Patrice Wendling

CHICAGO — African American women with breast cancer have less-favorable outcomes than white women even after differences in socioeconomic status are minimized, new research suggests.

The study included 96 self-described African American and 304 white women with invasive breast cancer who enrolled from 2001 to 2007 in the Clinical Breast Care Project, which provides women equal access to health care and standardized treatment through the U.S. Department of Defense.

With a median follow-up of 51 months (range 12–82 months), disease-free and overall survival rates were significantly lower for African American women (78%), compared with white women (93%), Rachel Ellsworth, Ph.D., and her associates reported in a poster at a symposium sponsored by the Society of Surgical Oncology.

The mortality rate was 5% for African American women and 1% for white women. The average age at diagnosis was significantly lower in African American women, with 15% diagnosed before age 40, compared with 4% of white women.

Stage at diagnosis did not differ significantly between the African American and white groups (stage I: 48% vs. 54%, respectively; stage II: 31% vs. 32%; stage III: 13% vs. 11%; and stage IV: 8% vs. 3%).

And although positive lymph nodes were identified more often in African American (43%) women than in white women (38%), the difference did not reach statistical significance, reported Dr. Ellsworth, director of translational breast genomics, Clinical Breast Care Project, Windber (Pa.) Research Institute.

Tumors from African American women were significantly more likely to be “triple negative,” or to test negative for estrogen receptor (ER), progesterone receptor, and the human epidermal growth factor receptor 2 (29% vs. 9% for white women). Triple-negative tumors do not respond to any form of endocrine therapy and are associated with a survival disadvantage.

In addition, breast tumors from African American women were significantly more likely than those from white women to have the BRCA1-like phenotype (24% vs. 5%, respectively). “These data suggest that the differences in breast tumor phenotype and clinical outcomes are molecular in nature,” the investigators wrote.

Many studies have used the higher stage at diagnosis to support the idea that survival differences are socioeconomic, Dr. Ellsworth said in an interview. However, stage at diagnosis did not differ significantly between the two groups in the current study, yet the mortality rates for the African American women continued to be worse. In addition, the pathological characteristics of their tumors were more aggressive.

“While some hold that factors such as ER status can be driven by poverty, we believe that high-grade, triple-negative, BRCA1-like characteristics are driven by molecular differences,” Dr. Ellsworth said. “We have performed gene expression analysis on both tumor and disease-free breast tissue in African American and [white] women and have found genes differentially expressed between ethnic groups. Thus, we believe this data strongly suggests that differences in tumor phenotype are driven by genetic differences.”

When asked whether enough evidence has accrued to settle the biology-versus-environment question, Dr. Ellsworth said, “There will always be individuals who will say that socioeconomic status does influence your tumor cell biology.”

At baseline, there were no significant differences between the African American and white women enrolled in the study in terms of use of screening mammography (99% vs. 98%, respectively), any comorbidity (79% vs. 85%), first parity at age 30 or younger (82% vs. 81%), menarche before age 13 (51% vs. 48%), ever having smoked (67% vs. 55%), body mass index greater than 25 kg/m

However, a significantly higher proportion of African Americans reported that they performed monthly breast self-exams (76% vs. 59%), used oral contraceptives (82% vs. 63%), and had high fat intake defined by a score of more than 24 on the Fat Intake Scale (92% vs. 76%).

A lower proportion breast-fed (37% vs. 51%), used hormone replacement therapy (42% vs. 57%), or consumed more than 500 mg/day of caffeine (40% vs. 68%), Dr. Ellsworth and associates wrote.

CHICAGO — African American women with breast cancer have less-favorable outcomes than white women even after differences in socioeconomic status are minimized, new research suggests.

The study included 96 self-described African American and 304 white women with invasive breast cancer who enrolled from 2001 to 2007 in the Clinical Breast Care Project, which provides women equal access to health care and standardized treatment through the U.S. Department of Defense.

With a median follow-up of 51 months (range 12–82 months), disease-free and overall survival rates were significantly lower for African American women (78%), compared with white women (93%), Rachel Ellsworth, Ph.D., and her associates reported in a poster at a symposium sponsored by the Society of Surgical Oncology.

The mortality rate was 5% for African American women and 1% for white women. The average age at diagnosis was significantly lower in African American women, with 15% diagnosed before age 40, compared with 4% of white women.

Stage at diagnosis did not differ significantly between the African American and white groups (stage I: 48% vs. 54%, respectively; stage II: 31% vs. 32%; stage III: 13% vs. 11%; and stage IV: 8% vs. 3%).

And although positive lymph nodes were identified more often in African American (43%) women than in white women (38%), the difference did not reach statistical significance, reported Dr. Ellsworth, director of translational breast genomics, Clinical Breast Care Project, Windber (Pa.) Research Institute.

Tumors from African American women were significantly more likely to be “triple negative,” or to test negative for estrogen receptor (ER), progesterone receptor, and the human epidermal growth factor receptor 2 (29% vs. 9% for white women). Triple-negative tumors do not respond to any form of endocrine therapy and are associated with a survival disadvantage.

In addition, breast tumors from African American women were significantly more likely than those from white women to have the BRCA1-like phenotype (24% vs. 5%, respectively). “These data suggest that the differences in breast tumor phenotype and clinical outcomes are molecular in nature,” the investigators wrote.

Many studies have used the higher stage at diagnosis to support the idea that survival differences are socioeconomic, Dr. Ellsworth said in an interview. However, stage at diagnosis did not differ significantly between the two groups in the current study, yet the mortality rates for the African American women continued to be worse. In addition, the pathological characteristics of their tumors were more aggressive.

“While some hold that factors such as ER status can be driven by poverty, we believe that high-grade, triple-negative, BRCA1-like characteristics are driven by molecular differences,” Dr. Ellsworth said. “We have performed gene expression analysis on both tumor and disease-free breast tissue in African American and [white] women and have found genes differentially expressed between ethnic groups. Thus, we believe this data strongly suggests that differences in tumor phenotype are driven by genetic differences.”

When asked whether enough evidence has accrued to settle the biology-versus-environment question, Dr. Ellsworth said, “There will always be individuals who will say that socioeconomic status does influence your tumor cell biology.”

At baseline, there were no significant differences between the African American and white women enrolled in the study in terms of use of screening mammography (99% vs. 98%, respectively), any comorbidity (79% vs. 85%), first parity at age 30 or younger (82% vs. 81%), menarche before age 13 (51% vs. 48%), ever having smoked (67% vs. 55%), body mass index greater than 25 kg/m

However, a significantly higher proportion of African Americans reported that they performed monthly breast self-exams (76% vs. 59%), used oral contraceptives (82% vs. 63%), and had high fat intake defined by a score of more than 24 on the Fat Intake Scale (92% vs. 76%).

A lower proportion breast-fed (37% vs. 51%), used hormone replacement therapy (42% vs. 57%), or consumed more than 500 mg/day of caffeine (40% vs. 68%), Dr. Ellsworth and associates wrote.

CHICAGO — African American women with breast cancer have less-favorable outcomes than white women even after differences in socioeconomic status are minimized, new research suggests.

The study included 96 self-described African American and 304 white women with invasive breast cancer who enrolled from 2001 to 2007 in the Clinical Breast Care Project, which provides women equal access to health care and standardized treatment through the U.S. Department of Defense.

With a median follow-up of 51 months (range 12–82 months), disease-free and overall survival rates were significantly lower for African American women (78%), compared with white women (93%), Rachel Ellsworth, Ph.D., and her associates reported in a poster at a symposium sponsored by the Society of Surgical Oncology.

The mortality rate was 5% for African American women and 1% for white women. The average age at diagnosis was significantly lower in African American women, with 15% diagnosed before age 40, compared with 4% of white women.

Stage at diagnosis did not differ significantly between the African American and white groups (stage I: 48% vs. 54%, respectively; stage II: 31% vs. 32%; stage III: 13% vs. 11%; and stage IV: 8% vs. 3%).

And although positive lymph nodes were identified more often in African American (43%) women than in white women (38%), the difference did not reach statistical significance, reported Dr. Ellsworth, director of translational breast genomics, Clinical Breast Care Project, Windber (Pa.) Research Institute.

Tumors from African American women were significantly more likely to be “triple negative,” or to test negative for estrogen receptor (ER), progesterone receptor, and the human epidermal growth factor receptor 2 (29% vs. 9% for white women). Triple-negative tumors do not respond to any form of endocrine therapy and are associated with a survival disadvantage.

In addition, breast tumors from African American women were significantly more likely than those from white women to have the BRCA1-like phenotype (24% vs. 5%, respectively). “These data suggest that the differences in breast tumor phenotype and clinical outcomes are molecular in nature,” the investigators wrote.

Many studies have used the higher stage at diagnosis to support the idea that survival differences are socioeconomic, Dr. Ellsworth said in an interview. However, stage at diagnosis did not differ significantly between the two groups in the current study, yet the mortality rates for the African American women continued to be worse. In addition, the pathological characteristics of their tumors were more aggressive.

“While some hold that factors such as ER status can be driven by poverty, we believe that high-grade, triple-negative, BRCA1-like characteristics are driven by molecular differences,” Dr. Ellsworth said. “We have performed gene expression analysis on both tumor and disease-free breast tissue in African American and [white] women and have found genes differentially expressed between ethnic groups. Thus, we believe this data strongly suggests that differences in tumor phenotype are driven by genetic differences.”

When asked whether enough evidence has accrued to settle the biology-versus-environment question, Dr. Ellsworth said, “There will always be individuals who will say that socioeconomic status does influence your tumor cell biology.”

At baseline, there were no significant differences between the African American and white women enrolled in the study in terms of use of screening mammography (99% vs. 98%, respectively), any comorbidity (79% vs. 85%), first parity at age 30 or younger (82% vs. 81%), menarche before age 13 (51% vs. 48%), ever having smoked (67% vs. 55%), body mass index greater than 25 kg/m

However, a significantly higher proportion of African Americans reported that they performed monthly breast self-exams (76% vs. 59%), used oral contraceptives (82% vs. 63%), and had high fat intake defined by a score of more than 24 on the Fat Intake Scale (92% vs. 76%).

A lower proportion breast-fed (37% vs. 51%), used hormone replacement therapy (42% vs. 57%), or consumed more than 500 mg/day of caffeine (40% vs. 68%), Dr. Ellsworth and associates wrote.

DALLAS — Use of the AMOR-IPAT protocol did not significantly reduce cesarean deliveries in a prospective randomized trial of 270 women.

AMOR-IPAT (Active Management of Risk in Pregnancy at Term), a controversial approach, involves prostaglandin-assisted preventive labor induction based on a risk-scoring system, Dr. James Nicholson reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The women enrolled in the study had at least one of six specific risk factors for delivery and were randomized at 37 weeks, 4 days' gestation to either AMOR-IPAT (n = 136) or usual care (n = 134). Their mean age was 23 years.

As expected, the AMOR-IPAT group experienced significantly higher rates of labor induction (60% vs. 22%) and prostaglandin usage (40% vs. 16%), and were delivered, on average, 1 week earlier than the usual-care group.

In an intent-to-treat analysis, the rate of cesarean delivery was not significantly different between the AMOR-IPAT and usual-care groups (10% vs. 15%).

However, the AMOR-IPAT group had a significantly lower neonatal intensive care unit admission rate of 1.5% compared with 6.7%.

In addition, two composite outcomes—uncomplicated vaginal birth (74% vs. 63%) and adverse outcome index (AOI) scores (mean 1.4 vs. 8.6)—were significantly improved in the AMOR-IPAT group.

“AMOR-IPAT may represent a legitimate response to our nation's increasing rates of adverse term outcomes,” said Dr. Nicholson of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

Audience members were quick to point out that the study failed to achieve its primary goal of lowering cesarean delivery rates and that some of the deliveries went against the current American College of Obstetricians and Gynecologists' recommendation to avoid delivery before 39 weeks' gestation.

Dr. Nicholson responded that the study included only women with very good ultrasound-based dating, and that while a significant number of women were delivered during their 38th week, the protocol actually led to fewer infants going to the neonatal intensive care unit.

“Clearly there is a conflict between our current methods of care and this method of care, so there would need to be changes in labor and delivery for structure and process if this method were to be used,” he said.

“During this conference I've heard a lot about the AOI scores … and I would suggest that if the AOI scores are really improved to the level seen in this study that we might take a look at our processes of care and consider some significant changes,” Dr. Nicholson commented.

Two previous retrospective, nonrandomized studies showed a significant decrease in cesarean deliveries with the AMOR-IPAT protocol (Ann. Fam. Med. 2007;5:310–9; Am. J. Obstet. Gynecol. 2004;191:1516–28).

The study was funded jointly by the National Institutes of Health and the First Hospital Foundation.

Dr. Nicholson disclosed that Forest Pharmaceuticals provided free samples of its dinoprostone cervical-ripening product to the university's hospital, but that none of the samples were used during the study.

DALLAS — Use of the AMOR-IPAT protocol did not significantly reduce cesarean deliveries in a prospective randomized trial of 270 women.

AMOR-IPAT (Active Management of Risk in Pregnancy at Term), a controversial approach, involves prostaglandin-assisted preventive labor induction based on a risk-scoring system, Dr. James Nicholson reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The women enrolled in the study had at least one of six specific risk factors for delivery and were randomized at 37 weeks, 4 days' gestation to either AMOR-IPAT (n = 136) or usual care (n = 134). Their mean age was 23 years.

As expected, the AMOR-IPAT group experienced significantly higher rates of labor induction (60% vs. 22%) and prostaglandin usage (40% vs. 16%), and were delivered, on average, 1 week earlier than the usual-care group.

In an intent-to-treat analysis, the rate of cesarean delivery was not significantly different between the AMOR-IPAT and usual-care groups (10% vs. 15%).

However, the AMOR-IPAT group had a significantly lower neonatal intensive care unit admission rate of 1.5% compared with 6.7%.

In addition, two composite outcomes—uncomplicated vaginal birth (74% vs. 63%) and adverse outcome index (AOI) scores (mean 1.4 vs. 8.6)—were significantly improved in the AMOR-IPAT group.

“AMOR-IPAT may represent a legitimate response to our nation's increasing rates of adverse term outcomes,” said Dr. Nicholson of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

Audience members were quick to point out that the study failed to achieve its primary goal of lowering cesarean delivery rates and that some of the deliveries went against the current American College of Obstetricians and Gynecologists' recommendation to avoid delivery before 39 weeks' gestation.

Dr. Nicholson responded that the study included only women with very good ultrasound-based dating, and that while a significant number of women were delivered during their 38th week, the protocol actually led to fewer infants going to the neonatal intensive care unit.

“Clearly there is a conflict between our current methods of care and this method of care, so there would need to be changes in labor and delivery for structure and process if this method were to be used,” he said.

“During this conference I've heard a lot about the AOI scores … and I would suggest that if the AOI scores are really improved to the level seen in this study that we might take a look at our processes of care and consider some significant changes,” Dr. Nicholson commented.

Two previous retrospective, nonrandomized studies showed a significant decrease in cesarean deliveries with the AMOR-IPAT protocol (Ann. Fam. Med. 2007;5:310–9; Am. J. Obstet. Gynecol. 2004;191:1516–28).

The study was funded jointly by the National Institutes of Health and the First Hospital Foundation.

Dr. Nicholson disclosed that Forest Pharmaceuticals provided free samples of its dinoprostone cervical-ripening product to the university's hospital, but that none of the samples were used during the study.

DALLAS — Use of the AMOR-IPAT protocol did not significantly reduce cesarean deliveries in a prospective randomized trial of 270 women.

AMOR-IPAT (Active Management of Risk in Pregnancy at Term), a controversial approach, involves prostaglandin-assisted preventive labor induction based on a risk-scoring system, Dr. James Nicholson reported at the annual meeting of the Society for Maternal-Fetal Medicine.

The women enrolled in the study had at least one of six specific risk factors for delivery and were randomized at 37 weeks, 4 days' gestation to either AMOR-IPAT (n = 136) or usual care (n = 134). Their mean age was 23 years.

As expected, the AMOR-IPAT group experienced significantly higher rates of labor induction (60% vs. 22%) and prostaglandin usage (40% vs. 16%), and were delivered, on average, 1 week earlier than the usual-care group.

In an intent-to-treat analysis, the rate of cesarean delivery was not significantly different between the AMOR-IPAT and usual-care groups (10% vs. 15%).

However, the AMOR-IPAT group had a significantly lower neonatal intensive care unit admission rate of 1.5% compared with 6.7%.

In addition, two composite outcomes—uncomplicated vaginal birth (74% vs. 63%) and adverse outcome index (AOI) scores (mean 1.4 vs. 8.6)—were significantly improved in the AMOR-IPAT group.

“AMOR-IPAT may represent a legitimate response to our nation's increasing rates of adverse term outcomes,” said Dr. Nicholson of the department of family medicine and community health, University of Pennsylvania, Philadelphia.

Audience members were quick to point out that the study failed to achieve its primary goal of lowering cesarean delivery rates and that some of the deliveries went against the current American College of Obstetricians and Gynecologists' recommendation to avoid delivery before 39 weeks' gestation.

Dr. Nicholson responded that the study included only women with very good ultrasound-based dating, and that while a significant number of women were delivered during their 38th week, the protocol actually led to fewer infants going to the neonatal intensive care unit.

“Clearly there is a conflict between our current methods of care and this method of care, so there would need to be changes in labor and delivery for structure and process if this method were to be used,” he said.

“During this conference I've heard a lot about the AOI scores … and I would suggest that if the AOI scores are really improved to the level seen in this study that we might take a look at our processes of care and consider some significant changes,” Dr. Nicholson commented.

Two previous retrospective, nonrandomized studies showed a significant decrease in cesarean deliveries with the AMOR-IPAT protocol (Ann. Fam. Med. 2007;5:310–9; Am. J. Obstet. Gynecol. 2004;191:1516–28).

The study was funded jointly by the National Institutes of Health and the First Hospital Foundation.

Dr. Nicholson disclosed that Forest Pharmaceuticals provided free samples of its dinoprostone cervical-ripening product to the university's hospital, but that none of the samples were used during the study.

DALLAS — Manual removal of the placenta during cesarean delivery did not significantly increase maternal blood loss when compared with spontaneous removal in a prospective, randomized controlled trial of 86 women.

The study's primary outcome of change in hematocrit was not significantly different between the 40 women whose placenta was delivered manually and the 46 women whose placenta was delivered spontaneously (4.4% vs. 4.9%). Mean pre- and postoperative hematocrit levels were 35% and 31% versus 35% and 30%, Dr. Shawana Swann reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In addition, there was no difference in the percentage of patients with a drop in hematocrit of greater than 3% (28% vs. 35%) or greater than 5% (15% vs. 17%), said Dr. Swann of the Medical University of South Carolina in Charleston. None of the women in the study developed endometritis or received blood transfusions during hospitalization.

Placental delivery time was shorter in the manual group with a mean time of 49 seconds versus 71 seconds in the spontaneous group. This was statistically significant, but not clinically significant, as the difference was just 22 seconds, said Dr. Swann, who presented the results on behalf of principal investigator Dr. Eva Pressman of the University of Rochester (N.Y.) and their associates.

The manual and spontaneous groups were similar in terms of age (32 vs. 31 years), parity (1), and median gestational age (39 weeks).

“We believe providers should not base the mode of placental delivery on blood loss considerations for scheduled cesarean deliveries,” Dr. Swann said.

Proponents of manual removal suggest that faster placental removal leads to more rapid closure of the uterine incision and therefore less bleeding from this site.

Those preferring spontaneous separation and controlled cord traction contend that allowing dilated sinuses in the uterine wall to contract prior to placental expulsion decreases bleeding from the placental bed, and that this method is associated with lower rates of infection, she said.

An audience member asked why the findings were different from those of more than a dozen previous trials comparing the two methods of placental removal, including a recent meta-analysis of six randomized trials involving more than 1,700 women (Am. J. Obstet. Gynecol. 2005;193:1607–17).

The investigators who conducted the meta-analysis had reported that a benefit for spontaneous removal was usually found in the few studies that recorded blood loss or changes in hemoglobin/hematocrit level. They concluded that spontaneous removal should be preferred to manual removal, given the significant decrease in endometritis (odds ratio 0.62) demonstrated in the five studies that reported this outcome.

Dr. Swann responded that most studies performed prior to 2002 used estimated blood loss rather than hematocrit levels as the outcomes measure. Limitations of the current study, she said, included not collecting data on body mass index, which may affect blood loss and rates of infection, and the fact that hematocrit levels can be affected by administration of intravenous fluid and extravascular fluid shifts during cesarean delivery.

The study was sponsored by the Medical University of South Carolina and the University of Rochester.

Dr. Swann did not disclose any relevant financial conflicts of interest.

DALLAS — Manual removal of the placenta during cesarean delivery did not significantly increase maternal blood loss when compared with spontaneous removal in a prospective, randomized controlled trial of 86 women.

The study's primary outcome of change in hematocrit was not significantly different between the 40 women whose placenta was delivered manually and the 46 women whose placenta was delivered spontaneously (4.4% vs. 4.9%). Mean pre- and postoperative hematocrit levels were 35% and 31% versus 35% and 30%, Dr. Shawana Swann reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In addition, there was no difference in the percentage of patients with a drop in hematocrit of greater than 3% (28% vs. 35%) or greater than 5% (15% vs. 17%), said Dr. Swann of the Medical University of South Carolina in Charleston. None of the women in the study developed endometritis or received blood transfusions during hospitalization.

Placental delivery time was shorter in the manual group with a mean time of 49 seconds versus 71 seconds in the spontaneous group. This was statistically significant, but not clinically significant, as the difference was just 22 seconds, said Dr. Swann, who presented the results on behalf of principal investigator Dr. Eva Pressman of the University of Rochester (N.Y.) and their associates.

The manual and spontaneous groups were similar in terms of age (32 vs. 31 years), parity (1), and median gestational age (39 weeks).

“We believe providers should not base the mode of placental delivery on blood loss considerations for scheduled cesarean deliveries,” Dr. Swann said.

Proponents of manual removal suggest that faster placental removal leads to more rapid closure of the uterine incision and therefore less bleeding from this site.

Those preferring spontaneous separation and controlled cord traction contend that allowing dilated sinuses in the uterine wall to contract prior to placental expulsion decreases bleeding from the placental bed, and that this method is associated with lower rates of infection, she said.

An audience member asked why the findings were different from those of more than a dozen previous trials comparing the two methods of placental removal, including a recent meta-analysis of six randomized trials involving more than 1,700 women (Am. J. Obstet. Gynecol. 2005;193:1607–17).

The investigators who conducted the meta-analysis had reported that a benefit for spontaneous removal was usually found in the few studies that recorded blood loss or changes in hemoglobin/hematocrit level. They concluded that spontaneous removal should be preferred to manual removal, given the significant decrease in endometritis (odds ratio 0.62) demonstrated in the five studies that reported this outcome.

Dr. Swann responded that most studies performed prior to 2002 used estimated blood loss rather than hematocrit levels as the outcomes measure. Limitations of the current study, she said, included not collecting data on body mass index, which may affect blood loss and rates of infection, and the fact that hematocrit levels can be affected by administration of intravenous fluid and extravascular fluid shifts during cesarean delivery.

The study was sponsored by the Medical University of South Carolina and the University of Rochester.

Dr. Swann did not disclose any relevant financial conflicts of interest.

DALLAS — Manual removal of the placenta during cesarean delivery did not significantly increase maternal blood loss when compared with spontaneous removal in a prospective, randomized controlled trial of 86 women.

The study's primary outcome of change in hematocrit was not significantly different between the 40 women whose placenta was delivered manually and the 46 women whose placenta was delivered spontaneously (4.4% vs. 4.9%). Mean pre- and postoperative hematocrit levels were 35% and 31% versus 35% and 30%, Dr. Shawana Swann reported at the annual meeting of the Society for Maternal-Fetal Medicine.

In addition, there was no difference in the percentage of patients with a drop in hematocrit of greater than 3% (28% vs. 35%) or greater than 5% (15% vs. 17%), said Dr. Swann of the Medical University of South Carolina in Charleston. None of the women in the study developed endometritis or received blood transfusions during hospitalization.

Placental delivery time was shorter in the manual group with a mean time of 49 seconds versus 71 seconds in the spontaneous group. This was statistically significant, but not clinically significant, as the difference was just 22 seconds, said Dr. Swann, who presented the results on behalf of principal investigator Dr. Eva Pressman of the University of Rochester (N.Y.) and their associates.

The manual and spontaneous groups were similar in terms of age (32 vs. 31 years), parity (1), and median gestational age (39 weeks).

“We believe providers should not base the mode of placental delivery on blood loss considerations for scheduled cesarean deliveries,” Dr. Swann said.

Proponents of manual removal suggest that faster placental removal leads to more rapid closure of the uterine incision and therefore less bleeding from this site.

Those preferring spontaneous separation and controlled cord traction contend that allowing dilated sinuses in the uterine wall to contract prior to placental expulsion decreases bleeding from the placental bed, and that this method is associated with lower rates of infection, she said.

An audience member asked why the findings were different from those of more than a dozen previous trials comparing the two methods of placental removal, including a recent meta-analysis of six randomized trials involving more than 1,700 women (Am. J. Obstet. Gynecol. 2005;193:1607–17).

The investigators who conducted the meta-analysis had reported that a benefit for spontaneous removal was usually found in the few studies that recorded blood loss or changes in hemoglobin/hematocrit level. They concluded that spontaneous removal should be preferred to manual removal, given the significant decrease in endometritis (odds ratio 0.62) demonstrated in the five studies that reported this outcome.

Dr. Swann responded that most studies performed prior to 2002 used estimated blood loss rather than hematocrit levels as the outcomes measure. Limitations of the current study, she said, included not collecting data on body mass index, which may affect blood loss and rates of infection, and the fact that hematocrit levels can be affected by administration of intravenous fluid and extravascular fluid shifts during cesarean delivery.

The study was sponsored by the Medical University of South Carolina and the University of Rochester.

Dr. Swann did not disclose any relevant financial conflicts of interest.

CHICAGO — Surgical resection remains the treatment of choice for carotid body tumors, as presented in a review of 88 patients at one center.

Radiation therapy and chemotherapy are unsuitable alternatives because these rare tumors are too slow growing, and radiation exposes the carotid arteries to radiation arteritis, accelerated atherosclerosis, and even necrosis, Dr. Thomas A. Whitehill said at a vascular surgery symposium sponsored by Northwestern University.

Preoperative percutaneous tumor embolization has been tried with mixed results, but can be an important adjunct when treating select patients with large tumors (greater than 6 cm). There has been one report of a successful use of covered stents to facilitate resection (J. Vasc. Surg. 2003;38:389–91).

The malignancy rate for carotid body tumors is hard to define because there are no reliable histologic markers, but is thought to range from 2% to 5%, he said. Even if benign on histologic exam, all tumors, once discovered, should be surgically removed because they will ultimately wrap around the internal and external carotid arteries, erode into the base of the skull, and entrap neighboring cranial nerves. Increasing size also can interfere with speech, swallowing, and respiration, said Dr. Whitehill of the vascular surgery division of University of Colorado Health Science Center, Denver.

From 1993 to 2007, Dr. Whitehill and colleagues surgically resected 88 Shamblin classification II or III carotid body tumors, with an average diameter of 10.4 cm (range 5–16 cm). The patients ranged in age from 30 to 40 years.

Surgery time ranged from 4 to 14 hours, with an average blood loss of 375 mL (range 50–1800 mL). An internal carotid artery (ICA) resection bypass was performed in three patients, and ICA ligation in none.

Complications were relatively low, Dr. Whitehill said, and included cranial nerve IX neuropraxia (4%) or injury (1%), cranial nerve XII neuropraxia (30%), and superior laryngeal nerve injury (10%). There were no strokes or deaths.

Surgical advances and the widespread use of CT and MRI have decreased the overall risk of postoperative stroke over the past 25 years from about 30% to less than 2%, although the incidence of cranial nerve injury remains high at 15%–35%, he said.

Skip Angiography, and Other Surgical Pearls

Dr. Thomas A. Whitehill offered tips for carotid body tumors.

▸ Skip the angiography suite when making the diagnosis, and focus on CT imaging, preferably axial cuts rather than reconstructions. MRI may be slightly better at evaluating distant, metastatic deposits at the skull base.

▸ A nerve stimulator may be useful for preoperative identification of the cranial nerve.

▸ Do preoperative vocal cord and speech evaluations.

▸ Consider serial embolization in patients who are too old or have too many comorbidities to tolerate surgery.

▸ On a side CT view, draw a line between the mastoid tip and the angle of the mandible to get an idea of how high an exposure is needed and to help with preoperative planning.

▸ Utilize nasotracheal intubation in most patients, as it provides greater mobility with the mandible when resecting large tumors.

▸ In high access cases, mobilize the parotid gland anteriorly, up to the level of the facial nerve.

▸ Gain vascular control, if possible, and mobilize the tumor circumferentially to assess the extent of disease.

▸ Resect the tumor from proximal to distal.

▸ Fine mosquito clamp dissection and 3–0 or 4–0 silk ligation can give the best hemostasis.

▸ Send all suspicious lymph nodes for frozen permanent sections.

▸ Rather than using maxillomandibular arch bar fixation to obtain mandibular subluxation, consider interdental cross-wiring between the maxilla and mandible using bicuspids in dentate patients and Steinmann pins in patients with no teeth.

▸ For very distal tumors, cutting the digastric muscle will get you within 2 cm of the skull base.

▸ For large tumors, ligating the external carotid artery near its takeoff provides greater mobility.

▸ Avoid ligation of the internal carotid artery.

▸ If a tumor is 6 cm or more in diameter, consider preoperative embolization.

▸ Pushing the tumor completely through the bifurcation or pulling it anteriorly through the bifurcation may improve exposure angles and ease dissection.

▸ Take your time after the tumor is cleared of the two carotid arteries. The posterior surface and medial side of the tumor still must be separated from the deeper parapharyngeal tissues. Haste at this stage can result in the superior or inferior laryngeal nerves being transected or medial pharyngeal injuries, causing substantial swelling and neck pain in patients.

CHICAGO — Surgical resection remains the treatment of choice for carotid body tumors, as presented in a review of 88 patients at one center.

Radiation therapy and chemotherapy are unsuitable alternatives because these rare tumors are too slow growing, and radiation exposes the carotid arteries to radiation arteritis, accelerated atherosclerosis, and even necrosis, Dr. Thomas A. Whitehill said at a vascular surgery symposium sponsored by Northwestern University.

Preoperative percutaneous tumor embolization has been tried with mixed results, but can be an important adjunct when treating select patients with large tumors (greater than 6 cm). There has been one report of a successful use of covered stents to facilitate resection (J. Vasc. Surg. 2003;38:389–91).

The malignancy rate for carotid body tumors is hard to define because there are no reliable histologic markers, but is thought to range from 2% to 5%, he said. Even if benign on histologic exam, all tumors, once discovered, should be surgically removed because they will ultimately wrap around the internal and external carotid arteries, erode into the base of the skull, and entrap neighboring cranial nerves. Increasing size also can interfere with speech, swallowing, and respiration, said Dr. Whitehill of the vascular surgery division of University of Colorado Health Science Center, Denver.

From 1993 to 2007, Dr. Whitehill and colleagues surgically resected 88 Shamblin classification II or III carotid body tumors, with an average diameter of 10.4 cm (range 5–16 cm). The patients ranged in age from 30 to 40 years.

Surgery time ranged from 4 to 14 hours, with an average blood loss of 375 mL (range 50–1800 mL). An internal carotid artery (ICA) resection bypass was performed in three patients, and ICA ligation in none.

Complications were relatively low, Dr. Whitehill said, and included cranial nerve IX neuropraxia (4%) or injury (1%), cranial nerve XII neuropraxia (30%), and superior laryngeal nerve injury (10%). There were no strokes or deaths.

Surgical advances and the widespread use of CT and MRI have decreased the overall risk of postoperative stroke over the past 25 years from about 30% to less than 2%, although the incidence of cranial nerve injury remains high at 15%–35%, he said.

Skip Angiography, and Other Surgical Pearls

Dr. Thomas A. Whitehill offered tips for carotid body tumors.

▸ Skip the angiography suite when making the diagnosis, and focus on CT imaging, preferably axial cuts rather than reconstructions. MRI may be slightly better at evaluating distant, metastatic deposits at the skull base.

▸ A nerve stimulator may be useful for preoperative identification of the cranial nerve.

▸ Do preoperative vocal cord and speech evaluations.

▸ Consider serial embolization in patients who are too old or have too many comorbidities to tolerate surgery.

▸ On a side CT view, draw a line between the mastoid tip and the angle of the mandible to get an idea of how high an exposure is needed and to help with preoperative planning.

▸ Utilize nasotracheal intubation in most patients, as it provides greater mobility with the mandible when resecting large tumors.

▸ In high access cases, mobilize the parotid gland anteriorly, up to the level of the facial nerve.

▸ Gain vascular control, if possible, and mobilize the tumor circumferentially to assess the extent of disease.

▸ Resect the tumor from proximal to distal.

▸ Fine mosquito clamp dissection and 3–0 or 4–0 silk ligation can give the best hemostasis.

▸ Send all suspicious lymph nodes for frozen permanent sections.

▸ Rather than using maxillomandibular arch bar fixation to obtain mandibular subluxation, consider interdental cross-wiring between the maxilla and mandible using bicuspids in dentate patients and Steinmann pins in patients with no teeth.

▸ For very distal tumors, cutting the digastric muscle will get you within 2 cm of the skull base.

▸ For large tumors, ligating the external carotid artery near its takeoff provides greater mobility.

▸ Avoid ligation of the internal carotid artery.

▸ If a tumor is 6 cm or more in diameter, consider preoperative embolization.

▸ Pushing the tumor completely through the bifurcation or pulling it anteriorly through the bifurcation may improve exposure angles and ease dissection.

▸ Take your time after the tumor is cleared of the two carotid arteries. The posterior surface and medial side of the tumor still must be separated from the deeper parapharyngeal tissues. Haste at this stage can result in the superior or inferior laryngeal nerves being transected or medial pharyngeal injuries, causing substantial swelling and neck pain in patients.

CHICAGO — Surgical resection remains the treatment of choice for carotid body tumors, as presented in a review of 88 patients at one center.

Radiation therapy and chemotherapy are unsuitable alternatives because these rare tumors are too slow growing, and radiation exposes the carotid arteries to radiation arteritis, accelerated atherosclerosis, and even necrosis, Dr. Thomas A. Whitehill said at a vascular surgery symposium sponsored by Northwestern University.

Preoperative percutaneous tumor embolization has been tried with mixed results, but can be an important adjunct when treating select patients with large tumors (greater than 6 cm). There has been one report of a successful use of covered stents to facilitate resection (J. Vasc. Surg. 2003;38:389–91).

The malignancy rate for carotid body tumors is hard to define because there are no reliable histologic markers, but is thought to range from 2% to 5%, he said. Even if benign on histologic exam, all tumors, once discovered, should be surgically removed because they will ultimately wrap around the internal and external carotid arteries, erode into the base of the skull, and entrap neighboring cranial nerves. Increasing size also can interfere with speech, swallowing, and respiration, said Dr. Whitehill of the vascular surgery division of University of Colorado Health Science Center, Denver.

From 1993 to 2007, Dr. Whitehill and colleagues surgically resected 88 Shamblin classification II or III carotid body tumors, with an average diameter of 10.4 cm (range 5–16 cm). The patients ranged in age from 30 to 40 years.

Surgery time ranged from 4 to 14 hours, with an average blood loss of 375 mL (range 50–1800 mL). An internal carotid artery (ICA) resection bypass was performed in three patients, and ICA ligation in none.

Complications were relatively low, Dr. Whitehill said, and included cranial nerve IX neuropraxia (4%) or injury (1%), cranial nerve XII neuropraxia (30%), and superior laryngeal nerve injury (10%). There were no strokes or deaths.

Surgical advances and the widespread use of CT and MRI have decreased the overall risk of postoperative stroke over the past 25 years from about 30% to less than 2%, although the incidence of cranial nerve injury remains high at 15%–35%, he said.

Skip Angiography, and Other Surgical Pearls

Dr. Thomas A. Whitehill offered tips for carotid body tumors.

▸ Skip the angiography suite when making the diagnosis, and focus on CT imaging, preferably axial cuts rather than reconstructions. MRI may be slightly better at evaluating distant, metastatic deposits at the skull base.

▸ A nerve stimulator may be useful for preoperative identification of the cranial nerve.

▸ Do preoperative vocal cord and speech evaluations.

▸ Consider serial embolization in patients who are too old or have too many comorbidities to tolerate surgery.

▸ On a side CT view, draw a line between the mastoid tip and the angle of the mandible to get an idea of how high an exposure is needed and to help with preoperative planning.

▸ Utilize nasotracheal intubation in most patients, as it provides greater mobility with the mandible when resecting large tumors.

▸ In high access cases, mobilize the parotid gland anteriorly, up to the level of the facial nerve.

▸ Gain vascular control, if possible, and mobilize the tumor circumferentially to assess the extent of disease.

▸ Resect the tumor from proximal to distal.

▸ Fine mosquito clamp dissection and 3–0 or 4–0 silk ligation can give the best hemostasis.

▸ Send all suspicious lymph nodes for frozen permanent sections.

▸ Rather than using maxillomandibular arch bar fixation to obtain mandibular subluxation, consider interdental cross-wiring between the maxilla and mandible using bicuspids in dentate patients and Steinmann pins in patients with no teeth.

▸ For very distal tumors, cutting the digastric muscle will get you within 2 cm of the skull base.

▸ For large tumors, ligating the external carotid artery near its takeoff provides greater mobility.

▸ Avoid ligation of the internal carotid artery.

▸ If a tumor is 6 cm or more in diameter, consider preoperative embolization.

▸ Pushing the tumor completely through the bifurcation or pulling it anteriorly through the bifurcation may improve exposure angles and ease dissection.

▸ Take your time after the tumor is cleared of the two carotid arteries. The posterior surface and medial side of the tumor still must be separated from the deeper parapharyngeal tissues. Haste at this stage can result in the superior or inferior laryngeal nerves being transected or medial pharyngeal injuries, causing substantial swelling and neck pain in patients.

CHICAGO — Decompression of the spinal cord within 24 hours of injury is safe and is associated with improved neurologic recovery, results from an ongoing, prospective, multicenter study suggest.

“Certainly we're not going to be getting a home run with early surgery, but the concept here is to try for the best outcome we can,” Dr. Michael G. Fehlings said of the 1-year results of the Surgical Treatment of Acute Spinal Cord Injury Study (STASCIS).

The study included 170 patients who had a subaxial cervical spinal cord injury (SCI) and evidence of spinal cord or canal compression on MRI or CT. Of these, 44% were defined as an American Spinal Injury Association (ASIA) Impairment grade A with no motor or sensory function preserved; 22% were rated as grade B, 16% as grade C, and 18% as grade D.

Patients received decompression by surgery or traction within 7 days of SCI, and were stratified as “early” if it was within 24 hours of injury or “delayed” if it was after 24 hours.

A total of 94 patients, mean age 40 years, had early decompression surgery, and 76 patients, mean age 42 years, underwent delayed decompression. The investigators assessed outcomes in 108 patients at 6 months, and in 64 patients at 1 year.

At 6 months, 24% of early decompression patients had a 2-grade or greater improvement on the ASIA scale, compared with 4% who had delayed decompression, said Dr. Fehlings, head of the Krembil Neuroscience Centre at the University Health Network in Toronto. There weren't enough patients at 1 year to segregate the data by ASIA grade, but significantly more patients in the early group had a combined 1- and 2-grade improvement on the ASIA scale, compared with those in the delayed-compression group.

Complications, particularly respiratory complications and length of stay in the ICU, were reduced by about 15% in the early decompression group versus the delayed-treatment group (37% vs. 49%).

Dr. Fehlings and coinvestigators hypothesized that traction would be one of the primary means of achieving decompression, but it was used in only 29% of the early group and in 21% of the delayed group. Traction was also not as successful as was anticipated, with only a 50% success rate.

The Spine Study Trauma Group, a group of the world's top 40 spine surgeons, will publish in the next year consensus-based recommendations that patients with acute spinal cord injury without other life-threatening conditions should have early decompression surgery within 24 hours, Dr. Fehlings said in an interview at the annual meeting of the American Association of Neurological Surgeons.

Presentation discussant Christopher Shields of the Kentucky Spinal Cord Injury Research Center in Louisville suggested 8–12 hours may have been a more appropriate cutoff point for early intervention. Dr. Fehlings said that animal studies suggest the time window for optimal decompression after spinal cord injury occurs within 8–24 hours after SCI. Based on the differences in metabolic rate between rats and humans, an 8- to 12-hour window roughly translates into 24 hours for humans. Also, the logistics are substantial in terms of transferring a patient to an SCI treatment facility, and getting that patient medically optimized, imaged, taken to surgery, and decompressed.

“The Spine Trauma Study Group has deemed that 24 hours is the cutoff for early surgical intervention, although my colleagues and I try hard in every case to minimize this time,” said Dr. Fehlings, professor of neurosurgery at the University of Toronto.

CHICAGO — Decompression of the spinal cord within 24 hours of injury is safe and is associated with improved neurologic recovery, results from an ongoing, prospective, multicenter study suggest.

“Certainly we're not going to be getting a home run with early surgery, but the concept here is to try for the best outcome we can,” Dr. Michael G. Fehlings said of the 1-year results of the Surgical Treatment of Acute Spinal Cord Injury Study (STASCIS).

The study included 170 patients who had a subaxial cervical spinal cord injury (SCI) and evidence of spinal cord or canal compression on MRI or CT. Of these, 44% were defined as an American Spinal Injury Association (ASIA) Impairment grade A with no motor or sensory function preserved; 22% were rated as grade B, 16% as grade C, and 18% as grade D.

Patients received decompression by surgery or traction within 7 days of SCI, and were stratified as “early” if it was within 24 hours of injury or “delayed” if it was after 24 hours.

A total of 94 patients, mean age 40 years, had early decompression surgery, and 76 patients, mean age 42 years, underwent delayed decompression. The investigators assessed outcomes in 108 patients at 6 months, and in 64 patients at 1 year.

At 6 months, 24% of early decompression patients had a 2-grade or greater improvement on the ASIA scale, compared with 4% who had delayed decompression, said Dr. Fehlings, head of the Krembil Neuroscience Centre at the University Health Network in Toronto. There weren't enough patients at 1 year to segregate the data by ASIA grade, but significantly more patients in the early group had a combined 1- and 2-grade improvement on the ASIA scale, compared with those in the delayed-compression group.

Complications, particularly respiratory complications and length of stay in the ICU, were reduced by about 15% in the early decompression group versus the delayed-treatment group (37% vs. 49%).

Dr. Fehlings and coinvestigators hypothesized that traction would be one of the primary means of achieving decompression, but it was used in only 29% of the early group and in 21% of the delayed group. Traction was also not as successful as was anticipated, with only a 50% success rate.

The Spine Study Trauma Group, a group of the world's top 40 spine surgeons, will publish in the next year consensus-based recommendations that patients with acute spinal cord injury without other life-threatening conditions should have early decompression surgery within 24 hours, Dr. Fehlings said in an interview at the annual meeting of the American Association of Neurological Surgeons.

Presentation discussant Christopher Shields of the Kentucky Spinal Cord Injury Research Center in Louisville suggested 8–12 hours may have been a more appropriate cutoff point for early intervention. Dr. Fehlings said that animal studies suggest the time window for optimal decompression after spinal cord injury occurs within 8–24 hours after SCI. Based on the differences in metabolic rate between rats and humans, an 8- to 12-hour window roughly translates into 24 hours for humans. Also, the logistics are substantial in terms of transferring a patient to an SCI treatment facility, and getting that patient medically optimized, imaged, taken to surgery, and decompressed.

“The Spine Trauma Study Group has deemed that 24 hours is the cutoff for early surgical intervention, although my colleagues and I try hard in every case to minimize this time,” said Dr. Fehlings, professor of neurosurgery at the University of Toronto.

CHICAGO — Decompression of the spinal cord within 24 hours of injury is safe and is associated with improved neurologic recovery, results from an ongoing, prospective, multicenter study suggest.

“Certainly we're not going to be getting a home run with early surgery, but the concept here is to try for the best outcome we can,” Dr. Michael G. Fehlings said of the 1-year results of the Surgical Treatment of Acute Spinal Cord Injury Study (STASCIS).

The study included 170 patients who had a subaxial cervical spinal cord injury (SCI) and evidence of spinal cord or canal compression on MRI or CT. Of these, 44% were defined as an American Spinal Injury Association (ASIA) Impairment grade A with no motor or sensory function preserved; 22% were rated as grade B, 16% as grade C, and 18% as grade D.

Patients received decompression by surgery or traction within 7 days of SCI, and were stratified as “early” if it was within 24 hours of injury or “delayed” if it was after 24 hours.

A total of 94 patients, mean age 40 years, had early decompression surgery, and 76 patients, mean age 42 years, underwent delayed decompression. The investigators assessed outcomes in 108 patients at 6 months, and in 64 patients at 1 year.

At 6 months, 24% of early decompression patients had a 2-grade or greater improvement on the ASIA scale, compared with 4% who had delayed decompression, said Dr. Fehlings, head of the Krembil Neuroscience Centre at the University Health Network in Toronto. There weren't enough patients at 1 year to segregate the data by ASIA grade, but significantly more patients in the early group had a combined 1- and 2-grade improvement on the ASIA scale, compared with those in the delayed-compression group.

Complications, particularly respiratory complications and length of stay in the ICU, were reduced by about 15% in the early decompression group versus the delayed-treatment group (37% vs. 49%).

Dr. Fehlings and coinvestigators hypothesized that traction would be one of the primary means of achieving decompression, but it was used in only 29% of the early group and in 21% of the delayed group. Traction was also not as successful as was anticipated, with only a 50% success rate.

The Spine Study Trauma Group, a group of the world's top 40 spine surgeons, will publish in the next year consensus-based recommendations that patients with acute spinal cord injury without other life-threatening conditions should have early decompression surgery within 24 hours, Dr. Fehlings said in an interview at the annual meeting of the American Association of Neurological Surgeons.

Presentation discussant Christopher Shields of the Kentucky Spinal Cord Injury Research Center in Louisville suggested 8–12 hours may have been a more appropriate cutoff point for early intervention. Dr. Fehlings said that animal studies suggest the time window for optimal decompression after spinal cord injury occurs within 8–24 hours after SCI. Based on the differences in metabolic rate between rats and humans, an 8- to 12-hour window roughly translates into 24 hours for humans. Also, the logistics are substantial in terms of transferring a patient to an SCI treatment facility, and getting that patient medically optimized, imaged, taken to surgery, and decompressed.

“The Spine Trauma Study Group has deemed that 24 hours is the cutoff for early surgical intervention, although my colleagues and I try hard in every case to minimize this time,” said Dr. Fehlings, professor of neurosurgery at the University of Toronto.

CHICAGO — Monitoring platelet response using a novel measuring tool allowed for tailored clopidogrel dosing and was associated with reduced major adverse cardiovascular events after percutaneous coronary intervention in a small, prospective study of 162 patients.

After 30 days of follow-up, none of the 78 patients whose therapy was adjusted using the vasodilator-stimulated phosphoprotein (VASP) index assay experienced a major adverse cardiovascular event (MACE), compared with 8 (10%) of the 84 patients in the standard-dosing group, lead investigator Dr. Laurent Bonello reported at the Innovation and Intervention (i2) Summit. The between-group difference in MACE, defined as cardiovascular death, acute or subacute stent thrombosis, or revascularization, was significant.

Overall MACE rates were driven by acute and subacute thrombosis, which was reported in 4 (5%) of the controls.

Thrombolysis in myocardial infarction (TIMI) major bleeding was reported in one patient in each group, and TIMI minor bleeding occurred in three patients in the control group and two in the VASP-guided group.

The VASP index is an assay that measures the degree of phosphorylation of the vasodilator phosphoprotein, which is directly dependent on the P2Y12 and adenosine diphosphate (ADP) receptors. These receptors are targets for clopidogrel, making the assay highly specific to the response to clopidogrel, said Dr. Bonello, of the Hôpital Universitaire Nord, Marseilles, France.

Several studies have established a link between low response to clopidogrel and ischemic events, including stent thrombosis, he said at the meeting, cosponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions.

All patients in the study were undergoing elective percutaneous coronary intervention for unstable angina or non-ST-elevation acute coronary syndrome, and were defined as low responders to clopidogrel, based on a platelet reactivity of 50% or more using the VASP index after a standard loading dose of 600 mg clopidogrel and 250 mg aspirin.

Patients in the control group underwent PCI after the standard clopidogrel dose, whereas patients in the VASP tailored-therapy group could receive three additional 600-mg doses, up to a maximum of 2,400 mg, every 24 hours until platelet activity dropped below 50% before undergoing PCI.

The dose adjustment was effective in 67 (86%) patients. Despite having received 2,400 mg of clopidogrel, 11 (14%) patients remained low responders, he said. The average clopidogrel dose was 1,620 mg in the VASP tailored-therapy group.

Baseline characteristics were similar between the VASP and control groups. In both groups, the mean age was 66 years and the mean body mass index was 27 kg/m2. Prior MI had occurred in 22 of the VASP patients and 20 of the control patients, a nonsignificant difference.

“Reaching a post-treatment platelet activity below 50% using the VASP index seems optimal to prevent MACE in patients without increasing bleeding,” Dr. Bonello concluded.

Discussant Dr. Paul Gurbel, of Sinai Hospital in Baltimore, said the study suffered from some data-collection and analysis issues, but was an initial attempt to move away from the “one-size-fits-all” dosing of P2Y12 inhibitors. It also identified a “ceiling effect” of clopidogrel on high platelet reactivity in select patients.

“The final take-home message is that high platelet reactivity is a quantifiable and modifiable cardiovascular risk factor, and we can't ignore it anymore,” Dr. Gurbel said.

Dr. Bonello said that the assay is commercially available, but that its use is currently restricted to the research setting.

Dr. Bonello did not disclose any conflict of interest. The study was supported by a grant from the French Federation of Cardiology.

'High platelet reactivity is a quantifiable and modifiable cardiovascular risk factor, and we can't ignore it anymore.' DR. GURBEL

CHICAGO — Monitoring platelet response using a novel measuring tool allowed for tailored clopidogrel dosing and was associated with reduced major adverse cardiovascular events after percutaneous coronary intervention in a small, prospective study of 162 patients.

After 30 days of follow-up, none of the 78 patients whose therapy was adjusted using the vasodilator-stimulated phosphoprotein (VASP) index assay experienced a major adverse cardiovascular event (MACE), compared with 8 (10%) of the 84 patients in the standard-dosing group, lead investigator Dr. Laurent Bonello reported at the Innovation and Intervention (i2) Summit. The between-group difference in MACE, defined as cardiovascular death, acute or subacute stent thrombosis, or revascularization, was significant.

Overall MACE rates were driven by acute and subacute thrombosis, which was reported in 4 (5%) of the controls.

Thrombolysis in myocardial infarction (TIMI) major bleeding was reported in one patient in each group, and TIMI minor bleeding occurred in three patients in the control group and two in the VASP-guided group.

The VASP index is an assay that measures the degree of phosphorylation of the vasodilator phosphoprotein, which is directly dependent on the P2Y12 and adenosine diphosphate (ADP) receptors. These receptors are targets for clopidogrel, making the assay highly specific to the response to clopidogrel, said Dr. Bonello, of the Hôpital Universitaire Nord, Marseilles, France.

Several studies have established a link between low response to clopidogrel and ischemic events, including stent thrombosis, he said at the meeting, cosponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions.

All patients in the study were undergoing elective percutaneous coronary intervention for unstable angina or non-ST-elevation acute coronary syndrome, and were defined as low responders to clopidogrel, based on a platelet reactivity of 50% or more using the VASP index after a standard loading dose of 600 mg clopidogrel and 250 mg aspirin.

Patients in the control group underwent PCI after the standard clopidogrel dose, whereas patients in the VASP tailored-therapy group could receive three additional 600-mg doses, up to a maximum of 2,400 mg, every 24 hours until platelet activity dropped below 50% before undergoing PCI.

The dose adjustment was effective in 67 (86%) patients. Despite having received 2,400 mg of clopidogrel, 11 (14%) patients remained low responders, he said. The average clopidogrel dose was 1,620 mg in the VASP tailored-therapy group.

Baseline characteristics were similar between the VASP and control groups. In both groups, the mean age was 66 years and the mean body mass index was 27 kg/m2. Prior MI had occurred in 22 of the VASP patients and 20 of the control patients, a nonsignificant difference.

“Reaching a post-treatment platelet activity below 50% using the VASP index seems optimal to prevent MACE in patients without increasing bleeding,” Dr. Bonello concluded.

Discussant Dr. Paul Gurbel, of Sinai Hospital in Baltimore, said the study suffered from some data-collection and analysis issues, but was an initial attempt to move away from the “one-size-fits-all” dosing of P2Y12 inhibitors. It also identified a “ceiling effect” of clopidogrel on high platelet reactivity in select patients.

“The final take-home message is that high platelet reactivity is a quantifiable and modifiable cardiovascular risk factor, and we can't ignore it anymore,” Dr. Gurbel said.

Dr. Bonello said that the assay is commercially available, but that its use is currently restricted to the research setting.

Dr. Bonello did not disclose any conflict of interest. The study was supported by a grant from the French Federation of Cardiology.

'High platelet reactivity is a quantifiable and modifiable cardiovascular risk factor, and we can't ignore it anymore.' DR. GURBEL

CHICAGO — Monitoring platelet response using a novel measuring tool allowed for tailored clopidogrel dosing and was associated with reduced major adverse cardiovascular events after percutaneous coronary intervention in a small, prospective study of 162 patients.

After 30 days of follow-up, none of the 78 patients whose therapy was adjusted using the vasodilator-stimulated phosphoprotein (VASP) index assay experienced a major adverse cardiovascular event (MACE), compared with 8 (10%) of the 84 patients in the standard-dosing group, lead investigator Dr. Laurent Bonello reported at the Innovation and Intervention (i2) Summit. The between-group difference in MACE, defined as cardiovascular death, acute or subacute stent thrombosis, or revascularization, was significant.

Overall MACE rates were driven by acute and subacute thrombosis, which was reported in 4 (5%) of the controls.

Thrombolysis in myocardial infarction (TIMI) major bleeding was reported in one patient in each group, and TIMI minor bleeding occurred in three patients in the control group and two in the VASP-guided group.

The VASP index is an assay that measures the degree of phosphorylation of the vasodilator phosphoprotein, which is directly dependent on the P2Y12 and adenosine diphosphate (ADP) receptors. These receptors are targets for clopidogrel, making the assay highly specific to the response to clopidogrel, said Dr. Bonello, of the Hôpital Universitaire Nord, Marseilles, France.

Several studies have established a link between low response to clopidogrel and ischemic events, including stent thrombosis, he said at the meeting, cosponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions.

All patients in the study were undergoing elective percutaneous coronary intervention for unstable angina or non-ST-elevation acute coronary syndrome, and were defined as low responders to clopidogrel, based on a platelet reactivity of 50% or more using the VASP index after a standard loading dose of 600 mg clopidogrel and 250 mg aspirin.

Patients in the control group underwent PCI after the standard clopidogrel dose, whereas patients in the VASP tailored-therapy group could receive three additional 600-mg doses, up to a maximum of 2,400 mg, every 24 hours until platelet activity dropped below 50% before undergoing PCI.

The dose adjustment was effective in 67 (86%) patients. Despite having received 2,400 mg of clopidogrel, 11 (14%) patients remained low responders, he said. The average clopidogrel dose was 1,620 mg in the VASP tailored-therapy group.

Baseline characteristics were similar between the VASP and control groups. In both groups, the mean age was 66 years and the mean body mass index was 27 kg/m2. Prior MI had occurred in 22 of the VASP patients and 20 of the control patients, a nonsignificant difference.

“Reaching a post-treatment platelet activity below 50% using the VASP index seems optimal to prevent MACE in patients without increasing bleeding,” Dr. Bonello concluded.

Discussant Dr. Paul Gurbel, of Sinai Hospital in Baltimore, said the study suffered from some data-collection and analysis issues, but was an initial attempt to move away from the “one-size-fits-all” dosing of P2Y12 inhibitors. It also identified a “ceiling effect” of clopidogrel on high platelet reactivity in select patients.

“The final take-home message is that high platelet reactivity is a quantifiable and modifiable cardiovascular risk factor, and we can't ignore it anymore,” Dr. Gurbel said.

Dr. Bonello said that the assay is commercially available, but that its use is currently restricted to the research setting.

Dr. Bonello did not disclose any conflict of interest. The study was supported by a grant from the French Federation of Cardiology.

'High platelet reactivity is a quantifiable and modifiable cardiovascular risk factor, and we can't ignore it anymore.' DR. GURBEL

CHICAGO — The rate of major adverse cardiac events was roughly halved at 8 months by the use of sirolimus-eluting stents, compared with bare-metal stents in a randomized trial of 745 patients who underwent percutaneous coronary intervention for ST-segment elevation MI.

The Multicentre Evaluation of Single High-Dose Bolus Tirofiban vs. Abciximab with Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study (MULTISTRATEGY) also found that tirofiban was noninferior to abciximab in resolving ST elevation at 90 minutes.

“These findings may provide a robust scientific rationale for high-dose tirofiban as an alternative to abciximab in patients with STEMI,” Dr. Marco Valgimigli said in a statement.

The open-label, 2-by-2 factorial trial showed that at 8 months, major adverse cardiac events (MACE) occurred in 29 of 372 patients (7.8%) treated with sirolimus-eluting stents and in 54 of 372 patients (14.5%) with bare-metal stents, Dr. Valgimigli reported on behalf of the MULTISTRATEGY investigators in a late-breaking clinical trial session at the Innovation and Intervention (i2) Summit. The difference was statistically significant.

The benefit was driven by a significant 69% relative risk reduction in target vessel vascularization from 10.2% to 3.2%.

Stent thrombosis was significantly lower in patients with sirolimus-eluting stents, regardless of which Academic Research Consortium definition was used, said Dr. Valgimigli, of the Cardiovascular Institute, University of Ferrara (Italy).

Results of the glycoprotein IIb/IIIa inhibitor arms of the study showed that tirofiban therapy was associated with a noninferior ST-segment resolution at 90 minutes following percutaneous coronary intervention when compared with abciximab.

In 722 patients with an interpretable ECG, at least 50% recovery from ST-elevation occurred in 308 of 361 (85.3%) patients in the tirofiban group and 302 of 361 (83.6%) patients in the abciximab group, according to Dr. Valgimigli's presentation and data published simultaneously online (doi:10.1001/jama.299.15.joc80026).

“Most importantly, these results proved to be consistent among multiple prespecified subgroups—including age, sex, diabetes, Killip class, stent type, number of diseased vessels, location of the infarction, time to treat the infarction—with no evidence of interaction between any of these groups and the study treatment,” Dr. Valgimigli said at the meeting, cosponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions.

Patient age was 64 years in the abciximab plus bare-metal stent (BMS) group, 63 years in the abciximab plus sirolimus-eluting stent (SES) group, 65 years in the tirofiban plus BMS group, and 63 years in the tirofiban plus SES group.

At 30 days, the incidence of MACE, death, or MI, and definite or definite/probable stent thrombosis, did not differ significantly between the two groups. However, the incidence of thrombocytopenia was significantly more common with abciximab.

At 8 months, there also was no significant difference between patients treated with tirofiban or abciximab in the incidence of MACE (9.8% vs. 12.4%), death or MI (6.2% vs. 7.3%), and target vessel revascularization (6.2% vs. 7.3%), said Dr. Valgimigli, who reported receiving honoraria and research support from Merck USA. The study was partially supported by Merck.

Discussant Dr. E. Magnus Ohman, professor of cardiovascular medicine, Duke Clinical Research Institute, in Durham, N.C., pointed out that the 25-mcg/kg bolus of tirofiban used in the trial with a standard 0.15-mcg/kg per minute infusion is much higher than the approved bolus dose of 10 mcg/kg. Americans have limited experience with this higher dose and with the drug in general, as it is used in less than 4% of percutaneous coronary intervention cases in the United States, he said.

He also said that that the study was underpowered for the clinical end points and that the rate of transfusion was numerically higher in the tirofiban group, “leaving open the issue of how safe is this higher dose of tirofiban studied in this trial.”

Dr. Ohman also questioned whether the 8-month follow-up on the stented patients was sufficient, given that late-stent thrombosis tends to occur after that period.

Regarding the tirofiban dose, Dr. Valgimigli said the investigators felt the 10-mcg bolus dosing was inadequate in patients with acute MI based on results of the TARGET trial, and that there is significant experience with the drug in Europe, where it is widely used. While bleeding is an important area of focus for practitioners, he said that very important data suggest that thrombocytopenia—which was significantly more common with abciximab than tirofiban—is an important clinical indicator as well.

Press briefing moderator Dr. William Knopf, chief operating officer at the Piedmont Heart Institute, Atlanta, said, “I think one of the most important things we learned from this trial is perhaps the correct dose of tirofiban that we can extrapolate into our patients.”

In the same trial, tirofiban was found noninferior to abciximab in resolving ST elevation at 90 minutes. DR. VALGIMIGLI

CHICAGO — The rate of major adverse cardiac events was roughly halved at 8 months by the use of sirolimus-eluting stents, compared with bare-metal stents in a randomized trial of 745 patients who underwent percutaneous coronary intervention for ST-segment elevation MI.

The Multicentre Evaluation of Single High-Dose Bolus Tirofiban vs. Abciximab with Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study (MULTISTRATEGY) also found that tirofiban was noninferior to abciximab in resolving ST elevation at 90 minutes.

“These findings may provide a robust scientific rationale for high-dose tirofiban as an alternative to abciximab in patients with STEMI,” Dr. Marco Valgimigli said in a statement.

The open-label, 2-by-2 factorial trial showed that at 8 months, major adverse cardiac events (MACE) occurred in 29 of 372 patients (7.8%) treated with sirolimus-eluting stents and in 54 of 372 patients (14.5%) with bare-metal stents, Dr. Valgimigli reported on behalf of the MULTISTRATEGY investigators in a late-breaking clinical trial session at the Innovation and Intervention (i2) Summit. The difference was statistically significant.

The benefit was driven by a significant 69% relative risk reduction in target vessel vascularization from 10.2% to 3.2%.

Stent thrombosis was significantly lower in patients with sirolimus-eluting stents, regardless of which Academic Research Consortium definition was used, said Dr. Valgimigli, of the Cardiovascular Institute, University of Ferrara (Italy).

Results of the glycoprotein IIb/IIIa inhibitor arms of the study showed that tirofiban therapy was associated with a noninferior ST-segment resolution at 90 minutes following percutaneous coronary intervention when compared with abciximab.

In 722 patients with an interpretable ECG, at least 50% recovery from ST-elevation occurred in 308 of 361 (85.3%) patients in the tirofiban group and 302 of 361 (83.6%) patients in the abciximab group, according to Dr. Valgimigli's presentation and data published simultaneously online (doi:10.1001/jama.299.15.joc80026).

“Most importantly, these results proved to be consistent among multiple prespecified subgroups—including age, sex, diabetes, Killip class, stent type, number of diseased vessels, location of the infarction, time to treat the infarction—with no evidence of interaction between any of these groups and the study treatment,” Dr. Valgimigli said at the meeting, cosponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions.

Patient age was 64 years in the abciximab plus bare-metal stent (BMS) group, 63 years in the abciximab plus sirolimus-eluting stent (SES) group, 65 years in the tirofiban plus BMS group, and 63 years in the tirofiban plus SES group.

At 30 days, the incidence of MACE, death, or MI, and definite or definite/probable stent thrombosis, did not differ significantly between the two groups. However, the incidence of thrombocytopenia was significantly more common with abciximab.

At 8 months, there also was no significant difference between patients treated with tirofiban or abciximab in the incidence of MACE (9.8% vs. 12.4%), death or MI (6.2% vs. 7.3%), and target vessel revascularization (6.2% vs. 7.3%), said Dr. Valgimigli, who reported receiving honoraria and research support from Merck USA. The study was partially supported by Merck.

Discussant Dr. E. Magnus Ohman, professor of cardiovascular medicine, Duke Clinical Research Institute, in Durham, N.C., pointed out that the 25-mcg/kg bolus of tirofiban used in the trial with a standard 0.15-mcg/kg per minute infusion is much higher than the approved bolus dose of 10 mcg/kg. Americans have limited experience with this higher dose and with the drug in general, as it is used in less than 4% of percutaneous coronary intervention cases in the United States, he said.

He also said that that the study was underpowered for the clinical end points and that the rate of transfusion was numerically higher in the tirofiban group, “leaving open the issue of how safe is this higher dose of tirofiban studied in this trial.”

Dr. Ohman also questioned whether the 8-month follow-up on the stented patients was sufficient, given that late-stent thrombosis tends to occur after that period.

Regarding the tirofiban dose, Dr. Valgimigli said the investigators felt the 10-mcg bolus dosing was inadequate in patients with acute MI based on results of the TARGET trial, and that there is significant experience with the drug in Europe, where it is widely used. While bleeding is an important area of focus for practitioners, he said that very important data suggest that thrombocytopenia—which was significantly more common with abciximab than tirofiban—is an important clinical indicator as well.

Press briefing moderator Dr. William Knopf, chief operating officer at the Piedmont Heart Institute, Atlanta, said, “I think one of the most important things we learned from this trial is perhaps the correct dose of tirofiban that we can extrapolate into our patients.”

In the same trial, tirofiban was found noninferior to abciximab in resolving ST elevation at 90 minutes. DR. VALGIMIGLI

CHICAGO — The rate of major adverse cardiac events was roughly halved at 8 months by the use of sirolimus-eluting stents, compared with bare-metal stents in a randomized trial of 745 patients who underwent percutaneous coronary intervention for ST-segment elevation MI.

The Multicentre Evaluation of Single High-Dose Bolus Tirofiban vs. Abciximab with Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study (MULTISTRATEGY) also found that tirofiban was noninferior to abciximab in resolving ST elevation at 90 minutes.

“These findings may provide a robust scientific rationale for high-dose tirofiban as an alternative to abciximab in patients with STEMI,” Dr. Marco Valgimigli said in a statement.

The open-label, 2-by-2 factorial trial showed that at 8 months, major adverse cardiac events (MACE) occurred in 29 of 372 patients (7.8%) treated with sirolimus-eluting stents and in 54 of 372 patients (14.5%) with bare-metal stents, Dr. Valgimigli reported on behalf of the MULTISTRATEGY investigators in a late-breaking clinical trial session at the Innovation and Intervention (i2) Summit. The difference was statistically significant.

The benefit was driven by a significant 69% relative risk reduction in target vessel vascularization from 10.2% to 3.2%.

Stent thrombosis was significantly lower in patients with sirolimus-eluting stents, regardless of which Academic Research Consortium definition was used, said Dr. Valgimigli, of the Cardiovascular Institute, University of Ferrara (Italy).

Results of the glycoprotein IIb/IIIa inhibitor arms of the study showed that tirofiban therapy was associated with a noninferior ST-segment resolution at 90 minutes following percutaneous coronary intervention when compared with abciximab.

In 722 patients with an interpretable ECG, at least 50% recovery from ST-elevation occurred in 308 of 361 (85.3%) patients in the tirofiban group and 302 of 361 (83.6%) patients in the abciximab group, according to Dr. Valgimigli's presentation and data published simultaneously online (doi:10.1001/jama.299.15.joc80026).

“Most importantly, these results proved to be consistent among multiple prespecified subgroups—including age, sex, diabetes, Killip class, stent type, number of diseased vessels, location of the infarction, time to treat the infarction—with no evidence of interaction between any of these groups and the study treatment,” Dr. Valgimigli said at the meeting, cosponsored by the American College of Cardiology and the Society for Cardiovascular Angiography and Interventions.

Patient age was 64 years in the abciximab plus bare-metal stent (BMS) group, 63 years in the abciximab plus sirolimus-eluting stent (SES) group, 65 years in the tirofiban plus BMS group, and 63 years in the tirofiban plus SES group.

At 30 days, the incidence of MACE, death, or MI, and definite or definite/probable stent thrombosis, did not differ significantly between the two groups. However, the incidence of thrombocytopenia was significantly more common with abciximab.

At 8 months, there also was no significant difference between patients treated with tirofiban or abciximab in the incidence of MACE (9.8% vs. 12.4%), death or MI (6.2% vs. 7.3%), and target vessel revascularization (6.2% vs. 7.3%), said Dr. Valgimigli, who reported receiving honoraria and research support from Merck USA. The study was partially supported by Merck.

Discussant Dr. E. Magnus Ohman, professor of cardiovascular medicine, Duke Clinical Research Institute, in Durham, N.C., pointed out that the 25-mcg/kg bolus of tirofiban used in the trial with a standard 0.15-mcg/kg per minute infusion is much higher than the approved bolus dose of 10 mcg/kg. Americans have limited experience with this higher dose and with the drug in general, as it is used in less than 4% of percutaneous coronary intervention cases in the United States, he said.

He also said that that the study was underpowered for the clinical end points and that the rate of transfusion was numerically higher in the tirofiban group, “leaving open the issue of how safe is this higher dose of tirofiban studied in this trial.”

Dr. Ohman also questioned whether the 8-month follow-up on the stented patients was sufficient, given that late-stent thrombosis tends to occur after that period.

Regarding the tirofiban dose, Dr. Valgimigli said the investigators felt the 10-mcg bolus dosing was inadequate in patients with acute MI based on results of the TARGET trial, and that there is significant experience with the drug in Europe, where it is widely used. While bleeding is an important area of focus for practitioners, he said that very important data suggest that thrombocytopenia—which was significantly more common with abciximab than tirofiban—is an important clinical indicator as well.

Press briefing moderator Dr. William Knopf, chief operating officer at the Piedmont Heart Institute, Atlanta, said, “I think one of the most important things we learned from this trial is perhaps the correct dose of tirofiban that we can extrapolate into our patients.”

In the same trial, tirofiban was found noninferior to abciximab in resolving ST elevation at 90 minutes. DR. VALGIMIGLI

CHICAGO — Placing an automated external defibrillator in the homes of patients with a previous anterior-wall MI did not reduce mortality in a large randomized, multicenter trial.

The primary end point of death from any cause was not significantly different between patients who were randomized to the control response of calling emergency medical services and performing CPR, and patients who were randomized to use of an automated external defibrillator (AED), followed by calling emergency services and performing CPR.

With a median follow-up of 37 months, 228 of the 3,506 (6.5%) patients in the control group died, compared with 222 of the 3,495 (6.4%) patients in the AED group (hazard ratio 0.97), Dr. Gust H. Bardy and his associates reported at the annual meeting of the American College of Cardiology.

Of the 450 deaths in the Home Automated External Defibrillator Trial (HAT), cardiac death occurred in 129 patients in the control arm and in 138 patients in the AED group (HR 1.07); noncardiac death occurred in 89 control patients and 81 AED patients (HR 0.91); and tachyarrhythmia occurred in 84 control patients and 85 AED patients (HR 0.91). Thirteen deaths could not be classified because of incomplete data.

Patients enrolled in HAT were not candidates for implantation of a cardioverter-defibrillator. In addition, unlike standard care, they were advised about the risk of sudden cardiac arrest, said Dr. Bardy of the Seattle Institute for Cardiac Research. The patients' median age was 62 years, and their median left ventricular ejection fraction was 45%.

AEDs were used in 32 patients, of which 14 received an appropriate shock. Of those 14 patients, 9 died within 48 hours, 1 died 48 hours after shock was delivered, and only 4 (28.6%) survived to the study's end. There were no inappropriate shocks in the study, which was sponsored by the National Heart, Lung, and Blood Institute and performed at 178 clinical sites in seven countries. Of note, AEDs were used by neighbors or visitors in seven patients in cardiac arrest, and two of those patients survived long term, he said.

With the exception of diabetes, there was no significant interaction between AED use and any outcome with regard to age (65 years or older vs. younger than 65 years), gender, Q-wave versus non-Q-wave MI status, heart failure class, revascularization, or nationality (United States vs. all other countries).

The lack of benefit observed with home AED therapy in HAT is likely attributable to the lower than expected rate of overall mortality and sudden cardiac arrest, Dr. Bardy explained. This likely reflects the participants' excellent adherence to pharmacologic therapies, such as beta-blockers, ACE inhibitors, and statins; their high rate of previous revascularization (72%); and their increased awareness of the risk of sudden cardiac death.

In addition, the study was based on the assumption that patients would be at home and in the presence of their spouses or partners more than 50% of the time. In reality, only 117 events occurred at home, and only 58 of those were witnessed. About one-third of deaths started at night, and many of the daytime patients were in asystole, said Dr. Bardy, who disclosed relationships with Cameron Health Inc.

Purchasing a home AED, which costs about $1,275, may be based on emotion rather than on success rates or cost efficacy, noted the authors of an editorial on HAT published in the New England Journal of Medicine simultaneously with the findings (doi:10.1056/NEJMoa0801651). “The results of the HAT study suggest that future efforts should turn away from improbable resuscitation efforts and toward education, modification of risk factors, and other methods for primary prevention of heart disease,” wrote Dr. David J. Callans of the University of Pennsylvania, Philadelphia.

CHICAGO — Placing an automated external defibrillator in the homes of patients with a previous anterior-wall MI did not reduce mortality in a large randomized, multicenter trial.

The primary end point of death from any cause was not significantly different between patients who were randomized to the control response of calling emergency medical services and performing CPR, and patients who were randomized to use of an automated external defibrillator (AED), followed by calling emergency services and performing CPR.

With a median follow-up of 37 months, 228 of the 3,506 (6.5%) patients in the control group died, compared with 222 of the 3,495 (6.4%) patients in the AED group (hazard ratio 0.97), Dr. Gust H. Bardy and his associates reported at the annual meeting of the American College of Cardiology.

Of the 450 deaths in the Home Automated External Defibrillator Trial (HAT), cardiac death occurred in 129 patients in the control arm and in 138 patients in the AED group (HR 1.07); noncardiac death occurred in 89 control patients and 81 AED patients (HR 0.91); and tachyarrhythmia occurred in 84 control patients and 85 AED patients (HR 0.91). Thirteen deaths could not be classified because of incomplete data.

Patients enrolled in HAT were not candidates for implantation of a cardioverter-defibrillator. In addition, unlike standard care, they were advised about the risk of sudden cardiac arrest, said Dr. Bardy of the Seattle Institute for Cardiac Research. The patients' median age was 62 years, and their median left ventricular ejection fraction was 45%.

AEDs were used in 32 patients, of which 14 received an appropriate shock. Of those 14 patients, 9 died within 48 hours, 1 died 48 hours after shock was delivered, and only 4 (28.6%) survived to the study's end. There were no inappropriate shocks in the study, which was sponsored by the National Heart, Lung, and Blood Institute and performed at 178 clinical sites in seven countries. Of note, AEDs were used by neighbors or visitors in seven patients in cardiac arrest, and two of those patients survived long term, he said.

With the exception of diabetes, there was no significant interaction between AED use and any outcome with regard to age (65 years or older vs. younger than 65 years), gender, Q-wave versus non-Q-wave MI status, heart failure class, revascularization, or nationality (United States vs. all other countries).

The lack of benefit observed with home AED therapy in HAT is likely attributable to the lower than expected rate of overall mortality and sudden cardiac arrest, Dr. Bardy explained. This likely reflects the participants' excellent adherence to pharmacologic therapies, such as beta-blockers, ACE inhibitors, and statins; their high rate of previous revascularization (72%); and their increased awareness of the risk of sudden cardiac death.

In addition, the study was based on the assumption that patients would be at home and in the presence of their spouses or partners more than 50% of the time. In reality, only 117 events occurred at home, and only 58 of those were witnessed. About one-third of deaths started at night, and many of the daytime patients were in asystole, said Dr. Bardy, who disclosed relationships with Cameron Health Inc.

Purchasing a home AED, which costs about $1,275, may be based on emotion rather than on success rates or cost efficacy, noted the authors of an editorial on HAT published in the New England Journal of Medicine simultaneously with the findings (doi:10.1056/NEJMoa0801651). “The results of the HAT study suggest that future efforts should turn away from improbable resuscitation efforts and toward education, modification of risk factors, and other methods for primary prevention of heart disease,” wrote Dr. David J. Callans of the University of Pennsylvania, Philadelphia.

CHICAGO — Placing an automated external defibrillator in the homes of patients with a previous anterior-wall MI did not reduce mortality in a large randomized, multicenter trial.

The primary end point of death from any cause was not significantly different between patients who were randomized to the control response of calling emergency medical services and performing CPR, and patients who were randomized to use of an automated external defibrillator (AED), followed by calling emergency services and performing CPR.

With a median follow-up of 37 months, 228 of the 3,506 (6.5%) patients in the control group died, compared with 222 of the 3,495 (6.4%) patients in the AED group (hazard ratio 0.97), Dr. Gust H. Bardy and his associates reported at the annual meeting of the American College of Cardiology.

Of the 450 deaths in the Home Automated External Defibrillator Trial (HAT), cardiac death occurred in 129 patients in the control arm and in 138 patients in the AED group (HR 1.07); noncardiac death occurred in 89 control patients and 81 AED patients (HR 0.91); and tachyarrhythmia occurred in 84 control patients and 85 AED patients (HR 0.91). Thirteen deaths could not be classified because of incomplete data.

Patients enrolled in HAT were not candidates for implantation of a cardioverter-defibrillator. In addition, unlike standard care, they were advised about the risk of sudden cardiac arrest, said Dr. Bardy of the Seattle Institute for Cardiac Research. The patients' median age was 62 years, and their median left ventricular ejection fraction was 45%.

AEDs were used in 32 patients, of which 14 received an appropriate shock. Of those 14 patients, 9 died within 48 hours, 1 died 48 hours after shock was delivered, and only 4 (28.6%) survived to the study's end. There were no inappropriate shocks in the study, which was sponsored by the National Heart, Lung, and Blood Institute and performed at 178 clinical sites in seven countries. Of note, AEDs were used by neighbors or visitors in seven patients in cardiac arrest, and two of those patients survived long term, he said.

With the exception of diabetes, there was no significant interaction between AED use and any outcome with regard to age (65 years or older vs. younger than 65 years), gender, Q-wave versus non-Q-wave MI status, heart failure class, revascularization, or nationality (United States vs. all other countries).

The lack of benefit observed with home AED therapy in HAT is likely attributable to the lower than expected rate of overall mortality and sudden cardiac arrest, Dr. Bardy explained. This likely reflects the participants' excellent adherence to pharmacologic therapies, such as beta-blockers, ACE inhibitors, and statins; their high rate of previous revascularization (72%); and their increased awareness of the risk of sudden cardiac death.

In addition, the study was based on the assumption that patients would be at home and in the presence of their spouses or partners more than 50% of the time. In reality, only 117 events occurred at home, and only 58 of those were witnessed. About one-third of deaths started at night, and many of the daytime patients were in asystole, said Dr. Bardy, who disclosed relationships with Cameron Health Inc.

Purchasing a home AED, which costs about $1,275, may be based on emotion rather than on success rates or cost efficacy, noted the authors of an editorial on HAT published in the New England Journal of Medicine simultaneously with the findings (doi:10.1056/NEJMoa0801651). “The results of the HAT study suggest that future efforts should turn away from improbable resuscitation efforts and toward education, modification of risk factors, and other methods for primary prevention of heart disease,” wrote Dr. David J. Callans of the University of Pennsylvania, Philadelphia.

CHICAGO – Sleep apnea was observed in more than half of children with migraine in a study presented at the annual meeting of the American Academy of Neurology.

Polysomnography revealed sleep apnea in 56% of children with migraine, compared with 30% of those with nonmigraine headache in a study of 90 children aged 5–19 years with headache and sleep complaints.

The association between sleep apnea and migraine was significant, with an odds ratio of 2.1, Dr. Martina Vendrame, chief resident, Temple University Hospital, Philadelphia, and colleagues reported.

Two-thirds of the children with migraine also had frequent arousal during sleep.

Children with chronic migraine, defined as 15 days or more of migraine per month, took longer to fall asleep, had a shorter total sleep time, woke more frequently during the night, and had shorter REM and slow-wave sleep.

“Clinicians should ask all children with headaches and their parents about sleep problems,” including snoring, awakenings during sleep, and day-time sleepiness, Dr. Vendrame told reporters during a press briefing at the meeting. If concerns are raised, patients should be referred to ENT specialists for evaluation and treatment of sleep apnea.

Two-thirds of children in the study identified with sleep apnea were evaluated by ENT specialists, and half underwent tonsillectomy. Of these, 80% had some benefit, including reduced migraine frequency, she said.

Dr. Vendrame acknowledged that the presence of headache could contribute to sleep disturbances, as children suffering from headache will often take daytime naps. In addition, it is widely accepted that headache and sleep disorders share common pathophysiologic mechanisms. Previous studies have evaluated the relationship between headache and sleep disturbances, but this is the first to use polysomnography in children, she said.

The study comprised 60 children with migraine, 11 with chronic daily headaches, 6 with tension headaches, and 13 with nonspecific headaches.

Sleep apnea was also noted among 54% of patients with nonspecific headache, and was observed more frequently in those with a higher body mass index.

Children with chronic daily headache had shorter total sleep time, longer sleep latency, shorter REM sleep, and a higher arousal index.

Among the six children with tension headaches, 50% suffered from teeth grinding, versus 2.4% of children with nontension headaches (OR 1.95).

When asked if the study was biased by having a population of children who already had reported headaches and sleep disturbances, Dr. Vendrame said she hopes to repeat the study in a general population of children, in children without headache, and over an extended period of time to minimize the “first night” effect experienced when children are away from home.

The study was conducted at St. Christopher Hospital for Children, Drexel University, Philadelphia; and the authors had no conflicts of interest to disclose.

CHICAGO – Sleep apnea was observed in more than half of children with migraine in a study presented at the annual meeting of the American Academy of Neurology.

Polysomnography revealed sleep apnea in 56% of children with migraine, compared with 30% of those with nonmigraine headache in a study of 90 children aged 5–19 years with headache and sleep complaints.

The association between sleep apnea and migraine was significant, with an odds ratio of 2.1, Dr. Martina Vendrame, chief resident, Temple University Hospital, Philadelphia, and colleagues reported.

Two-thirds of the children with migraine also had frequent arousal during sleep.

Children with chronic migraine, defined as 15 days or more of migraine per month, took longer to fall asleep, had a shorter total sleep time, woke more frequently during the night, and had shorter REM and slow-wave sleep.

“Clinicians should ask all children with headaches and their parents about sleep problems,” including snoring, awakenings during sleep, and day-time sleepiness, Dr. Vendrame told reporters during a press briefing at the meeting. If concerns are raised, patients should be referred to ENT specialists for evaluation and treatment of sleep apnea.

Two-thirds of children in the study identified with sleep apnea were evaluated by ENT specialists, and half underwent tonsillectomy. Of these, 80% had some benefit, including reduced migraine frequency, she said.

Dr. Vendrame acknowledged that the presence of headache could contribute to sleep disturbances, as children suffering from headache will often take daytime naps. In addition, it is widely accepted that headache and sleep disorders share common pathophysiologic mechanisms. Previous studies have evaluated the relationship between headache and sleep disturbances, but this is the first to use polysomnography in children, she said.

The study comprised 60 children with migraine, 11 with chronic daily headaches, 6 with tension headaches, and 13 with nonspecific headaches.

Sleep apnea was also noted among 54% of patients with nonspecific headache, and was observed more frequently in those with a higher body mass index.

Children with chronic daily headache had shorter total sleep time, longer sleep latency, shorter REM sleep, and a higher arousal index.

Among the six children with tension headaches, 50% suffered from teeth grinding, versus 2.4% of children with nontension headaches (OR 1.95).

When asked if the study was biased by having a population of children who already had reported headaches and sleep disturbances, Dr. Vendrame said she hopes to repeat the study in a general population of children, in children without headache, and over an extended period of time to minimize the “first night” effect experienced when children are away from home.

The study was conducted at St. Christopher Hospital for Children, Drexel University, Philadelphia; and the authors had no conflicts of interest to disclose.

CHICAGO – Sleep apnea was observed in more than half of children with migraine in a study presented at the annual meeting of the American Academy of Neurology.

Polysomnography revealed sleep apnea in 56% of children with migraine, compared with 30% of those with nonmigraine headache in a study of 90 children aged 5–19 years with headache and sleep complaints.

The association between sleep apnea and migraine was significant, with an odds ratio of 2.1, Dr. Martina Vendrame, chief resident, Temple University Hospital, Philadelphia, and colleagues reported.

Two-thirds of the children with migraine also had frequent arousal during sleep.

Children with chronic migraine, defined as 15 days or more of migraine per month, took longer to fall asleep, had a shorter total sleep time, woke more frequently during the night, and had shorter REM and slow-wave sleep.

“Clinicians should ask all children with headaches and their parents about sleep problems,” including snoring, awakenings during sleep, and day-time sleepiness, Dr. Vendrame told reporters during a press briefing at the meeting. If concerns are raised, patients should be referred to ENT specialists for evaluation and treatment of sleep apnea.

Two-thirds of children in the study identified with sleep apnea were evaluated by ENT specialists, and half underwent tonsillectomy. Of these, 80% had some benefit, including reduced migraine frequency, she said.

Dr. Vendrame acknowledged that the presence of headache could contribute to sleep disturbances, as children suffering from headache will often take daytime naps. In addition, it is widely accepted that headache and sleep disorders share common pathophysiologic mechanisms. Previous studies have evaluated the relationship between headache and sleep disturbances, but this is the first to use polysomnography in children, she said.

The study comprised 60 children with migraine, 11 with chronic daily headaches, 6 with tension headaches, and 13 with nonspecific headaches.

Sleep apnea was also noted among 54% of patients with nonspecific headache, and was observed more frequently in those with a higher body mass index.

Children with chronic daily headache had shorter total sleep time, longer sleep latency, shorter REM sleep, and a higher arousal index.

Among the six children with tension headaches, 50% suffered from teeth grinding, versus 2.4% of children with nontension headaches (OR 1.95).

When asked if the study was biased by having a population of children who already had reported headaches and sleep disturbances, Dr. Vendrame said she hopes to repeat the study in a general population of children, in children without headache, and over an extended period of time to minimize the “first night” effect experienced when children are away from home.

The study was conducted at St. Christopher Hospital for Children, Drexel University, Philadelphia; and the authors had no conflicts of interest to disclose.

CHICAGO – Heavy drinking and smoking are associated with a significantly earlier age of development of late-onset Alzheimer's disease, according to findings presented at the annual meeting of the American Academy of Neurology.

In a retrospective analysis of 686 patients diagnosed with possible or probable Alzheimer's disease (AD), people who were heavy drinkers, defined as having more than two drinks of wine, beer, or spirits per day, developed Alzheimer's 5 years earlier than those who were not drinkers (onset 71 vs. 76 years).

People who smoked at least a pack of cigarettes per day developed the disease 2 years sooner than nonsmokers (73 vs. 75 years).

The combination of heavy drinking and smoking reduced the age at onset by 6–7 years, compared with those who did not drink or smoke heavily, lead investigator Dr. Ranjan Duara, medical director of the Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, and associates reported in a poster.

Genetic testing revealed that 27% of patients were positive for the apolipoprotein (APOE) ϵ4 allele, which has long been considered a risk factor for Alzheimer's. Patients with APOE ϵ4 developed the disease 3 years sooner than those without the gene variant. Gender had no significant influence on age of onset.

Identification of heavy smoking and heavy drinking as modifiable risk factors may potentially reduce the prevalence of Alzheimer's disease, especially among those with increased genetic risk, Dr. Duara said during a press briefing at the meeting.

Because the prevalence of Alzheimer's increases with age and roughly doubles every 5 years from age 65 years onward, a 5-year delay in disease onset could reduce the prevalence of Alzheimer's by almost 50%, he explained. Late-onset Alzheimer's is the most common form of the disease, representing roughly 85% of cases.

The investigators observed an additive, but not synergistic effect of the three risk factors. The average age at onset was 73 years among patients with the APOE ϵ4 allele who were also heavy smokers, 74 years for patients with APOE ϵ4 who drank heavily, and 68.5 years for those with all three risk factors. In contrast, the average age at onset was 77 years among patients with none of the three risk factors.

When asked if physicians should be screening patients in midlife for the APOE ϵ4 genotype, Dr. Duara responded that the general consensus has been that it is not a useful screening measure for evaluating overall risk of developing Alzheimer's. However, genetic testing for APOE ϵ4 could be of potential use in patients with a family history of the disease, and may ultimately be recommended as a risk screener as more information becomes available on the interaction of APOE ϵ4 with other risk factors.

In the meantime, Dr. Duara suggested that public health agencies and hospitals should emphasize to school-age children onward the importance of not smoking and limiting alcohol consumption to two or fewer drinks per day, in combination with regular exercise, a healthy diet, and an active social life.

At baseline, the mean Mini-Mental State Examination score was 18, women accounted for 64% of patients, 371 patients never smoked cigarettes, 129 smoked less than one pack per day, 94 smoked one pack per day, and 92 smoked at least one pack per day. In all, 340 patients never drank, 218 drank less than one drink a day, 78 drank one to two drinks a day, and 50 drank two or more drinks per day.

Dr. Duara acknowledged that the study was limited by several factors, including its retrospective design, use of informant-based reports on age of onset and risk factors, lack of dose-response assessment, and clinic-based population.

The study was funded by the Florida Department of Elder Affairs, and the investigators reported no disclosures.

The combination of heavy drinking and smoking reduced the age of onset of AD by 6–7 years. DR. DUARA

CHICAGO – Heavy drinking and smoking are associated with a significantly earlier age of development of late-onset Alzheimer's disease, according to findings presented at the annual meeting of the American Academy of Neurology.

In a retrospective analysis of 686 patients diagnosed with possible or probable Alzheimer's disease (AD), people who were heavy drinkers, defined as having more than two drinks of wine, beer, or spirits per day, developed Alzheimer's 5 years earlier than those who were not drinkers (onset 71 vs. 76 years).

People who smoked at least a pack of cigarettes per day developed the disease 2 years sooner than nonsmokers (73 vs. 75 years).

The combination of heavy drinking and smoking reduced the age at onset by 6–7 years, compared with those who did not drink or smoke heavily, lead investigator Dr. Ranjan Duara, medical director of the Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, and associates reported in a poster.

Genetic testing revealed that 27% of patients were positive for the apolipoprotein (APOE) ϵ4 allele, which has long been considered a risk factor for Alzheimer's. Patients with APOE ϵ4 developed the disease 3 years sooner than those without the gene variant. Gender had no significant influence on age of onset.

Identification of heavy smoking and heavy drinking as modifiable risk factors may potentially reduce the prevalence of Alzheimer's disease, especially among those with increased genetic risk, Dr. Duara said during a press briefing at the meeting.

Because the prevalence of Alzheimer's increases with age and roughly doubles every 5 years from age 65 years onward, a 5-year delay in disease onset could reduce the prevalence of Alzheimer's by almost 50%, he explained. Late-onset Alzheimer's is the most common form of the disease, representing roughly 85% of cases.

The investigators observed an additive, but not synergistic effect of the three risk factors. The average age at onset was 73 years among patients with the APOE ϵ4 allele who were also heavy smokers, 74 years for patients with APOE ϵ4 who drank heavily, and 68.5 years for those with all three risk factors. In contrast, the average age at onset was 77 years among patients with none of the three risk factors.

When asked if physicians should be screening patients in midlife for the APOE ϵ4 genotype, Dr. Duara responded that the general consensus has been that it is not a useful screening measure for evaluating overall risk of developing Alzheimer's. However, genetic testing for APOE ϵ4 could be of potential use in patients with a family history of the disease, and may ultimately be recommended as a risk screener as more information becomes available on the interaction of APOE ϵ4 with other risk factors.

In the meantime, Dr. Duara suggested that public health agencies and hospitals should emphasize to school-age children onward the importance of not smoking and limiting alcohol consumption to two or fewer drinks per day, in combination with regular exercise, a healthy diet, and an active social life.

At baseline, the mean Mini-Mental State Examination score was 18, women accounted for 64% of patients, 371 patients never smoked cigarettes, 129 smoked less than one pack per day, 94 smoked one pack per day, and 92 smoked at least one pack per day. In all, 340 patients never drank, 218 drank less than one drink a day, 78 drank one to two drinks a day, and 50 drank two or more drinks per day.

Dr. Duara acknowledged that the study was limited by several factors, including its retrospective design, use of informant-based reports on age of onset and risk factors, lack of dose-response assessment, and clinic-based population.

The study was funded by the Florida Department of Elder Affairs, and the investigators reported no disclosures.

The combination of heavy drinking and smoking reduced the age of onset of AD by 6–7 years. DR. DUARA

CHICAGO – Heavy drinking and smoking are associated with a significantly earlier age of development of late-onset Alzheimer's disease, according to findings presented at the annual meeting of the American Academy of Neurology.

In a retrospective analysis of 686 patients diagnosed with possible or probable Alzheimer's disease (AD), people who were heavy drinkers, defined as having more than two drinks of wine, beer, or spirits per day, developed Alzheimer's 5 years earlier than those who were not drinkers (onset 71 vs. 76 years).

People who smoked at least a pack of cigarettes per day developed the disease 2 years sooner than nonsmokers (73 vs. 75 years).

The combination of heavy drinking and smoking reduced the age at onset by 6–7 years, compared with those who did not drink or smoke heavily, lead investigator Dr. Ranjan Duara, medical director of the Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, and associates reported in a poster.

Genetic testing revealed that 27% of patients were positive for the apolipoprotein (APOE) ϵ4 allele, which has long been considered a risk factor for Alzheimer's. Patients with APOE ϵ4 developed the disease 3 years sooner than those without the gene variant. Gender had no significant influence on age of onset.

Identification of heavy smoking and heavy drinking as modifiable risk factors may potentially reduce the prevalence of Alzheimer's disease, especially among those with increased genetic risk, Dr. Duara said during a press briefing at the meeting.

Because the prevalence of Alzheimer's increases with age and roughly doubles every 5 years from age 65 years onward, a 5-year delay in disease onset could reduce the prevalence of Alzheimer's by almost 50%, he explained. Late-onset Alzheimer's is the most common form of the disease, representing roughly 85% of cases.

The investigators observed an additive, but not synergistic effect of the three risk factors. The average age at onset was 73 years among patients with the APOE ϵ4 allele who were also heavy smokers, 74 years for patients with APOE ϵ4 who drank heavily, and 68.5 years for those with all three risk factors. In contrast, the average age at onset was 77 years among patients with none of the three risk factors.

When asked if physicians should be screening patients in midlife for the APOE ϵ4 genotype, Dr. Duara responded that the general consensus has been that it is not a useful screening measure for evaluating overall risk of developing Alzheimer's. However, genetic testing for APOE ϵ4 could be of potential use in patients with a family history of the disease, and may ultimately be recommended as a risk screener as more information becomes available on the interaction of APOE ϵ4 with other risk factors.

In the meantime, Dr. Duara suggested that public health agencies and hospitals should emphasize to school-age children onward the importance of not smoking and limiting alcohol consumption to two or fewer drinks per day, in combination with regular exercise, a healthy diet, and an active social life.

At baseline, the mean Mini-Mental State Examination score was 18, women accounted for 64% of patients, 371 patients never smoked cigarettes, 129 smoked less than one pack per day, 94 smoked one pack per day, and 92 smoked at least one pack per day. In all, 340 patients never drank, 218 drank less than one drink a day, 78 drank one to two drinks a day, and 50 drank two or more drinks per day.

Dr. Duara acknowledged that the study was limited by several factors, including its retrospective design, use of informant-based reports on age of onset and risk factors, lack of dose-response assessment, and clinic-based population.

The study was funded by the Florida Department of Elder Affairs, and the investigators reported no disclosures.

The combination of heavy drinking and smoking reduced the age of onset of AD by 6–7 years. DR. DUARA