Elizabeth Mechcatie

Golimumab, the first once-monthly, injectable tumor necrosis factor-alpha antagonist, was recently approved for treating adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, and active ankylosing spondylitis, based on data from five studies of more than 2,500 patients.

The Food and Drug Administration approved the TNF inhibitor for use in combination with methotrexate in patients with RA; with or without methotrexate for psoriatic arthritis; and for use alone in patients with ankylosing spondylitis. It not been approved for pediatric use. Recommended dosage (50 mg administered subcutaneously once a month) is the same for all indications.

Golimumab will be marketed as Simponi by Centocor Ortho Biotech Inc., and has been available since its approval on April 24, according to a spokesperson for the company. The annual cost of golimumab is $18,900, which is based on the list price and is comparable with the cost of other subcutaneous biologics that are used to treat these three indications, he said.

Medicare and some private insurance carriers have adopted a fourth tier of copayment that requires patients to pay 40% of the price of particularly costly drugs.

Dr. John Kay, a lead investigator in the phase II and III trials, said in an interview that “having another TNF antagonist available allows patients who are inadequate responders to one or more of the currently available TNF agents to have an alternative agent to treat their disease.”

Golimumab “can be dosed less frequently, allowing the patient more flexibility,” said Dr. Kay, director of clinical trials in the rheumatology unit at Massachusetts General Hospital, Boston.

Dr. Kay served as a consultant to Centocor and as a member of the steering committee for clinical trials; he was on the steering committee for the GO-AFTER (Golimumab After Former Anti-TNF Therapy Evaluated in RA) study of 461 patients who were treated previously with at least one anti-TNF-alpha treatment and had stopped treatment for various reasons.

Approval for the three indications was based on five simultaneous phase III trials of more than 2,000 patients with RA, psoriatic arthritis, and ankylosing spondylitis, which included three studies of 1,542 patients with moderately to severely active RA who had had the disease for 1-9 years.

The three RA studies were the GO-AFTER study and two other studies (one that evaluated golimumab in 637 patients who were naive to methotrexate and who had not been previously treated with a TNF-blocker, and another that evaluated golimumab in 444 patients with inadequate responses to methotrexate). In the three studies, a greater proportion of patients achieved American College of Rheumatology responses at 14 weeks (in two studies) and at 24 weeks (all three studies), compared with the proportion of patients achieving those responses on methotrexate alone.

As with other TNF blockers, the label for golimumab has a boxed warning about the risk of tuberculosis and invasive fungal infections associated with treatment, and the FDA is requiring a risk evaluation mitigation strategy to address the potential serious risks associated with golimumab.

Golimumab, the first once-monthly, injectable tumor necrosis factor-alpha antagonist, was recently approved for treating adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, and active ankylosing spondylitis, based on data from five studies of more than 2,500 patients.

The Food and Drug Administration approved the TNF inhibitor for use in combination with methotrexate in patients with RA; with or without methotrexate for psoriatic arthritis; and for use alone in patients with ankylosing spondylitis. It not been approved for pediatric use. Recommended dosage (50 mg administered subcutaneously once a month) is the same for all indications.

Golimumab will be marketed as Simponi by Centocor Ortho Biotech Inc., and has been available since its approval on April 24, according to a spokesperson for the company. The annual cost of golimumab is $18,900, which is based on the list price and is comparable with the cost of other subcutaneous biologics that are used to treat these three indications, he said.

Medicare and some private insurance carriers have adopted a fourth tier of copayment that requires patients to pay 40% of the price of particularly costly drugs.

Dr. John Kay, a lead investigator in the phase II and III trials, said in an interview that “having another TNF antagonist available allows patients who are inadequate responders to one or more of the currently available TNF agents to have an alternative agent to treat their disease.”

Golimumab “can be dosed less frequently, allowing the patient more flexibility,” said Dr. Kay, director of clinical trials in the rheumatology unit at Massachusetts General Hospital, Boston.

Dr. Kay served as a consultant to Centocor and as a member of the steering committee for clinical trials; he was on the steering committee for the GO-AFTER (Golimumab After Former Anti-TNF Therapy Evaluated in RA) study of 461 patients who were treated previously with at least one anti-TNF-alpha treatment and had stopped treatment for various reasons.

Approval for the three indications was based on five simultaneous phase III trials of more than 2,000 patients with RA, psoriatic arthritis, and ankylosing spondylitis, which included three studies of 1,542 patients with moderately to severely active RA who had had the disease for 1-9 years.

The three RA studies were the GO-AFTER study and two other studies (one that evaluated golimumab in 637 patients who were naive to methotrexate and who had not been previously treated with a TNF-blocker, and another that evaluated golimumab in 444 patients with inadequate responses to methotrexate). In the three studies, a greater proportion of patients achieved American College of Rheumatology responses at 14 weeks (in two studies) and at 24 weeks (all three studies), compared with the proportion of patients achieving those responses on methotrexate alone.

As with other TNF blockers, the label for golimumab has a boxed warning about the risk of tuberculosis and invasive fungal infections associated with treatment, and the FDA is requiring a risk evaluation mitigation strategy to address the potential serious risks associated with golimumab.

Golimumab, the first once-monthly, injectable tumor necrosis factor-alpha antagonist, was recently approved for treating adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, and active ankylosing spondylitis, based on data from five studies of more than 2,500 patients.

The Food and Drug Administration approved the TNF inhibitor for use in combination with methotrexate in patients with RA; with or without methotrexate for psoriatic arthritis; and for use alone in patients with ankylosing spondylitis. It not been approved for pediatric use. Recommended dosage (50 mg administered subcutaneously once a month) is the same for all indications.

Golimumab will be marketed as Simponi by Centocor Ortho Biotech Inc., and has been available since its approval on April 24, according to a spokesperson for the company. The annual cost of golimumab is $18,900, which is based on the list price and is comparable with the cost of other subcutaneous biologics that are used to treat these three indications, he said.

Medicare and some private insurance carriers have adopted a fourth tier of copayment that requires patients to pay 40% of the price of particularly costly drugs.

Dr. John Kay, a lead investigator in the phase II and III trials, said in an interview that “having another TNF antagonist available allows patients who are inadequate responders to one or more of the currently available TNF agents to have an alternative agent to treat their disease.”

Golimumab “can be dosed less frequently, allowing the patient more flexibility,” said Dr. Kay, director of clinical trials in the rheumatology unit at Massachusetts General Hospital, Boston.

Dr. Kay served as a consultant to Centocor and as a member of the steering committee for clinical trials; he was on the steering committee for the GO-AFTER (Golimumab After Former Anti-TNF Therapy Evaluated in RA) study of 461 patients who were treated previously with at least one anti-TNF-alpha treatment and had stopped treatment for various reasons.

Approval for the three indications was based on five simultaneous phase III trials of more than 2,000 patients with RA, psoriatic arthritis, and ankylosing spondylitis, which included three studies of 1,542 patients with moderately to severely active RA who had had the disease for 1-9 years.

The three RA studies were the GO-AFTER study and two other studies (one that evaluated golimumab in 637 patients who were naive to methotrexate and who had not been previously treated with a TNF-blocker, and another that evaluated golimumab in 444 patients with inadequate responses to methotrexate). In the three studies, a greater proportion of patients achieved American College of Rheumatology responses at 14 weeks (in two studies) and at 24 weeks (all three studies), compared with the proportion of patients achieving those responses on methotrexate alone.

As with other TNF blockers, the label for golimumab has a boxed warning about the risk of tuberculosis and invasive fungal infections associated with treatment, and the FDA is requiring a risk evaluation mitigation strategy to address the potential serious risks associated with golimumab.

Sleeping more or less than 7-8 hours a night was associated with a significantly greater risk of developing type 2 diabetes or impaired glucose tolerance, in a 6-year study of 276 adults.

The results “concur with a growing body of epidemiological evidence showing a U-shaped relationship between sleep duration and body weight, type 2 diabetes, coronary heart disease, and all-cause mortality,” wrote Dr. Jean-Philippe Chaput of Laval University, Quebec City, and his associates. The study is in press at Sleep Medicine (doi:10.1016/j.sleep.2008.09.016

Among the 276 men and women (aged 21-64) in the current cohort study, 21% who slept an average of 6 hours or less a night and 19% of those who slept an average of 9 hours or more a night developed type 2 diabetes or impaired glucose tolerance (IGT) over a mean of 6 years, compared with 7% of those who slept an average of 7-8 hours a night.

After adjustment for confounding factors associated with sleep duration and/or type 2 diabetes/IGT, such as age, smoking habits, shift work, and vigorous physical activity, those who slept 6 hours or less a night had a 2.78 times greater risk of developing diabetes and those who slept 9 or more hours a night had a 2.54 times greater risk, compared with those who slept 7-8 hours; the differences were significant.

After adjustment for waist circumference, the increased relative risk for the groups who slept more or less than 7-8 hours remained significant. There were no sex differences in risk.

Previous data have suggested that prolonged partial sleep deprivation could predispose people to abnormal metabolic regulation, including clinical diabetes, and that partial sleep restriction can cause changes in metabolic and endocrine functions, such as insulin resistance and reduced carbohydrate tolerance.

The mechanism underlying the impact of too much sleep is more speculative, they wrote. One possible explanation is that sleep disorders associated with more sleep, such as sleep-disordered breathing, are also associated with obesity, insulin resistance, and diabetes.

The subjects in the study were part of the Quebec Family Study, a study on the influence of genetics on the etiology of obesity, fitness, and cardiovascular and diabetes risk factors, in 1,650 people from 375 families.

Sleeping more or less than 7-8 hours a night was associated with a significantly greater risk of developing type 2 diabetes or impaired glucose tolerance, in a 6-year study of 276 adults.

The results “concur with a growing body of epidemiological evidence showing a U-shaped relationship between sleep duration and body weight, type 2 diabetes, coronary heart disease, and all-cause mortality,” wrote Dr. Jean-Philippe Chaput of Laval University, Quebec City, and his associates. The study is in press at Sleep Medicine (doi:10.1016/j.sleep.2008.09.016

Among the 276 men and women (aged 21-64) in the current cohort study, 21% who slept an average of 6 hours or less a night and 19% of those who slept an average of 9 hours or more a night developed type 2 diabetes or impaired glucose tolerance (IGT) over a mean of 6 years, compared with 7% of those who slept an average of 7-8 hours a night.

After adjustment for confounding factors associated with sleep duration and/or type 2 diabetes/IGT, such as age, smoking habits, shift work, and vigorous physical activity, those who slept 6 hours or less a night had a 2.78 times greater risk of developing diabetes and those who slept 9 or more hours a night had a 2.54 times greater risk, compared with those who slept 7-8 hours; the differences were significant.

After adjustment for waist circumference, the increased relative risk for the groups who slept more or less than 7-8 hours remained significant. There were no sex differences in risk.

Previous data have suggested that prolonged partial sleep deprivation could predispose people to abnormal metabolic regulation, including clinical diabetes, and that partial sleep restriction can cause changes in metabolic and endocrine functions, such as insulin resistance and reduced carbohydrate tolerance.

The mechanism underlying the impact of too much sleep is more speculative, they wrote. One possible explanation is that sleep disorders associated with more sleep, such as sleep-disordered breathing, are also associated with obesity, insulin resistance, and diabetes.

The subjects in the study were part of the Quebec Family Study, a study on the influence of genetics on the etiology of obesity, fitness, and cardiovascular and diabetes risk factors, in 1,650 people from 375 families.

Sleeping more or less than 7-8 hours a night was associated with a significantly greater risk of developing type 2 diabetes or impaired glucose tolerance, in a 6-year study of 276 adults.

The results “concur with a growing body of epidemiological evidence showing a U-shaped relationship between sleep duration and body weight, type 2 diabetes, coronary heart disease, and all-cause mortality,” wrote Dr. Jean-Philippe Chaput of Laval University, Quebec City, and his associates. The study is in press at Sleep Medicine (doi:10.1016/j.sleep.2008.09.016

Among the 276 men and women (aged 21-64) in the current cohort study, 21% who slept an average of 6 hours or less a night and 19% of those who slept an average of 9 hours or more a night developed type 2 diabetes or impaired glucose tolerance (IGT) over a mean of 6 years, compared with 7% of those who slept an average of 7-8 hours a night.

After adjustment for confounding factors associated with sleep duration and/or type 2 diabetes/IGT, such as age, smoking habits, shift work, and vigorous physical activity, those who slept 6 hours or less a night had a 2.78 times greater risk of developing diabetes and those who slept 9 or more hours a night had a 2.54 times greater risk, compared with those who slept 7-8 hours; the differences were significant.

After adjustment for waist circumference, the increased relative risk for the groups who slept more or less than 7-8 hours remained significant. There were no sex differences in risk.

Previous data have suggested that prolonged partial sleep deprivation could predispose people to abnormal metabolic regulation, including clinical diabetes, and that partial sleep restriction can cause changes in metabolic and endocrine functions, such as insulin resistance and reduced carbohydrate tolerance.

The mechanism underlying the impact of too much sleep is more speculative, they wrote. One possible explanation is that sleep disorders associated with more sleep, such as sleep-disordered breathing, are also associated with obesity, insulin resistance, and diabetes.

The subjects in the study were part of the Quebec Family Study, a study on the influence of genetics on the etiology of obesity, fitness, and cardiovascular and diabetes risk factors, in 1,650 people from 375 families.

Two retrospective reviews reveal trends in acute myocardial infarction and mortality associated with cardiogenic shock in hospitalized patients.

One study compared incidence and survival rates of initial acute myocardial infarction (AMI) diagnosed either by ECG or by serum biomarkers, in 9,824 men and women aged 40-89 years, in the Framingham Heart Study between 1960 and 1999. Of the 941 first AMIs documented during this time, 639 (68%) were diagnosed with an ECG and 302 (32%) were diagnosed with a biomarker.

During this time, there was a 50% drop in the rates of AMI diagnosed with ECGs. But the rates of AMI diagnosed with biomarker measurements increased by about twofold, “offering a possible explanation for apparently steady national rates of overall AMI in the face of improvements in primary prevention,” the authors concluded (Circulation 2009;119:1203-10).

Significant reductions in AMIs diagnosed by ECGs were noted among men aged 50-59 years, men aged 70-79 years, and women aged 70-79 years. Statistically significant increases in AMIs diagnosed with biomarkers were seen among men aged 50-59 and 70-79, and among women aged 70-79. Changes among AMIs in both categories were “largely flat” for those aged 60-69, they said.

“The advent of increasingly sensitive biomarkers for AMI has substantially influenced AMI detection rates in the United States over the past several decades,” concluded the authors, led by Dr. Nisha I. Parikh of the National Heart, Lung, and Blood Institute's Framingham (Mass.) Heart Study, and Beth Israel Deaconess Medical Center, Boston.

“National MI trend data may be biased by a diagnostic drift resulting from the advent of diagnostic biomarker tests for AMI,” they said, adding that this “may explain the paradoxical stability of AMI rates in the United States despite concomitant improvements in CHD risk factors.”

In addition, 30-day, 1-year, and 5-year AMI case fatality rates dropped by 60% between 1960 and 1990, a highly statistically significant effect, with parallel declines observed for both AMIs diagnosed with ECG and those diagnosed with biomarkers.

“The marked improvements in the short- and long-term prognosis associated with AMI likely reflect advances in medical care and greater use of evidence-based cardiac therapies,” Robert J. Goldberg, Ph.D., professor of medicine and epidemiology at the University of Massachusetts, Worcester, wrote in an editorial (Circulation 2009;119:1189-91).

Dr. Goldberg was the lead author of the second study, which analyzed trends in hospital mortality from cardiogenic shock complicating AMI—the most common cause of death in hospitals associated with AMI—among patients enrolled in the Worcester (Mass.) Heart Attack study.

Of the more than 13,000 people hospitalized with an AMI in the Worcester metropolitan area during 15 annual periods between 1975 and 2005, 6.6% developed cardiogenic shock.

The incidence of cardiogenic shock associated with AMI was relatively stable between 1975 and the late 1980s, at an average 7.5%.

Subsequently, the incidence was “somewhat inconsistent,” until 1990, when the rate dropped to 4.8%, and reached a low of 4.1% in 2003.

This lower incidence of cardiogenic shock is “all the more impressive” considering that the patient population has gotten much older and diabetes, heart failure, and other serious comorbidities have become more common, noted Dr. Goldberg and his associates (Circulation 2009;119:1211-9).

About 65% of those who developed cardiogenic shock died in the hospital, compared with 11% of those who did not develop cardiogenic shock, a significant increased risk of death during hospitalization. Over the 30-year period, the risk of dying in the hospital was nearly 18 times greater among those who developed cardiogenic shock than among those who did not. In patients hospitalized during 2003 and 2005, the mortality risk among those with cardiogenic shock remained high, although the absolute risk was lower: 12.5 times greater than those who did not develop cardiogenic shock.

Short-term death rates dropped significantly during the period studied: In 1975 and 1978, 76% of patients who developed cardiogenic shock and 16.5% of those who did not died in the hospital. But in 2003 and 2005, 45% of those who developed cardiogenic shock died while in the hospital, compared with 7% of those who did not. In 2003 and 2005, hospital mortality associated with cardiogenic shock increased with older age, from nearly 36% in patients aged 65-74 years, to 57% in those aged 75-84 and almost 65% in those aged 85 years and older.

Noting that the rate of cardiogenic shock after AMI remains relatively high, despite apparent drops over the past 30 years, the authors wrote, “it remains to be seen whether current efforts aimed at reducing the extent of prehospital delay and door-to-balloon times may lead to further declines in the incidence” and fatality rates.

None of the other authors of the two studies had conflicts of interest to report.

Both studies were supported by the National Institutes of Health/National Heart, Lung, and Blood Institute.

Two retrospective reviews reveal trends in acute myocardial infarction and mortality associated with cardiogenic shock in hospitalized patients.

One study compared incidence and survival rates of initial acute myocardial infarction (AMI) diagnosed either by ECG or by serum biomarkers, in 9,824 men and women aged 40-89 years, in the Framingham Heart Study between 1960 and 1999. Of the 941 first AMIs documented during this time, 639 (68%) were diagnosed with an ECG and 302 (32%) were diagnosed with a biomarker.

During this time, there was a 50% drop in the rates of AMI diagnosed with ECGs. But the rates of AMI diagnosed with biomarker measurements increased by about twofold, “offering a possible explanation for apparently steady national rates of overall AMI in the face of improvements in primary prevention,” the authors concluded (Circulation 2009;119:1203-10).

Significant reductions in AMIs diagnosed by ECGs were noted among men aged 50-59 years, men aged 70-79 years, and women aged 70-79 years. Statistically significant increases in AMIs diagnosed with biomarkers were seen among men aged 50-59 and 70-79, and among women aged 70-79. Changes among AMIs in both categories were “largely flat” for those aged 60-69, they said.

“The advent of increasingly sensitive biomarkers for AMI has substantially influenced AMI detection rates in the United States over the past several decades,” concluded the authors, led by Dr. Nisha I. Parikh of the National Heart, Lung, and Blood Institute's Framingham (Mass.) Heart Study, and Beth Israel Deaconess Medical Center, Boston.

“National MI trend data may be biased by a diagnostic drift resulting from the advent of diagnostic biomarker tests for AMI,” they said, adding that this “may explain the paradoxical stability of AMI rates in the United States despite concomitant improvements in CHD risk factors.”

In addition, 30-day, 1-year, and 5-year AMI case fatality rates dropped by 60% between 1960 and 1990, a highly statistically significant effect, with parallel declines observed for both AMIs diagnosed with ECG and those diagnosed with biomarkers.

“The marked improvements in the short- and long-term prognosis associated with AMI likely reflect advances in medical care and greater use of evidence-based cardiac therapies,” Robert J. Goldberg, Ph.D., professor of medicine and epidemiology at the University of Massachusetts, Worcester, wrote in an editorial (Circulation 2009;119:1189-91).

Dr. Goldberg was the lead author of the second study, which analyzed trends in hospital mortality from cardiogenic shock complicating AMI—the most common cause of death in hospitals associated with AMI—among patients enrolled in the Worcester (Mass.) Heart Attack study.

Of the more than 13,000 people hospitalized with an AMI in the Worcester metropolitan area during 15 annual periods between 1975 and 2005, 6.6% developed cardiogenic shock.

The incidence of cardiogenic shock associated with AMI was relatively stable between 1975 and the late 1980s, at an average 7.5%.

Subsequently, the incidence was “somewhat inconsistent,” until 1990, when the rate dropped to 4.8%, and reached a low of 4.1% in 2003.

This lower incidence of cardiogenic shock is “all the more impressive” considering that the patient population has gotten much older and diabetes, heart failure, and other serious comorbidities have become more common, noted Dr. Goldberg and his associates (Circulation 2009;119:1211-9).

About 65% of those who developed cardiogenic shock died in the hospital, compared with 11% of those who did not develop cardiogenic shock, a significant increased risk of death during hospitalization. Over the 30-year period, the risk of dying in the hospital was nearly 18 times greater among those who developed cardiogenic shock than among those who did not. In patients hospitalized during 2003 and 2005, the mortality risk among those with cardiogenic shock remained high, although the absolute risk was lower: 12.5 times greater than those who did not develop cardiogenic shock.

Short-term death rates dropped significantly during the period studied: In 1975 and 1978, 76% of patients who developed cardiogenic shock and 16.5% of those who did not died in the hospital. But in 2003 and 2005, 45% of those who developed cardiogenic shock died while in the hospital, compared with 7% of those who did not. In 2003 and 2005, hospital mortality associated with cardiogenic shock increased with older age, from nearly 36% in patients aged 65-74 years, to 57% in those aged 75-84 and almost 65% in those aged 85 years and older.

Noting that the rate of cardiogenic shock after AMI remains relatively high, despite apparent drops over the past 30 years, the authors wrote, “it remains to be seen whether current efforts aimed at reducing the extent of prehospital delay and door-to-balloon times may lead to further declines in the incidence” and fatality rates.

None of the other authors of the two studies had conflicts of interest to report.

Both studies were supported by the National Institutes of Health/National Heart, Lung, and Blood Institute.

Two retrospective reviews reveal trends in acute myocardial infarction and mortality associated with cardiogenic shock in hospitalized patients.

One study compared incidence and survival rates of initial acute myocardial infarction (AMI) diagnosed either by ECG or by serum biomarkers, in 9,824 men and women aged 40-89 years, in the Framingham Heart Study between 1960 and 1999. Of the 941 first AMIs documented during this time, 639 (68%) were diagnosed with an ECG and 302 (32%) were diagnosed with a biomarker.

During this time, there was a 50% drop in the rates of AMI diagnosed with ECGs. But the rates of AMI diagnosed with biomarker measurements increased by about twofold, “offering a possible explanation for apparently steady national rates of overall AMI in the face of improvements in primary prevention,” the authors concluded (Circulation 2009;119:1203-10).

Significant reductions in AMIs diagnosed by ECGs were noted among men aged 50-59 years, men aged 70-79 years, and women aged 70-79 years. Statistically significant increases in AMIs diagnosed with biomarkers were seen among men aged 50-59 and 70-79, and among women aged 70-79. Changes among AMIs in both categories were “largely flat” for those aged 60-69, they said.

“The advent of increasingly sensitive biomarkers for AMI has substantially influenced AMI detection rates in the United States over the past several decades,” concluded the authors, led by Dr. Nisha I. Parikh of the National Heart, Lung, and Blood Institute's Framingham (Mass.) Heart Study, and Beth Israel Deaconess Medical Center, Boston.

“National MI trend data may be biased by a diagnostic drift resulting from the advent of diagnostic biomarker tests for AMI,” they said, adding that this “may explain the paradoxical stability of AMI rates in the United States despite concomitant improvements in CHD risk factors.”

In addition, 30-day, 1-year, and 5-year AMI case fatality rates dropped by 60% between 1960 and 1990, a highly statistically significant effect, with parallel declines observed for both AMIs diagnosed with ECG and those diagnosed with biomarkers.

“The marked improvements in the short- and long-term prognosis associated with AMI likely reflect advances in medical care and greater use of evidence-based cardiac therapies,” Robert J. Goldberg, Ph.D., professor of medicine and epidemiology at the University of Massachusetts, Worcester, wrote in an editorial (Circulation 2009;119:1189-91).

Dr. Goldberg was the lead author of the second study, which analyzed trends in hospital mortality from cardiogenic shock complicating AMI—the most common cause of death in hospitals associated with AMI—among patients enrolled in the Worcester (Mass.) Heart Attack study.

Of the more than 13,000 people hospitalized with an AMI in the Worcester metropolitan area during 15 annual periods between 1975 and 2005, 6.6% developed cardiogenic shock.

The incidence of cardiogenic shock associated with AMI was relatively stable between 1975 and the late 1980s, at an average 7.5%.

Subsequently, the incidence was “somewhat inconsistent,” until 1990, when the rate dropped to 4.8%, and reached a low of 4.1% in 2003.

This lower incidence of cardiogenic shock is “all the more impressive” considering that the patient population has gotten much older and diabetes, heart failure, and other serious comorbidities have become more common, noted Dr. Goldberg and his associates (Circulation 2009;119:1211-9).

About 65% of those who developed cardiogenic shock died in the hospital, compared with 11% of those who did not develop cardiogenic shock, a significant increased risk of death during hospitalization. Over the 30-year period, the risk of dying in the hospital was nearly 18 times greater among those who developed cardiogenic shock than among those who did not. In patients hospitalized during 2003 and 2005, the mortality risk among those with cardiogenic shock remained high, although the absolute risk was lower: 12.5 times greater than those who did not develop cardiogenic shock.

Short-term death rates dropped significantly during the period studied: In 1975 and 1978, 76% of patients who developed cardiogenic shock and 16.5% of those who did not died in the hospital. But in 2003 and 2005, 45% of those who developed cardiogenic shock died while in the hospital, compared with 7% of those who did not. In 2003 and 2005, hospital mortality associated with cardiogenic shock increased with older age, from nearly 36% in patients aged 65-74 years, to 57% in those aged 75-84 and almost 65% in those aged 85 years and older.

Noting that the rate of cardiogenic shock after AMI remains relatively high, despite apparent drops over the past 30 years, the authors wrote, “it remains to be seen whether current efforts aimed at reducing the extent of prehospital delay and door-to-balloon times may lead to further declines in the incidence” and fatality rates.

None of the other authors of the two studies had conflicts of interest to report.

Both studies were supported by the National Institutes of Health/National Heart, Lung, and Blood Institute.

Almost 90% of patients with a prehospital electrocardiographic diagnosis of ST-elevation myocardial infarction had a “door-to-balloon” time of 90 minutes or less, a study has shown.

The 86% rate—the average of the 10 regional networks of U.S. hospitals studied, surpassed the target— at least a 75% rate— set by the American College of Cardiology Door-to-Balloon (D2B) Alliance in 2006, reported Dr. Ivan Rokos, an emergency physician at the University of California, Los Angeles, and his associates.

Moreover, each individual center in the study achieved the D2B Alliance's target, ranging from 77% in Atlanta to 97% in Minneapolis/St. Paul, they reported (J. Am. Coll. Cardiol. Intv. 2009;2:339-46).

Regional STEMI Receiving Center (SRC) networks—established in 2006 as a grassroots effort to coordinate care with an ECG diagnosis of STEMI identified by EMS personnel before patients reach the hospital—contributed data to the study. SRC hospitals and networks, managed independently, meet criteria that include equipping EMS personnel with 12-lead ECG machines to diagnose acute STEMI in any patient who has called 911 with symptoms suggestive of acute cardiac ischemia. They also follow a protocol that directs paramedics to transport patients with a presumed STEMI on the ECG to the nearest designated SRC, a hospital that provides primary percutaneous coronary intervention (PPCI).

The study analyses were performed using pooled data on patients from the 10 networks, which represent 72 hospitals that range from urban to semirural. Five of the networks were based in California, in Marin, Ventura, Los Angeles, Orange, and San Diego counties. The other networks were in Medford, Ore.; Royal Oak, Mich.; Charlotte N.C.; Atlanta; and Minneapolis-St. Paul, Minn.

These results indicate that “when we collaborate, we can put together a seamless system so instead of having EMS, the ED, and cardiology all sort of coexist, as they have done literally for decades, they are now coordinated into one seamless care unit that can deliver very fast care,” Dr. Rokos said in an interview. He emphasized the multidisciplinary nature of the collaboration that also includes quality improvement staff and administrators.

The study also shows that in areas with such networks, 911 “can provide entire communities with access to quality STEMI care,” he added.

In the study, 2,712 patients were diagnosed with a STEMI with an ECG before arriving at the hospital, and were transported directly to the nearest SRC, where 76% of the patients underwent PPCI. The primary end point was the proportion of patients who had an intervention within 90 minutes or less. Shorter door-to-balloon times were secondary end points: 50% of the patients had a D2B time of 60 minutes or less, 25% had a time of 45 minutes or less, and 8% had a time of 30 minutes or less.

A unique finding of the study was that the rate of EMS contact to balloon time of 90 minutes or less was 68% among the five regions that measured this.

The study results indicate that “successful use and broad translation” of prehospital ECGs “could be achieved with the creation of regional SRC networks focused on prehospital cardiac triage,” the investigators said.

The authors pointed out that in 2005, the rate of door-to balloon times of 90 minutes or less at four major hospitals in Los Angeles County was less than 50% for STEMI patients transported to the hospital by EMS, even though EMS providers routinely performed pre-hospital ECGs. In the current study, however, the rate was 90% among the patients in the L.A. County region.

Acquiring an ECG before arriving at the hospital “represents an evidence-based yet underused strategy to reduce door-to-balloon times,” they added.

In the interview, Dr. Rokos said the finding that “a quarter of our patients had a door-to-balloon time of 45 minutes or less, which is twice the speed of our national benchmark, is truly remarkable,” especially considering that this was not dependent on building new cath labs, but “coordinating existing cath labs, paramedics, and hospitals.”

In an accompanying editorial, Dr. Christopher Granger of Duke Clinical Research Institute, Durham, N.C., said that the study's “most important lesson … is that reperfusion with primary PCI can be provided more rapidly if EMS is placed in its rightful position as the front line for integrated STEMI care” (J. Am. Coll. Cardiol. Intv. 2009;2:347-9).

Expanding what the 10 networks have done “on a national scale—refined and coupled with better EMS support, data collection and feedback—will improve care and save lives,” he added.

Ten regional networks equipped EMS personnel with 12-lead ECG machines to speed diagnosis of STEMI. Courtesy Philips Healthcare

Almost 90% of patients with a prehospital electrocardiographic diagnosis of ST-elevation myocardial infarction had a “door-to-balloon” time of 90 minutes or less, a study has shown.

The 86% rate—the average of the 10 regional networks of U.S. hospitals studied, surpassed the target— at least a 75% rate— set by the American College of Cardiology Door-to-Balloon (D2B) Alliance in 2006, reported Dr. Ivan Rokos, an emergency physician at the University of California, Los Angeles, and his associates.

Moreover, each individual center in the study achieved the D2B Alliance's target, ranging from 77% in Atlanta to 97% in Minneapolis/St. Paul, they reported (J. Am. Coll. Cardiol. Intv. 2009;2:339-46).

Regional STEMI Receiving Center (SRC) networks—established in 2006 as a grassroots effort to coordinate care with an ECG diagnosis of STEMI identified by EMS personnel before patients reach the hospital—contributed data to the study. SRC hospitals and networks, managed independently, meet criteria that include equipping EMS personnel with 12-lead ECG machines to diagnose acute STEMI in any patient who has called 911 with symptoms suggestive of acute cardiac ischemia. They also follow a protocol that directs paramedics to transport patients with a presumed STEMI on the ECG to the nearest designated SRC, a hospital that provides primary percutaneous coronary intervention (PPCI).

The study analyses were performed using pooled data on patients from the 10 networks, which represent 72 hospitals that range from urban to semirural. Five of the networks were based in California, in Marin, Ventura, Los Angeles, Orange, and San Diego counties. The other networks were in Medford, Ore.; Royal Oak, Mich.; Charlotte N.C.; Atlanta; and Minneapolis-St. Paul, Minn.

These results indicate that “when we collaborate, we can put together a seamless system so instead of having EMS, the ED, and cardiology all sort of coexist, as they have done literally for decades, they are now coordinated into one seamless care unit that can deliver very fast care,” Dr. Rokos said in an interview. He emphasized the multidisciplinary nature of the collaboration that also includes quality improvement staff and administrators.

The study also shows that in areas with such networks, 911 “can provide entire communities with access to quality STEMI care,” he added.

In the study, 2,712 patients were diagnosed with a STEMI with an ECG before arriving at the hospital, and were transported directly to the nearest SRC, where 76% of the patients underwent PPCI. The primary end point was the proportion of patients who had an intervention within 90 minutes or less. Shorter door-to-balloon times were secondary end points: 50% of the patients had a D2B time of 60 minutes or less, 25% had a time of 45 minutes or less, and 8% had a time of 30 minutes or less.

A unique finding of the study was that the rate of EMS contact to balloon time of 90 minutes or less was 68% among the five regions that measured this.

The study results indicate that “successful use and broad translation” of prehospital ECGs “could be achieved with the creation of regional SRC networks focused on prehospital cardiac triage,” the investigators said.

The authors pointed out that in 2005, the rate of door-to balloon times of 90 minutes or less at four major hospitals in Los Angeles County was less than 50% for STEMI patients transported to the hospital by EMS, even though EMS providers routinely performed pre-hospital ECGs. In the current study, however, the rate was 90% among the patients in the L.A. County region.

Acquiring an ECG before arriving at the hospital “represents an evidence-based yet underused strategy to reduce door-to-balloon times,” they added.

In the interview, Dr. Rokos said the finding that “a quarter of our patients had a door-to-balloon time of 45 minutes or less, which is twice the speed of our national benchmark, is truly remarkable,” especially considering that this was not dependent on building new cath labs, but “coordinating existing cath labs, paramedics, and hospitals.”

In an accompanying editorial, Dr. Christopher Granger of Duke Clinical Research Institute, Durham, N.C., said that the study's “most important lesson … is that reperfusion with primary PCI can be provided more rapidly if EMS is placed in its rightful position as the front line for integrated STEMI care” (J. Am. Coll. Cardiol. Intv. 2009;2:347-9).

Expanding what the 10 networks have done “on a national scale—refined and coupled with better EMS support, data collection and feedback—will improve care and save lives,” he added.

Ten regional networks equipped EMS personnel with 12-lead ECG machines to speed diagnosis of STEMI. Courtesy Philips Healthcare

Almost 90% of patients with a prehospital electrocardiographic diagnosis of ST-elevation myocardial infarction had a “door-to-balloon” time of 90 minutes or less, a study has shown.

The 86% rate—the average of the 10 regional networks of U.S. hospitals studied, surpassed the target— at least a 75% rate— set by the American College of Cardiology Door-to-Balloon (D2B) Alliance in 2006, reported Dr. Ivan Rokos, an emergency physician at the University of California, Los Angeles, and his associates.

Moreover, each individual center in the study achieved the D2B Alliance's target, ranging from 77% in Atlanta to 97% in Minneapolis/St. Paul, they reported (J. Am. Coll. Cardiol. Intv. 2009;2:339-46).

Regional STEMI Receiving Center (SRC) networks—established in 2006 as a grassroots effort to coordinate care with an ECG diagnosis of STEMI identified by EMS personnel before patients reach the hospital—contributed data to the study. SRC hospitals and networks, managed independently, meet criteria that include equipping EMS personnel with 12-lead ECG machines to diagnose acute STEMI in any patient who has called 911 with symptoms suggestive of acute cardiac ischemia. They also follow a protocol that directs paramedics to transport patients with a presumed STEMI on the ECG to the nearest designated SRC, a hospital that provides primary percutaneous coronary intervention (PPCI).

The study analyses were performed using pooled data on patients from the 10 networks, which represent 72 hospitals that range from urban to semirural. Five of the networks were based in California, in Marin, Ventura, Los Angeles, Orange, and San Diego counties. The other networks were in Medford, Ore.; Royal Oak, Mich.; Charlotte N.C.; Atlanta; and Minneapolis-St. Paul, Minn.

These results indicate that “when we collaborate, we can put together a seamless system so instead of having EMS, the ED, and cardiology all sort of coexist, as they have done literally for decades, they are now coordinated into one seamless care unit that can deliver very fast care,” Dr. Rokos said in an interview. He emphasized the multidisciplinary nature of the collaboration that also includes quality improvement staff and administrators.

The study also shows that in areas with such networks, 911 “can provide entire communities with access to quality STEMI care,” he added.

In the study, 2,712 patients were diagnosed with a STEMI with an ECG before arriving at the hospital, and were transported directly to the nearest SRC, where 76% of the patients underwent PPCI. The primary end point was the proportion of patients who had an intervention within 90 minutes or less. Shorter door-to-balloon times were secondary end points: 50% of the patients had a D2B time of 60 minutes or less, 25% had a time of 45 minutes or less, and 8% had a time of 30 minutes or less.

A unique finding of the study was that the rate of EMS contact to balloon time of 90 minutes or less was 68% among the five regions that measured this.

The study results indicate that “successful use and broad translation” of prehospital ECGs “could be achieved with the creation of regional SRC networks focused on prehospital cardiac triage,” the investigators said.

The authors pointed out that in 2005, the rate of door-to balloon times of 90 minutes or less at four major hospitals in Los Angeles County was less than 50% for STEMI patients transported to the hospital by EMS, even though EMS providers routinely performed pre-hospital ECGs. In the current study, however, the rate was 90% among the patients in the L.A. County region.

Acquiring an ECG before arriving at the hospital “represents an evidence-based yet underused strategy to reduce door-to-balloon times,” they added.

In the interview, Dr. Rokos said the finding that “a quarter of our patients had a door-to-balloon time of 45 minutes or less, which is twice the speed of our national benchmark, is truly remarkable,” especially considering that this was not dependent on building new cath labs, but “coordinating existing cath labs, paramedics, and hospitals.”

In an accompanying editorial, Dr. Christopher Granger of Duke Clinical Research Institute, Durham, N.C., said that the study's “most important lesson … is that reperfusion with primary PCI can be provided more rapidly if EMS is placed in its rightful position as the front line for integrated STEMI care” (J. Am. Coll. Cardiol. Intv. 2009;2:347-9).

Expanding what the 10 networks have done “on a national scale—refined and coupled with better EMS support, data collection and feedback—will improve care and save lives,” he added.

Ten regional networks equipped EMS personnel with 12-lead ECG machines to speed diagnosis of STEMI. Courtesy Philips Healthcare

ADELPHI, MD. — A federal panel agreed that data on the oral anticoagulant rivaroxaban indicate that the drug's benefits in preventing venous thromboembolic events after hip and knee replacement surgery outweigh its potential risks of excess bleeding and potential risk of severe hepatotoxicity.

At a meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs Advisory Committee, the panel voted 15-2 that data from four clinical trials demonstrated that rivaroxaban has a favorable risk-benefit profile for the proposed indication—the prophylaxis of venous thromboembolism, in patients undergoing hip or knee replacement surgery. The recommended dosage is 10 mg once daily for 35 days (after hip surgery) or 14 days (after knee replacement).

Most of the panelists agreed that potential hepatoxicity should not preclude approval, although long-term data to assess hepatoxicity were critical. Panelists were concerned about off-label use of the drug and emphasized the importance of advising clinicians to avoid prescribing the drug for longer periods and for other uses, and of continuing to follow patients on rivaroxaban in clinical trials and clinical practice for hepatoxicity.

If approved, rivaroxaban, an oral, direct Factor Xa inhibitor manufactured by Johnson & Johnson Pharmaceutical Research & Development LLC, would be the first oral anticoagulant approved for these indications, as well as the first oral anticoagulant approved since warfarin.

The FDA usually follows the recommendations of its advisory panels.

The proposed regimen was compared with enoxaparin in four international studies of more than 12,000 patients (6,183 patients on rivaroxaban) after total hip or knee replacement surgery. Patients with significant liver disease were excluded. In the four studies, the composite end point of venographic evidence of deep-vein thrombosis (DVT), nonfatal pulmonary embolus (PE), or death was significantly lower among those treated with rivaroxaban, but patients on the drug had a higher rate of bleeding. In an analysis of pooled data from the four studies, the major bleeding rate was 0.4% among those on rivaroxaban, compared with 0.2% among those on enoxaparin. The one bleeding-related death in all four studies was in a patient on rivaroxaban.

There was also a greater number of serious ALT elevations (0.3% vs. 0.2%) among those on rivaroxaban, which was not a significant difference. A composite marker of liver injury—an ALT greater than three times the upper limit of normal with a total bilirubin greater than two times the upper limit of normal—was also more common among those on rivaroxaban (0.15% vs. 0.11%), but this was not a statistically significant difference.

The consumer representative on the panel was Dr. Sidney Wolfe, director of the Public Citizen Health Research Group. He voted no on the risk-benefit question and said he was concerned about the bleeding risk and was “very uncomfortable about the certainty of long-term use and the absence of long-term safety data on hepatoxicity.” Because there is no need for a regular blood test, as there is with warfarin, he expects it will be used “massively” for off-label indications for which there are no data.

If approved, Johnson & Johnson plans to market rivaroxaban as Xarelto.

ADELPHI, MD. — A federal panel agreed that data on the oral anticoagulant rivaroxaban indicate that the drug's benefits in preventing venous thromboembolic events after hip and knee replacement surgery outweigh its potential risks of excess bleeding and potential risk of severe hepatotoxicity.

At a meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs Advisory Committee, the panel voted 15-2 that data from four clinical trials demonstrated that rivaroxaban has a favorable risk-benefit profile for the proposed indication—the prophylaxis of venous thromboembolism, in patients undergoing hip or knee replacement surgery. The recommended dosage is 10 mg once daily for 35 days (after hip surgery) or 14 days (after knee replacement).

Most of the panelists agreed that potential hepatoxicity should not preclude approval, although long-term data to assess hepatoxicity were critical. Panelists were concerned about off-label use of the drug and emphasized the importance of advising clinicians to avoid prescribing the drug for longer periods and for other uses, and of continuing to follow patients on rivaroxaban in clinical trials and clinical practice for hepatoxicity.

If approved, rivaroxaban, an oral, direct Factor Xa inhibitor manufactured by Johnson & Johnson Pharmaceutical Research & Development LLC, would be the first oral anticoagulant approved for these indications, as well as the first oral anticoagulant approved since warfarin.

The FDA usually follows the recommendations of its advisory panels.

The proposed regimen was compared with enoxaparin in four international studies of more than 12,000 patients (6,183 patients on rivaroxaban) after total hip or knee replacement surgery. Patients with significant liver disease were excluded. In the four studies, the composite end point of venographic evidence of deep-vein thrombosis (DVT), nonfatal pulmonary embolus (PE), or death was significantly lower among those treated with rivaroxaban, but patients on the drug had a higher rate of bleeding. In an analysis of pooled data from the four studies, the major bleeding rate was 0.4% among those on rivaroxaban, compared with 0.2% among those on enoxaparin. The one bleeding-related death in all four studies was in a patient on rivaroxaban.

There was also a greater number of serious ALT elevations (0.3% vs. 0.2%) among those on rivaroxaban, which was not a significant difference. A composite marker of liver injury—an ALT greater than three times the upper limit of normal with a total bilirubin greater than two times the upper limit of normal—was also more common among those on rivaroxaban (0.15% vs. 0.11%), but this was not a statistically significant difference.

The consumer representative on the panel was Dr. Sidney Wolfe, director of the Public Citizen Health Research Group. He voted no on the risk-benefit question and said he was concerned about the bleeding risk and was “very uncomfortable about the certainty of long-term use and the absence of long-term safety data on hepatoxicity.” Because there is no need for a regular blood test, as there is with warfarin, he expects it will be used “massively” for off-label indications for which there are no data.

If approved, Johnson & Johnson plans to market rivaroxaban as Xarelto.

ADELPHI, MD. — A federal panel agreed that data on the oral anticoagulant rivaroxaban indicate that the drug's benefits in preventing venous thromboembolic events after hip and knee replacement surgery outweigh its potential risks of excess bleeding and potential risk of severe hepatotoxicity.

At a meeting of the Food and Drug Administration's Cardiovascular and Renal Drugs Advisory Committee, the panel voted 15-2 that data from four clinical trials demonstrated that rivaroxaban has a favorable risk-benefit profile for the proposed indication—the prophylaxis of venous thromboembolism, in patients undergoing hip or knee replacement surgery. The recommended dosage is 10 mg once daily for 35 days (after hip surgery) or 14 days (after knee replacement).

Most of the panelists agreed that potential hepatoxicity should not preclude approval, although long-term data to assess hepatoxicity were critical. Panelists were concerned about off-label use of the drug and emphasized the importance of advising clinicians to avoid prescribing the drug for longer periods and for other uses, and of continuing to follow patients on rivaroxaban in clinical trials and clinical practice for hepatoxicity.

If approved, rivaroxaban, an oral, direct Factor Xa inhibitor manufactured by Johnson & Johnson Pharmaceutical Research & Development LLC, would be the first oral anticoagulant approved for these indications, as well as the first oral anticoagulant approved since warfarin.

The FDA usually follows the recommendations of its advisory panels.

The proposed regimen was compared with enoxaparin in four international studies of more than 12,000 patients (6,183 patients on rivaroxaban) after total hip or knee replacement surgery. Patients with significant liver disease were excluded. In the four studies, the composite end point of venographic evidence of deep-vein thrombosis (DVT), nonfatal pulmonary embolus (PE), or death was significantly lower among those treated with rivaroxaban, but patients on the drug had a higher rate of bleeding. In an analysis of pooled data from the four studies, the major bleeding rate was 0.4% among those on rivaroxaban, compared with 0.2% among those on enoxaparin. The one bleeding-related death in all four studies was in a patient on rivaroxaban.

There was also a greater number of serious ALT elevations (0.3% vs. 0.2%) among those on rivaroxaban, which was not a significant difference. A composite marker of liver injury—an ALT greater than three times the upper limit of normal with a total bilirubin greater than two times the upper limit of normal—was also more common among those on rivaroxaban (0.15% vs. 0.11%), but this was not a statistically significant difference.

The consumer representative on the panel was Dr. Sidney Wolfe, director of the Public Citizen Health Research Group. He voted no on the risk-benefit question and said he was concerned about the bleeding risk and was “very uncomfortable about the certainty of long-term use and the absence of long-term safety data on hepatoxicity.” Because there is no need for a regular blood test, as there is with warfarin, he expects it will be used “massively” for off-label indications for which there are no data.

If approved, Johnson & Johnson plans to market rivaroxaban as Xarelto.

The updated Infanrix insert is available at www.fda.gov/cber/label/infanrixLB.pdf

More safety information has been added to the package insert for Infanrix, the Food and Drug Administration said.

The insert now includes the statement that Infanrix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) “may be used to complete a DTaP vaccination series initiated” with Pediarix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B [Recombinant] and Inactivated Poliovirus Vaccine Combined), because both vaccines use the same pertussis antigen components, according to a statement issued by the FDA.

Infanrix is administered as a five-dose series at 2, 4, and 6 months, with booster doses at 15-20 months and at 4-6 years. Both vaccines are marketed by GlaxoSmithKline Biologicals. Pediarix is recommended as a three-dose primary series, starting as early as 6 weeks of age.

Also added were data on safety and immune responses on the concomitant administration of Infanrix with other vaccines.

The information was added when the insert was revised to conform with guidelines outlined in the FDA's Physician Labeling Rule, according to a GSK spokesperson. The rule requires that the package inserts of approved products be reordered and reorganized into a more user-friendly format.

The updated Infanrix insert is available at www.fda.gov/cber/label/infanrixLB.pdf

More safety information has been added to the package insert for Infanrix, the Food and Drug Administration said.

The insert now includes the statement that Infanrix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) “may be used to complete a DTaP vaccination series initiated” with Pediarix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B [Recombinant] and Inactivated Poliovirus Vaccine Combined), because both vaccines use the same pertussis antigen components, according to a statement issued by the FDA.

Infanrix is administered as a five-dose series at 2, 4, and 6 months, with booster doses at 15-20 months and at 4-6 years. Both vaccines are marketed by GlaxoSmithKline Biologicals. Pediarix is recommended as a three-dose primary series, starting as early as 6 weeks of age.

Also added were data on safety and immune responses on the concomitant administration of Infanrix with other vaccines.

The information was added when the insert was revised to conform with guidelines outlined in the FDA's Physician Labeling Rule, according to a GSK spokesperson. The rule requires that the package inserts of approved products be reordered and reorganized into a more user-friendly format.

The updated Infanrix insert is available at www.fda.gov/cber/label/infanrixLB.pdf

More safety information has been added to the package insert for Infanrix, the Food and Drug Administration said.

The insert now includes the statement that Infanrix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) “may be used to complete a DTaP vaccination series initiated” with Pediarix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B [Recombinant] and Inactivated Poliovirus Vaccine Combined), because both vaccines use the same pertussis antigen components, according to a statement issued by the FDA.

Infanrix is administered as a five-dose series at 2, 4, and 6 months, with booster doses at 15-20 months and at 4-6 years. Both vaccines are marketed by GlaxoSmithKline Biologicals. Pediarix is recommended as a three-dose primary series, starting as early as 6 weeks of age.

Also added were data on safety and immune responses on the concomitant administration of Infanrix with other vaccines.

The information was added when the insert was revised to conform with guidelines outlined in the FDA's Physician Labeling Rule, according to a GSK spokesperson. The rule requires that the package inserts of approved products be reordered and reorganized into a more user-friendly format.

ADELPHI, MD. — A Food and Drug Administration panel voted 10-3 that dronedarone, an amiodarone analogue, be approved for treating patients with nonpermanent atrial fibrillation, with recommendations that the label include a boxed warning cautioning against use of the drug in patients with heart failure.

At a meeting of the FDA's Cardiovascular and Renal Drugs Advisory Committee, panelists supporting approval agreed that the claim for dronedarone should be narrower than the primary end point in the ATHENA trial, which was defined as time to first event of cardiovascular hospitalization or death from any cause.

Panelists supporting approval agreed that the indication should make clear that cardiac hospitalizations, but not mortality, were reduced in patients treated with dronedarone in the study.

The multinational ATHENA trial compared 400 mg of dronedarone twice a day to placebo in 4,628 patients (approximately 1,400 in the United States) with at least one episode of atrial fibrillation (AF) or atrial flutter (AFL) and at least one normal ECG during the previous 6 months.

After 2 years, dronedarone was associated with a 24% reduction in the combined risk of cardiovascular hospitalization or all-cause death, a highly statistically significant difference. But most of the benefit was due to the difference in cardiac hospitalizations, and nearly all that effect was due to hospitalizations for AF.

Manufacturer Sanofi Aventis has proposed that dronedarone be approved for treating patients with either a recent history of or current nonpermanent atrial fibrillation or flutter with associated risk factors, and also for the claim that treatment has been shown to decrease the combined risk of cardiovascular hospitalization or death.

Dr. Sanjay Kaul, director of the cardiovascular diseases fellowship training program at Cedars-Sinai Heart Institute in Los Angeles, described his vote as a “cautious yes,” supporting approval for patients at low to intermediate risk who have a history of nonpermanent AF, excluding patients with New York Heart Association (NYHA) class III heart failure, and left ventricular dysfunction (an ejection fraction under 35%). Dr. Kaul said the manufacturer should conduct a long-term study comparing dronedarone to amiodarone, which remains the treatment of choice for patients with structural heart disease.

Dr. Lewis Nelson, director of the medical toxicology fellowship at New York University, voted against approval. He said more information is needed on the drug's effects in patients with renal failure and cardiac failure, drug interactions, and long-term adverse effects.

Sanofi-Adventis has proposed that dronedarone be approved for patients with “a recent history of or current nonpermanent atrial fibrillation or flutter with associated risk factors,” and that it not be used to treat patients with symptoms of heart failure at rest, or with minimal exertion within the immediately preceding month, or patients who have been hospitalized for HF within the immediately preceding month.

The FDA meeting was held almost 4 years after the company first filed for approval of dronedarone in June 2005.

The FDA did not approve dronedarone because it was associated with a greater rate of mortality, hospitalization for heart failure, and hospitalization for cardiovascular causes in the ANDROMEDA (Antiarrhythmic Trial With Dronedarone in Moderate to Severe CHF Evaluating Morbidity Decrease) study, which compared 400 mg of dronedarone twice a day to placebo in patients with NYHA Class class II-IV heart failure, and was stopped early when these associations became evident. The company filed another new drug application in July 2008, which included the previous data and the results of the ATHENA study.

The two populations differed: Those in ANDROMEDA had been recently hospitalized or had had a clinic visit for heart failure, requiring at least intravenous diuretics. In ATHENA, patients with NYHA class IV were excluded, which was the major difference between the two studies.

Gastrointestinal side effects—particularly nausea, vomiting and diarrhea—were the most common side effects associated with dronedarone in ATHENA. In studies, the rate of increases in serum creatinine has been higher among those treated with dronedarone, but this plateaus early and is reversible. Thyroid-related adverse events have been low, and pulmonary-related adverse events, which have been associated with amiodarone, have been uncommon and similar to placebo, according to the company.

If approved, Sanofi-Aventis plans to market dronedarone as Multaq.

The FDA usually follows the recommendations of its advisory panels.

ADELPHI, MD. — A Food and Drug Administration panel voted 10-3 that dronedarone, an amiodarone analogue, be approved for treating patients with nonpermanent atrial fibrillation, with recommendations that the label include a boxed warning cautioning against use of the drug in patients with heart failure.

At a meeting of the FDA's Cardiovascular and Renal Drugs Advisory Committee, panelists supporting approval agreed that the claim for dronedarone should be narrower than the primary end point in the ATHENA trial, which was defined as time to first event of cardiovascular hospitalization or death from any cause.

Panelists supporting approval agreed that the indication should make clear that cardiac hospitalizations, but not mortality, were reduced in patients treated with dronedarone in the study.

The multinational ATHENA trial compared 400 mg of dronedarone twice a day to placebo in 4,628 patients (approximately 1,400 in the United States) with at least one episode of atrial fibrillation (AF) or atrial flutter (AFL) and at least one normal ECG during the previous 6 months.

After 2 years, dronedarone was associated with a 24% reduction in the combined risk of cardiovascular hospitalization or all-cause death, a highly statistically significant difference. But most of the benefit was due to the difference in cardiac hospitalizations, and nearly all that effect was due to hospitalizations for AF.

Manufacturer Sanofi Aventis has proposed that dronedarone be approved for treating patients with either a recent history of or current nonpermanent atrial fibrillation or flutter with associated risk factors, and also for the claim that treatment has been shown to decrease the combined risk of cardiovascular hospitalization or death.

Dr. Sanjay Kaul, director of the cardiovascular diseases fellowship training program at Cedars-Sinai Heart Institute in Los Angeles, described his vote as a “cautious yes,” supporting approval for patients at low to intermediate risk who have a history of nonpermanent AF, excluding patients with New York Heart Association (NYHA) class III heart failure, and left ventricular dysfunction (an ejection fraction under 35%). Dr. Kaul said the manufacturer should conduct a long-term study comparing dronedarone to amiodarone, which remains the treatment of choice for patients with structural heart disease.

Dr. Lewis Nelson, director of the medical toxicology fellowship at New York University, voted against approval. He said more information is needed on the drug's effects in patients with renal failure and cardiac failure, drug interactions, and long-term adverse effects.

Sanofi-Adventis has proposed that dronedarone be approved for patients with “a recent history of or current nonpermanent atrial fibrillation or flutter with associated risk factors,” and that it not be used to treat patients with symptoms of heart failure at rest, or with minimal exertion within the immediately preceding month, or patients who have been hospitalized for HF within the immediately preceding month.

The FDA meeting was held almost 4 years after the company first filed for approval of dronedarone in June 2005.

The FDA did not approve dronedarone because it was associated with a greater rate of mortality, hospitalization for heart failure, and hospitalization for cardiovascular causes in the ANDROMEDA (Antiarrhythmic Trial With Dronedarone in Moderate to Severe CHF Evaluating Morbidity Decrease) study, which compared 400 mg of dronedarone twice a day to placebo in patients with NYHA Class class II-IV heart failure, and was stopped early when these associations became evident. The company filed another new drug application in July 2008, which included the previous data and the results of the ATHENA study.

The two populations differed: Those in ANDROMEDA had been recently hospitalized or had had a clinic visit for heart failure, requiring at least intravenous diuretics. In ATHENA, patients with NYHA class IV were excluded, which was the major difference between the two studies.

Gastrointestinal side effects—particularly nausea, vomiting and diarrhea—were the most common side effects associated with dronedarone in ATHENA. In studies, the rate of increases in serum creatinine has been higher among those treated with dronedarone, but this plateaus early and is reversible. Thyroid-related adverse events have been low, and pulmonary-related adverse events, which have been associated with amiodarone, have been uncommon and similar to placebo, according to the company.

If approved, Sanofi-Aventis plans to market dronedarone as Multaq.

The FDA usually follows the recommendations of its advisory panels.

ADELPHI, MD. — A Food and Drug Administration panel voted 10-3 that dronedarone, an amiodarone analogue, be approved for treating patients with nonpermanent atrial fibrillation, with recommendations that the label include a boxed warning cautioning against use of the drug in patients with heart failure.

At a meeting of the FDA's Cardiovascular and Renal Drugs Advisory Committee, panelists supporting approval agreed that the claim for dronedarone should be narrower than the primary end point in the ATHENA trial, which was defined as time to first event of cardiovascular hospitalization or death from any cause.

Panelists supporting approval agreed that the indication should make clear that cardiac hospitalizations, but not mortality, were reduced in patients treated with dronedarone in the study.

The multinational ATHENA trial compared 400 mg of dronedarone twice a day to placebo in 4,628 patients (approximately 1,400 in the United States) with at least one episode of atrial fibrillation (AF) or atrial flutter (AFL) and at least one normal ECG during the previous 6 months.

After 2 years, dronedarone was associated with a 24% reduction in the combined risk of cardiovascular hospitalization or all-cause death, a highly statistically significant difference. But most of the benefit was due to the difference in cardiac hospitalizations, and nearly all that effect was due to hospitalizations for AF.

Manufacturer Sanofi Aventis has proposed that dronedarone be approved for treating patients with either a recent history of or current nonpermanent atrial fibrillation or flutter with associated risk factors, and also for the claim that treatment has been shown to decrease the combined risk of cardiovascular hospitalization or death.

Dr. Sanjay Kaul, director of the cardiovascular diseases fellowship training program at Cedars-Sinai Heart Institute in Los Angeles, described his vote as a “cautious yes,” supporting approval for patients at low to intermediate risk who have a history of nonpermanent AF, excluding patients with New York Heart Association (NYHA) class III heart failure, and left ventricular dysfunction (an ejection fraction under 35%). Dr. Kaul said the manufacturer should conduct a long-term study comparing dronedarone to amiodarone, which remains the treatment of choice for patients with structural heart disease.

Dr. Lewis Nelson, director of the medical toxicology fellowship at New York University, voted against approval. He said more information is needed on the drug's effects in patients with renal failure and cardiac failure, drug interactions, and long-term adverse effects.

Sanofi-Adventis has proposed that dronedarone be approved for patients with “a recent history of or current nonpermanent atrial fibrillation or flutter with associated risk factors,” and that it not be used to treat patients with symptoms of heart failure at rest, or with minimal exertion within the immediately preceding month, or patients who have been hospitalized for HF within the immediately preceding month.

The FDA meeting was held almost 4 years after the company first filed for approval of dronedarone in June 2005.

The FDA did not approve dronedarone because it was associated with a greater rate of mortality, hospitalization for heart failure, and hospitalization for cardiovascular causes in the ANDROMEDA (Antiarrhythmic Trial With Dronedarone in Moderate to Severe CHF Evaluating Morbidity Decrease) study, which compared 400 mg of dronedarone twice a day to placebo in patients with NYHA Class class II-IV heart failure, and was stopped early when these associations became evident. The company filed another new drug application in July 2008, which included the previous data and the results of the ATHENA study.

The two populations differed: Those in ANDROMEDA had been recently hospitalized or had had a clinic visit for heart failure, requiring at least intravenous diuretics. In ATHENA, patients with NYHA class IV were excluded, which was the major difference between the two studies.

Gastrointestinal side effects—particularly nausea, vomiting and diarrhea—were the most common side effects associated with dronedarone in ATHENA. In studies, the rate of increases in serum creatinine has been higher among those treated with dronedarone, but this plateaus early and is reversible. Thyroid-related adverse events have been low, and pulmonary-related adverse events, which have been associated with amiodarone, have been uncommon and similar to placebo, according to the company.

If approved, Sanofi-Aventis plans to market dronedarone as Multaq.

The FDA usually follows the recommendations of its advisory panels.

A diuretic, an antidepressant, and an unapproved stimulant are among the undeclared active drug ingredients identified in over-the-counter weight loss products, the Food and Drug Administration announced.

In a statement, the agency said that four ingredients—the antidepressant fluoxetine; the diuretic furosemide; fenproporex, an amphetamine derivative and controlled substance that is not approved in the United States; and cetilistat, a drug being studied for obesity in the United States and elsewhere—have been detected in OTC weight-loss products sold in the United States.

The illegal products are marketed as Herbal Xenicol, Slimbionic, and Xsvelten, and have been added to a list compiled by the FDA of OTC weight-loss products that have been found to contain undeclared active pharmaceutical ingredients, which now includes 72 products. Previously identified ingredients include sibutramine, the active ingredient in the FDA-approved obesity drug Meridia; the antiepileptic drug phenytoin; and rimonabant, an obesity drug that was denied approval in the United States.

The products are sold on Web sites and in retail stores and beauty salons. Most appear to be manufactured in China, according to the FDA, which is working on getting these products recalled.

More information, including the full list of products, is available at www.fda.gov/cder/consumerinfo/weight_loss_products.htmwww.fda.gov/MedWatch/report.htm

A diuretic, an antidepressant, and an unapproved stimulant are among the undeclared active drug ingredients identified in over-the-counter weight loss products, the Food and Drug Administration announced.

In a statement, the agency said that four ingredients—the antidepressant fluoxetine; the diuretic furosemide; fenproporex, an amphetamine derivative and controlled substance that is not approved in the United States; and cetilistat, a drug being studied for obesity in the United States and elsewhere—have been detected in OTC weight-loss products sold in the United States.

The illegal products are marketed as Herbal Xenicol, Slimbionic, and Xsvelten, and have been added to a list compiled by the FDA of OTC weight-loss products that have been found to contain undeclared active pharmaceutical ingredients, which now includes 72 products. Previously identified ingredients include sibutramine, the active ingredient in the FDA-approved obesity drug Meridia; the antiepileptic drug phenytoin; and rimonabant, an obesity drug that was denied approval in the United States.

The products are sold on Web sites and in retail stores and beauty salons. Most appear to be manufactured in China, according to the FDA, which is working on getting these products recalled.

More information, including the full list of products, is available at www.fda.gov/cder/consumerinfo/weight_loss_products.htmwww.fda.gov/MedWatch/report.htm

A diuretic, an antidepressant, and an unapproved stimulant are among the undeclared active drug ingredients identified in over-the-counter weight loss products, the Food and Drug Administration announced.

In a statement, the agency said that four ingredients—the antidepressant fluoxetine; the diuretic furosemide; fenproporex, an amphetamine derivative and controlled substance that is not approved in the United States; and cetilistat, a drug being studied for obesity in the United States and elsewhere—have been detected in OTC weight-loss products sold in the United States.

The illegal products are marketed as Herbal Xenicol, Slimbionic, and Xsvelten, and have been added to a list compiled by the FDA of OTC weight-loss products that have been found to contain undeclared active pharmaceutical ingredients, which now includes 72 products. Previously identified ingredients include sibutramine, the active ingredient in the FDA-approved obesity drug Meridia; the antiepileptic drug phenytoin; and rimonabant, an obesity drug that was denied approval in the United States.

The products are sold on Web sites and in retail stores and beauty salons. Most appear to be manufactured in China, according to the FDA, which is working on getting these products recalled.

More information, including the full list of products, is available at www.fda.gov/cder/consumerinfo/weight_loss_products.htmwww.fda.gov/MedWatch/report.htm

A test that detects the genotypes of human papilloma virus (HPV) 16 and 18, which cause the majority of cervical cancer cases, was recently approved by the Food and Drug Administration.

The test, which will be marketed as the Cervista HPV 16/18 test, is the first DNA-based test for these HPV types, according to a written statement issued by the FDA. HPV types 16 and 18 cause of about 70% of cervical cancers.

The FDA also approved the Cervista HPV HR test, another DNA-based test, which detects “essentially all of the high-risk HPV types in cervical cell samples.”

Both tests, which are manufactured by Hologic Inc., can be combined with cytology to assess the risk of cervical disease in women aged 30 years and older, with borderline cytology results, according to the agency statement.

“Results from these two tests, when considered with a physician's assessment of the patient's history, other risk factors, and professional guidelines, can help physicians better determine risk and could lead to better patient management,” Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in the statement.

The Cervista HPV HR test was approved specifically for screening cervical cytology results with atypical squamous cells of undetermined significance to determine the need for referral to colposcopy, according to a statement issued by Hologic.

The company adds that the results of the Cervista HPV 16/18 test “are not intended to prevent women from proceeding to colposcopy.”

A test that detects the genotypes of human papilloma virus (HPV) 16 and 18, which cause the majority of cervical cancer cases, was recently approved by the Food and Drug Administration.

The test, which will be marketed as the Cervista HPV 16/18 test, is the first DNA-based test for these HPV types, according to a written statement issued by the FDA. HPV types 16 and 18 cause of about 70% of cervical cancers.

The FDA also approved the Cervista HPV HR test, another DNA-based test, which detects “essentially all of the high-risk HPV types in cervical cell samples.”

Both tests, which are manufactured by Hologic Inc., can be combined with cytology to assess the risk of cervical disease in women aged 30 years and older, with borderline cytology results, according to the agency statement.

“Results from these two tests, when considered with a physician's assessment of the patient's history, other risk factors, and professional guidelines, can help physicians better determine risk and could lead to better patient management,” Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in the statement.

The Cervista HPV HR test was approved specifically for screening cervical cytology results with atypical squamous cells of undetermined significance to determine the need for referral to colposcopy, according to a statement issued by Hologic.

The company adds that the results of the Cervista HPV 16/18 test “are not intended to prevent women from proceeding to colposcopy.”

A test that detects the genotypes of human papilloma virus (HPV) 16 and 18, which cause the majority of cervical cancer cases, was recently approved by the Food and Drug Administration.

The test, which will be marketed as the Cervista HPV 16/18 test, is the first DNA-based test for these HPV types, according to a written statement issued by the FDA. HPV types 16 and 18 cause of about 70% of cervical cancers.

The FDA also approved the Cervista HPV HR test, another DNA-based test, which detects “essentially all of the high-risk HPV types in cervical cell samples.”

Both tests, which are manufactured by Hologic Inc., can be combined with cytology to assess the risk of cervical disease in women aged 30 years and older, with borderline cytology results, according to the agency statement.

“Results from these two tests, when considered with a physician's assessment of the patient's history, other risk factors, and professional guidelines, can help physicians better determine risk and could lead to better patient management,” Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said in the statement.

The Cervista HPV HR test was approved specifically for screening cervical cytology results with atypical squamous cells of undetermined significance to determine the need for referral to colposcopy, according to a statement issued by Hologic.

The company adds that the results of the Cervista HPV 16/18 test “are not intended to prevent women from proceeding to colposcopy.”

The risk of having a stroke during pregnancy is 15 times higher among women with active migraines, and the association is independent of preeclampsia, according to a large, population-based case-control study that analyzed national hospital-discharge data.

The study also identified significant associations between migraines during pregnancy and other vascular events, including myocardial infarctions, and vascular risk factors, such as smoking. The association between stroke and migraines was the strongest in the study and is consistent with previous findings that a migraine diagnosis is 17-fold greater among women who have a stroke during pregnancy (BMJ 2009;338:b664 [doi:10.1136/bmj.b664P]).

“Obstetricians, general practitioners, and neurologists should all realize that these results do not apply to every woman with migraine during pregnancy,” wrote study investigators Dr. Cheryl Bushnell of the department of neurology, Wake Forest University Health Sciences, Winston-Salem, N.C., and her associates. Still, “for pregnant women admitted to hospital with active migraines, modifiable cardiovascular risk factors and complications of pregnancy such as preeclampsia, should be recognized and treated,” they advised.

The researchers used ICD-9 diagnosis codes from a nationwide sample of inpatients that was culled from a database of 1,000 U.S. hospitals from 2000–2003. Almost 34,000 of the pregnancy-related discharges during this time also had a migraine diagnosis code, a migraine diagnosis rate of 185 per 100,000 deliveries. The researchers noted that this rate was lower than expected, probably because only women with active migraines during hospitalization were included in the analysis.

Migraines increased with maternal age; women 40 years and older had a 2.4-fold greater risk of having a migraine diagnosis at discharge than did women younger than 20 years. White women were more likely to have a migraine diagnosis than were women of other ethnicities and races.

Among women with a migraine diagnosis, the overall risk for all types of stroke was increased by nearly 16-fold. For individual types of strokes, the risk was highest for ischemic stroke, which was increased by nearly 31-fold among those women with a migraine diagnosis at discharge. There was no association between migraine and a diagnostic code of cerebral venous thrombosis or subarachnoid hemorrhage.

Migraine diagnostic codes were also significantly associated with codes for other vascular events: Among women with a migraine during pregnancy, a diagnosis of an MI was five times more likely, a heart disease diagnosis was about twice as likely, a diagnosis of a pulmonary embolism was about three times as likely, and a diagnosis of thrombophilia was almost four times as likely.

“The most logical explanation for the relation between migraine and vascular disease during pregnancy is the existence of overlapping pathophysiological mechanisms in both conditions, compounded by the physiological changes during pregnancy,” Dr. Bushnell and associates wrote. They added that the increases in blood volume and other physiological changes during pregnancy “favor thrombosis,” which may “compound the interactions between migraine and vascular complications.”

Women with a migraine diagnosis code were also almost nine times more likely to have a diagnosis of hypertension, about twice as likely to have a diagnosis of preeclampsia/gestational hypertension, and were nearly three times more likely to smoke cigarettes. A statistical analysis that adjusted the associations for age and removed the effect of preeclampsia indicated that stroke was independently associated with a migraine diagnosis, at a 15-fold greater risk.

The researchers noted that a strength of the study was its size: It is probably the largest study to date on the characteristics of migraine headaches during pregnancy, they said.

The investigators reported that they had no financial conflicts of interest.

The risk of having a stroke during pregnancy is 15 times higher among women with active migraines, and the association is independent of preeclampsia, according to a large, population-based case-control study that analyzed national hospital-discharge data.

The study also identified significant associations between migraines during pregnancy and other vascular events, including myocardial infarctions, and vascular risk factors, such as smoking. The association between stroke and migraines was the strongest in the study and is consistent with previous findings that a migraine diagnosis is 17-fold greater among women who have a stroke during pregnancy (BMJ 2009;338:b664 [doi:10.1136/bmj.b664P]).

“Obstetricians, general practitioners, and neurologists should all realize that these results do not apply to every woman with migraine during pregnancy,” wrote study investigators Dr. Cheryl Bushnell of the department of neurology, Wake Forest University Health Sciences, Winston-Salem, N.C., and her associates. Still, “for pregnant women admitted to hospital with active migraines, modifiable cardiovascular risk factors and complications of pregnancy such as preeclampsia, should be recognized and treated,” they advised.

The researchers used ICD-9 diagnosis codes from a nationwide sample of inpatients that was culled from a database of 1,000 U.S. hospitals from 2000–2003. Almost 34,000 of the pregnancy-related discharges during this time also had a migraine diagnosis code, a migraine diagnosis rate of 185 per 100,000 deliveries. The researchers noted that this rate was lower than expected, probably because only women with active migraines during hospitalization were included in the analysis.

Migraines increased with maternal age; women 40 years and older had a 2.4-fold greater risk of having a migraine diagnosis at discharge than did women younger than 20 years. White women were more likely to have a migraine diagnosis than were women of other ethnicities and races.

Among women with a migraine diagnosis, the overall risk for all types of stroke was increased by nearly 16-fold. For individual types of strokes, the risk was highest for ischemic stroke, which was increased by nearly 31-fold among those women with a migraine diagnosis at discharge. There was no association between migraine and a diagnostic code of cerebral venous thrombosis or subarachnoid hemorrhage.

Migraine diagnostic codes were also significantly associated with codes for other vascular events: Among women with a migraine during pregnancy, a diagnosis of an MI was five times more likely, a heart disease diagnosis was about twice as likely, a diagnosis of a pulmonary embolism was about three times as likely, and a diagnosis of thrombophilia was almost four times as likely.

“The most logical explanation for the relation between migraine and vascular disease during pregnancy is the existence of overlapping pathophysiological mechanisms in both conditions, compounded by the physiological changes during pregnancy,” Dr. Bushnell and associates wrote. They added that the increases in blood volume and other physiological changes during pregnancy “favor thrombosis,” which may “compound the interactions between migraine and vascular complications.”

Women with a migraine diagnosis code were also almost nine times more likely to have a diagnosis of hypertension, about twice as likely to have a diagnosis of preeclampsia/gestational hypertension, and were nearly three times more likely to smoke cigarettes. A statistical analysis that adjusted the associations for age and removed the effect of preeclampsia indicated that stroke was independently associated with a migraine diagnosis, at a 15-fold greater risk.

The researchers noted that a strength of the study was its size: It is probably the largest study to date on the characteristics of migraine headaches during pregnancy, they said.

The investigators reported that they had no financial conflicts of interest.

The risk of having a stroke during pregnancy is 15 times higher among women with active migraines, and the association is independent of preeclampsia, according to a large, population-based case-control study that analyzed national hospital-discharge data.

The study also identified significant associations between migraines during pregnancy and other vascular events, including myocardial infarctions, and vascular risk factors, such as smoking. The association between stroke and migraines was the strongest in the study and is consistent with previous findings that a migraine diagnosis is 17-fold greater among women who have a stroke during pregnancy (BMJ 2009;338:b664 [doi:10.1136/bmj.b664P]).

“Obstetricians, general practitioners, and neurologists should all realize that these results do not apply to every woman with migraine during pregnancy,” wrote study investigators Dr. Cheryl Bushnell of the department of neurology, Wake Forest University Health Sciences, Winston-Salem, N.C., and her associates. Still, “for pregnant women admitted to hospital with active migraines, modifiable cardiovascular risk factors and complications of pregnancy such as preeclampsia, should be recognized and treated,” they advised.

The researchers used ICD-9 diagnosis codes from a nationwide sample of inpatients that was culled from a database of 1,000 U.S. hospitals from 2000–2003. Almost 34,000 of the pregnancy-related discharges during this time also had a migraine diagnosis code, a migraine diagnosis rate of 185 per 100,000 deliveries. The researchers noted that this rate was lower than expected, probably because only women with active migraines during hospitalization were included in the analysis.

Migraines increased with maternal age; women 40 years and older had a 2.4-fold greater risk of having a migraine diagnosis at discharge than did women younger than 20 years. White women were more likely to have a migraine diagnosis than were women of other ethnicities and races.

Among women with a migraine diagnosis, the overall risk for all types of stroke was increased by nearly 16-fold. For individual types of strokes, the risk was highest for ischemic stroke, which was increased by nearly 31-fold among those women with a migraine diagnosis at discharge. There was no association between migraine and a diagnostic code of cerebral venous thrombosis or subarachnoid hemorrhage.

Migraine diagnostic codes were also significantly associated with codes for other vascular events: Among women with a migraine during pregnancy, a diagnosis of an MI was five times more likely, a heart disease diagnosis was about twice as likely, a diagnosis of a pulmonary embolism was about three times as likely, and a diagnosis of thrombophilia was almost four times as likely.

“The most logical explanation for the relation between migraine and vascular disease during pregnancy is the existence of overlapping pathophysiological mechanisms in both conditions, compounded by the physiological changes during pregnancy,” Dr. Bushnell and associates wrote. They added that the increases in blood volume and other physiological changes during pregnancy “favor thrombosis,” which may “compound the interactions between migraine and vascular complications.”

Women with a migraine diagnosis code were also almost nine times more likely to have a diagnosis of hypertension, about twice as likely to have a diagnosis of preeclampsia/gestational hypertension, and were nearly three times more likely to smoke cigarettes. A statistical analysis that adjusted the associations for age and removed the effect of preeclampsia indicated that stroke was independently associated with a migraine diagnosis, at a 15-fold greater risk.

The researchers noted that a strength of the study was its size: It is probably the largest study to date on the characteristics of migraine headaches during pregnancy, they said.

The investigators reported that they had no financial conflicts of interest.