PedNIHSS should be applicable in other settings. Because all of the raters in the current study were pediatric neurologists or trainees, a separate study is needed to assess the PedNIHSS in the hands of other specialists, Dr. Ichord said.

The interrater reliability in the study compared favorably with that seen in studies of the adult NIHSS. The pediatric version also found good interrater reliability for facial weakness, dysarthria, and ataxia, which was not seen with the adult stroke scale. The reasons for this difference are unclear.

The PedNIHSS was drafted by a consensus panel of pediatric and adult stroke experts. They limited the use of the pediatric scale to ages 2-18 years because younger children have limited language abilities, which are needed for use of the PedNIHSS. Neonates and children younger than 2 years of age with acute ischemic stroke also frequently present without focal deficits, and so may require a scale with less emphasis on focal sensorimotor deficits, the investigators suggested.

A study is underway to compare PedNIHSS scores with infarct volume and with functional outcomes at 3 and 12 months.

Ischemic stroke is one of the top 10 causes of death among children, affecting 1.2-7.9 per 100,000 children aged 1 month to 18 years in North America and Europe, the investigators noted. Some 40%-60% of survivors are left with long-term motor and cognitive deficits that interfere with function.

Dr. Ichord and one of her associates in the study are on the clinical event committee for the Berlin Heart Trial for pediatric ventricular assist devices.