Susan London

SEATTLE – Both a high rate of trichomoniasis among sexually active teenage and adult women who seek self-testing and the elevated rate of adverse reproductive health outcomes in infected women raise the question of whether trichomoniasis should be a reportable infection in the United States, Charlotte A. Gaydos said.

Some 10% of the more than 1,500 women who were recruited through the Internet and offered free self-testing, and who then submitted vaginal samples, were positive for this sexually transmitted infection (STI) in an observational study reported at the annual meeting of the Society for Adolescent Health and Medicine. Rates were highest among those aged 25-29 years and among blacks.

These findings, coupled with the adverse health effects of trichomoniasis, may have implications for tracking the infection in the population, according to lead investigator Charlotte A. Gaydos, Dr.P.H., a professor in the division of infectious diseases at Johns Hopkins University in Baltimore.

Trichomoniasis is currently not reportable to the Centers for Disease Control and Prevention, she noted. But study estimates from the CDC suggest that there are 7-8 million new cases every year in the United States.

Infected men and – in particular – women have elevated rates of adverse reproductive health outcomes, including pelvic inflammatory disease, low infant birth weight, and premature delivery. Furthermore, this STI has been increasingly implicated as a risk factor for HIV transmission, she said.

"My question to the proponents of adolescent health and health for women in general is, should we start to do surveillance for Trichomonas [vaginalis] in the United States, so that we can have good data?" Dr. Gaydos asked. "I think more studies are needed."

Additionally, "should we make this a reportable infection in the future?" she inquired, given the many negative outcomes associated with trichomoniasis and the fact that it can be asymptomatic.

The investigators studied women who were recruited through IWantTheKit.org, an educational Internet program on STIs that offers free self-testing to sexually active individuals aged 14 years or older in Denver, Philadelphia, Alaska, Maryland, West Virginia, selected counties in Illinois, and Washington, D.C.

"We know that submission of self-collected samples at home can remove some barriers for adolescents and other women in testing for sexually transmitted diseases," Dr. Gaydos commented. "We have shown in the past that an Internet-recruited population can do this for Chlamydia and gonorrhea."

Starting in mid-2006, the program added testing for trichomoniasis to its existing testing for Chlamydia and gonorrhea. Women ordered the kit online and sent self-collected vaginal samples by U.S. mail to the testing lab. They also completed questionnaires on demographics and risk factors.

The lab tested for trichomoniasis using a nucleic acid amplification test, which has a sensitivity of about 90%, compared with roughly 50% for wet prep and 70% for culture, according to Dr. Gaydos.

The women were instructed to call for their test results in 1-2 weeks, and – should they forget to call – to indicate their preferred method of notification (e-mail, cell phone, letter, or text message).

A total of 1,525 women requested and returned self-collected vaginal swab kits in 2006-2010.

Overall, 10% of women tested positive for trichomoniasis, Dr. Gaydos reported. In addition, 10% tested positive for Chlamydia, 1% tested positive for gonorrhea, and 18% tested positive for at least one of the three infections studied.

By age, the rate of trichomoniasis ranged from 8.3% among those aged 20-24 years to 11.5% among 25- to 29-year-olds. And by race, it ranged from 0% among Asian women to 13.2% among black women.

In a multivariate analysis, women were more likely to have trichomoniasis if they were black compared with white, Asian, or other race/ethnicity (odds ratio, 2.69); did not have health insurance (OR, 1.57); did not have a bachelor’s degree (OR, 5.53); had 2-15, or 16 or more partners in the past year vs. none or a single partner (OR, 1.60 and 3.51); were bisexual (OR, 2.00); did not always use a condom (3.04); or had a partner who had an STI (OR, 1.71).

Age, having had trichomoniasis previously, and having had any STI in the past were not independent risk factors for trichomoniasis, according to Dr. Gaydos.

Participants reported hearing about the program in a variety of ways. "About 30% say that they found it surfing the Internet, and about 28% say they heard about it on the radio, which is how we advertise the presence of the kit in our local areas most of the time," Dr. Gaydos said. Additionally, small proportions reported learning about the program from friends, fliers, and partners.

"Interestingly enough, when we queried the men, a much higher percentage answer on their questionnaire that they were told by their partner," she commented. "So the men are not telling their female partners to get tested, but the females are telling their male partners to get tested."

The study had its limitations, Dr. Gaydos acknowledged. "Obviously, it is biased because it’s selecting people who are empowered to think about their own sexual health. They are interested in finding out if they are infected, and they do report high [levels of] risk factors, which are similar to those that we see in STD clinics," she said.

Dr. Gaydos reported that she has received free diagnostic kits from Gen-Probe Inc.

SEATTLE – Both a high rate of trichomoniasis among sexually active teenage and adult women who seek self-testing and the elevated rate of adverse reproductive health outcomes in infected women raise the question of whether trichomoniasis should be a reportable infection in the United States, Charlotte A. Gaydos said.

Some 10% of the more than 1,500 women who were recruited through the Internet and offered free self-testing, and who then submitted vaginal samples, were positive for this sexually transmitted infection (STI) in an observational study reported at the annual meeting of the Society for Adolescent Health and Medicine. Rates were highest among those aged 25-29 years and among blacks.

These findings, coupled with the adverse health effects of trichomoniasis, may have implications for tracking the infection in the population, according to lead investigator Charlotte A. Gaydos, Dr.P.H., a professor in the division of infectious diseases at Johns Hopkins University in Baltimore.

Trichomoniasis is currently not reportable to the Centers for Disease Control and Prevention, she noted. But study estimates from the CDC suggest that there are 7-8 million new cases every year in the United States.

Infected men and – in particular – women have elevated rates of adverse reproductive health outcomes, including pelvic inflammatory disease, low infant birth weight, and premature delivery. Furthermore, this STI has been increasingly implicated as a risk factor for HIV transmission, she said.

"My question to the proponents of adolescent health and health for women in general is, should we start to do surveillance for Trichomonas [vaginalis] in the United States, so that we can have good data?" Dr. Gaydos asked. "I think more studies are needed."

Additionally, "should we make this a reportable infection in the future?" she inquired, given the many negative outcomes associated with trichomoniasis and the fact that it can be asymptomatic.

The investigators studied women who were recruited through IWantTheKit.org, an educational Internet program on STIs that offers free self-testing to sexually active individuals aged 14 years or older in Denver, Philadelphia, Alaska, Maryland, West Virginia, selected counties in Illinois, and Washington, D.C.

"We know that submission of self-collected samples at home can remove some barriers for adolescents and other women in testing for sexually transmitted diseases," Dr. Gaydos commented. "We have shown in the past that an Internet-recruited population can do this for Chlamydia and gonorrhea."

Starting in mid-2006, the program added testing for trichomoniasis to its existing testing for Chlamydia and gonorrhea. Women ordered the kit online and sent self-collected vaginal samples by U.S. mail to the testing lab. They also completed questionnaires on demographics and risk factors.

The lab tested for trichomoniasis using a nucleic acid amplification test, which has a sensitivity of about 90%, compared with roughly 50% for wet prep and 70% for culture, according to Dr. Gaydos.

The women were instructed to call for their test results in 1-2 weeks, and – should they forget to call – to indicate their preferred method of notification (e-mail, cell phone, letter, or text message).

A total of 1,525 women requested and returned self-collected vaginal swab kits in 2006-2010.

Overall, 10% of women tested positive for trichomoniasis, Dr. Gaydos reported. In addition, 10% tested positive for Chlamydia, 1% tested positive for gonorrhea, and 18% tested positive for at least one of the three infections studied.

By age, the rate of trichomoniasis ranged from 8.3% among those aged 20-24 years to 11.5% among 25- to 29-year-olds. And by race, it ranged from 0% among Asian women to 13.2% among black women.

In a multivariate analysis, women were more likely to have trichomoniasis if they were black compared with white, Asian, or other race/ethnicity (odds ratio, 2.69); did not have health insurance (OR, 1.57); did not have a bachelor’s degree (OR, 5.53); had 2-15, or 16 or more partners in the past year vs. none or a single partner (OR, 1.60 and 3.51); were bisexual (OR, 2.00); did not always use a condom (3.04); or had a partner who had an STI (OR, 1.71).

Age, having had trichomoniasis previously, and having had any STI in the past were not independent risk factors for trichomoniasis, according to Dr. Gaydos.

Participants reported hearing about the program in a variety of ways. "About 30% say that they found it surfing the Internet, and about 28% say they heard about it on the radio, which is how we advertise the presence of the kit in our local areas most of the time," Dr. Gaydos said. Additionally, small proportions reported learning about the program from friends, fliers, and partners.

"Interestingly enough, when we queried the men, a much higher percentage answer on their questionnaire that they were told by their partner," she commented. "So the men are not telling their female partners to get tested, but the females are telling their male partners to get tested."

The study had its limitations, Dr. Gaydos acknowledged. "Obviously, it is biased because it’s selecting people who are empowered to think about their own sexual health. They are interested in finding out if they are infected, and they do report high [levels of] risk factors, which are similar to those that we see in STD clinics," she said.

Dr. Gaydos reported that she has received free diagnostic kits from Gen-Probe Inc.

SEATTLE – Both a high rate of trichomoniasis among sexually active teenage and adult women who seek self-testing and the elevated rate of adverse reproductive health outcomes in infected women raise the question of whether trichomoniasis should be a reportable infection in the United States, Charlotte A. Gaydos said.

Some 10% of the more than 1,500 women who were recruited through the Internet and offered free self-testing, and who then submitted vaginal samples, were positive for this sexually transmitted infection (STI) in an observational study reported at the annual meeting of the Society for Adolescent Health and Medicine. Rates were highest among those aged 25-29 years and among blacks.

These findings, coupled with the adverse health effects of trichomoniasis, may have implications for tracking the infection in the population, according to lead investigator Charlotte A. Gaydos, Dr.P.H., a professor in the division of infectious diseases at Johns Hopkins University in Baltimore.

Trichomoniasis is currently not reportable to the Centers for Disease Control and Prevention, she noted. But study estimates from the CDC suggest that there are 7-8 million new cases every year in the United States.

Infected men and – in particular – women have elevated rates of adverse reproductive health outcomes, including pelvic inflammatory disease, low infant birth weight, and premature delivery. Furthermore, this STI has been increasingly implicated as a risk factor for HIV transmission, she said.

"My question to the proponents of adolescent health and health for women in general is, should we start to do surveillance for Trichomonas [vaginalis] in the United States, so that we can have good data?" Dr. Gaydos asked. "I think more studies are needed."

Additionally, "should we make this a reportable infection in the future?" she inquired, given the many negative outcomes associated with trichomoniasis and the fact that it can be asymptomatic.

The investigators studied women who were recruited through IWantTheKit.org, an educational Internet program on STIs that offers free self-testing to sexually active individuals aged 14 years or older in Denver, Philadelphia, Alaska, Maryland, West Virginia, selected counties in Illinois, and Washington, D.C.

"We know that submission of self-collected samples at home can remove some barriers for adolescents and other women in testing for sexually transmitted diseases," Dr. Gaydos commented. "We have shown in the past that an Internet-recruited population can do this for Chlamydia and gonorrhea."

Starting in mid-2006, the program added testing for trichomoniasis to its existing testing for Chlamydia and gonorrhea. Women ordered the kit online and sent self-collected vaginal samples by U.S. mail to the testing lab. They also completed questionnaires on demographics and risk factors.

The lab tested for trichomoniasis using a nucleic acid amplification test, which has a sensitivity of about 90%, compared with roughly 50% for wet prep and 70% for culture, according to Dr. Gaydos.

The women were instructed to call for their test results in 1-2 weeks, and – should they forget to call – to indicate their preferred method of notification (e-mail, cell phone, letter, or text message).

A total of 1,525 women requested and returned self-collected vaginal swab kits in 2006-2010.

Overall, 10% of women tested positive for trichomoniasis, Dr. Gaydos reported. In addition, 10% tested positive for Chlamydia, 1% tested positive for gonorrhea, and 18% tested positive for at least one of the three infections studied.

By age, the rate of trichomoniasis ranged from 8.3% among those aged 20-24 years to 11.5% among 25- to 29-year-olds. And by race, it ranged from 0% among Asian women to 13.2% among black women.

In a multivariate analysis, women were more likely to have trichomoniasis if they were black compared with white, Asian, or other race/ethnicity (odds ratio, 2.69); did not have health insurance (OR, 1.57); did not have a bachelor’s degree (OR, 5.53); had 2-15, or 16 or more partners in the past year vs. none or a single partner (OR, 1.60 and 3.51); were bisexual (OR, 2.00); did not always use a condom (3.04); or had a partner who had an STI (OR, 1.71).

Age, having had trichomoniasis previously, and having had any STI in the past were not independent risk factors for trichomoniasis, according to Dr. Gaydos.

Participants reported hearing about the program in a variety of ways. "About 30% say that they found it surfing the Internet, and about 28% say they heard about it on the radio, which is how we advertise the presence of the kit in our local areas most of the time," Dr. Gaydos said. Additionally, small proportions reported learning about the program from friends, fliers, and partners.

"Interestingly enough, when we queried the men, a much higher percentage answer on their questionnaire that they were told by their partner," she commented. "So the men are not telling their female partners to get tested, but the females are telling their male partners to get tested."

The study had its limitations, Dr. Gaydos acknowledged. "Obviously, it is biased because it’s selecting people who are empowered to think about their own sexual health. They are interested in finding out if they are infected, and they do report high [levels of] risk factors, which are similar to those that we see in STD clinics," she said.

Dr. Gaydos reported that she has received free diagnostic kits from Gen-Probe Inc.

DENVER – Exacerbations of chronic obstructive pulmonary disease show distinctly different temporal patterns of onset and resolution, which may have implications for treatment and prognosis, researchers reported.

In a prospective cohort study among patients with COPD who kept daily diaries for at least 2 years, 56% of exacerbations started suddenly; the rest began gradually.

The sudden-onset type were 18% shorter in duration than were the gradual-onset type, reported presenting author Gavin C. Donaldson, Ph.D., a senior lecturer and respiratory medicine specialist at the University College London.

The nature of onset of an exacerbation "is of particular interest because it is the prodrome that is reported to the physician when the patient comes into the clinic and dictates the courses of therapy that they receive," he noted at the International Conference of the American Thoracic Society. Hence, a better understanding of these events could help physicians to time therapy more appropriately, to patient benefit.

Study results additionally showed that patients frequently had episodes of symptom worsening that resolved without ever turning into exacerbations.

"We have all had this concept of ‘a patient is either exacerbating or is stable,’ " Dr. Donaldson commented. "There is increasing evidence coming out that patients actually fluctuate around a level which is not clinically significant, and we are finding that these sorts of symptom episodes are really part of that fluctuation. They are not particularly clinically important [that is, the patient doesn’t report it], but it may be important in terms of their disease progression."

Patients participating in the London COPD study recorded peak flow readings and various symptoms – including major (dyspnea, sputum purulence, and sputum volume) and minor (nasal discharge/congestion, wheeze, sore throat, and cough) symptoms – on a daily basis.

The investigators used the diary data to identify episodes of worsening symptoms and to identify exacerbations (defined according to standard criteria as requiring an increase in at least two symptoms, one of them major, on 2 consecutive days).

Results were based on 212 patients who had an average age of 68 years. In all, 64% were men, and 33% were current smokers. Their FEV₁ (forced expiratory volume in 1 second) was 45% of that predicted.

All patients had at least 2 years of follow-up, and the total follow-up for the cohort was 890 patient-years.

The patients experienced 4,439 episodes of worsening symptoms, slightly more than half of which resolved spontaneously and the rest of which resulted in a defined COPD exacerbation. The median number of exacerbations was 2.33 per patient per year.

Analyses revealed two distinct patterns of exacerbation onset, according to Dr. Donaldson. With the sudden-onset pattern (seen in 56%), the median time between initial worsening of symptoms and exacerbation was 0 days. With the gradual-onset pattern (seen in 44%), the time to exacerbation was 4 days.

In addition, the time between the start of an exacerbation and recovery to baseline health status was a significant 18% shorter for sudden-onset vs. gradual-onset exacerbations (11 days vs. 13 days; P less than .001).

The treatments that patients received did not seem to affect these onset or recovery patterns, he noted. If anything, there was a greater tendency for treatment in the exacerbations that went on longer.

Multiple logistic regression analyses showed that certain factors predicted the nature of onset and recovery, according to Dr. Donaldson. Exacerbations were more likely to have a sudden onset in patients who were current smokers (odds ratio, 1.28), had cold symptoms (OR, 1.27), and – especially – had purulent sputum at the time (OR, 13.47). There was less likelihood of a sudden onset in patients with a higher body mass index (OR, 0.98) or cardiovascular disease (OR, 0.78), or if the exacerbations occurred during the spring (OR, 0.71).

Exacerbations were more likely to have a long recovery time (defined as recovery taking more than 12 days) if they had a gradual onset (OR, 1.39) and also if patients were male (OR, 1.27) or had cold symptoms (OR, 1.30), and if they occurred in the winter (OR, 1.36). There was less likelihood of a long recovery time in patients having purulent sputum (OR, 0.91).

Dr. Donaldson did not report any relevant conflicts of interest.

DENVER – Exacerbations of chronic obstructive pulmonary disease show distinctly different temporal patterns of onset and resolution, which may have implications for treatment and prognosis, researchers reported.

In a prospective cohort study among patients with COPD who kept daily diaries for at least 2 years, 56% of exacerbations started suddenly; the rest began gradually.

The sudden-onset type were 18% shorter in duration than were the gradual-onset type, reported presenting author Gavin C. Donaldson, Ph.D., a senior lecturer and respiratory medicine specialist at the University College London.

The nature of onset of an exacerbation "is of particular interest because it is the prodrome that is reported to the physician when the patient comes into the clinic and dictates the courses of therapy that they receive," he noted at the International Conference of the American Thoracic Society. Hence, a better understanding of these events could help physicians to time therapy more appropriately, to patient benefit.

Study results additionally showed that patients frequently had episodes of symptom worsening that resolved without ever turning into exacerbations.

"We have all had this concept of ‘a patient is either exacerbating or is stable,’ " Dr. Donaldson commented. "There is increasing evidence coming out that patients actually fluctuate around a level which is not clinically significant, and we are finding that these sorts of symptom episodes are really part of that fluctuation. They are not particularly clinically important [that is, the patient doesn’t report it], but it may be important in terms of their disease progression."

Patients participating in the London COPD study recorded peak flow readings and various symptoms – including major (dyspnea, sputum purulence, and sputum volume) and minor (nasal discharge/congestion, wheeze, sore throat, and cough) symptoms – on a daily basis.

The investigators used the diary data to identify episodes of worsening symptoms and to identify exacerbations (defined according to standard criteria as requiring an increase in at least two symptoms, one of them major, on 2 consecutive days).

Results were based on 212 patients who had an average age of 68 years. In all, 64% were men, and 33% were current smokers. Their FEV₁ (forced expiratory volume in 1 second) was 45% of that predicted.

All patients had at least 2 years of follow-up, and the total follow-up for the cohort was 890 patient-years.

The patients experienced 4,439 episodes of worsening symptoms, slightly more than half of which resolved spontaneously and the rest of which resulted in a defined COPD exacerbation. The median number of exacerbations was 2.33 per patient per year.

Analyses revealed two distinct patterns of exacerbation onset, according to Dr. Donaldson. With the sudden-onset pattern (seen in 56%), the median time between initial worsening of symptoms and exacerbation was 0 days. With the gradual-onset pattern (seen in 44%), the time to exacerbation was 4 days.

In addition, the time between the start of an exacerbation and recovery to baseline health status was a significant 18% shorter for sudden-onset vs. gradual-onset exacerbations (11 days vs. 13 days; P less than .001).

The treatments that patients received did not seem to affect these onset or recovery patterns, he noted. If anything, there was a greater tendency for treatment in the exacerbations that went on longer.

Multiple logistic regression analyses showed that certain factors predicted the nature of onset and recovery, according to Dr. Donaldson. Exacerbations were more likely to have a sudden onset in patients who were current smokers (odds ratio, 1.28), had cold symptoms (OR, 1.27), and – especially – had purulent sputum at the time (OR, 13.47). There was less likelihood of a sudden onset in patients with a higher body mass index (OR, 0.98) or cardiovascular disease (OR, 0.78), or if the exacerbations occurred during the spring (OR, 0.71).

Exacerbations were more likely to have a long recovery time (defined as recovery taking more than 12 days) if they had a gradual onset (OR, 1.39) and also if patients were male (OR, 1.27) or had cold symptoms (OR, 1.30), and if they occurred in the winter (OR, 1.36). There was less likelihood of a long recovery time in patients having purulent sputum (OR, 0.91).

Dr. Donaldson did not report any relevant conflicts of interest.

DENVER – Exacerbations of chronic obstructive pulmonary disease show distinctly different temporal patterns of onset and resolution, which may have implications for treatment and prognosis, researchers reported.

In a prospective cohort study among patients with COPD who kept daily diaries for at least 2 years, 56% of exacerbations started suddenly; the rest began gradually.

The sudden-onset type were 18% shorter in duration than were the gradual-onset type, reported presenting author Gavin C. Donaldson, Ph.D., a senior lecturer and respiratory medicine specialist at the University College London.

The nature of onset of an exacerbation "is of particular interest because it is the prodrome that is reported to the physician when the patient comes into the clinic and dictates the courses of therapy that they receive," he noted at the International Conference of the American Thoracic Society. Hence, a better understanding of these events could help physicians to time therapy more appropriately, to patient benefit.

Study results additionally showed that patients frequently had episodes of symptom worsening that resolved without ever turning into exacerbations.

"We have all had this concept of ‘a patient is either exacerbating or is stable,’ " Dr. Donaldson commented. "There is increasing evidence coming out that patients actually fluctuate around a level which is not clinically significant, and we are finding that these sorts of symptom episodes are really part of that fluctuation. They are not particularly clinically important [that is, the patient doesn’t report it], but it may be important in terms of their disease progression."

Patients participating in the London COPD study recorded peak flow readings and various symptoms – including major (dyspnea, sputum purulence, and sputum volume) and minor (nasal discharge/congestion, wheeze, sore throat, and cough) symptoms – on a daily basis.

The investigators used the diary data to identify episodes of worsening symptoms and to identify exacerbations (defined according to standard criteria as requiring an increase in at least two symptoms, one of them major, on 2 consecutive days).

Results were based on 212 patients who had an average age of 68 years. In all, 64% were men, and 33% were current smokers. Their FEV₁ (forced expiratory volume in 1 second) was 45% of that predicted.

All patients had at least 2 years of follow-up, and the total follow-up for the cohort was 890 patient-years.

The patients experienced 4,439 episodes of worsening symptoms, slightly more than half of which resolved spontaneously and the rest of which resulted in a defined COPD exacerbation. The median number of exacerbations was 2.33 per patient per year.

Analyses revealed two distinct patterns of exacerbation onset, according to Dr. Donaldson. With the sudden-onset pattern (seen in 56%), the median time between initial worsening of symptoms and exacerbation was 0 days. With the gradual-onset pattern (seen in 44%), the time to exacerbation was 4 days.

In addition, the time between the start of an exacerbation and recovery to baseline health status was a significant 18% shorter for sudden-onset vs. gradual-onset exacerbations (11 days vs. 13 days; P less than .001).

The treatments that patients received did not seem to affect these onset or recovery patterns, he noted. If anything, there was a greater tendency for treatment in the exacerbations that went on longer.

Multiple logistic regression analyses showed that certain factors predicted the nature of onset and recovery, according to Dr. Donaldson. Exacerbations were more likely to have a sudden onset in patients who were current smokers (odds ratio, 1.28), had cold symptoms (OR, 1.27), and – especially – had purulent sputum at the time (OR, 13.47). There was less likelihood of a sudden onset in patients with a higher body mass index (OR, 0.98) or cardiovascular disease (OR, 0.78), or if the exacerbations occurred during the spring (OR, 0.71).

Exacerbations were more likely to have a long recovery time (defined as recovery taking more than 12 days) if they had a gradual onset (OR, 1.39) and also if patients were male (OR, 1.27) or had cold symptoms (OR, 1.30), and if they occurred in the winter (OR, 1.36). There was less likelihood of a long recovery time in patients having purulent sputum (OR, 0.91).

Dr. Donaldson did not report any relevant conflicts of interest.

DENVER – Exacerbations of chronic obstructive pulmonary disease show distinctly different temporal patterns of onset and resolution, which may have implications for treatment and prognosis, researchers reported.

In a prospective cohort study among patients with COPD who kept daily diaries for at least 2 years, 56% of exacerbations started suddenly; the rest began gradually.

The sudden-onset type were 18% shorter in duration than were the gradual-onset type, reported presenting author Gavin C. Donaldson, Ph.D., a senior lecturer and respiratory medicine specialist at the University College London.

The nature of onset of an exacerbation "is of particular interest because it is the prodrome that is reported to the physician when the patient comes into the clinic and dictates the courses of therapy that they receive," he noted at the International Conference of the American Thoracic Society. Hence, a better understanding of these events could help physicians to time therapy more appropriately, to patient benefit.

Study results additionally showed that patients frequently had episodes of symptom worsening that resolved without ever turning into exacerbations.

"We have all had this concept of ‘a patient is either exacerbating or is stable,’ " Dr. Donaldson commented. "There is increasing evidence coming out that patients actually fluctuate around a level which is not clinically significant, and we are finding that these sorts of symptom episodes are really part of that fluctuation. They are not particularly clinically important [that is, the patient doesn’t report it], but it may be important in terms of their disease progression."

Patients participating in the London COPD study recorded peak flow readings and various symptoms – including major (dyspnea, sputum purulence, and sputum volume) and minor (nasal discharge/congestion, wheeze, sore throat, and cough) symptoms – on a daily basis.

The investigators used the diary data to identify episodes of worsening symptoms and to identify exacerbations (defined according to standard criteria as requiring an increase in at least two symptoms, one of them major, on 2 consecutive days).

Results were based on 212 patients who had an average age of 68 years. In all, 64% were men, and 33% were current smokers. Their FEV₁ (forced expiratory volume in 1 second) was 45% of that predicted.

All patients had at least 2 years of follow-up, and the total follow-up for the cohort was 890 patient-years.

The patients experienced 4,439 episodes of worsening symptoms, slightly more than half of which resolved spontaneously and the rest of which resulted in a defined COPD exacerbation. The median number of exacerbations was 2.33 per patient per year.

Analyses revealed two distinct patterns of exacerbation onset, according to Dr. Donaldson. With the sudden-onset pattern (seen in 56%), the median time between initial worsening of symptoms and exacerbation was 0 days. With the gradual-onset pattern (seen in 44%), the time to exacerbation was 4 days.

In addition, the time between the start of an exacerbation and recovery to baseline health status was a significant 18% shorter for sudden-onset vs. gradual-onset exacerbations (11 days vs. 13 days; P less than .001).

The treatments that patients received did not seem to affect these onset or recovery patterns, he noted. If anything, there was a greater tendency for treatment in the exacerbations that went on longer.

Multiple logistic regression analyses showed that certain factors predicted the nature of onset and recovery, according to Dr. Donaldson. Exacerbations were more likely to have a sudden onset in patients who were current smokers (odds ratio, 1.28), had cold symptoms (OR, 1.27), and – especially – had purulent sputum at the time (OR, 13.47). There was less likelihood of a sudden onset in patients with a higher body mass index (OR, 0.98) or cardiovascular disease (OR, 0.78), or if the exacerbations occurred during the spring (OR, 0.71).

Exacerbations were more likely to have a long recovery time (defined as recovery taking more than 12 days) if they had a gradual onset (OR, 1.39) and also if patients were male (OR, 1.27) or had cold symptoms (OR, 1.30), and if they occurred in the winter (OR, 1.36). There was less likelihood of a long recovery time in patients having purulent sputum (OR, 0.91).

Dr. Donaldson did not report any relevant conflicts of interest.

DENVER – Exacerbations of chronic obstructive pulmonary disease show distinctly different temporal patterns of onset and resolution, which may have implications for treatment and prognosis, researchers reported.

In a prospective cohort study among patients with COPD who kept daily diaries for at least 2 years, 56% of exacerbations started suddenly; the rest began gradually.

The sudden-onset type were 18% shorter in duration than were the gradual-onset type, reported presenting author Gavin C. Donaldson, Ph.D., a senior lecturer and respiratory medicine specialist at the University College London.

The nature of onset of an exacerbation "is of particular interest because it is the prodrome that is reported to the physician when the patient comes into the clinic and dictates the courses of therapy that they receive," he noted at the International Conference of the American Thoracic Society. Hence, a better understanding of these events could help physicians to time therapy more appropriately, to patient benefit.

Study results additionally showed that patients frequently had episodes of symptom worsening that resolved without ever turning into exacerbations.

"We have all had this concept of ‘a patient is either exacerbating or is stable,’ " Dr. Donaldson commented. "There is increasing evidence coming out that patients actually fluctuate around a level which is not clinically significant, and we are finding that these sorts of symptom episodes are really part of that fluctuation. They are not particularly clinically important [that is, the patient doesn’t report it], but it may be important in terms of their disease progression."

Patients participating in the London COPD study recorded peak flow readings and various symptoms – including major (dyspnea, sputum purulence, and sputum volume) and minor (nasal discharge/congestion, wheeze, sore throat, and cough) symptoms – on a daily basis.

The investigators used the diary data to identify episodes of worsening symptoms and to identify exacerbations (defined according to standard criteria as requiring an increase in at least two symptoms, one of them major, on 2 consecutive days).

Results were based on 212 patients who had an average age of 68 years. In all, 64% were men, and 33% were current smokers. Their FEV₁ (forced expiratory volume in 1 second) was 45% of that predicted.

All patients had at least 2 years of follow-up, and the total follow-up for the cohort was 890 patient-years.

The patients experienced 4,439 episodes of worsening symptoms, slightly more than half of which resolved spontaneously and the rest of which resulted in a defined COPD exacerbation. The median number of exacerbations was 2.33 per patient per year.

Analyses revealed two distinct patterns of exacerbation onset, according to Dr. Donaldson. With the sudden-onset pattern (seen in 56%), the median time between initial worsening of symptoms and exacerbation was 0 days. With the gradual-onset pattern (seen in 44%), the time to exacerbation was 4 days.

In addition, the time between the start of an exacerbation and recovery to baseline health status was a significant 18% shorter for sudden-onset vs. gradual-onset exacerbations (11 days vs. 13 days; P less than .001).

The treatments that patients received did not seem to affect these onset or recovery patterns, he noted. If anything, there was a greater tendency for treatment in the exacerbations that went on longer.

Multiple logistic regression analyses showed that certain factors predicted the nature of onset and recovery, according to Dr. Donaldson. Exacerbations were more likely to have a sudden onset in patients who were current smokers (odds ratio, 1.28), had cold symptoms (OR, 1.27), and – especially – had purulent sputum at the time (OR, 13.47). There was less likelihood of a sudden onset in patients with a higher body mass index (OR, 0.98) or cardiovascular disease (OR, 0.78), or if the exacerbations occurred during the spring (OR, 0.71).

Exacerbations were more likely to have a long recovery time (defined as recovery taking more than 12 days) if they had a gradual onset (OR, 1.39) and also if patients were male (OR, 1.27) or had cold symptoms (OR, 1.30), and if they occurred in the winter (OR, 1.36). There was less likelihood of a long recovery time in patients having purulent sputum (OR, 0.91).

Dr. Donaldson did not report any relevant conflicts of interest.

DENVER – Exacerbations of chronic obstructive pulmonary disease show distinctly different temporal patterns of onset and resolution, which may have implications for treatment and prognosis, researchers reported.

In a prospective cohort study among patients with COPD who kept daily diaries for at least 2 years, 56% of exacerbations started suddenly; the rest began gradually.

The sudden-onset type were 18% shorter in duration than were the gradual-onset type, reported presenting author Gavin C. Donaldson, Ph.D., a senior lecturer and respiratory medicine specialist at the University College London.

The nature of onset of an exacerbation "is of particular interest because it is the prodrome that is reported to the physician when the patient comes into the clinic and dictates the courses of therapy that they receive," he noted at the International Conference of the American Thoracic Society. Hence, a better understanding of these events could help physicians to time therapy more appropriately, to patient benefit.

Study results additionally showed that patients frequently had episodes of symptom worsening that resolved without ever turning into exacerbations.

"We have all had this concept of ‘a patient is either exacerbating or is stable,’ " Dr. Donaldson commented. "There is increasing evidence coming out that patients actually fluctuate around a level which is not clinically significant, and we are finding that these sorts of symptom episodes are really part of that fluctuation. They are not particularly clinically important [that is, the patient doesn’t report it], but it may be important in terms of their disease progression."

Patients participating in the London COPD study recorded peak flow readings and various symptoms – including major (dyspnea, sputum purulence, and sputum volume) and minor (nasal discharge/congestion, wheeze, sore throat, and cough) symptoms – on a daily basis.

The investigators used the diary data to identify episodes of worsening symptoms and to identify exacerbations (defined according to standard criteria as requiring an increase in at least two symptoms, one of them major, on 2 consecutive days).

Results were based on 212 patients who had an average age of 68 years. In all, 64% were men, and 33% were current smokers. Their FEV₁ (forced expiratory volume in 1 second) was 45% of that predicted.

All patients had at least 2 years of follow-up, and the total follow-up for the cohort was 890 patient-years.

The patients experienced 4,439 episodes of worsening symptoms, slightly more than half of which resolved spontaneously and the rest of which resulted in a defined COPD exacerbation. The median number of exacerbations was 2.33 per patient per year.

Analyses revealed two distinct patterns of exacerbation onset, according to Dr. Donaldson. With the sudden-onset pattern (seen in 56%), the median time between initial worsening of symptoms and exacerbation was 0 days. With the gradual-onset pattern (seen in 44%), the time to exacerbation was 4 days.

In addition, the time between the start of an exacerbation and recovery to baseline health status was a significant 18% shorter for sudden-onset vs. gradual-onset exacerbations (11 days vs. 13 days; P less than .001).

The treatments that patients received did not seem to affect these onset or recovery patterns, he noted. If anything, there was a greater tendency for treatment in the exacerbations that went on longer.

Multiple logistic regression analyses showed that certain factors predicted the nature of onset and recovery, according to Dr. Donaldson. Exacerbations were more likely to have a sudden onset in patients who were current smokers (odds ratio, 1.28), had cold symptoms (OR, 1.27), and – especially – had purulent sputum at the time (OR, 13.47). There was less likelihood of a sudden onset in patients with a higher body mass index (OR, 0.98) or cardiovascular disease (OR, 0.78), or if the exacerbations occurred during the spring (OR, 0.71).

Exacerbations were more likely to have a long recovery time (defined as recovery taking more than 12 days) if they had a gradual onset (OR, 1.39) and also if patients were male (OR, 1.27) or had cold symptoms (OR, 1.30), and if they occurred in the winter (OR, 1.36). There was less likelihood of a long recovery time in patients having purulent sputum (OR, 0.91).

Dr. Donaldson did not report any relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

DENVER – Shorter combination therapy was at least as efficacious as conventional longer monotherapy for preventing tuberculosis in patients with latent infection, according to final results of the phase III PREVENT TB trial.

The trial, also known as TB Trials Consortium Study 26, was conducted among more than 8,000 patients with latent TB infection who were at high risk for progression.

After 33 months, the cumulative rate of TB disease was 0.19% in the group given 3 months of weekly rifapentine plus isoniazid under direct observation (3HP), compared with 0.43% in the group given 9 months of daily isoniazid on a self-administered basis (9H).

The difference between groups was well within the trial’s boundary set for noninferiority, lead investigator Dr. Timothy R. Sterling reported at an international conference of the American Thoracic Society.

In addition, although patients in the group given the shorter combination therapy were more likely to stop treatment specifically because of adverse events, they were still far more likely to complete treatment.

Taken together, the trial’s findings suggest that "3HP is an alternative to 9H for treatment of latent [TB] infection in persons at high risk for progression to tuberculosis," he said.

"3HP was as effective as 9H in this clinical trial, but in operational settings, 3HP could be more effective than 9H, particularly if 3HP is given under direct observation and 9H has completion rates of approximately 30%-60%," Dr. Sterling further noted. "And, with greater effectiveness, there would be more tuberculosis prevented."

The trial enrolled 8,053 patients older than 2 years of age from the United States, Canada, Brazil, and Spain who had a positive tuberculin skin test (or alternately, in the case of young children, close contact with someone with TB), plus factors putting them at high risk for progression.

The patients were randomly assigned in nearly equal numbers to two groups treated on an open-label basis.

The 3HP group was given once-weekly, directly observed treatment with rifapentine (brand name Priftin; 900 mg) plus isoniazid (brand name Nydrazid, also known as isonicotinic acid hydrazide or INH; 15-25 mg/kg) for 3 months. The 9H group was given daily self-administered isoniazid (5-15 mg/kg) for 9 months.

All patients also received vitamin B₆. They were followed up for 33 months from the time of enrollment.

The patients had a median age of 37 years and 58% were white, reported Dr. Sterling, who is a professor of medicine and director of epidemiology research in the division of infectious diseases at the Vanderbilt Institute for Global Health in Nashville, Tenn. Overall, 3% were HIV positive.

In modified intention-to-treat analyses, the cumulative rate of culture-confirmed TB was 0.19% in the rifapentine plus isoniazid group, compared with 0.43% in the isoniazid-only group. The upper bound of the 95% confidence interval for the difference between these rates was 0.01% – far below the trial’s predefined noninferiority margin of 0.75%.

In per-protocol analyses, the cumulative rates were 0.13% and 0.32%, respectively. The upper bound of the 95% confidence interval for the difference between these rates was 0.06%, again well below the noninferiority margin.

In additional findings, compared with the 9H isoniazid-only regimen, the 3HP rifapentine plus isoniazid regimen was associated with a higher treatment completion rate (82% vs. 69%) and a lower rate of hepatotoxicity caused by the drug(s) (0.5% vs. 2.7%).

However, the 3HP regimen was also associated with higher rates of any adverse event attributable to the drug(s) (8.1% vs. 5.5%) and of permanent drug discontinuation because of adverse events (4.7% vs. 3.6%). These findings might have been caused by the decreased tolerability of the combination regimen, Dr. Sterling speculated, or to this group’s more frequent contact with study personnel or the trial’s open-label design with a novel regimen.

Neither rates of grade 3 and 4 toxicity nor rates of death differed significantly between groups, he noted.

The Centers for Disease Control and Prevention and the American Thoracic Society will be updating their TB recommendations when the data are published, according to Dr. Sterling.

"Uptake of the [3HP] regimen will depend on availability of rifapentine; but the manufacturer, Sanofi-Aventis, is committed to this," he added.

It will be important for TB treatment programs to be able to monitor for adverse events, Dr. Sterling, cautioned, given that previous experience suggests some TB regimens have poorer tolerability when used in the general population than when used in a clinical trial.

The shorter, more potent TB treatment regimen might improve patient adherence, said Dr. Kenneth Castro, director of the Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), at the Centers for Disease Control and Prevention.

"As someone who has been in the business of fighting TB for a long time, I can’t tell you how pleased I am to be able to offer a 3-month regimen: 12 doses and you are done," Dr. Castro said in a telebriefing May 16. Practitioners are always struggling to get patients to complete a 9-month regimen for TB, but with limited success, he said.

"This provides a fantastic opportunity to have the desired impact as a preventive therapy regimen [for TB]," Dr. Castro said.

Dr. Sterling reported that he had no relevant conflicts of interest. Sanofi-Aventis, manufacturer of rifapentine, provided the drug for the trial. Dr. Castro also had no relevant conflicts of interest.

SAN DIEGO – For men undergoing heart transplantation, the sex of their donor may mean the difference between life and death, according to a pair of large retrospective cohort studies

The studies, which were reported at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), each analyzed data from more than 60,000 recipients over periods spanning several decades.

Their conclusion: Men were more likely to die if they received a heart from a female donor vs. a male donor, with the elevation in risk largely resulting from excess deaths in the first year. Overall mortality was 13% higher for these men after potential confounders were taken into account.

In contrast, women undergoing heart transplantation had a similar risk of death regardless of whether their donor was male or female.

A possible explanation for the higher risk of death in men with female donors, according to Dr. Ingo Kaczmarek, a cardiac surgeon at the Transplantation Center Munich of Ludwig-Maximilians University of Munich and the lead investigator of one of the studies, is that women’s hearts are smaller than men’s, even given the same body height and weight (J. Am. Coll. Cardiol. 2002;39:1055-60).

Additionally, medication nonadherence may play a part. "In our population ... I can tell you that females take their medication and males don’t," he said. "And that might be a big confounder that you can’t measure."

Although her study took donor characteristics into account, it is still possible that the smaller size of female hearts played a role, agreed Dr. Kiran K. Khush, lead investigator of the other study. "But I think there are probably also some immunological processes involved and sex differences that we don’t completely understand," she added.

This new information helps explain why some patients fare better than others after heart transplantation, but it would not necessarily alter her practice, said Dr. Khush, a cardiologist and instructor in cardiovascular medicine at Stanford (Calif.) University.

"I would worry about it clinically, but I’m not sure that would preclude me from accepting a female graft for a male recipient, because – as we all know – when you have a very sick recipient who is in imminent danger of dying, you just want to have a heart for that patient," she commented.

However, she added, perhaps given a situation wherein several highest-priority patients on the waiting list were otherwise similar, sex matching might be something to consider.

Dr. Khush and her colleagues analyzed data from the ISHLT database, the largest repository of heart transplant outcomes, for the years 1990-2008, restricting analyses to 60,584 adult recipients having at least 2 years of follow-up post transplantation.

"The ISHLT database pulls data from a lot of different transplant centers worldwide," she noted, including ones in North America, Europe, Australia, and New Zealand, among others. "So this really represents a truly international experience."

Fully 79% of the heart transplant recipients were men. On average, the men were 52 years old and the women were 49 years old at the time of transplantation.

Men’s odds of acute rejection within 2 years of transplantation were higher if their donor was female vs. male before adjustment for more than a dozen potential confounders (odds ratio, 1.22), although not afterward. Women’s odds of this outcome did not differ by the sex of their donor.

The donor’s sex did not affect the likelihood of cardiac allograft vasculopathy for either group before adjustment. But afterward, men actually had a lower risk of this outcome if their donor was female (OR, 0.77).

Here, Dr. Khush sounded a note of caution about the variability in assessing and defining vasculopathy across centers. "Some use angiography, some use IVUS [intravascular ultrasound], maybe some use clinical suspicion," she explained, and disease extent is often not documented. "So I think this is a really hard end point to interpret because the definition is so vague."

But there is no gray area when it comes to defining death, she noted, and results showed that men were more likely to die after transplantation if their donor was female vs. male, both before statistical adjustment (hazard ratio, 1.18) and afterward (HR, 1.13). The donor’s sex had no influence on this outcome among women.

Temporal patterns, assessed with follow-up out to 20 years, suggested that the poorer survival of men who were given a female heart was largely because of increased mortality in the first year post transplantation.

Men also had a higher risk of graft failure resulting in death or retransplantation (after censoring for death from other causes) if their donor was female (HR, 1.17).

A study caveat was that the numbers of patients were limited for several of the outcomes because of missing data, acknowledged Dr. Khush. "It is very difficult to account for center-specific differences – for example, differences in patient populations and management practices," she further noted. And unknown confounders could have influenced the findings.

Dr. Kaczmarek and his coinvestigators similarly analyzed data from the ISHLT database, but for a wider range of years (1980-2009). Their analyses were based on 67,833 heart transplant recipients.

Overall, 80% were men. On average, the men were 53 years old and the women were 51 years old. One-quarter of men received a female donor heart, and slightly fewer than one-half of women received a male donor heart.

The 15-year survival rate was best for women who were given a female heart and worst for men who were given a female heart. "The curves divide in the first year," Dr. Kaczmarek pointed out. "In the long run, they seem to be parallel, but women with female hearts do a bit better."

The 1-year rate of survival ranged from a low of 78% among men who were given a female heart to a high of 84% among men who were given a male heart. "This [latter] effect lasts for a few years, and then the better combination is female donor, female recipient," he said.

When patients who died in the first year post transplantation were excluded, the survival curves diverged gradually over time, but still arrived at the same final pattern, with long-term survival best for women who were given a female heart and worst for men who were given a female heart.

"We have seen that acute rejection contributes to that effect," Dr. Kaczmarek commented. "Acute rejection [rates] are a bit higher in male recipients who receive female donor hearts."

Results were similar when the investigators focused just on the subgroup of patients from their own institution in Munich.

"I want to carefully conclude that the combination of male recipient, female donor carries a higher risk for early mortality, whereas other gender constellations yield similar outcomes," said Dr. Kaczmarek.

"In the long-term follow-up, female recipients reveal superior results, especially the combination of female recipient and female donor," he concluded.

Dr. Khush reported having no conflicts of interest related to the research. Dr. Kaczmarek reported receiving travel or research grants from Novartis, Astellas, Roche, Orion Pharma, and Berlin Heart.

SAN DIEGO – For men undergoing heart transplantation, the sex of their donor may mean the difference between life and death, according to a pair of large retrospective cohort studies

The studies, which were reported at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), each analyzed data from more than 60,000 recipients over periods spanning several decades.

Their conclusion: Men were more likely to die if they received a heart from a female donor vs. a male donor, with the elevation in risk largely resulting from excess deaths in the first year. Overall mortality was 13% higher for these men after potential confounders were taken into account.

In contrast, women undergoing heart transplantation had a similar risk of death regardless of whether their donor was male or female.

A possible explanation for the higher risk of death in men with female donors, according to Dr. Ingo Kaczmarek, a cardiac surgeon at the Transplantation Center Munich of Ludwig-Maximilians University of Munich and the lead investigator of one of the studies, is that women’s hearts are smaller than men’s, even given the same body height and weight (J. Am. Coll. Cardiol. 2002;39:1055-60).

Additionally, medication nonadherence may play a part. "In our population ... I can tell you that females take their medication and males don’t," he said. "And that might be a big confounder that you can’t measure."

Although her study took donor characteristics into account, it is still possible that the smaller size of female hearts played a role, agreed Dr. Kiran K. Khush, lead investigator of the other study. "But I think there are probably also some immunological processes involved and sex differences that we don’t completely understand," she added.

This new information helps explain why some patients fare better than others after heart transplantation, but it would not necessarily alter her practice, said Dr. Khush, a cardiologist and instructor in cardiovascular medicine at Stanford (Calif.) University.

"I would worry about it clinically, but I’m not sure that would preclude me from accepting a female graft for a male recipient, because – as we all know – when you have a very sick recipient who is in imminent danger of dying, you just want to have a heart for that patient," she commented.

However, she added, perhaps given a situation wherein several highest-priority patients on the waiting list were otherwise similar, sex matching might be something to consider.

Dr. Khush and her colleagues analyzed data from the ISHLT database, the largest repository of heart transplant outcomes, for the years 1990-2008, restricting analyses to 60,584 adult recipients having at least 2 years of follow-up post transplantation.

"The ISHLT database pulls data from a lot of different transplant centers worldwide," she noted, including ones in North America, Europe, Australia, and New Zealand, among others. "So this really represents a truly international experience."

Fully 79% of the heart transplant recipients were men. On average, the men were 52 years old and the women were 49 years old at the time of transplantation.

Men’s odds of acute rejection within 2 years of transplantation were higher if their donor was female vs. male before adjustment for more than a dozen potential confounders (odds ratio, 1.22), although not afterward. Women’s odds of this outcome did not differ by the sex of their donor.

The donor’s sex did not affect the likelihood of cardiac allograft vasculopathy for either group before adjustment. But afterward, men actually had a lower risk of this outcome if their donor was female (OR, 0.77).

Here, Dr. Khush sounded a note of caution about the variability in assessing and defining vasculopathy across centers. "Some use angiography, some use IVUS [intravascular ultrasound], maybe some use clinical suspicion," she explained, and disease extent is often not documented. "So I think this is a really hard end point to interpret because the definition is so vague."

But there is no gray area when it comes to defining death, she noted, and results showed that men were more likely to die after transplantation if their donor was female vs. male, both before statistical adjustment (hazard ratio, 1.18) and afterward (HR, 1.13). The donor’s sex had no influence on this outcome among women.

Temporal patterns, assessed with follow-up out to 20 years, suggested that the poorer survival of men who were given a female heart was largely because of increased mortality in the first year post transplantation.

Men also had a higher risk of graft failure resulting in death or retransplantation (after censoring for death from other causes) if their donor was female (HR, 1.17).

A study caveat was that the numbers of patients were limited for several of the outcomes because of missing data, acknowledged Dr. Khush. "It is very difficult to account for center-specific differences – for example, differences in patient populations and management practices," she further noted. And unknown confounders could have influenced the findings.

Dr. Kaczmarek and his coinvestigators similarly analyzed data from the ISHLT database, but for a wider range of years (1980-2009). Their analyses were based on 67,833 heart transplant recipients.

Overall, 80% were men. On average, the men were 53 years old and the women were 51 years old. One-quarter of men received a female donor heart, and slightly fewer than one-half of women received a male donor heart.

The 15-year survival rate was best for women who were given a female heart and worst for men who were given a female heart. "The curves divide in the first year," Dr. Kaczmarek pointed out. "In the long run, they seem to be parallel, but women with female hearts do a bit better."

The 1-year rate of survival ranged from a low of 78% among men who were given a female heart to a high of 84% among men who were given a male heart. "This [latter] effect lasts for a few years, and then the better combination is female donor, female recipient," he said.

When patients who died in the first year post transplantation were excluded, the survival curves diverged gradually over time, but still arrived at the same final pattern, with long-term survival best for women who were given a female heart and worst for men who were given a female heart.

"We have seen that acute rejection contributes to that effect," Dr. Kaczmarek commented. "Acute rejection [rates] are a bit higher in male recipients who receive female donor hearts."

Results were similar when the investigators focused just on the subgroup of patients from their own institution in Munich.

"I want to carefully conclude that the combination of male recipient, female donor carries a higher risk for early mortality, whereas other gender constellations yield similar outcomes," said Dr. Kaczmarek.

"In the long-term follow-up, female recipients reveal superior results, especially the combination of female recipient and female donor," he concluded.

Dr. Khush reported having no conflicts of interest related to the research. Dr. Kaczmarek reported receiving travel or research grants from Novartis, Astellas, Roche, Orion Pharma, and Berlin Heart.

SAN DIEGO – For men undergoing heart transplantation, the sex of their donor may mean the difference between life and death, according to a pair of large retrospective cohort studies

The studies, which were reported at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), each analyzed data from more than 60,000 recipients over periods spanning several decades.

Their conclusion: Men were more likely to die if they received a heart from a female donor vs. a male donor, with the elevation in risk largely resulting from excess deaths in the first year. Overall mortality was 13% higher for these men after potential confounders were taken into account.

In contrast, women undergoing heart transplantation had a similar risk of death regardless of whether their donor was male or female.

A possible explanation for the higher risk of death in men with female donors, according to Dr. Ingo Kaczmarek, a cardiac surgeon at the Transplantation Center Munich of Ludwig-Maximilians University of Munich and the lead investigator of one of the studies, is that women’s hearts are smaller than men’s, even given the same body height and weight (J. Am. Coll. Cardiol. 2002;39:1055-60).

Additionally, medication nonadherence may play a part. "In our population ... I can tell you that females take their medication and males don’t," he said. "And that might be a big confounder that you can’t measure."

Although her study took donor characteristics into account, it is still possible that the smaller size of female hearts played a role, agreed Dr. Kiran K. Khush, lead investigator of the other study. "But I think there are probably also some immunological processes involved and sex differences that we don’t completely understand," she added.

This new information helps explain why some patients fare better than others after heart transplantation, but it would not necessarily alter her practice, said Dr. Khush, a cardiologist and instructor in cardiovascular medicine at Stanford (Calif.) University.

"I would worry about it clinically, but I’m not sure that would preclude me from accepting a female graft for a male recipient, because – as we all know – when you have a very sick recipient who is in imminent danger of dying, you just want to have a heart for that patient," she commented.

However, she added, perhaps given a situation wherein several highest-priority patients on the waiting list were otherwise similar, sex matching might be something to consider.

Dr. Khush and her colleagues analyzed data from the ISHLT database, the largest repository of heart transplant outcomes, for the years 1990-2008, restricting analyses to 60,584 adult recipients having at least 2 years of follow-up post transplantation.

"The ISHLT database pulls data from a lot of different transplant centers worldwide," she noted, including ones in North America, Europe, Australia, and New Zealand, among others. "So this really represents a truly international experience."

Fully 79% of the heart transplant recipients were men. On average, the men were 52 years old and the women were 49 years old at the time of transplantation.

Men’s odds of acute rejection within 2 years of transplantation were higher if their donor was female vs. male before adjustment for more than a dozen potential confounders (odds ratio, 1.22), although not afterward. Women’s odds of this outcome did not differ by the sex of their donor.

The donor’s sex did not affect the likelihood of cardiac allograft vasculopathy for either group before adjustment. But afterward, men actually had a lower risk of this outcome if their donor was female (OR, 0.77).

Here, Dr. Khush sounded a note of caution about the variability in assessing and defining vasculopathy across centers. "Some use angiography, some use IVUS [intravascular ultrasound], maybe some use clinical suspicion," she explained, and disease extent is often not documented. "So I think this is a really hard end point to interpret because the definition is so vague."

But there is no gray area when it comes to defining death, she noted, and results showed that men were more likely to die after transplantation if their donor was female vs. male, both before statistical adjustment (hazard ratio, 1.18) and afterward (HR, 1.13). The donor’s sex had no influence on this outcome among women.

Temporal patterns, assessed with follow-up out to 20 years, suggested that the poorer survival of men who were given a female heart was largely because of increased mortality in the first year post transplantation.

Men also had a higher risk of graft failure resulting in death or retransplantation (after censoring for death from other causes) if their donor was female (HR, 1.17).

A study caveat was that the numbers of patients were limited for several of the outcomes because of missing data, acknowledged Dr. Khush. "It is very difficult to account for center-specific differences – for example, differences in patient populations and management practices," she further noted. And unknown confounders could have influenced the findings.

Dr. Kaczmarek and his coinvestigators similarly analyzed data from the ISHLT database, but for a wider range of years (1980-2009). Their analyses were based on 67,833 heart transplant recipients.

Overall, 80% were men. On average, the men were 53 years old and the women were 51 years old. One-quarter of men received a female donor heart, and slightly fewer than one-half of women received a male donor heart.

The 15-year survival rate was best for women who were given a female heart and worst for men who were given a female heart. "The curves divide in the first year," Dr. Kaczmarek pointed out. "In the long run, they seem to be parallel, but women with female hearts do a bit better."

The 1-year rate of survival ranged from a low of 78% among men who were given a female heart to a high of 84% among men who were given a male heart. "This [latter] effect lasts for a few years, and then the better combination is female donor, female recipient," he said.

When patients who died in the first year post transplantation were excluded, the survival curves diverged gradually over time, but still arrived at the same final pattern, with long-term survival best for women who were given a female heart and worst for men who were given a female heart.

"We have seen that acute rejection contributes to that effect," Dr. Kaczmarek commented. "Acute rejection [rates] are a bit higher in male recipients who receive female donor hearts."

Results were similar when the investigators focused just on the subgroup of patients from their own institution in Munich.

"I want to carefully conclude that the combination of male recipient, female donor carries a higher risk for early mortality, whereas other gender constellations yield similar outcomes," said Dr. Kaczmarek.

"In the long-term follow-up, female recipients reveal superior results, especially the combination of female recipient and female donor," he concluded.

Dr. Khush reported having no conflicts of interest related to the research. Dr. Kaczmarek reported receiving travel or research grants from Novartis, Astellas, Roche, Orion Pharma, and Berlin Heart.

SAN DIEGO – Cardiac transplant recipients who are given hearts from donors with left ventricular hypertrophy are not at increased risk of death, Dr. Omar Wever Pinzon reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective nationwide study of more than 2,500 adults who underwent cardiac transplantation during a recent 4-year period, nearly half of the donor hearts had LVH, although it was mild in most cases.

Recipients who had been given hearts with LVH did not have poorer survival overall than did their counterparts who had been given hearts without this high-risk characteristic. But getting a heart with LVH did reduce survival if, in addition, the donor was older than 55 years or the graft had a longer ischemic time.

"Overall survival of recipients of donor hearts with LVH is similar to those without LVH, which indicates that the current donor selection and allocation algorithms successfully mitigate the risk that donor LVH could pose to recipient survival," Dr. Pinzon said. However, "the combination of donor LVH with certain other high-risk characteristics can result in excess mortality."

Because few donor hearts had moderate or severe LVH, "I think we have to be very cautious" when using those hearts, he added. "But I would say [hearts having an interventricular septum and posterior wall thickness] up to 1.3 cm may be safe in the absence of other high-risk characteristics."

The scarcity of donor hearts – coupled with growing knowledge about the impact of various donor characteristics on recipient outcomes – has led to strategies to make more hearts available for transplantation, according to Dr. Pinzon.

"Thanks to these strategies, patients with left ventricular hypertrophy, considered a high-risk characteristic, are more likely now to become donors," he commented. However, some studies have raised concerns that such hearts are more susceptible to ischemic graft injury, which could translate into poorer outcomes for the recipients.

Using data from the United Network for Organ Sharing and the Organ Procurement and Transplantation Network, the investigators studied 2,626 adult patients who underwent a first, single-organ heart transplantation in 2006-2010.

On the basis of the thickness of the interventricular septum and posterior wall, donor hearts were classified as having no LVH (less than 1.1 cm) or LVH that was mild (1.1-1.3 cm), moderate (1.4-1.6 cm), or severe (1.7 cm or greater).

Study results showed that the transplant recipients were 52 years old on average, and 78% were men. The donors were 33 years old on average, and 72% were men.

Fully 44% of the donor hearts had some degree of LVH, reported Dr. Pinzon, who is a heart failure/transplant fellow with the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City. The LVH was mild in most cases (38%) but occasionally moderate (5%) or severe (1%).

Relative to their peers who had been given donor hearts without LVH, recipients who had been given donor hearts with LVH had a higher body mass index and a higher ratio of donor-to-recipient BMI, had been on the waiting list for a shorter time, and were marginally more likely to have a graft ischemic time exceeding 4 hours.

During a follow-up period of 3.3 years post transplantation, 13% of the recipients died or – rarely – underwent retransplantation.

In univariate and multivariate analyses, neither recipients of donor hearts with mild LVH nor recipients of donor hearts with moderate or severe LVH were more likely to die than their counterparts whose donor hearts did not have any LVH, Dr. Pinzon reported.

However, recipients’ risk of death increased with the age of their donor (hazard ratio, 1.01) and with their own serum creatinine level (HR, 1.31) and mean pulmonary artery pressure (HR, 1.01).

Also, they were more likely to die if their donor had used tobacco (HR, 1.32), or if they themselves were older than 55 years of age (HR, 1.30) or had been on extracorporeal membrane oxygenation support (HR, 6.0).

Further analyses revealed an interaction between donor heart LVH and donor age. Among recipients whose donor was older than 55 years, those getting a heart with any LVH had roughly six times the risk of death (P = .01). But there was no such association among recipients whose donors were younger.

There was also an interaction between donor heart LVH and graft ischemic time. Among recipients whose graft had an ischemic time of 4 hours or longer, those receiving a heart with moderate or severe LVH had twice the risk of death (P = .04). There was no such association among recipients whose graft ischemic time was shorter.

The presence of LVH in a donor heart does not adversely affect the survival of transplant recipients, concluded Dr. Pinzon.

But "organ selection and allocation is not a random process," and transplantation involving hearts with moderate or severe LVH was rare. "This indicates that these patients were carefully selected, which can bias our results," he cautioned; therefore, the safety of using such hearts remains uncertain.

Dr. Pinzon reported that he had no relevant conflicts of interest.

SAN DIEGO – Cardiac transplant recipients who are given hearts from donors with left ventricular hypertrophy are not at increased risk of death, Dr. Omar Wever Pinzon reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective nationwide study of more than 2,500 adults who underwent cardiac transplantation during a recent 4-year period, nearly half of the donor hearts had LVH, although it was mild in most cases.

Recipients who had been given hearts with LVH did not have poorer survival overall than did their counterparts who had been given hearts without this high-risk characteristic. But getting a heart with LVH did reduce survival if, in addition, the donor was older than 55 years or the graft had a longer ischemic time.

"Overall survival of recipients of donor hearts with LVH is similar to those without LVH, which indicates that the current donor selection and allocation algorithms successfully mitigate the risk that donor LVH could pose to recipient survival," Dr. Pinzon said. However, "the combination of donor LVH with certain other high-risk characteristics can result in excess mortality."

Because few donor hearts had moderate or severe LVH, "I think we have to be very cautious" when using those hearts, he added. "But I would say [hearts having an interventricular septum and posterior wall thickness] up to 1.3 cm may be safe in the absence of other high-risk characteristics."

The scarcity of donor hearts – coupled with growing knowledge about the impact of various donor characteristics on recipient outcomes – has led to strategies to make more hearts available for transplantation, according to Dr. Pinzon.

"Thanks to these strategies, patients with left ventricular hypertrophy, considered a high-risk characteristic, are more likely now to become donors," he commented. However, some studies have raised concerns that such hearts are more susceptible to ischemic graft injury, which could translate into poorer outcomes for the recipients.

Using data from the United Network for Organ Sharing and the Organ Procurement and Transplantation Network, the investigators studied 2,626 adult patients who underwent a first, single-organ heart transplantation in 2006-2010.

On the basis of the thickness of the interventricular septum and posterior wall, donor hearts were classified as having no LVH (less than 1.1 cm) or LVH that was mild (1.1-1.3 cm), moderate (1.4-1.6 cm), or severe (1.7 cm or greater).

Study results showed that the transplant recipients were 52 years old on average, and 78% were men. The donors were 33 years old on average, and 72% were men.

Fully 44% of the donor hearts had some degree of LVH, reported Dr. Pinzon, who is a heart failure/transplant fellow with the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City. The LVH was mild in most cases (38%) but occasionally moderate (5%) or severe (1%).

Relative to their peers who had been given donor hearts without LVH, recipients who had been given donor hearts with LVH had a higher body mass index and a higher ratio of donor-to-recipient BMI, had been on the waiting list for a shorter time, and were marginally more likely to have a graft ischemic time exceeding 4 hours.

During a follow-up period of 3.3 years post transplantation, 13% of the recipients died or – rarely – underwent retransplantation.

In univariate and multivariate analyses, neither recipients of donor hearts with mild LVH nor recipients of donor hearts with moderate or severe LVH were more likely to die than their counterparts whose donor hearts did not have any LVH, Dr. Pinzon reported.

However, recipients’ risk of death increased with the age of their donor (hazard ratio, 1.01) and with their own serum creatinine level (HR, 1.31) and mean pulmonary artery pressure (HR, 1.01).

Also, they were more likely to die if their donor had used tobacco (HR, 1.32), or if they themselves were older than 55 years of age (HR, 1.30) or had been on extracorporeal membrane oxygenation support (HR, 6.0).

Further analyses revealed an interaction between donor heart LVH and donor age. Among recipients whose donor was older than 55 years, those getting a heart with any LVH had roughly six times the risk of death (P = .01). But there was no such association among recipients whose donors were younger.

There was also an interaction between donor heart LVH and graft ischemic time. Among recipients whose graft had an ischemic time of 4 hours or longer, those receiving a heart with moderate or severe LVH had twice the risk of death (P = .04). There was no such association among recipients whose graft ischemic time was shorter.

The presence of LVH in a donor heart does not adversely affect the survival of transplant recipients, concluded Dr. Pinzon.

But "organ selection and allocation is not a random process," and transplantation involving hearts with moderate or severe LVH was rare. "This indicates that these patients were carefully selected, which can bias our results," he cautioned; therefore, the safety of using such hearts remains uncertain.

Dr. Pinzon reported that he had no relevant conflicts of interest.

SAN DIEGO – Cardiac transplant recipients who are given hearts from donors with left ventricular hypertrophy are not at increased risk of death, Dr. Omar Wever Pinzon reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective nationwide study of more than 2,500 adults who underwent cardiac transplantation during a recent 4-year period, nearly half of the donor hearts had LVH, although it was mild in most cases.

Recipients who had been given hearts with LVH did not have poorer survival overall than did their counterparts who had been given hearts without this high-risk characteristic. But getting a heart with LVH did reduce survival if, in addition, the donor was older than 55 years or the graft had a longer ischemic time.

"Overall survival of recipients of donor hearts with LVH is similar to those without LVH, which indicates that the current donor selection and allocation algorithms successfully mitigate the risk that donor LVH could pose to recipient survival," Dr. Pinzon said. However, "the combination of donor LVH with certain other high-risk characteristics can result in excess mortality."

Because few donor hearts had moderate or severe LVH, "I think we have to be very cautious" when using those hearts, he added. "But I would say [hearts having an interventricular septum and posterior wall thickness] up to 1.3 cm may be safe in the absence of other high-risk characteristics."

The scarcity of donor hearts – coupled with growing knowledge about the impact of various donor characteristics on recipient outcomes – has led to strategies to make more hearts available for transplantation, according to Dr. Pinzon.

"Thanks to these strategies, patients with left ventricular hypertrophy, considered a high-risk characteristic, are more likely now to become donors," he commented. However, some studies have raised concerns that such hearts are more susceptible to ischemic graft injury, which could translate into poorer outcomes for the recipients.

Using data from the United Network for Organ Sharing and the Organ Procurement and Transplantation Network, the investigators studied 2,626 adult patients who underwent a first, single-organ heart transplantation in 2006-2010.

On the basis of the thickness of the interventricular septum and posterior wall, donor hearts were classified as having no LVH (less than 1.1 cm) or LVH that was mild (1.1-1.3 cm), moderate (1.4-1.6 cm), or severe (1.7 cm or greater).

Study results showed that the transplant recipients were 52 years old on average, and 78% were men. The donors were 33 years old on average, and 72% were men.

Fully 44% of the donor hearts had some degree of LVH, reported Dr. Pinzon, who is a heart failure/transplant fellow with the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City. The LVH was mild in most cases (38%) but occasionally moderate (5%) or severe (1%).

Relative to their peers who had been given donor hearts without LVH, recipients who had been given donor hearts with LVH had a higher body mass index and a higher ratio of donor-to-recipient BMI, had been on the waiting list for a shorter time, and were marginally more likely to have a graft ischemic time exceeding 4 hours.

During a follow-up period of 3.3 years post transplantation, 13% of the recipients died or – rarely – underwent retransplantation.

In univariate and multivariate analyses, neither recipients of donor hearts with mild LVH nor recipients of donor hearts with moderate or severe LVH were more likely to die than their counterparts whose donor hearts did not have any LVH, Dr. Pinzon reported.

However, recipients’ risk of death increased with the age of their donor (hazard ratio, 1.01) and with their own serum creatinine level (HR, 1.31) and mean pulmonary artery pressure (HR, 1.01).

Also, they were more likely to die if their donor had used tobacco (HR, 1.32), or if they themselves were older than 55 years of age (HR, 1.30) or had been on extracorporeal membrane oxygenation support (HR, 6.0).

Further analyses revealed an interaction between donor heart LVH and donor age. Among recipients whose donor was older than 55 years, those getting a heart with any LVH had roughly six times the risk of death (P = .01). But there was no such association among recipients whose donors were younger.

There was also an interaction between donor heart LVH and graft ischemic time. Among recipients whose graft had an ischemic time of 4 hours or longer, those receiving a heart with moderate or severe LVH had twice the risk of death (P = .04). There was no such association among recipients whose graft ischemic time was shorter.

The presence of LVH in a donor heart does not adversely affect the survival of transplant recipients, concluded Dr. Pinzon.

But "organ selection and allocation is not a random process," and transplantation involving hearts with moderate or severe LVH was rare. "This indicates that these patients were carefully selected, which can bias our results," he cautioned; therefore, the safety of using such hearts remains uncertain.

Dr. Pinzon reported that he had no relevant conflicts of interest.

SAN DIEGO – Transplantation physicians may be increasingly avoiding the use of hearts from donors who have high-risk characteristics, even as demand for transplantable hearts continues to outstrip supply, suggests a retrospective study of more than 42,000 heart transplant recipients.

The percentages of transplanted hearts from donors who have characteristics that are associated with an elevated risk of poor outcomes for the recipient (such as older age or hypertension) initially increased during the recent 2-decade study period. But thereafter, they plateaued or fell – in some cases to levels seen at the start of the period.

There are two possible explanations for the declining use of hearts from high-risk donors, lead investigator Dr. Jose N. Nativi told attendees of the annual meeting of the International Society for Heart and Lung Transplantation.

"One hypothesis is that there is a concern about adverse outcomes" for recipients who would be given these hearts, in the wake of publications describing actual experience with their use, he explained.

"The second hypothesis is that, probably, we have another option to offer these patients, that is, the increasing utilization of left ventricular assist devices," Dr. Nativi said. "So for a patient who is critically ill, instead of offering them a high-risk donor, now we have the luxury in some centers to offer them an alternative, that is, mechanical support."

There have been several key milestones in efforts to make more organs available for transplantation in the United States, according to Dr. Nativi, a fellow in cardiology with the University of Utah and the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City.

The Crystal City Conference in 2001 resulted in a formal recommendation to expand the use of hearts from high-risk donors (Circulation 2002;106:836-41). And the Organ Donation Breakthrough Collaborative in 2003 encouraged increased consent and donation by people with high-risk features (Crit. Care Nurs. Q. 2008;31:190-210).

"These efforts are resulting in the expansion of acceptable donor criteria toward high-risk donors," he said. "But the high-risk donor still remains a matter of controversy."

In the year after the collaborative, there was an increase in the number of all types of organs donated – with the sole exception of hearts. "So we are still struggling to find donors for heart recipients," Dr. Nativi commented.

To assess temporal patterns in the use of hearts from high-risk donors, the investigators analyzed data from the U.S. Scientific Registry of Transplant Recipients, identifying adult patients who underwent single-organ heart transplantation in 1987-2009.

They were divided into three eras by transplantation date: era 1 (1987-1996), when standard donor criteria were used; era 2 (1997-2003), when there was increasing acceptance of the high-risk donor, and reports about the use of organs from such donors increased; and era 3 (2004-2009), after the collaborative was established.

Results were based on 42,023 patients who underwent transplantation during the study period (42% in era 1, 32% in era 2, and 26% in era 3), Dr. Nativi reported.

In multivariate analyses that included more than 40 donor characteristics as well as a transplant center’s patient volume, recipients were more likely to die in the first year post transplantation if their donor was older than 40 years of age (hazard ratio, 1.2), was female (HR, 1.2), had a cerebrovascular cause of death (HR, 1.6), or had a history of hypertension (HR,1.3).

Temporal trends showed a biphasic pattern for three of these high-risk characteristics, with the percentage of hearts having the characteristic increasing significantly between era 1 and era 2, but then decreasing significantly between era 2 and era 3.

For example, the percentage of hearts from donors older than 40 years averaged 21%, 30%, and 28% in eras 1, 2, and 3, respectively. The pattern was similar for hearts from donors who were female (29%, 31%, and 27%) and those having a cerebrovascular cause of death (26%, 29%, and 23%).

The percentage of hearts from donors having hypertension increased from 4% to 11% between eras 1 and 2, and again from 11% to 13% between eras 2 and 3. But in clinical terms, the latter change was really more of a plateau, according to Dr. Nativi.

He acknowledged that factors other than physicians’ decision to avoid the use of hearts from high-risk donors may have contributed to the observed trends. For example, "changes in donor characteristics may have been affected by a potentially changing donor pool," but that possibility is more difficult to study, he said.

Dr. Nativi reported that he had no relevant financial disclosures.

SAN DIEGO – Transplantation physicians may be increasingly avoiding the use of hearts from donors who have high-risk characteristics, even as demand for transplantable hearts continues to outstrip supply, suggests a retrospective study of more than 42,000 heart transplant recipients.

The percentages of transplanted hearts from donors who have characteristics that are associated with an elevated risk of poor outcomes for the recipient (such as older age or hypertension) initially increased during the recent 2-decade study period. But thereafter, they plateaued or fell – in some cases to levels seen at the start of the period.

There are two possible explanations for the declining use of hearts from high-risk donors, lead investigator Dr. Jose N. Nativi told attendees of the annual meeting of the International Society for Heart and Lung Transplantation.

"One hypothesis is that there is a concern about adverse outcomes" for recipients who would be given these hearts, in the wake of publications describing actual experience with their use, he explained.

"The second hypothesis is that, probably, we have another option to offer these patients, that is, the increasing utilization of left ventricular assist devices," Dr. Nativi said. "So for a patient who is critically ill, instead of offering them a high-risk donor, now we have the luxury in some centers to offer them an alternative, that is, mechanical support."

There have been several key milestones in efforts to make more organs available for transplantation in the United States, according to Dr. Nativi, a fellow in cardiology with the University of Utah and the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City.

The Crystal City Conference in 2001 resulted in a formal recommendation to expand the use of hearts from high-risk donors (Circulation 2002;106:836-41). And the Organ Donation Breakthrough Collaborative in 2003 encouraged increased consent and donation by people with high-risk features (Crit. Care Nurs. Q. 2008;31:190-210).

"These efforts are resulting in the expansion of acceptable donor criteria toward high-risk donors," he said. "But the high-risk donor still remains a matter of controversy."

In the year after the collaborative, there was an increase in the number of all types of organs donated – with the sole exception of hearts. "So we are still struggling to find donors for heart recipients," Dr. Nativi commented.

To assess temporal patterns in the use of hearts from high-risk donors, the investigators analyzed data from the U.S. Scientific Registry of Transplant Recipients, identifying adult patients who underwent single-organ heart transplantation in 1987-2009.

They were divided into three eras by transplantation date: era 1 (1987-1996), when standard donor criteria were used; era 2 (1997-2003), when there was increasing acceptance of the high-risk donor, and reports about the use of organs from such donors increased; and era 3 (2004-2009), after the collaborative was established.

Results were based on 42,023 patients who underwent transplantation during the study period (42% in era 1, 32% in era 2, and 26% in era 3), Dr. Nativi reported.

In multivariate analyses that included more than 40 donor characteristics as well as a transplant center’s patient volume, recipients were more likely to die in the first year post transplantation if their donor was older than 40 years of age (hazard ratio, 1.2), was female (HR, 1.2), had a cerebrovascular cause of death (HR, 1.6), or had a history of hypertension (HR,1.3).

Temporal trends showed a biphasic pattern for three of these high-risk characteristics, with the percentage of hearts having the characteristic increasing significantly between era 1 and era 2, but then decreasing significantly between era 2 and era 3.

For example, the percentage of hearts from donors older than 40 years averaged 21%, 30%, and 28% in eras 1, 2, and 3, respectively. The pattern was similar for hearts from donors who were female (29%, 31%, and 27%) and those having a cerebrovascular cause of death (26%, 29%, and 23%).

The percentage of hearts from donors having hypertension increased from 4% to 11% between eras 1 and 2, and again from 11% to 13% between eras 2 and 3. But in clinical terms, the latter change was really more of a plateau, according to Dr. Nativi.

He acknowledged that factors other than physicians’ decision to avoid the use of hearts from high-risk donors may have contributed to the observed trends. For example, "changes in donor characteristics may have been affected by a potentially changing donor pool," but that possibility is more difficult to study, he said.

Dr. Nativi reported that he had no relevant financial disclosures.

SAN DIEGO – Transplantation physicians may be increasingly avoiding the use of hearts from donors who have high-risk characteristics, even as demand for transplantable hearts continues to outstrip supply, suggests a retrospective study of more than 42,000 heart transplant recipients.

The percentages of transplanted hearts from donors who have characteristics that are associated with an elevated risk of poor outcomes for the recipient (such as older age or hypertension) initially increased during the recent 2-decade study period. But thereafter, they plateaued or fell – in some cases to levels seen at the start of the period.

There are two possible explanations for the declining use of hearts from high-risk donors, lead investigator Dr. Jose N. Nativi told attendees of the annual meeting of the International Society for Heart and Lung Transplantation.

"One hypothesis is that there is a concern about adverse outcomes" for recipients who would be given these hearts, in the wake of publications describing actual experience with their use, he explained.

"The second hypothesis is that, probably, we have another option to offer these patients, that is, the increasing utilization of left ventricular assist devices," Dr. Nativi said. "So for a patient who is critically ill, instead of offering them a high-risk donor, now we have the luxury in some centers to offer them an alternative, that is, mechanical support."

There have been several key milestones in efforts to make more organs available for transplantation in the United States, according to Dr. Nativi, a fellow in cardiology with the University of Utah and the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City.

The Crystal City Conference in 2001 resulted in a formal recommendation to expand the use of hearts from high-risk donors (Circulation 2002;106:836-41). And the Organ Donation Breakthrough Collaborative in 2003 encouraged increased consent and donation by people with high-risk features (Crit. Care Nurs. Q. 2008;31:190-210).

"These efforts are resulting in the expansion of acceptable donor criteria toward high-risk donors," he said. "But the high-risk donor still remains a matter of controversy."

In the year after the collaborative, there was an increase in the number of all types of organs donated – with the sole exception of hearts. "So we are still struggling to find donors for heart recipients," Dr. Nativi commented.

To assess temporal patterns in the use of hearts from high-risk donors, the investigators analyzed data from the U.S. Scientific Registry of Transplant Recipients, identifying adult patients who underwent single-organ heart transplantation in 1987-2009.

They were divided into three eras by transplantation date: era 1 (1987-1996), when standard donor criteria were used; era 2 (1997-2003), when there was increasing acceptance of the high-risk donor, and reports about the use of organs from such donors increased; and era 3 (2004-2009), after the collaborative was established.

Results were based on 42,023 patients who underwent transplantation during the study period (42% in era 1, 32% in era 2, and 26% in era 3), Dr. Nativi reported.

In multivariate analyses that included more than 40 donor characteristics as well as a transplant center’s patient volume, recipients were more likely to die in the first year post transplantation if their donor was older than 40 years of age (hazard ratio, 1.2), was female (HR, 1.2), had a cerebrovascular cause of death (HR, 1.6), or had a history of hypertension (HR,1.3).

Temporal trends showed a biphasic pattern for three of these high-risk characteristics, with the percentage of hearts having the characteristic increasing significantly between era 1 and era 2, but then decreasing significantly between era 2 and era 3.

For example, the percentage of hearts from donors older than 40 years averaged 21%, 30%, and 28% in eras 1, 2, and 3, respectively. The pattern was similar for hearts from donors who were female (29%, 31%, and 27%) and those having a cerebrovascular cause of death (26%, 29%, and 23%).

The percentage of hearts from donors having hypertension increased from 4% to 11% between eras 1 and 2, and again from 11% to 13% between eras 2 and 3. But in clinical terms, the latter change was really more of a plateau, according to Dr. Nativi.

He acknowledged that factors other than physicians’ decision to avoid the use of hearts from high-risk donors may have contributed to the observed trends. For example, "changes in donor characteristics may have been affected by a potentially changing donor pool," but that possibility is more difficult to study, he said.

Dr. Nativi reported that he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.