Sherry Boschert

NEWPORT BEACH, CALIF. — Screening for postpartum depression at the 2-month well-child visit caught most cases of maternal depression that developed within 6 months of delivery, according to a study of 199 young mothers.

In addition, an electronic medical record system that prompted health care providers to screen for postpartum depression in the study made screening routine and prompted referrals for all mothers who screened positive for depression, added Dr. Karolyn Kabir, who presented the results at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

Patients in the current study averaged 18 years of age, were ethnically and racially diverse, and had completed 10th grade on average. Half lived with their parents, and 70% were primiparous.

For the study, the system cued nurses to ask mothers who brought their babies in for well-child visits through 6 months of age to complete the Edinburgh Postnatal Depression Scale (EPDS). The health care provider who then saw the patient got a second electronic prompt to enter the EPDS score, and the provider could not close the electronic chart before entering the score or selecting one of several reasons for not entering a score.

Results showed that providers administered and scored the EPDS correctly 98% of the time, reported Dr. Kabir of the University of Colorado, Denver, and her associates.

If the EPDS score was positive for postpartum depression (a score of 10 or greater), the health care provider could not close the electronic chart before recording a management plan. All mothers with positive screens in the study were referred for mental health care, she said. In a previous study by other investigators, only half of mothers who screened positive for postpartum depression were referred to a mental health provider.

In the current study, 20% of all screens were positive. EPDS scores were unstable in the first 3 weeks after delivery. Most of the positive screens were picked up at the 2-month visit, when the prevalence of postpartum depression was 17%. The prevalence fell to 10% at the 4-month visit and rose to 19% at the 6-month visit, suggesting that if you can't screen for depression at the 2-month well-child visit, wait until the 6-month visit to screen, Dr. Kabir said.

Repeat screening of the mothers who screened negative at 2 months added only two incident cases of postpartum depression at the 4-month and 6-month well-child visits, she said.

The study cohort came from the Colorado Adolescent Maternity Program, a project for mothers younger than age 22 years; 85% were insured by Medicaid. Previous studies have shown that postpartum depression occurs most frequently in young women of lower socioeconomic status.

In general, risk factors for postpartum depression include having an unstable relationship with the father of the baby, inadequate social support, high life stress, and a prior history of depression or other mental illness, although many women who develop postpartum depression have none of these particular risk factors.

In the current study, 5% of mothers had a history of depression prior to pregnancy, and 22% had a history of depression during their index pregnancy, Dr. Kabir said.

“Universal screening for maternal depression as a standard component of routine well-child care is gaining support,” she noted. Studies have shown that treating depressed mothers benefits both the mother and the child.

ELSEVIER GLOBAL MEDICAL NEWS

NEWPORT BEACH, CALIF. — Screening for postpartum depression at the 2-month well-child visit caught most cases of maternal depression that developed within 6 months of delivery, according to a study of 199 young mothers.

In addition, an electronic medical record system that prompted health care providers to screen for postpartum depression in the study made screening routine and prompted referrals for all mothers who screened positive for depression, added Dr. Karolyn Kabir, who presented the results at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

Patients in the current study averaged 18 years of age, were ethnically and racially diverse, and had completed 10th grade on average. Half lived with their parents, and 70% were primiparous.

For the study, the system cued nurses to ask mothers who brought their babies in for well-child visits through 6 months of age to complete the Edinburgh Postnatal Depression Scale (EPDS). The health care provider who then saw the patient got a second electronic prompt to enter the EPDS score, and the provider could not close the electronic chart before entering the score or selecting one of several reasons for not entering a score.

Results showed that providers administered and scored the EPDS correctly 98% of the time, reported Dr. Kabir of the University of Colorado, Denver, and her associates.

If the EPDS score was positive for postpartum depression (a score of 10 or greater), the health care provider could not close the electronic chart before recording a management plan. All mothers with positive screens in the study were referred for mental health care, she said. In a previous study by other investigators, only half of mothers who screened positive for postpartum depression were referred to a mental health provider.

In the current study, 20% of all screens were positive. EPDS scores were unstable in the first 3 weeks after delivery. Most of the positive screens were picked up at the 2-month visit, when the prevalence of postpartum depression was 17%. The prevalence fell to 10% at the 4-month visit and rose to 19% at the 6-month visit, suggesting that if you can't screen for depression at the 2-month well-child visit, wait until the 6-month visit to screen, Dr. Kabir said.

Repeat screening of the mothers who screened negative at 2 months added only two incident cases of postpartum depression at the 4-month and 6-month well-child visits, she said.

The study cohort came from the Colorado Adolescent Maternity Program, a project for mothers younger than age 22 years; 85% were insured by Medicaid. Previous studies have shown that postpartum depression occurs most frequently in young women of lower socioeconomic status.

In general, risk factors for postpartum depression include having an unstable relationship with the father of the baby, inadequate social support, high life stress, and a prior history of depression or other mental illness, although many women who develop postpartum depression have none of these particular risk factors.

In the current study, 5% of mothers had a history of depression prior to pregnancy, and 22% had a history of depression during their index pregnancy, Dr. Kabir said.

“Universal screening for maternal depression as a standard component of routine well-child care is gaining support,” she noted. Studies have shown that treating depressed mothers benefits both the mother and the child.

ELSEVIER GLOBAL MEDICAL NEWS

NEWPORT BEACH, CALIF. — Screening for postpartum depression at the 2-month well-child visit caught most cases of maternal depression that developed within 6 months of delivery, according to a study of 199 young mothers.

In addition, an electronic medical record system that prompted health care providers to screen for postpartum depression in the study made screening routine and prompted referrals for all mothers who screened positive for depression, added Dr. Karolyn Kabir, who presented the results at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

Patients in the current study averaged 18 years of age, were ethnically and racially diverse, and had completed 10th grade on average. Half lived with their parents, and 70% were primiparous.

For the study, the system cued nurses to ask mothers who brought their babies in for well-child visits through 6 months of age to complete the Edinburgh Postnatal Depression Scale (EPDS). The health care provider who then saw the patient got a second electronic prompt to enter the EPDS score, and the provider could not close the electronic chart before entering the score or selecting one of several reasons for not entering a score.

Results showed that providers administered and scored the EPDS correctly 98% of the time, reported Dr. Kabir of the University of Colorado, Denver, and her associates.

If the EPDS score was positive for postpartum depression (a score of 10 or greater), the health care provider could not close the electronic chart before recording a management plan. All mothers with positive screens in the study were referred for mental health care, she said. In a previous study by other investigators, only half of mothers who screened positive for postpartum depression were referred to a mental health provider.

In the current study, 20% of all screens were positive. EPDS scores were unstable in the first 3 weeks after delivery. Most of the positive screens were picked up at the 2-month visit, when the prevalence of postpartum depression was 17%. The prevalence fell to 10% at the 4-month visit and rose to 19% at the 6-month visit, suggesting that if you can't screen for depression at the 2-month well-child visit, wait until the 6-month visit to screen, Dr. Kabir said.

Repeat screening of the mothers who screened negative at 2 months added only two incident cases of postpartum depression at the 4-month and 6-month well-child visits, she said.

The study cohort came from the Colorado Adolescent Maternity Program, a project for mothers younger than age 22 years; 85% were insured by Medicaid. Previous studies have shown that postpartum depression occurs most frequently in young women of lower socioeconomic status.

In general, risk factors for postpartum depression include having an unstable relationship with the father of the baby, inadequate social support, high life stress, and a prior history of depression or other mental illness, although many women who develop postpartum depression have none of these particular risk factors.

In the current study, 5% of mothers had a history of depression prior to pregnancy, and 22% had a history of depression during their index pregnancy, Dr. Kabir said.

“Universal screening for maternal depression as a standard component of routine well-child care is gaining support,” she noted. Studies have shown that treating depressed mothers benefits both the mother and the child.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Complications after total knee or hip arthroplasty in patients with diabetes were significantly more common in those with higher hemoglobin A_1c levels, a retrospective study of 119 patients found.

The overall rate of medical and surgical complications was more than 50% in patients with a hemoglobin A_1c (HbA_1c) level greater than 7%, and less than 40% in those with an HbA_1c level below 7%, researchers reported.

American Diabetes Association recommendations set a treatment goal of an HbA_1c level below 7%.

“Patients with significantly elevated HbA_1c levels should have their glycemic control better optimized prior to undergoing total hip [or knee] arthroplasty, as well as in the perioperative period,” Dr. Yossef C. Blum said during a poster session at the annual meeting of the American Academy of Orthopaedic Surgeons.

In a review of inpatient and outpatient charts of total knee or hip arthroplasty performed by a single surgeon at one institution from 2000 to 2007, Dr. Blum, of Montefiore Medical Center, New York, and his associates found 199 patients whose HbA_1c level had been measured in the year before surgery or within 3 months after the surgery. Those with conditions other than diabetes that led to an immunosuppressed state, such as HIV or rheumatoid arthritis, were excluded.

Patients did not have to have a diagnosis of diabetes to be included—just an HbA_1c measurement—because up to a third of people with diabetes do not have a formal diagnosis, they reported.

In all, 73% of the patients underwent total knee arthroplasty and 27% had total hip arthroplasty. Their mean age was 68 years. The cohort was 76% men, 34% white, 34% black, 23% Hispanic, and 9% other races or ethnicities. Their mean body mass index was 34 kg/m

A multivariate analysis looking for associations between HbA_1c levels and outcomes within 3 months of the surgery showed that higher HbA_1c levels were significantly associated with a higher risk for any complications, and surgical site and wound complications after surgery.

Only four surgical site infections occurred—too few to demonstrate a specific association between HbA_1c levels and wound infection—but “it is notable that three of four infections occurred in patients with an HbA_1c [level] above 7.5%,” Dr. Blum said, adding that although too few complications occurred to show a significant association with HbA_1c levels, an association might be seen in a larger study.

The current study found no association between HbA_1c level and the risk of non-surgical-site infections, urinary retention, or discharge after surgery to an inpatient facility. Overall, 43% of the patients developed medical or surgical complications.

“Future studies with [more] patients may help determine a cut-off HbA_1c level above which total hip [or knee] arthroplasty can be considered too high risk,” Dr. Blum said.

A 2003 review by other investigators of 290 diabetes patients who underwent noncardiac surgeries found that those with an HbA_1C level above 7% had a statistically significant increased risk for postoperative complications. But there have been few studies to date on the results of total knee arthroplasty in diabetes patients, and even fewer studies on the results of total hip arthroplasty in diabetes patients, he noted.

Some reports suggest a risk of 1%–7% for deep infection in diabetes patients after total knee arthroplasty, and overall wound complication rates of 1%–12%. A 1983 study of outcomes after total hip arthroplasty in diabetes patients reported superficial infections in 10% of the patients and deep infections in 7%.

SAN FRANCISCO — Complications after total knee or hip arthroplasty in patients with diabetes were significantly more common in those with higher hemoglobin A_1c levels, a retrospective study of 119 patients found.

The overall rate of medical and surgical complications was more than 50% in patients with a hemoglobin A_1c (HbA_1c) level greater than 7%, and less than 40% in those with an HbA_1c level below 7%, researchers reported.

American Diabetes Association recommendations set a treatment goal of an HbA_1c level below 7%.

“Patients with significantly elevated HbA_1c levels should have their glycemic control better optimized prior to undergoing total hip [or knee] arthroplasty, as well as in the perioperative period,” Dr. Yossef C. Blum said during a poster session at the annual meeting of the American Academy of Orthopaedic Surgeons.

In a review of inpatient and outpatient charts of total knee or hip arthroplasty performed by a single surgeon at one institution from 2000 to 2007, Dr. Blum, of Montefiore Medical Center, New York, and his associates found 199 patients whose HbA_1c level had been measured in the year before surgery or within 3 months after the surgery. Those with conditions other than diabetes that led to an immunosuppressed state, such as HIV or rheumatoid arthritis, were excluded.

Patients did not have to have a diagnosis of diabetes to be included—just an HbA_1c measurement—because up to a third of people with diabetes do not have a formal diagnosis, they reported.

In all, 73% of the patients underwent total knee arthroplasty and 27% had total hip arthroplasty. Their mean age was 68 years. The cohort was 76% men, 34% white, 34% black, 23% Hispanic, and 9% other races or ethnicities. Their mean body mass index was 34 kg/m

A multivariate analysis looking for associations between HbA_1c levels and outcomes within 3 months of the surgery showed that higher HbA_1c levels were significantly associated with a higher risk for any complications, and surgical site and wound complications after surgery.

Only four surgical site infections occurred—too few to demonstrate a specific association between HbA_1c levels and wound infection—but “it is notable that three of four infections occurred in patients with an HbA_1c [level] above 7.5%,” Dr. Blum said, adding that although too few complications occurred to show a significant association with HbA_1c levels, an association might be seen in a larger study.

The current study found no association between HbA_1c level and the risk of non-surgical-site infections, urinary retention, or discharge after surgery to an inpatient facility. Overall, 43% of the patients developed medical or surgical complications.

“Future studies with [more] patients may help determine a cut-off HbA_1c level above which total hip [or knee] arthroplasty can be considered too high risk,” Dr. Blum said.

A 2003 review by other investigators of 290 diabetes patients who underwent noncardiac surgeries found that those with an HbA_1C level above 7% had a statistically significant increased risk for postoperative complications. But there have been few studies to date on the results of total knee arthroplasty in diabetes patients, and even fewer studies on the results of total hip arthroplasty in diabetes patients, he noted.

Some reports suggest a risk of 1%–7% for deep infection in diabetes patients after total knee arthroplasty, and overall wound complication rates of 1%–12%. A 1983 study of outcomes after total hip arthroplasty in diabetes patients reported superficial infections in 10% of the patients and deep infections in 7%.

SAN FRANCISCO — Complications after total knee or hip arthroplasty in patients with diabetes were significantly more common in those with higher hemoglobin A_1c levels, a retrospective study of 119 patients found.

The overall rate of medical and surgical complications was more than 50% in patients with a hemoglobin A_1c (HbA_1c) level greater than 7%, and less than 40% in those with an HbA_1c level below 7%, researchers reported.

American Diabetes Association recommendations set a treatment goal of an HbA_1c level below 7%.

“Patients with significantly elevated HbA_1c levels should have their glycemic control better optimized prior to undergoing total hip [or knee] arthroplasty, as well as in the perioperative period,” Dr. Yossef C. Blum said during a poster session at the annual meeting of the American Academy of Orthopaedic Surgeons.

In a review of inpatient and outpatient charts of total knee or hip arthroplasty performed by a single surgeon at one institution from 2000 to 2007, Dr. Blum, of Montefiore Medical Center, New York, and his associates found 199 patients whose HbA_1c level had been measured in the year before surgery or within 3 months after the surgery. Those with conditions other than diabetes that led to an immunosuppressed state, such as HIV or rheumatoid arthritis, were excluded.

Patients did not have to have a diagnosis of diabetes to be included—just an HbA_1c measurement—because up to a third of people with diabetes do not have a formal diagnosis, they reported.

In all, 73% of the patients underwent total knee arthroplasty and 27% had total hip arthroplasty. Their mean age was 68 years. The cohort was 76% men, 34% white, 34% black, 23% Hispanic, and 9% other races or ethnicities. Their mean body mass index was 34 kg/m

A multivariate analysis looking for associations between HbA_1c levels and outcomes within 3 months of the surgery showed that higher HbA_1c levels were significantly associated with a higher risk for any complications, and surgical site and wound complications after surgery.

Only four surgical site infections occurred—too few to demonstrate a specific association between HbA_1c levels and wound infection—but “it is notable that three of four infections occurred in patients with an HbA_1c [level] above 7.5%,” Dr. Blum said, adding that although too few complications occurred to show a significant association with HbA_1c levels, an association might be seen in a larger study.

The current study found no association between HbA_1c level and the risk of non-surgical-site infections, urinary retention, or discharge after surgery to an inpatient facility. Overall, 43% of the patients developed medical or surgical complications.

“Future studies with [more] patients may help determine a cut-off HbA_1c level above which total hip [or knee] arthroplasty can be considered too high risk,” Dr. Blum said.

A 2003 review by other investigators of 290 diabetes patients who underwent noncardiac surgeries found that those with an HbA_1C level above 7% had a statistically significant increased risk for postoperative complications. But there have been few studies to date on the results of total knee arthroplasty in diabetes patients, and even fewer studies on the results of total hip arthroplasty in diabetes patients, he noted.

Some reports suggest a risk of 1%–7% for deep infection in diabetes patients after total knee arthroplasty, and overall wound complication rates of 1%–12%. A 1983 study of outcomes after total hip arthroplasty in diabetes patients reported superficial infections in 10% of the patients and deep infections in 7%.

SAN FRANCISCO — Adding an injection of pramlintide at mealtime to basal insulin therapy worked as well as mealtime rapid-acting insulin to control postprandial glucose levels, but caused less weight gain and hypoglycemia, a study of 112 patients with type 2 diabetes found.

The randomized, open-label, 6-month trial showed that 30% of 56 patients in the pramlintide group and 11% of 56 patients in the rapid-acting insulin group achieved the primary composite end point of a hemoglobin A_1c (HbA_1c) level of 7% or lower, no increase in body weight, and no severe hypoglycemia. The difference was significant, Dr. Matthew Riddle of the Oregon Health and Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

Pramlintide is a synthetic analogue of the hormone amylin, with similar glucoregulatory properties. It is approved as adjunctive therapy for patients with type 1 or type 2 diabetes who use mealtime insulin and have not achieved good glucose control despite optimal insulin therapy, with or without oral medications. It is not approved as an alternative to mealtime insulin, said Dr. Riddle, who is an adviser and consultant for Amylin Pharmaceuticals Inc., which markets pramlintide and funded the study.

A prior study by Dr. Riddle and his associates suggested patients with type 2 diabetes on basal insulin glargine could get good postprandial glucose control and cut HbA_1c levels by adding mealtime pramlintide without prandial insulin, and without weight gain (Diabetes Care 2007;30:2794-9).

The current study enrolled adults with type 2 diabetes who had baseline HbA_1c levels of 7%–10%, were on any combination of oral diabetes medications (metformin, sulfonylureas, or thiazolidinediones), and who were not taking insulin or had used insulin for no more than 6 months at doses of less than 50 U/day.

Both groups started basal insulin (glargine or detemir) on day 1 and titrated as needed, with a fasting plasma glucose goal of 70–100 mg/dL. The pramlintide group started pramlintide (120 mcg before major meals) on day 1 and could titrate down to 60 mcg if needed because of nausea. The rapid-acting insulin group used basal insulin alone for 4 weeks to decrease the risk of insulin-induced hypoglycemia, then added rapid-acting insulin (5 U with major meals).

By week 24, a baseline average HbA_1c level of 8.3% in each group had decreased by 0.9% in the pramlintide group and by 1.1% with rapid-acting insulin. In the pramlintide group, 45% of patients reached an HbA_1c level of less than 7%, and 29% reached levels below 6.5%, compared with 55% and 32%, respectively, in the rapid-acting insulin group. The differences were not statistically significant in the intent-to-treat analyses.

After 6 months, patients in the rapid-acting insulin group gained an average of 4.2 kg, compared with 0.3 kg in the pramlintide group. Hypoglycemia was seen in 55% of the pramlintide group and 82% of the rapid-acting insulin group. Nausea affected 21% of pramlintide patients and none in the prandial insulin group. Two patients stopped pramlintide because of nausea.

Dr. Riddle also has been an adviser and consultant and has received research support from Eli Lilly & Co., Novo Nordisk Inc., and Sanofi-Aventis, which also make insulin and oral glucose control agents.

SAN FRANCISCO — Adding an injection of pramlintide at mealtime to basal insulin therapy worked as well as mealtime rapid-acting insulin to control postprandial glucose levels, but caused less weight gain and hypoglycemia, a study of 112 patients with type 2 diabetes found.

The randomized, open-label, 6-month trial showed that 30% of 56 patients in the pramlintide group and 11% of 56 patients in the rapid-acting insulin group achieved the primary composite end point of a hemoglobin A_1c (HbA_1c) level of 7% or lower, no increase in body weight, and no severe hypoglycemia. The difference was significant, Dr. Matthew Riddle of the Oregon Health and Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

Pramlintide is a synthetic analogue of the hormone amylin, with similar glucoregulatory properties. It is approved as adjunctive therapy for patients with type 1 or type 2 diabetes who use mealtime insulin and have not achieved good glucose control despite optimal insulin therapy, with or without oral medications. It is not approved as an alternative to mealtime insulin, said Dr. Riddle, who is an adviser and consultant for Amylin Pharmaceuticals Inc., which markets pramlintide and funded the study.

A prior study by Dr. Riddle and his associates suggested patients with type 2 diabetes on basal insulin glargine could get good postprandial glucose control and cut HbA_1c levels by adding mealtime pramlintide without prandial insulin, and without weight gain (Diabetes Care 2007;30:2794-9).

The current study enrolled adults with type 2 diabetes who had baseline HbA_1c levels of 7%–10%, were on any combination of oral diabetes medications (metformin, sulfonylureas, or thiazolidinediones), and who were not taking insulin or had used insulin for no more than 6 months at doses of less than 50 U/day.

Both groups started basal insulin (glargine or detemir) on day 1 and titrated as needed, with a fasting plasma glucose goal of 70–100 mg/dL. The pramlintide group started pramlintide (120 mcg before major meals) on day 1 and could titrate down to 60 mcg if needed because of nausea. The rapid-acting insulin group used basal insulin alone for 4 weeks to decrease the risk of insulin-induced hypoglycemia, then added rapid-acting insulin (5 U with major meals).

By week 24, a baseline average HbA_1c level of 8.3% in each group had decreased by 0.9% in the pramlintide group and by 1.1% with rapid-acting insulin. In the pramlintide group, 45% of patients reached an HbA_1c level of less than 7%, and 29% reached levels below 6.5%, compared with 55% and 32%, respectively, in the rapid-acting insulin group. The differences were not statistically significant in the intent-to-treat analyses.

After 6 months, patients in the rapid-acting insulin group gained an average of 4.2 kg, compared with 0.3 kg in the pramlintide group. Hypoglycemia was seen in 55% of the pramlintide group and 82% of the rapid-acting insulin group. Nausea affected 21% of pramlintide patients and none in the prandial insulin group. Two patients stopped pramlintide because of nausea.

Dr. Riddle also has been an adviser and consultant and has received research support from Eli Lilly & Co., Novo Nordisk Inc., and Sanofi-Aventis, which also make insulin and oral glucose control agents.

SAN FRANCISCO — Adding an injection of pramlintide at mealtime to basal insulin therapy worked as well as mealtime rapid-acting insulin to control postprandial glucose levels, but caused less weight gain and hypoglycemia, a study of 112 patients with type 2 diabetes found.

The randomized, open-label, 6-month trial showed that 30% of 56 patients in the pramlintide group and 11% of 56 patients in the rapid-acting insulin group achieved the primary composite end point of a hemoglobin A_1c (HbA_1c) level of 7% or lower, no increase in body weight, and no severe hypoglycemia. The difference was significant, Dr. Matthew Riddle of the Oregon Health and Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

Pramlintide is a synthetic analogue of the hormone amylin, with similar glucoregulatory properties. It is approved as adjunctive therapy for patients with type 1 or type 2 diabetes who use mealtime insulin and have not achieved good glucose control despite optimal insulin therapy, with or without oral medications. It is not approved as an alternative to mealtime insulin, said Dr. Riddle, who is an adviser and consultant for Amylin Pharmaceuticals Inc., which markets pramlintide and funded the study.

A prior study by Dr. Riddle and his associates suggested patients with type 2 diabetes on basal insulin glargine could get good postprandial glucose control and cut HbA_1c levels by adding mealtime pramlintide without prandial insulin, and without weight gain (Diabetes Care 2007;30:2794-9).

The current study enrolled adults with type 2 diabetes who had baseline HbA_1c levels of 7%–10%, were on any combination of oral diabetes medications (metformin, sulfonylureas, or thiazolidinediones), and who were not taking insulin or had used insulin for no more than 6 months at doses of less than 50 U/day.

Both groups started basal insulin (glargine or detemir) on day 1 and titrated as needed, with a fasting plasma glucose goal of 70–100 mg/dL. The pramlintide group started pramlintide (120 mcg before major meals) on day 1 and could titrate down to 60 mcg if needed because of nausea. The rapid-acting insulin group used basal insulin alone for 4 weeks to decrease the risk of insulin-induced hypoglycemia, then added rapid-acting insulin (5 U with major meals).

By week 24, a baseline average HbA_1c level of 8.3% in each group had decreased by 0.9% in the pramlintide group and by 1.1% with rapid-acting insulin. In the pramlintide group, 45% of patients reached an HbA_1c level of less than 7%, and 29% reached levels below 6.5%, compared with 55% and 32%, respectively, in the rapid-acting insulin group. The differences were not statistically significant in the intent-to-treat analyses.

After 6 months, patients in the rapid-acting insulin group gained an average of 4.2 kg, compared with 0.3 kg in the pramlintide group. Hypoglycemia was seen in 55% of the pramlintide group and 82% of the rapid-acting insulin group. Nausea affected 21% of pramlintide patients and none in the prandial insulin group. Two patients stopped pramlintide because of nausea.

Dr. Riddle also has been an adviser and consultant and has received research support from Eli Lilly & Co., Novo Nordisk Inc., and Sanofi-Aventis, which also make insulin and oral glucose control agents.

SAN FRANCISCO — An investigational agent, dronedarone, reduced by 24% the risk of hospitalization for cardiovascular problems or death from any cause in moderate- to high-risk patients with atrial fibrillation or flutter in the largest study of any antiarrhythmic medication for atrial fibrillation.

A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation (ATHENA trial) randomized 4,628 patients at 551 sites in 37 countries to treatment with dronedarone 400 mg b.i.d. or placebo, with a follow-up of at least 1 year. The overall rate of treatment-related adverse events did not differ between groups, and 30% in each group discontinued treatment prematurely, Dr. Stefan H. Hohnloser reported at the annual meeting of the Heart Rhythm Society.

The results have raised hopes that physicians may soon have a safer alternative to amiodarone for treating atrial fibrillation. Dronedarone's mechanism of action is similar but without the iodine moiety of amiodarone, which can cause hyperthyroidism, among the drug's other side effects.

The study was funded by Sanofi Aventis, which makes dronedarone.

The drug also showed significant benefits compared with placebo in several predefined secondary outcomes, including a 29% reduction in deaths from cardiovascular causes, a difference that mainly was due to a significant 45% decrease in the risk of cardiac arrhythmic deaths, said Dr. Hohnloser, lead investigator in the study and professor of medicine at J.W. Goethe University, Frankfurt, Germany. He has no association with Sanofi Aventis other than receiving research funding.

There was no significant difference between groups in cardiac nonarrhythmic deaths.

Cardiovascular-related hospitalizations were reduced 29% in the dronedarone group compared with placebo, mainly because of a 37% decrease in admissions to treat atrial fibrillation and a 30% reduction in admissions to treat acute coronary syndromes.

The study enrolled patients with paroxysmal or persistent atrial fibrillation who were at least 75 years of age or were at least 70 years of age with one or more additional risk factors, such as drug treatment for hypertension, diabetes, prior stroke or transient ischemic attack, enlarged left atrium, or depressed left ventricular function.

The cohort represents “the typical elderly atrial fibrillation population at risk for hospitalization,” Dr. Hohnloser noted. The mean age was 72 years, and 47% were female. At randomization, 25% were in atrial fibrillation, 60% had structural heart disease, 86% were being treated for hypertension, 30% had coronary artery disease, 16% had valvular heart disease, and 6% had nonischemic cardiomyopathy. A history of New York Heart Association (NYHA) functional class II or III was found in 21%, and 12% had ejection fractions below 45%. Only 6% were so-called lone atrial fibrillators.

The study excluded patients with recently decompensated heart failure or NYHA class IV heart failure, among others, because a previous study of dronedarone in heart failure was cancelled prematurely when it became clear that more patients on dronedarone were dying.

In the ATHENA trial, the beneficial effects of dronedarone for the treatment of atrial fibrillation or flutter held steady across clinically important subgroups, with no difference on the basis of the presence or absence of class II or III heart failure, age, gender, or ejection fractions if divided into quartiles. Results also did not vary by the presence or absence of structural heart disease or of atrial fibrillation at baseline, or by the use of some antihypertensive agents.

At baseline, medication use was similar between groups, with 71% on β-blockers, 70% on ACE inhibitors, 39% on statins, 60% on vitamin K antagonists for anticoagulation therapy, and 44% on antithrombotic therapy with aspirin.

Side effects were seen in 69% of patients on placebo and 72% on dronedarone. Only GI side effects were significantly more common with dronedarone (26%), compared with placebo (22%).

No differences were seen in skin-related side effects, thyroid-related events, or serious adverse events. Dronedarone interferes with the tubular secretion of creatinine, which produced a 5% increase in blood levels of creatinine, compared with a 1% increase on placebo.

Sanofi Aventis plans to resubmit a new drug application to the Food and Drug Administration and a dossier to the European Medicines Agency in late 2008 based on the ATHENA data. The FDA in August 2007 turned down a request for approval that had relied on two previous trials using a combined end point of all-cause hospitalizations or deaths.

The ATHENA trial's primary combined end point of cardiovascular-related hospitalizations or all-cause mortality has never been used in studies of antiarrhythmic agents, which is why the company chose to compare dronedarone with placebo. A separate comparison with amiodarone is ongoing—the Efficacy and Safety of Dronedarone Versus Amiodarone for Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation (DIONYSOS) trial.

SAN FRANCISCO — An investigational agent, dronedarone, reduced by 24% the risk of hospitalization for cardiovascular problems or death from any cause in moderate- to high-risk patients with atrial fibrillation or flutter in the largest study of any antiarrhythmic medication for atrial fibrillation.

A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation (ATHENA trial) randomized 4,628 patients at 551 sites in 37 countries to treatment with dronedarone 400 mg b.i.d. or placebo, with a follow-up of at least 1 year. The overall rate of treatment-related adverse events did not differ between groups, and 30% in each group discontinued treatment prematurely, Dr. Stefan H. Hohnloser reported at the annual meeting of the Heart Rhythm Society.

The results have raised hopes that physicians may soon have a safer alternative to amiodarone for treating atrial fibrillation. Dronedarone's mechanism of action is similar but without the iodine moiety of amiodarone, which can cause hyperthyroidism, among the drug's other side effects.

The study was funded by Sanofi Aventis, which makes dronedarone.

The drug also showed significant benefits compared with placebo in several predefined secondary outcomes, including a 29% reduction in deaths from cardiovascular causes, a difference that mainly was due to a significant 45% decrease in the risk of cardiac arrhythmic deaths, said Dr. Hohnloser, lead investigator in the study and professor of medicine at J.W. Goethe University, Frankfurt, Germany. He has no association with Sanofi Aventis other than receiving research funding.

There was no significant difference between groups in cardiac nonarrhythmic deaths.

Cardiovascular-related hospitalizations were reduced 29% in the dronedarone group compared with placebo, mainly because of a 37% decrease in admissions to treat atrial fibrillation and a 30% reduction in admissions to treat acute coronary syndromes.

The study enrolled patients with paroxysmal or persistent atrial fibrillation who were at least 75 years of age or were at least 70 years of age with one or more additional risk factors, such as drug treatment for hypertension, diabetes, prior stroke or transient ischemic attack, enlarged left atrium, or depressed left ventricular function.

The cohort represents “the typical elderly atrial fibrillation population at risk for hospitalization,” Dr. Hohnloser noted. The mean age was 72 years, and 47% were female. At randomization, 25% were in atrial fibrillation, 60% had structural heart disease, 86% were being treated for hypertension, 30% had coronary artery disease, 16% had valvular heart disease, and 6% had nonischemic cardiomyopathy. A history of New York Heart Association (NYHA) functional class II or III was found in 21%, and 12% had ejection fractions below 45%. Only 6% were so-called lone atrial fibrillators.

The study excluded patients with recently decompensated heart failure or NYHA class IV heart failure, among others, because a previous study of dronedarone in heart failure was cancelled prematurely when it became clear that more patients on dronedarone were dying.

In the ATHENA trial, the beneficial effects of dronedarone for the treatment of atrial fibrillation or flutter held steady across clinically important subgroups, with no difference on the basis of the presence or absence of class II or III heart failure, age, gender, or ejection fractions if divided into quartiles. Results also did not vary by the presence or absence of structural heart disease or of atrial fibrillation at baseline, or by the use of some antihypertensive agents.

At baseline, medication use was similar between groups, with 71% on β-blockers, 70% on ACE inhibitors, 39% on statins, 60% on vitamin K antagonists for anticoagulation therapy, and 44% on antithrombotic therapy with aspirin.

Side effects were seen in 69% of patients on placebo and 72% on dronedarone. Only GI side effects were significantly more common with dronedarone (26%), compared with placebo (22%).

No differences were seen in skin-related side effects, thyroid-related events, or serious adverse events. Dronedarone interferes with the tubular secretion of creatinine, which produced a 5% increase in blood levels of creatinine, compared with a 1% increase on placebo.

Sanofi Aventis plans to resubmit a new drug application to the Food and Drug Administration and a dossier to the European Medicines Agency in late 2008 based on the ATHENA data. The FDA in August 2007 turned down a request for approval that had relied on two previous trials using a combined end point of all-cause hospitalizations or deaths.

The ATHENA trial's primary combined end point of cardiovascular-related hospitalizations or all-cause mortality has never been used in studies of antiarrhythmic agents, which is why the company chose to compare dronedarone with placebo. A separate comparison with amiodarone is ongoing—the Efficacy and Safety of Dronedarone Versus Amiodarone for Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation (DIONYSOS) trial.

SAN FRANCISCO — An investigational agent, dronedarone, reduced by 24% the risk of hospitalization for cardiovascular problems or death from any cause in moderate- to high-risk patients with atrial fibrillation or flutter in the largest study of any antiarrhythmic medication for atrial fibrillation.

A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation (ATHENA trial) randomized 4,628 patients at 551 sites in 37 countries to treatment with dronedarone 400 mg b.i.d. or placebo, with a follow-up of at least 1 year. The overall rate of treatment-related adverse events did not differ between groups, and 30% in each group discontinued treatment prematurely, Dr. Stefan H. Hohnloser reported at the annual meeting of the Heart Rhythm Society.

The results have raised hopes that physicians may soon have a safer alternative to amiodarone for treating atrial fibrillation. Dronedarone's mechanism of action is similar but without the iodine moiety of amiodarone, which can cause hyperthyroidism, among the drug's other side effects.

The study was funded by Sanofi Aventis, which makes dronedarone.

The drug also showed significant benefits compared with placebo in several predefined secondary outcomes, including a 29% reduction in deaths from cardiovascular causes, a difference that mainly was due to a significant 45% decrease in the risk of cardiac arrhythmic deaths, said Dr. Hohnloser, lead investigator in the study and professor of medicine at J.W. Goethe University, Frankfurt, Germany. He has no association with Sanofi Aventis other than receiving research funding.

There was no significant difference between groups in cardiac nonarrhythmic deaths.

Cardiovascular-related hospitalizations were reduced 29% in the dronedarone group compared with placebo, mainly because of a 37% decrease in admissions to treat atrial fibrillation and a 30% reduction in admissions to treat acute coronary syndromes.

The study enrolled patients with paroxysmal or persistent atrial fibrillation who were at least 75 years of age or were at least 70 years of age with one or more additional risk factors, such as drug treatment for hypertension, diabetes, prior stroke or transient ischemic attack, enlarged left atrium, or depressed left ventricular function.

The cohort represents “the typical elderly atrial fibrillation population at risk for hospitalization,” Dr. Hohnloser noted. The mean age was 72 years, and 47% were female. At randomization, 25% were in atrial fibrillation, 60% had structural heart disease, 86% were being treated for hypertension, 30% had coronary artery disease, 16% had valvular heart disease, and 6% had nonischemic cardiomyopathy. A history of New York Heart Association (NYHA) functional class II or III was found in 21%, and 12% had ejection fractions below 45%. Only 6% were so-called lone atrial fibrillators.

The study excluded patients with recently decompensated heart failure or NYHA class IV heart failure, among others, because a previous study of dronedarone in heart failure was cancelled prematurely when it became clear that more patients on dronedarone were dying.

In the ATHENA trial, the beneficial effects of dronedarone for the treatment of atrial fibrillation or flutter held steady across clinically important subgroups, with no difference on the basis of the presence or absence of class II or III heart failure, age, gender, or ejection fractions if divided into quartiles. Results also did not vary by the presence or absence of structural heart disease or of atrial fibrillation at baseline, or by the use of some antihypertensive agents.

At baseline, medication use was similar between groups, with 71% on β-blockers, 70% on ACE inhibitors, 39% on statins, 60% on vitamin K antagonists for anticoagulation therapy, and 44% on antithrombotic therapy with aspirin.

Side effects were seen in 69% of patients on placebo and 72% on dronedarone. Only GI side effects were significantly more common with dronedarone (26%), compared with placebo (22%).

No differences were seen in skin-related side effects, thyroid-related events, or serious adverse events. Dronedarone interferes with the tubular secretion of creatinine, which produced a 5% increase in blood levels of creatinine, compared with a 1% increase on placebo.

Sanofi Aventis plans to resubmit a new drug application to the Food and Drug Administration and a dossier to the European Medicines Agency in late 2008 based on the ATHENA data. The FDA in August 2007 turned down a request for approval that had relied on two previous trials using a combined end point of all-cause hospitalizations or deaths.

The ATHENA trial's primary combined end point of cardiovascular-related hospitalizations or all-cause mortality has never been used in studies of antiarrhythmic agents, which is why the company chose to compare dronedarone with placebo. A separate comparison with amiodarone is ongoing—the Efficacy and Safety of Dronedarone Versus Amiodarone for Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation (DIONYSOS) trial.

SAN FRANCISCO — Giving antiarrhythmic medications in the 6 weeks after ablation for atrial fibrillation cut the rate of clinically significant arrhythmias and the need for cardioversion or hospitalization.

The Antiarrhythmics After Ablation of Atrial Fibrillation (5A) study findings provide the first evidence to support prescribing antiarrhythmics to reduce arrhythmias occuring after ablation, and were contrary to expectations, Dr. Jean-Francois Roux said at the annual meeting of the Heart Rhythm Society. He said he has no association with companies making the medications studied.

The trial was halted early after data on 110 of a planned 160 patients showed significant benefits from the postprocedure antiarrhythmics. The nonblinded study randomized 53 patients undergoing ablation to start antiarrhythmia therapy the night of the procedure, using propafenone or flecainide for those with structural heart disease, or dofetilide or sotalol if they had heart disease. The other 57 received only atrioventricular nodal blocking agents after ablation.

Nine patients (17%) in the antiarrhythmics group and 23 (40%) in the control group developed clinically significant atrial arrhythmias or couldn't tolerate the medications, said Dr. Roux of the University of Pennsylvania, Philadelphia, and associates. Significant arrhythmias were defined as atrial fibrillation for more than 24 hours, arrhythmias requiring initiating or changing antiarrhythmic medication, or arrhythmia-related hospitalizations or electrical cardioversions.

Patients were monitored transtelephonically for 4 weeks postablation and seen 6 weeks after the procedure. Their mean age was 55 years; 71% were men. The groups' baseline characteristics were similar, with an average left atrial size of 4.2 cm, normal left ventricular ejection fractions, and prior atrial fibrillation for an average of 71 months in the medication group and 81 months in the controls. Before ablation, around 94% of patients used antiarrhythmic therapy, and 25% of each group had undergone previous atrial ablation. Three patients in the treated group stopped therapy due to side effects such as severe fatigue, rash, and headaches.

Using the end points of arrhythmias for more than 24 hours or cardioversion or hospitalization for arrhythmia, rates still were significantly lower in the treated group (6 patients; 11%), compared with the control group (15; 26%). Patients will be tracked for 6 and 12 months to see how the postablation therapy affects long-term arrhythmia rates.

Patients treated with amiodarone in the 3 months before ablation were excluded. A separate study compares postablation therapy with amiodarone or dronedarone.

SAN FRANCISCO — Giving antiarrhythmic medications in the 6 weeks after ablation for atrial fibrillation cut the rate of clinically significant arrhythmias and the need for cardioversion or hospitalization.

The Antiarrhythmics After Ablation of Atrial Fibrillation (5A) study findings provide the first evidence to support prescribing antiarrhythmics to reduce arrhythmias occuring after ablation, and were contrary to expectations, Dr. Jean-Francois Roux said at the annual meeting of the Heart Rhythm Society. He said he has no association with companies making the medications studied.

The trial was halted early after data on 110 of a planned 160 patients showed significant benefits from the postprocedure antiarrhythmics. The nonblinded study randomized 53 patients undergoing ablation to start antiarrhythmia therapy the night of the procedure, using propafenone or flecainide for those with structural heart disease, or dofetilide or sotalol if they had heart disease. The other 57 received only atrioventricular nodal blocking agents after ablation.

Nine patients (17%) in the antiarrhythmics group and 23 (40%) in the control group developed clinically significant atrial arrhythmias or couldn't tolerate the medications, said Dr. Roux of the University of Pennsylvania, Philadelphia, and associates. Significant arrhythmias were defined as atrial fibrillation for more than 24 hours, arrhythmias requiring initiating or changing antiarrhythmic medication, or arrhythmia-related hospitalizations or electrical cardioversions.

Patients were monitored transtelephonically for 4 weeks postablation and seen 6 weeks after the procedure. Their mean age was 55 years; 71% were men. The groups' baseline characteristics were similar, with an average left atrial size of 4.2 cm, normal left ventricular ejection fractions, and prior atrial fibrillation for an average of 71 months in the medication group and 81 months in the controls. Before ablation, around 94% of patients used antiarrhythmic therapy, and 25% of each group had undergone previous atrial ablation. Three patients in the treated group stopped therapy due to side effects such as severe fatigue, rash, and headaches.

Using the end points of arrhythmias for more than 24 hours or cardioversion or hospitalization for arrhythmia, rates still were significantly lower in the treated group (6 patients; 11%), compared with the control group (15; 26%). Patients will be tracked for 6 and 12 months to see how the postablation therapy affects long-term arrhythmia rates.

Patients treated with amiodarone in the 3 months before ablation were excluded. A separate study compares postablation therapy with amiodarone or dronedarone.

SAN FRANCISCO — Giving antiarrhythmic medications in the 6 weeks after ablation for atrial fibrillation cut the rate of clinically significant arrhythmias and the need for cardioversion or hospitalization.

The Antiarrhythmics After Ablation of Atrial Fibrillation (5A) study findings provide the first evidence to support prescribing antiarrhythmics to reduce arrhythmias occuring after ablation, and were contrary to expectations, Dr. Jean-Francois Roux said at the annual meeting of the Heart Rhythm Society. He said he has no association with companies making the medications studied.

The trial was halted early after data on 110 of a planned 160 patients showed significant benefits from the postprocedure antiarrhythmics. The nonblinded study randomized 53 patients undergoing ablation to start antiarrhythmia therapy the night of the procedure, using propafenone or flecainide for those with structural heart disease, or dofetilide or sotalol if they had heart disease. The other 57 received only atrioventricular nodal blocking agents after ablation.

Nine patients (17%) in the antiarrhythmics group and 23 (40%) in the control group developed clinically significant atrial arrhythmias or couldn't tolerate the medications, said Dr. Roux of the University of Pennsylvania, Philadelphia, and associates. Significant arrhythmias were defined as atrial fibrillation for more than 24 hours, arrhythmias requiring initiating or changing antiarrhythmic medication, or arrhythmia-related hospitalizations or electrical cardioversions.

Patients were monitored transtelephonically for 4 weeks postablation and seen 6 weeks after the procedure. Their mean age was 55 years; 71% were men. The groups' baseline characteristics were similar, with an average left atrial size of 4.2 cm, normal left ventricular ejection fractions, and prior atrial fibrillation for an average of 71 months in the medication group and 81 months in the controls. Before ablation, around 94% of patients used antiarrhythmic therapy, and 25% of each group had undergone previous atrial ablation. Three patients in the treated group stopped therapy due to side effects such as severe fatigue, rash, and headaches.

Using the end points of arrhythmias for more than 24 hours or cardioversion or hospitalization for arrhythmia, rates still were significantly lower in the treated group (6 patients; 11%), compared with the control group (15; 26%). Patients will be tracked for 6 and 12 months to see how the postablation therapy affects long-term arrhythmia rates.

Patients treated with amiodarone in the 3 months before ablation were excluded. A separate study compares postablation therapy with amiodarone or dronedarone.

SAN FRANCISCO — Giving antiarrhythmic medications in the first 6 weeks after ablation for atrial fibrillation reduced the rate of clinically significant arrhythmias and the need for cardioversion or hospitalization in a study of 110 patients.

The findings of the Antiarrhythmics After Ablation of Atrial Fibrillation (5A) study provide the first evidence to support the common practice of prescribing antiarrhythmics to reduce arrhythmias that frequently occur after ablation, and were contrary to what the investigators expected, Dr. Jean-Francois Roux said at the annual meeting of the Heart Rhythm Society. Dr. Roux said he has no association with companies that make the medications studied.

The trial was terminated early, after data on 110 out of a planned 160 patients showed significant benefits from the postprocedure antiarrhythmic drugs.

Of the 110 patients in the nonblinded study of patients scheduled to undergo ablation, 53 were randomized to start antiarrhythmia therapy the night of the procedure, using propafenone or flecainide for patients with structural heart disease, or dofetilide or sotalol if they had heart disease. The other 57 patients received only atrioventricular nodal blocking agents after ablation.

Nine patients (17%) in the antiarrhythmics group and 23 (40%) in the control group developed clinically significant atrial arrhythmias or could not tolerate the medications, reported Dr. Roux of the University of Pennsylvania, Philadelphia, and his associates. Significant arrhythmias were defined as atrial fibrillation lasting longer than 24 hours, arrhythmias requiring initiating or changing antiarrhythmic medication, or arrhythmia-related hospitalizations or electrical cardioversions.

Patients were monitored by transtelephonic devices for 4 weeks following ablation and seen 6 weeks after the procedure.

The patients' mean age was 55 years, and 71% were male. Baseline characteristics were similar between groups, with an average left atrial size of 4.2 cm, normal left ventricular ejection fractions, and prior atrial fibrillation lasting an average of 71 months in the medication group and 81 months in the no-medication group. Antiarrhythmic therapy had been used before ablation by 93%-94% of patients. A quarter of each group had undergone previous atrial ablation.

Three of the patients randomized to antiarrhythmics during the study stopped therapy because of side effects including rash, headaches, and severe fatigue.

Using just the “hard” end points of arrhythmias lasting longer than 24 hours or cardioversion or hospitalization for arrhythmia, rates still were significantly lower in the treated group (6 patients, or 11%) compared with the control group (15 patients, or 26%), he said.

Physicians tend to think of ablation and antiarrhythmic drug therapy as separate treatments, but “there can be synergies between the two,” Dr. Roux said. Even some patients who hadn't responded to antiarrhythmic therapy before ablation had protective effects against postablation arrhythmias with drug therapy, he said.

A previous study suggested that about 75% of physicians empirically prescribe antiarrhythmic therapy after ablation, and the rest do not.

Before the 5A study, physicians at Dr. Roux's institution were similarly divided in this practice. “After the study, in our group, especially among electrophysiologists, everyone now will put patients on drugs for that 6-week period” after ablation, he said.

Investigators will continue to follow patients for 6 and 12 months to see how the 6-week postablation therapy affects long-term arrhythmia rates.

The study excluded patients who had been treated with amiodarone within 3 months prior to ablation. A separate study is comparing postablation treatment using amiodarone or dronedarone.

SAN FRANCISCO — Giving antiarrhythmic medications in the first 6 weeks after ablation for atrial fibrillation reduced the rate of clinically significant arrhythmias and the need for cardioversion or hospitalization in a study of 110 patients.

The findings of the Antiarrhythmics After Ablation of Atrial Fibrillation (5A) study provide the first evidence to support the common practice of prescribing antiarrhythmics to reduce arrhythmias that frequently occur after ablation, and were contrary to what the investigators expected, Dr. Jean-Francois Roux said at the annual meeting of the Heart Rhythm Society. Dr. Roux said he has no association with companies that make the medications studied.

The trial was terminated early, after data on 110 out of a planned 160 patients showed significant benefits from the postprocedure antiarrhythmic drugs.

Of the 110 patients in the nonblinded study of patients scheduled to undergo ablation, 53 were randomized to start antiarrhythmia therapy the night of the procedure, using propafenone or flecainide for patients with structural heart disease, or dofetilide or sotalol if they had heart disease. The other 57 patients received only atrioventricular nodal blocking agents after ablation.

Nine patients (17%) in the antiarrhythmics group and 23 (40%) in the control group developed clinically significant atrial arrhythmias or could not tolerate the medications, reported Dr. Roux of the University of Pennsylvania, Philadelphia, and his associates. Significant arrhythmias were defined as atrial fibrillation lasting longer than 24 hours, arrhythmias requiring initiating or changing antiarrhythmic medication, or arrhythmia-related hospitalizations or electrical cardioversions.

Patients were monitored by transtelephonic devices for 4 weeks following ablation and seen 6 weeks after the procedure.

The patients' mean age was 55 years, and 71% were male. Baseline characteristics were similar between groups, with an average left atrial size of 4.2 cm, normal left ventricular ejection fractions, and prior atrial fibrillation lasting an average of 71 months in the medication group and 81 months in the no-medication group. Antiarrhythmic therapy had been used before ablation by 93%-94% of patients. A quarter of each group had undergone previous atrial ablation.

Three of the patients randomized to antiarrhythmics during the study stopped therapy because of side effects including rash, headaches, and severe fatigue.

Using just the “hard” end points of arrhythmias lasting longer than 24 hours or cardioversion or hospitalization for arrhythmia, rates still were significantly lower in the treated group (6 patients, or 11%) compared with the control group (15 patients, or 26%), he said.

Physicians tend to think of ablation and antiarrhythmic drug therapy as separate treatments, but “there can be synergies between the two,” Dr. Roux said. Even some patients who hadn't responded to antiarrhythmic therapy before ablation had protective effects against postablation arrhythmias with drug therapy, he said.

A previous study suggested that about 75% of physicians empirically prescribe antiarrhythmic therapy after ablation, and the rest do not.

Before the 5A study, physicians at Dr. Roux's institution were similarly divided in this practice. “After the study, in our group, especially among electrophysiologists, everyone now will put patients on drugs for that 6-week period” after ablation, he said.

Investigators will continue to follow patients for 6 and 12 months to see how the 6-week postablation therapy affects long-term arrhythmia rates.

The study excluded patients who had been treated with amiodarone within 3 months prior to ablation. A separate study is comparing postablation treatment using amiodarone or dronedarone.

SAN FRANCISCO — Giving antiarrhythmic medications in the first 6 weeks after ablation for atrial fibrillation reduced the rate of clinically significant arrhythmias and the need for cardioversion or hospitalization in a study of 110 patients.

The findings of the Antiarrhythmics After Ablation of Atrial Fibrillation (5A) study provide the first evidence to support the common practice of prescribing antiarrhythmics to reduce arrhythmias that frequently occur after ablation, and were contrary to what the investigators expected, Dr. Jean-Francois Roux said at the annual meeting of the Heart Rhythm Society. Dr. Roux said he has no association with companies that make the medications studied.

The trial was terminated early, after data on 110 out of a planned 160 patients showed significant benefits from the postprocedure antiarrhythmic drugs.

Of the 110 patients in the nonblinded study of patients scheduled to undergo ablation, 53 were randomized to start antiarrhythmia therapy the night of the procedure, using propafenone or flecainide for patients with structural heart disease, or dofetilide or sotalol if they had heart disease. The other 57 patients received only atrioventricular nodal blocking agents after ablation.

Nine patients (17%) in the antiarrhythmics group and 23 (40%) in the control group developed clinically significant atrial arrhythmias or could not tolerate the medications, reported Dr. Roux of the University of Pennsylvania, Philadelphia, and his associates. Significant arrhythmias were defined as atrial fibrillation lasting longer than 24 hours, arrhythmias requiring initiating or changing antiarrhythmic medication, or arrhythmia-related hospitalizations or electrical cardioversions.

Patients were monitored by transtelephonic devices for 4 weeks following ablation and seen 6 weeks after the procedure.

The patients' mean age was 55 years, and 71% were male. Baseline characteristics were similar between groups, with an average left atrial size of 4.2 cm, normal left ventricular ejection fractions, and prior atrial fibrillation lasting an average of 71 months in the medication group and 81 months in the no-medication group. Antiarrhythmic therapy had been used before ablation by 93%-94% of patients. A quarter of each group had undergone previous atrial ablation.

Three of the patients randomized to antiarrhythmics during the study stopped therapy because of side effects including rash, headaches, and severe fatigue.

Using just the “hard” end points of arrhythmias lasting longer than 24 hours or cardioversion or hospitalization for arrhythmia, rates still were significantly lower in the treated group (6 patients, or 11%) compared with the control group (15 patients, or 26%), he said.

Physicians tend to think of ablation and antiarrhythmic drug therapy as separate treatments, but “there can be synergies between the two,” Dr. Roux said. Even some patients who hadn't responded to antiarrhythmic therapy before ablation had protective effects against postablation arrhythmias with drug therapy, he said.

A previous study suggested that about 75% of physicians empirically prescribe antiarrhythmic therapy after ablation, and the rest do not.

Before the 5A study, physicians at Dr. Roux's institution were similarly divided in this practice. “After the study, in our group, especially among electrophysiologists, everyone now will put patients on drugs for that 6-week period” after ablation, he said.

Investigators will continue to follow patients for 6 and 12 months to see how the 6-week postablation therapy affects long-term arrhythmia rates.

The study excluded patients who had been treated with amiodarone within 3 months prior to ablation. A separate study is comparing postablation treatment using amiodarone or dronedarone.

SAN FRANCISCO — Several analyses of data from a longitudinal study of 3,075 elderly African American and white patients have helped identify some of the causes of health disparities between races in older adults, sometimes with surprising results.

Investigators presented their findings in a joint session at the annual meeting of the Gerontological Society of America. The results can inform the clinical care of older African Americans, several speakers said.

For example, depression was strongly associated with widespread bodily pain in African American men, but not in white men. Socioeconomic status played a big role in racial disparities in death rates. Lung function did not seem to influence racial differences seen in physical performance, contrary to expectations.

All of the studies analyzed data from the Health, Aging, and Body Composition (Health ABC) study of 3,075 well-functioning, community-dwelling adults aged 70–79 years at baseline in 1997–1998. The cohort was 42% African American and 48% female and resided in Memphis or Pittsburgh. They were followed with annual clinic visits and interim 6-month phone calls for the first 6 years.

Widespread pain was present in 8% of women regardless of race and in 3% of African American men and 4% of white men after investigations controlled for factors including osteoporosis, arthritis, and depression, reported Gregory H. Hicks, Ph.D., of the University of Delaware, Newark. He analyzed data on 2,423 patients in the Health ABC study who had appropriate records.

African Americans were significantly less likely than whites (28% vs. 53%) to report widespread pain, after accounting for the effects of demographics, socioeconomic status, psychosocial factors, health status, and biological factors.

Depressive symptoms increased the risk of widespread pain ninefold in African Americans, but did not significantly affect risk in whites. Feeling fearful quadrupled the odds for widespread pain in whites, but not for African Americans.

Osteoporosis was associated with a threefold increase in the risk of widespread pain in whites and an eightfold increase in African Americans. Arthritis was associated with a 10-fold increase in the risk of widespread pain in whites and a 13-fold increase in African Americans.

“So from a clinical perspective, it may be that addressing depression may be more important in African Americans, addressing fear may be more important in whites, and addressing osteoporosis is important in both” in order to manage widespread pain, Dr. Hicks said.

Drinking, smoking, and body mass index did not affect rates of widespread pain.

Roland J. Thorpe Jr., Ph.D., and his associates focused a separate analysis on 2,863 Health ABC patients with valid spirometry results in their records. African American patients performed worse on physical performance measures than did whites, but lung function did not explain this difference, said Dr. Thorpe of Johns Hopkins University, Baltimore.

In the African American group, 59% of women and 75% of men found it “very easy” to walk a quarter-mile in the clinic, compared with 75% of women and 82% of men in the white group. Normal gait was slower than 1 m/sec (predictive of mobility limitation) in 42% of women and 25% of men in the African American group and in 16% of women and 8% of men in the white group. A score of less than 2 (representing poor functional status) on a composite of physical activity tests was seen in 52% of women and 33% of men in the African American group, and in 31% of women and 17% of men among whites.

Spirometry results showed normal lung function in 54% of black women and 30% of black men, compared with 35% of white women and 35% of white men.

“Lung function had little bearing on differences in physical functioning” between races, Dr. Thorpe said. “This was contrary to our expectations.” He speculated that other factors that might explain these disparities could include perceived discrimination, residential segregation, or other socioeconomic dimensions.

Annemarie Koster, Ph.D., and her associates at the National Institutes of Health, Bethesda, Md., studied data on 2,937 patients with 8 years of follow-up in the Health ABC study to look at mortality rates and causes. A previous report in 2003 found that age-adjusted all-cause death rates were 30% higher and life expectancy was 2 years shorter in African Americans, compared with whites.

In the current study, half of the African American patients and 25% of whites died during 8 years of follow-up.

After demographic variables were adjusted for, African Americans had a 60% higher risk of mortality. Socioeconomic factors explained about 60% of this difference, Dr. Koster said, and behavioral factors explained another 30% of the difference.

Factors assessed included education level, income, social support, smoking, body mass index, self-rated health, and having supplemental health insurance in addition to Medicare.

After adjusting for both demographics and socioeconomic status, African Americans still had a 25% higher risk of mortality, she said.

A 60% increased risk of death from coronary heart disease in blacks, compared with whites, resulted primarily from socioeconomic status, which accounted for 96% of the increase. Socioeconomic status explained nearly a third of a 75% increase in risk of death from cancer in blacks, and the lack of supplemental health insurance accounted for 18% of the cancer death risk increase, she added.

After adjustment for demographic variables, African Americans had a 60% higher risk of mortality than did whites. DR. KOSTER

SAN FRANCISCO — Several analyses of data from a longitudinal study of 3,075 elderly African American and white patients have helped identify some of the causes of health disparities between races in older adults, sometimes with surprising results.

Investigators presented their findings in a joint session at the annual meeting of the Gerontological Society of America. The results can inform the clinical care of older African Americans, several speakers said.

For example, depression was strongly associated with widespread bodily pain in African American men, but not in white men. Socioeconomic status played a big role in racial disparities in death rates. Lung function did not seem to influence racial differences seen in physical performance, contrary to expectations.

All of the studies analyzed data from the Health, Aging, and Body Composition (Health ABC) study of 3,075 well-functioning, community-dwelling adults aged 70–79 years at baseline in 1997–1998. The cohort was 42% African American and 48% female and resided in Memphis or Pittsburgh. They were followed with annual clinic visits and interim 6-month phone calls for the first 6 years.

Widespread pain was present in 8% of women regardless of race and in 3% of African American men and 4% of white men after investigations controlled for factors including osteoporosis, arthritis, and depression, reported Gregory H. Hicks, Ph.D., of the University of Delaware, Newark. He analyzed data on 2,423 patients in the Health ABC study who had appropriate records.

African Americans were significantly less likely than whites (28% vs. 53%) to report widespread pain, after accounting for the effects of demographics, socioeconomic status, psychosocial factors, health status, and biological factors.

Depressive symptoms increased the risk of widespread pain ninefold in African Americans, but did not significantly affect risk in whites. Feeling fearful quadrupled the odds for widespread pain in whites, but not for African Americans.

Osteoporosis was associated with a threefold increase in the risk of widespread pain in whites and an eightfold increase in African Americans. Arthritis was associated with a 10-fold increase in the risk of widespread pain in whites and a 13-fold increase in African Americans.

“So from a clinical perspective, it may be that addressing depression may be more important in African Americans, addressing fear may be more important in whites, and addressing osteoporosis is important in both” in order to manage widespread pain, Dr. Hicks said.

Drinking, smoking, and body mass index did not affect rates of widespread pain.

Roland J. Thorpe Jr., Ph.D., and his associates focused a separate analysis on 2,863 Health ABC patients with valid spirometry results in their records. African American patients performed worse on physical performance measures than did whites, but lung function did not explain this difference, said Dr. Thorpe of Johns Hopkins University, Baltimore.

In the African American group, 59% of women and 75% of men found it “very easy” to walk a quarter-mile in the clinic, compared with 75% of women and 82% of men in the white group. Normal gait was slower than 1 m/sec (predictive of mobility limitation) in 42% of women and 25% of men in the African American group and in 16% of women and 8% of men in the white group. A score of less than 2 (representing poor functional status) on a composite of physical activity tests was seen in 52% of women and 33% of men in the African American group, and in 31% of women and 17% of men among whites.

Spirometry results showed normal lung function in 54% of black women and 30% of black men, compared with 35% of white women and 35% of white men.

“Lung function had little bearing on differences in physical functioning” between races, Dr. Thorpe said. “This was contrary to our expectations.” He speculated that other factors that might explain these disparities could include perceived discrimination, residential segregation, or other socioeconomic dimensions.

Annemarie Koster, Ph.D., and her associates at the National Institutes of Health, Bethesda, Md., studied data on 2,937 patients with 8 years of follow-up in the Health ABC study to look at mortality rates and causes. A previous report in 2003 found that age-adjusted all-cause death rates were 30% higher and life expectancy was 2 years shorter in African Americans, compared with whites.

In the current study, half of the African American patients and 25% of whites died during 8 years of follow-up.

After demographic variables were adjusted for, African Americans had a 60% higher risk of mortality. Socioeconomic factors explained about 60% of this difference, Dr. Koster said, and behavioral factors explained another 30% of the difference.

Factors assessed included education level, income, social support, smoking, body mass index, self-rated health, and having supplemental health insurance in addition to Medicare.

After adjusting for both demographics and socioeconomic status, African Americans still had a 25% higher risk of mortality, she said.

A 60% increased risk of death from coronary heart disease in blacks, compared with whites, resulted primarily from socioeconomic status, which accounted for 96% of the increase. Socioeconomic status explained nearly a third of a 75% increase in risk of death from cancer in blacks, and the lack of supplemental health insurance accounted for 18% of the cancer death risk increase, she added.

After adjustment for demographic variables, African Americans had a 60% higher risk of mortality than did whites. DR. KOSTER

SAN FRANCISCO — Several analyses of data from a longitudinal study of 3,075 elderly African American and white patients have helped identify some of the causes of health disparities between races in older adults, sometimes with surprising results.

Investigators presented their findings in a joint session at the annual meeting of the Gerontological Society of America. The results can inform the clinical care of older African Americans, several speakers said.

For example, depression was strongly associated with widespread bodily pain in African American men, but not in white men. Socioeconomic status played a big role in racial disparities in death rates. Lung function did not seem to influence racial differences seen in physical performance, contrary to expectations.

All of the studies analyzed data from the Health, Aging, and Body Composition (Health ABC) study of 3,075 well-functioning, community-dwelling adults aged 70–79 years at baseline in 1997–1998. The cohort was 42% African American and 48% female and resided in Memphis or Pittsburgh. They were followed with annual clinic visits and interim 6-month phone calls for the first 6 years.

Widespread pain was present in 8% of women regardless of race and in 3% of African American men and 4% of white men after investigations controlled for factors including osteoporosis, arthritis, and depression, reported Gregory H. Hicks, Ph.D., of the University of Delaware, Newark. He analyzed data on 2,423 patients in the Health ABC study who had appropriate records.

African Americans were significantly less likely than whites (28% vs. 53%) to report widespread pain, after accounting for the effects of demographics, socioeconomic status, psychosocial factors, health status, and biological factors.

Depressive symptoms increased the risk of widespread pain ninefold in African Americans, but did not significantly affect risk in whites. Feeling fearful quadrupled the odds for widespread pain in whites, but not for African Americans.

Osteoporosis was associated with a threefold increase in the risk of widespread pain in whites and an eightfold increase in African Americans. Arthritis was associated with a 10-fold increase in the risk of widespread pain in whites and a 13-fold increase in African Americans.

“So from a clinical perspective, it may be that addressing depression may be more important in African Americans, addressing fear may be more important in whites, and addressing osteoporosis is important in both” in order to manage widespread pain, Dr. Hicks said.

Drinking, smoking, and body mass index did not affect rates of widespread pain.

Roland J. Thorpe Jr., Ph.D., and his associates focused a separate analysis on 2,863 Health ABC patients with valid spirometry results in their records. African American patients performed worse on physical performance measures than did whites, but lung function did not explain this difference, said Dr. Thorpe of Johns Hopkins University, Baltimore.

In the African American group, 59% of women and 75% of men found it “very easy” to walk a quarter-mile in the clinic, compared with 75% of women and 82% of men in the white group. Normal gait was slower than 1 m/sec (predictive of mobility limitation) in 42% of women and 25% of men in the African American group and in 16% of women and 8% of men in the white group. A score of less than 2 (representing poor functional status) on a composite of physical activity tests was seen in 52% of women and 33% of men in the African American group, and in 31% of women and 17% of men among whites.

Spirometry results showed normal lung function in 54% of black women and 30% of black men, compared with 35% of white women and 35% of white men.

“Lung function had little bearing on differences in physical functioning” between races, Dr. Thorpe said. “This was contrary to our expectations.” He speculated that other factors that might explain these disparities could include perceived discrimination, residential segregation, or other socioeconomic dimensions.

Annemarie Koster, Ph.D., and her associates at the National Institutes of Health, Bethesda, Md., studied data on 2,937 patients with 8 years of follow-up in the Health ABC study to look at mortality rates and causes. A previous report in 2003 found that age-adjusted all-cause death rates were 30% higher and life expectancy was 2 years shorter in African Americans, compared with whites.

In the current study, half of the African American patients and 25% of whites died during 8 years of follow-up.

After demographic variables were adjusted for, African Americans had a 60% higher risk of mortality. Socioeconomic factors explained about 60% of this difference, Dr. Koster said, and behavioral factors explained another 30% of the difference.

Factors assessed included education level, income, social support, smoking, body mass index, self-rated health, and having supplemental health insurance in addition to Medicare.

After adjusting for both demographics and socioeconomic status, African Americans still had a 25% higher risk of mortality, she said.

A 60% increased risk of death from coronary heart disease in blacks, compared with whites, resulted primarily from socioeconomic status, which accounted for 96% of the increase. Socioeconomic status explained nearly a third of a 75% increase in risk of death from cancer in blacks, and the lack of supplemental health insurance accounted for 18% of the cancer death risk increase, she added.

After adjustment for demographic variables, African Americans had a 60% higher risk of mortality than did whites. DR. KOSTER

SAN FRANCISCO — The real-world efficacy of exenatide to lower hemoglobin A_1c levels in patients with type 2 diabetes may not always match the success seen in clinical trials, a small retrospective study suggests.

Only 12 (40%) of 30 patients with type 2 diabetes who added the incretin mimetic exenatide to ongoing treatment with oral medications or insulin were still taking exenatide 2 years later. For the group as a whole, much of the weight lost after 6 months of exenatide therapy was regained by 2 years, so final weights were not significantly different from baseline weights, the intent-to-treat analysis found. Hemoglobin A_1c (HbA_1c) levels did not change significantly for the group as a whole, study investigator Dr. Jennifer A. Loh of Georgetown University, Washington, reported at the annual scientific sessions of the American Diabetes Association.

A separate comparison found trends toward decreased HbA_1c levels in the 15 patients who were taking oral medications plus exenatide, and increased HbA_1c levels in the 15 patients using the off-label combination of insulin and exenatide.

Significant decreases in weight were achieved and sustained only in six patients who took exenatide for 2 years and also were on oral medications, not insulin.

“Real-world efficacy is not sustained in all patients; however, there is a small proportion of these patients who did have sustained efficacy in our group,” she said. Further research would be helpful to identify the patients most likely to benefit from exenatide therapy, added Dr. Loh. She and coinvestigator Dr. Stephen C. Clement, also of the university, reported no potential conflicts of interest.

Phase III clinical trials have reported significant, long-term efficacy in lowering HbA_1c levels and reducing weight in patients with type 2 diabetes. Weight declined by 2.8 kg on average, and HbA_1c levels fell by 0.8% in a 30-week randomized, double-blind controlled trial (Diabetes Care 2005;28:1092-100). In three open-label extension studies lasting 82–156 weeks, HbA_1c levels decreased by 1.1%–1.3%, and average weight decreased by 4.7–5.3 kg, she noted.

Those open-label studies did not use intent-to-treat analyses, however, and did not include off-label use of insulin. Clinical practices in the studies may not reflect real-world practices, Dr. Loh said.

In the current study, the investigators retrospectively reviewed data on 47 adults who were treated by a single physician and who started exenatide in 2005, shortly after approval of the drug. In all, 17 patients had incomplete data, including 1 patient who simply refused to be weighed. “This is the real world,” Dr. Loh noted.

Of the 30 patients with complete data, 18 (60%) stopped taking exenatide by 2 years. A total of 12 patients stopped because of treatment “failure” and 6 stopped because of side effects.

Patients were moderately obese, with an average body mass index of 35 kg/m

HbA_1c levels did not change significantly, and averaged 7.7% after 2 years.

The researchers conducted a subanalysis of the 12 patients who stayed on exenatide for 2 years. They found a significant (1.07%) decrease in HbA_1c levels, and a significant 4.9-kg loss in weight compared with baseline in the six patients who were taking exenatide and oral medications, but no significant changes were seen in the six patients on exenatide and insulin. The efficacy seen with exenatide and oral medications in those who continued exenatide therapy mirrored results from clinical trials, she noted.

“This is such a small study,” cautioned one of the moderators of the session, Dr. Steven Edelman, director of the diabetes care clinic at the Veterans Affairs San Diego Healthcare System. Previous studies did not include insulin, which makes them difficult to compare, he added.

SAN FRANCISCO — The real-world efficacy of exenatide to lower hemoglobin A_1c levels in patients with type 2 diabetes may not always match the success seen in clinical trials, a small retrospective study suggests.

Only 12 (40%) of 30 patients with type 2 diabetes who added the incretin mimetic exenatide to ongoing treatment with oral medications or insulin were still taking exenatide 2 years later. For the group as a whole, much of the weight lost after 6 months of exenatide therapy was regained by 2 years, so final weights were not significantly different from baseline weights, the intent-to-treat analysis found. Hemoglobin A_1c (HbA_1c) levels did not change significantly for the group as a whole, study investigator Dr. Jennifer A. Loh of Georgetown University, Washington, reported at the annual scientific sessions of the American Diabetes Association.

A separate comparison found trends toward decreased HbA_1c levels in the 15 patients who were taking oral medications plus exenatide, and increased HbA_1c levels in the 15 patients using the off-label combination of insulin and exenatide.

Significant decreases in weight were achieved and sustained only in six patients who took exenatide for 2 years and also were on oral medications, not insulin.

“Real-world efficacy is not sustained in all patients; however, there is a small proportion of these patients who did have sustained efficacy in our group,” she said. Further research would be helpful to identify the patients most likely to benefit from exenatide therapy, added Dr. Loh. She and coinvestigator Dr. Stephen C. Clement, also of the university, reported no potential conflicts of interest.

Phase III clinical trials have reported significant, long-term efficacy in lowering HbA_1c levels and reducing weight in patients with type 2 diabetes. Weight declined by 2.8 kg on average, and HbA_1c levels fell by 0.8% in a 30-week randomized, double-blind controlled trial (Diabetes Care 2005;28:1092-100). In three open-label extension studies lasting 82–156 weeks, HbA_1c levels decreased by 1.1%–1.3%, and average weight decreased by 4.7–5.3 kg, she noted.

Those open-label studies did not use intent-to-treat analyses, however, and did not include off-label use of insulin. Clinical practices in the studies may not reflect real-world practices, Dr. Loh said.

In the current study, the investigators retrospectively reviewed data on 47 adults who were treated by a single physician and who started exenatide in 2005, shortly after approval of the drug. In all, 17 patients had incomplete data, including 1 patient who simply refused to be weighed. “This is the real world,” Dr. Loh noted.

Of the 30 patients with complete data, 18 (60%) stopped taking exenatide by 2 years. A total of 12 patients stopped because of treatment “failure” and 6 stopped because of side effects.

Patients were moderately obese, with an average body mass index of 35 kg/m

HbA_1c levels did not change significantly, and averaged 7.7% after 2 years.

The researchers conducted a subanalysis of the 12 patients who stayed on exenatide for 2 years. They found a significant (1.07%) decrease in HbA_1c levels, and a significant 4.9-kg loss in weight compared with baseline in the six patients who were taking exenatide and oral medications, but no significant changes were seen in the six patients on exenatide and insulin. The efficacy seen with exenatide and oral medications in those who continued exenatide therapy mirrored results from clinical trials, she noted.

“This is such a small study,” cautioned one of the moderators of the session, Dr. Steven Edelman, director of the diabetes care clinic at the Veterans Affairs San Diego Healthcare System. Previous studies did not include insulin, which makes them difficult to compare, he added.

SAN FRANCISCO — The real-world efficacy of exenatide to lower hemoglobin A_1c levels in patients with type 2 diabetes may not always match the success seen in clinical trials, a small retrospective study suggests.

Only 12 (40%) of 30 patients with type 2 diabetes who added the incretin mimetic exenatide to ongoing treatment with oral medications or insulin were still taking exenatide 2 years later. For the group as a whole, much of the weight lost after 6 months of exenatide therapy was regained by 2 years, so final weights were not significantly different from baseline weights, the intent-to-treat analysis found. Hemoglobin A_1c (HbA_1c) levels did not change significantly for the group as a whole, study investigator Dr. Jennifer A. Loh of Georgetown University, Washington, reported at the annual scientific sessions of the American Diabetes Association.

A separate comparison found trends toward decreased HbA_1c levels in the 15 patients who were taking oral medications plus exenatide, and increased HbA_1c levels in the 15 patients using the off-label combination of insulin and exenatide.

Significant decreases in weight were achieved and sustained only in six patients who took exenatide for 2 years and also were on oral medications, not insulin.

“Real-world efficacy is not sustained in all patients; however, there is a small proportion of these patients who did have sustained efficacy in our group,” she said. Further research would be helpful to identify the patients most likely to benefit from exenatide therapy, added Dr. Loh. She and coinvestigator Dr. Stephen C. Clement, also of the university, reported no potential conflicts of interest.

Phase III clinical trials have reported significant, long-term efficacy in lowering HbA_1c levels and reducing weight in patients with type 2 diabetes. Weight declined by 2.8 kg on average, and HbA_1c levels fell by 0.8% in a 30-week randomized, double-blind controlled trial (Diabetes Care 2005;28:1092-100). In three open-label extension studies lasting 82–156 weeks, HbA_1c levels decreased by 1.1%–1.3%, and average weight decreased by 4.7–5.3 kg, she noted.

Those open-label studies did not use intent-to-treat analyses, however, and did not include off-label use of insulin. Clinical practices in the studies may not reflect real-world practices, Dr. Loh said.

In the current study, the investigators retrospectively reviewed data on 47 adults who were treated by a single physician and who started exenatide in 2005, shortly after approval of the drug. In all, 17 patients had incomplete data, including 1 patient who simply refused to be weighed. “This is the real world,” Dr. Loh noted.

Of the 30 patients with complete data, 18 (60%) stopped taking exenatide by 2 years. A total of 12 patients stopped because of treatment “failure” and 6 stopped because of side effects.

Patients were moderately obese, with an average body mass index of 35 kg/m

HbA_1c levels did not change significantly, and averaged 7.7% after 2 years.

The researchers conducted a subanalysis of the 12 patients who stayed on exenatide for 2 years. They found a significant (1.07%) decrease in HbA_1c levels, and a significant 4.9-kg loss in weight compared with baseline in the six patients who were taking exenatide and oral medications, but no significant changes were seen in the six patients on exenatide and insulin. The efficacy seen with exenatide and oral medications in those who continued exenatide therapy mirrored results from clinical trials, she noted.

“This is such a small study,” cautioned one of the moderators of the session, Dr. Steven Edelman, director of the diabetes care clinic at the Veterans Affairs San Diego Healthcare System. Previous studies did not include insulin, which makes them difficult to compare, he added.

SAN FRANCISCO — Basal or mealtime insulin worked equally well to treat patients with type 2 diabetes after a myocardial infarction, but the mealtime group needed more insulin in a randomized, open-label study of 1,112 patients.

Previous epidemiological studies have shown an association between postprandial hyperglycemia and acute MI or death in people with diabetes. Every 1-mmol/L decrease in postprandial hyperglycemia after glucose challenge was thought to be associated with a 9% reduction in risk for MI or death in patients with diabetes.

Postprandial glucose levels in the current study were significantly higher in patients who used basal insulin therapy than in those on prandial insulin therapy, but there was no significant difference between groups in the primary end point of cardiovascular outcomes including cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for acute coronary syndromes, Dr. Itamar Raz and his associates reported.

The planned 3-year study was stopped early because of the lack of difference after a mean of 2.6 years. In the basal insulin group, 32% of patients had at least one cardiovascular event, compared with 31% in the prandial insulin group, he said at the annual scientific sessions of the American Diabetes Association.

Hemoglobin A_1c (HbA_1c) levels ended up being similar between groups, according to a preliminary intent-to-treat analysis of data from the HEART2D (Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Type 2 Diabetes Mellitus) trial.

Approximately half of patients in each group reached group-specific blood glucose targets, but patients in the prandial insulin group needed more insulin to reach them, said Dr. Raz of the Hadassah University Medical Center, Jerusalem.

Insulin-naive patients were randomized within 21 days of an acute MI to diabetes therapy with either prandial insulin (lispro t.i.d.) or basal insulin (twice-daily NPH insulin or once-daily glargine). The prandial group aimed for a 2-hour postprandial glucose level less than 7.5 mmol/L, and the basal group target was a fasting and plasma blood glucose level less than 6.7 mmol/L.

Both groups aimed for an HbA_1c level below 7%, and rescue therapy was started if the HbA_1c level was higher than 8% on two consecutive visits. For rescue, the prandial group added bedtime NPH, and the basal group converted to 70% human insulin isophane suspensions with 30% human insulin injection (Humulin 70–30).

Eli Lilly & Co., which makes insulin lispro and Humulin 70–30, sponsored the study, and some of Dr. Raz's coinvestigators were Lilly employees. Dr. Raz has been an adviser or consultant to Sanofi-Aventis, which makes insulin glargine, and to other companies including Merck & Co., the American Type Culture Collection, Keryx Biopharmaceuticals Inc., Johnson & Johnson, Pfizer Inc., and Oramed Pharmaceuticals.

Concomitant cardiovascular medications were used by 95% of patients in each group.

Patients had a mean age of 61 years, and just over a third in each group were older than 65 years. All had diabetes for at least 3 months at enrollment, no clinical signs of heart failure, and a left ventricular ejection fraction of 30% or greater.

There were 51 deaths in each group during the trial, mainly because of cardiovascular causes. Stroke killed 3 patients in the prandial insulin group and 2 in the basal group, and cardiovascular events killed 44 patients in the prandial group and 42 in the basal group.

SAN FRANCISCO — Basal or mealtime insulin worked equally well to treat patients with type 2 diabetes after a myocardial infarction, but the mealtime group needed more insulin in a randomized, open-label study of 1,112 patients.

Previous epidemiological studies have shown an association between postprandial hyperglycemia and acute MI or death in people with diabetes. Every 1-mmol/L decrease in postprandial hyperglycemia after glucose challenge was thought to be associated with a 9% reduction in risk for MI or death in patients with diabetes.

Postprandial glucose levels in the current study were significantly higher in patients who used basal insulin therapy than in those on prandial insulin therapy, but there was no significant difference between groups in the primary end point of cardiovascular outcomes including cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for acute coronary syndromes, Dr. Itamar Raz and his associates reported.

The planned 3-year study was stopped early because of the lack of difference after a mean of 2.6 years. In the basal insulin group, 32% of patients had at least one cardiovascular event, compared with 31% in the prandial insulin group, he said at the annual scientific sessions of the American Diabetes Association.

Hemoglobin A_1c (HbA_1c) levels ended up being similar between groups, according to a preliminary intent-to-treat analysis of data from the HEART2D (Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Type 2 Diabetes Mellitus) trial.

Approximately half of patients in each group reached group-specific blood glucose targets, but patients in the prandial insulin group needed more insulin to reach them, said Dr. Raz of the Hadassah University Medical Center, Jerusalem.

Insulin-naive patients were randomized within 21 days of an acute MI to diabetes therapy with either prandial insulin (lispro t.i.d.) or basal insulin (twice-daily NPH insulin or once-daily glargine). The prandial group aimed for a 2-hour postprandial glucose level less than 7.5 mmol/L, and the basal group target was a fasting and plasma blood glucose level less than 6.7 mmol/L.

Both groups aimed for an HbA_1c level below 7%, and rescue therapy was started if the HbA_1c level was higher than 8% on two consecutive visits. For rescue, the prandial group added bedtime NPH, and the basal group converted to 70% human insulin isophane suspensions with 30% human insulin injection (Humulin 70–30).

Eli Lilly & Co., which makes insulin lispro and Humulin 70–30, sponsored the study, and some of Dr. Raz's coinvestigators were Lilly employees. Dr. Raz has been an adviser or consultant to Sanofi-Aventis, which makes insulin glargine, and to other companies including Merck & Co., the American Type Culture Collection, Keryx Biopharmaceuticals Inc., Johnson & Johnson, Pfizer Inc., and Oramed Pharmaceuticals.

Concomitant cardiovascular medications were used by 95% of patients in each group.

Patients had a mean age of 61 years, and just over a third in each group were older than 65 years. All had diabetes for at least 3 months at enrollment, no clinical signs of heart failure, and a left ventricular ejection fraction of 30% or greater.

There were 51 deaths in each group during the trial, mainly because of cardiovascular causes. Stroke killed 3 patients in the prandial insulin group and 2 in the basal group, and cardiovascular events killed 44 patients in the prandial group and 42 in the basal group.

SAN FRANCISCO — Basal or mealtime insulin worked equally well to treat patients with type 2 diabetes after a myocardial infarction, but the mealtime group needed more insulin in a randomized, open-label study of 1,112 patients.

Previous epidemiological studies have shown an association between postprandial hyperglycemia and acute MI or death in people with diabetes. Every 1-mmol/L decrease in postprandial hyperglycemia after glucose challenge was thought to be associated with a 9% reduction in risk for MI or death in patients with diabetes.

Postprandial glucose levels in the current study were significantly higher in patients who used basal insulin therapy than in those on prandial insulin therapy, but there was no significant difference between groups in the primary end point of cardiovascular outcomes including cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for acute coronary syndromes, Dr. Itamar Raz and his associates reported.

The planned 3-year study was stopped early because of the lack of difference after a mean of 2.6 years. In the basal insulin group, 32% of patients had at least one cardiovascular event, compared with 31% in the prandial insulin group, he said at the annual scientific sessions of the American Diabetes Association.

Hemoglobin A_1c (HbA_1c) levels ended up being similar between groups, according to a preliminary intent-to-treat analysis of data from the HEART2D (Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Type 2 Diabetes Mellitus) trial.

Approximately half of patients in each group reached group-specific blood glucose targets, but patients in the prandial insulin group needed more insulin to reach them, said Dr. Raz of the Hadassah University Medical Center, Jerusalem.

Insulin-naive patients were randomized within 21 days of an acute MI to diabetes therapy with either prandial insulin (lispro t.i.d.) or basal insulin (twice-daily NPH insulin or once-daily glargine). The prandial group aimed for a 2-hour postprandial glucose level less than 7.5 mmol/L, and the basal group target was a fasting and plasma blood glucose level less than 6.7 mmol/L.

Both groups aimed for an HbA_1c level below 7%, and rescue therapy was started if the HbA_1c level was higher than 8% on two consecutive visits. For rescue, the prandial group added bedtime NPH, and the basal group converted to 70% human insulin isophane suspensions with 30% human insulin injection (Humulin 70–30).

Eli Lilly & Co., which makes insulin lispro and Humulin 70–30, sponsored the study, and some of Dr. Raz's coinvestigators were Lilly employees. Dr. Raz has been an adviser or consultant to Sanofi-Aventis, which makes insulin glargine, and to other companies including Merck & Co., the American Type Culture Collection, Keryx Biopharmaceuticals Inc., Johnson & Johnson, Pfizer Inc., and Oramed Pharmaceuticals.

Concomitant cardiovascular medications were used by 95% of patients in each group.

Patients had a mean age of 61 years, and just over a third in each group were older than 65 years. All had diabetes for at least 3 months at enrollment, no clinical signs of heart failure, and a left ventricular ejection fraction of 30% or greater.

There were 51 deaths in each group during the trial, mainly because of cardiovascular causes. Stroke killed 3 patients in the prandial insulin group and 2 in the basal group, and cardiovascular events killed 44 patients in the prandial group and 42 in the basal group.

NEWPORT BEACH, CALIF. — Gonadal suppression, ovarian pexy, in vitro fertilization plus embryo freezing, oocyte freezing, or banking frozen ovarian tissue are five strategies that offer some hope of future reproduction to young cancer survivors, though none of these strategies have high rates of success, according to a Portland, Ore., pediatric endocrinologist.

The American Society of Clinical Oncology recommends that physicians discuss reproductive issues with every patient before treating cancer and refer to reproductive specialists when appropriate.

Ovarian failure occurs in about 15% of females with acute myelogenous leukemia, 44% with non-Hodgkin's lymphoma, and 32% with Hodgkin's disease, according to one study. Overall, the literature suggests that 34% of females who undergo chemotherapy develop ovarian failure, though alkylating agents such as cyclophosphamide are four times as toxic to the ovaries as other agents, Dr. David M. Lee of Oregon Health and Science University, Portland, said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. Radiation therapy can cause ovarian failure or affect the uterus so that subsequent pregnancies carry an increased risk for preterm labor, low birth weight, or miscarriage. Cranial radiation can change hormone output so the patient ends up hypogonadic.

The patient's age and maturity help determine the choice of options for reproductive preservation. For prepubertal patients, the only option is ovarian tissue banking. For postpubertal females who are mature enough socially and physically to undergo hormonal stimulation and oocyte freezing, “that's probably your best course to take” if there's time before or in between cancer treatments, he said. For other postpubertal females of reproductive age, embryo freezing is a possibility.

Dr. Lee summarized the advantages and disadvantages of the different strategies:

▸ Gonadal suppression. The idea is that giving GnRH before chemotherapy could put patients into a hormonally prepubertal state in which they might be less susceptible to ovarian failure. Three small, nonrandomized studies using historical controls suggest some protective effect in patients getting GnRH before alkylating chemotherapy for Hodgkin's disease and non-Hodgkin's lymphoma.

The only prospective, randomized study found no benefit, however—four of eight women given GnRH and six of nine controls had amenorrhea after chemotherapy, he noted. “I think it depends on the clinical situation. I think it's reasonable. There are more studies ongoing” that might provide answers in 3–5 years, he added.

▸ Ovarian pexying. Using surgical techniques to temporarily move ovaries out of the way of radiation therapy might help, yet ovarian failure still occurs in 29%–83% of patients with cervical cancer treated with radiation despite ovarian pexying. The technique cannot avoid chemotherapy toxicity to ovaries.

▸ IVF plus embryo freezing. This proven technique can be helpful if there's a window of time between surgery and chemotherapy for cancer. “It's not experimental. We do it all the time,” but it results in a 20%–30% chance of pregnancy per frozen/thawed embryo, he said. The need for hormonal stimulation is a barrier in some patients. The patient needs to have a partner or be mature enough to pick a sperm donor. If the patient doesn't survive the cancer, “orphan embryos” are left behind.

▸ Oocyte freezing. Harvesting and freezing mature eggs, which later can be fertilized, has led to more than 400 pregnancies. Because the eggs aren't fertilized when frozen, the patient doesn't need to choose a partner at that time and won't leave orphan embryos.

The technique still requires in vitro fertilization-like stimulation, yielding 15–20 mature eggs from older adolescents.

Freezing mature eggs is trickier than freezing embryos, resulting in a 1%–4% chance of pregnancy per oocyte frozen.

▸ Ovarian tissue freezing. Freezing prepubertal ovarian tissue does not require hormonal stimulation or sexual maturity and preserves hundreds of thousands of immature oocytes. Extensive culture or grafting is necessary, however, for a thawed oocyte to reach maturity in this strategy.

Autografting has led to approximately a dozen pregnancies after ovarian tissue freezing, but the technique is still in early development, Dr. Lee said.

NEWPORT BEACH, CALIF. — Gonadal suppression, ovarian pexy, in vitro fertilization plus embryo freezing, oocyte freezing, or banking frozen ovarian tissue are five strategies that offer some hope of future reproduction to young cancer survivors, though none of these strategies have high rates of success, according to a Portland, Ore., pediatric endocrinologist.

The American Society of Clinical Oncology recommends that physicians discuss reproductive issues with every patient before treating cancer and refer to reproductive specialists when appropriate.

Ovarian failure occurs in about 15% of females with acute myelogenous leukemia, 44% with non-Hodgkin's lymphoma, and 32% with Hodgkin's disease, according to one study. Overall, the literature suggests that 34% of females who undergo chemotherapy develop ovarian failure, though alkylating agents such as cyclophosphamide are four times as toxic to the ovaries as other agents, Dr. David M. Lee of Oregon Health and Science University, Portland, said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. Radiation therapy can cause ovarian failure or affect the uterus so that subsequent pregnancies carry an increased risk for preterm labor, low birth weight, or miscarriage. Cranial radiation can change hormone output so the patient ends up hypogonadic.

The patient's age and maturity help determine the choice of options for reproductive preservation. For prepubertal patients, the only option is ovarian tissue banking. For postpubertal females who are mature enough socially and physically to undergo hormonal stimulation and oocyte freezing, “that's probably your best course to take” if there's time before or in between cancer treatments, he said. For other postpubertal females of reproductive age, embryo freezing is a possibility.

Dr. Lee summarized the advantages and disadvantages of the different strategies:

▸ Gonadal suppression. The idea is that giving GnRH before chemotherapy could put patients into a hormonally prepubertal state in which they might be less susceptible to ovarian failure. Three small, nonrandomized studies using historical controls suggest some protective effect in patients getting GnRH before alkylating chemotherapy for Hodgkin's disease and non-Hodgkin's lymphoma.

The only prospective, randomized study found no benefit, however—four of eight women given GnRH and six of nine controls had amenorrhea after chemotherapy, he noted. “I think it depends on the clinical situation. I think it's reasonable. There are more studies ongoing” that might provide answers in 3–5 years, he added.

▸ Ovarian pexying. Using surgical techniques to temporarily move ovaries out of the way of radiation therapy might help, yet ovarian failure still occurs in 29%–83% of patients with cervical cancer treated with radiation despite ovarian pexying. The technique cannot avoid chemotherapy toxicity to ovaries.

▸ IVF plus embryo freezing. This proven technique can be helpful if there's a window of time between surgery and chemotherapy for cancer. “It's not experimental. We do it all the time,” but it results in a 20%–30% chance of pregnancy per frozen/thawed embryo, he said. The need for hormonal stimulation is a barrier in some patients. The patient needs to have a partner or be mature enough to pick a sperm donor. If the patient doesn't survive the cancer, “orphan embryos” are left behind.

▸ Oocyte freezing. Harvesting and freezing mature eggs, which later can be fertilized, has led to more than 400 pregnancies. Because the eggs aren't fertilized when frozen, the patient doesn't need to choose a partner at that time and won't leave orphan embryos.

The technique still requires in vitro fertilization-like stimulation, yielding 15–20 mature eggs from older adolescents.

Freezing mature eggs is trickier than freezing embryos, resulting in a 1%–4% chance of pregnancy per oocyte frozen.

▸ Ovarian tissue freezing. Freezing prepubertal ovarian tissue does not require hormonal stimulation or sexual maturity and preserves hundreds of thousands of immature oocytes. Extensive culture or grafting is necessary, however, for a thawed oocyte to reach maturity in this strategy.

Autografting has led to approximately a dozen pregnancies after ovarian tissue freezing, but the technique is still in early development, Dr. Lee said.

NEWPORT BEACH, CALIF. — Gonadal suppression, ovarian pexy, in vitro fertilization plus embryo freezing, oocyte freezing, or banking frozen ovarian tissue are five strategies that offer some hope of future reproduction to young cancer survivors, though none of these strategies have high rates of success, according to a Portland, Ore., pediatric endocrinologist.

The American Society of Clinical Oncology recommends that physicians discuss reproductive issues with every patient before treating cancer and refer to reproductive specialists when appropriate.

Ovarian failure occurs in about 15% of females with acute myelogenous leukemia, 44% with non-Hodgkin's lymphoma, and 32% with Hodgkin's disease, according to one study. Overall, the literature suggests that 34% of females who undergo chemotherapy develop ovarian failure, though alkylating agents such as cyclophosphamide are four times as toxic to the ovaries as other agents, Dr. David M. Lee of Oregon Health and Science University, Portland, said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology. Radiation therapy can cause ovarian failure or affect the uterus so that subsequent pregnancies carry an increased risk for preterm labor, low birth weight, or miscarriage. Cranial radiation can change hormone output so the patient ends up hypogonadic.

The patient's age and maturity help determine the choice of options for reproductive preservation. For prepubertal patients, the only option is ovarian tissue banking. For postpubertal females who are mature enough socially and physically to undergo hormonal stimulation and oocyte freezing, “that's probably your best course to take” if there's time before or in between cancer treatments, he said. For other postpubertal females of reproductive age, embryo freezing is a possibility.

Dr. Lee summarized the advantages and disadvantages of the different strategies:

▸ Gonadal suppression. The idea is that giving GnRH before chemotherapy could put patients into a hormonally prepubertal state in which they might be less susceptible to ovarian failure. Three small, nonrandomized studies using historical controls suggest some protective effect in patients getting GnRH before alkylating chemotherapy for Hodgkin's disease and non-Hodgkin's lymphoma.

The only prospective, randomized study found no benefit, however—four of eight women given GnRH and six of nine controls had amenorrhea after chemotherapy, he noted. “I think it depends on the clinical situation. I think it's reasonable. There are more studies ongoing” that might provide answers in 3–5 years, he added.

▸ Ovarian pexying. Using surgical techniques to temporarily move ovaries out of the way of radiation therapy might help, yet ovarian failure still occurs in 29%–83% of patients with cervical cancer treated with radiation despite ovarian pexying. The technique cannot avoid chemotherapy toxicity to ovaries.

▸ IVF plus embryo freezing. This proven technique can be helpful if there's a window of time between surgery and chemotherapy for cancer. “It's not experimental. We do it all the time,” but it results in a 20%–30% chance of pregnancy per frozen/thawed embryo, he said. The need for hormonal stimulation is a barrier in some patients. The patient needs to have a partner or be mature enough to pick a sperm donor. If the patient doesn't survive the cancer, “orphan embryos” are left behind.

▸ Oocyte freezing. Harvesting and freezing mature eggs, which later can be fertilized, has led to more than 400 pregnancies. Because the eggs aren't fertilized when frozen, the patient doesn't need to choose a partner at that time and won't leave orphan embryos.

The technique still requires in vitro fertilization-like stimulation, yielding 15–20 mature eggs from older adolescents.

Freezing mature eggs is trickier than freezing embryos, resulting in a 1%–4% chance of pregnancy per oocyte frozen.

▸ Ovarian tissue freezing. Freezing prepubertal ovarian tissue does not require hormonal stimulation or sexual maturity and preserves hundreds of thousands of immature oocytes. Extensive culture or grafting is necessary, however, for a thawed oocyte to reach maturity in this strategy.

Autografting has led to approximately a dozen pregnancies after ovarian tissue freezing, but the technique is still in early development, Dr. Lee said.