SAN DIEGO – Obesity is a risk factor for colonic diverticulosis among women but not men, while a low-fiber diet was not found to be a risk factor in a recent study reported at the annual Digestive Disease Week.

“The classic teaching in medical school is that a low-fiber diet increases constipation, which in turn increases the risk of diverticula,” explained lead author Dr. Anne Peery, assistant professor of medicine at the University of North Carolina, Chapel Hill. “This is in textbooks and on your boards. But there is no association between low-fiber dietary intake and diverticula.

“There is, however, evidence from other studies that a high-fiber diet and increased physical activity decrease the risk of developing complications from diverticula,” Dr. Peery added. She noted that the study was designed to look at risk factors for developing diverticula, not at complications.

“The provocative findings from our study are twofold: We found that the prevalence of diverticula is higher in men and lower in women younger than age 50, and that obesity is a risk factor for diverticula in women but not in men,” Dr Peery said.

“The age-related gender differences we identified were quite surprising, and suggest that something is going on in women under the age of 50 that may be estrogen-related. This opens up an avenue of research,” she noted.

Colonic diverticula are common, and they are important because of complications such as hemorrhage, perforation, and inflammation. They also pose a substantial health burden, accounting for 2.5 million office visits and 4,500 deaths each year in the United States.

“Despite this, we know very little about risk factors for colonic diverticula,” Dr. Peery noted.

The prospective study recruited 624 patients between the ages of 30 years and 80 years undergoing a first screening colonoscopy between 2013 and 2015 at the University of North Carolina in Chapel Hill. Prior to undergoing the procedure, each participant was interviewed using validated instruments to assess diet and physical activity. Each participant had a detailed examination for colonic diverticula, with a research assistant present during the entire colonoscopy.

“The presence or absence of diverticula reported in previous studies were extracted from colonoscopy reports. Our study assessed risk factors prior to undergoing colonoscopy,” she emphasized. “This is one of the study strengths.”

Not surprisingly, the study showed that the prevalence of diverticula (or “tics”) increased with age. Younger than age 50, the prevalence was higher in men than in women, after which prevalence equalized with age.

In the study population, 124 men had diverticula and 150 did not; 136 women had diverticula and 214 did not. Women with diverticula were more likely to be older, white, and have a higher body mass index (BMI).

The investigators looked at several measures of obesity, including BMI, waist circumference, and waist-to-height ratio. Women with greater BMI were at increased risk for diverticula, a risk relationship that was not seen in men. The risk of developing six or more diverticula was more than twofold greater in obese women.

Men with a greater waist circumference (more than 102 cm) had no increased risk for diverticula, while women with a greater waist circumference (more than 88 cm) were at increased risk of any diverticula, as well as having six or more diverticula.

A similar pattern was observed for waist-to-height ratio, which some experts believe is related to obesity, according to Dr. Peery. No association was found in men. But for women, a high-risk waist-to-height ratio increased the risk of diverticula, and the risk of having six or more diverticula was almost twice as great in these women, compared with men.

The investigators then measured the association between dietary fiber and physical activity with diverticula. No associations with diverticula were found in any quartile (lowest to highest) for both physical activity and dietary fiber intake.

In an interview, Dr. Peery speculated on why women have a lower prevalence of “tics,” compared with men younger than age 50. She said there are gender-related differences in the way fat is stored and metabolized.

“Obese women have more visceral adiposity that men, and they tend to eat more carbohydrates, while obese men have higher alcohol and meat intake. These differences will be studied in greater depth as they relate to diverticula and complications,” she noted.

SAN DIEGO – Obesity is a risk factor for colonic diverticulosis among women but not men, while a low-fiber diet was not found to be a risk factor in a recent study reported at the annual Digestive Disease Week.

“The classic teaching in medical school is that a low-fiber diet increases constipation, which in turn increases the risk of diverticula,” explained lead author Dr. Anne Peery, assistant professor of medicine at the University of North Carolina, Chapel Hill. “This is in textbooks and on your boards. But there is no association between low-fiber dietary intake and diverticula.

“There is, however, evidence from other studies that a high-fiber diet and increased physical activity decrease the risk of developing complications from diverticula,” Dr. Peery added. She noted that the study was designed to look at risk factors for developing diverticula, not at complications.

“The provocative findings from our study are twofold: We found that the prevalence of diverticula is higher in men and lower in women younger than age 50, and that obesity is a risk factor for diverticula in women but not in men,” Dr Peery said.

“The age-related gender differences we identified were quite surprising, and suggest that something is going on in women under the age of 50 that may be estrogen-related. This opens up an avenue of research,” she noted.

Colonic diverticula are common, and they are important because of complications such as hemorrhage, perforation, and inflammation. They also pose a substantial health burden, accounting for 2.5 million office visits and 4,500 deaths each year in the United States.

“Despite this, we know very little about risk factors for colonic diverticula,” Dr. Peery noted.

The prospective study recruited 624 patients between the ages of 30 years and 80 years undergoing a first screening colonoscopy between 2013 and 2015 at the University of North Carolina in Chapel Hill. Prior to undergoing the procedure, each participant was interviewed using validated instruments to assess diet and physical activity. Each participant had a detailed examination for colonic diverticula, with a research assistant present during the entire colonoscopy.

“The presence or absence of diverticula reported in previous studies were extracted from colonoscopy reports. Our study assessed risk factors prior to undergoing colonoscopy,” she emphasized. “This is one of the study strengths.”

Not surprisingly, the study showed that the prevalence of diverticula (or “tics”) increased with age. Younger than age 50, the prevalence was higher in men than in women, after which prevalence equalized with age.

In the study population, 124 men had diverticula and 150 did not; 136 women had diverticula and 214 did not. Women with diverticula were more likely to be older, white, and have a higher body mass index (BMI).

The investigators looked at several measures of obesity, including BMI, waist circumference, and waist-to-height ratio. Women with greater BMI were at increased risk for diverticula, a risk relationship that was not seen in men. The risk of developing six or more diverticula was more than twofold greater in obese women.

Men with a greater waist circumference (more than 102 cm) had no increased risk for diverticula, while women with a greater waist circumference (more than 88 cm) were at increased risk of any diverticula, as well as having six or more diverticula.

A similar pattern was observed for waist-to-height ratio, which some experts believe is related to obesity, according to Dr. Peery. No association was found in men. But for women, a high-risk waist-to-height ratio increased the risk of diverticula, and the risk of having six or more diverticula was almost twice as great in these women, compared with men.

The investigators then measured the association between dietary fiber and physical activity with diverticula. No associations with diverticula were found in any quartile (lowest to highest) for both physical activity and dietary fiber intake.

In an interview, Dr. Peery speculated on why women have a lower prevalence of “tics,” compared with men younger than age 50. She said there are gender-related differences in the way fat is stored and metabolized.

“Obese women have more visceral adiposity that men, and they tend to eat more carbohydrates, while obese men have higher alcohol and meat intake. These differences will be studied in greater depth as they relate to diverticula and complications,” she noted.

SAN DIEGO – Obesity is a risk factor for colonic diverticulosis among women but not men, while a low-fiber diet was not found to be a risk factor in a recent study reported at the annual Digestive Disease Week.

“The classic teaching in medical school is that a low-fiber diet increases constipation, which in turn increases the risk of diverticula,” explained lead author Dr. Anne Peery, assistant professor of medicine at the University of North Carolina, Chapel Hill. “This is in textbooks and on your boards. But there is no association between low-fiber dietary intake and diverticula.

“There is, however, evidence from other studies that a high-fiber diet and increased physical activity decrease the risk of developing complications from diverticula,” Dr. Peery added. She noted that the study was designed to look at risk factors for developing diverticula, not at complications.

“The provocative findings from our study are twofold: We found that the prevalence of diverticula is higher in men and lower in women younger than age 50, and that obesity is a risk factor for diverticula in women but not in men,” Dr Peery said.

“The age-related gender differences we identified were quite surprising, and suggest that something is going on in women under the age of 50 that may be estrogen-related. This opens up an avenue of research,” she noted.

Colonic diverticula are common, and they are important because of complications such as hemorrhage, perforation, and inflammation. They also pose a substantial health burden, accounting for 2.5 million office visits and 4,500 deaths each year in the United States.

“Despite this, we know very little about risk factors for colonic diverticula,” Dr. Peery noted.

The prospective study recruited 624 patients between the ages of 30 years and 80 years undergoing a first screening colonoscopy between 2013 and 2015 at the University of North Carolina in Chapel Hill. Prior to undergoing the procedure, each participant was interviewed using validated instruments to assess diet and physical activity. Each participant had a detailed examination for colonic diverticula, with a research assistant present during the entire colonoscopy.

“The presence or absence of diverticula reported in previous studies were extracted from colonoscopy reports. Our study assessed risk factors prior to undergoing colonoscopy,” she emphasized. “This is one of the study strengths.”

Not surprisingly, the study showed that the prevalence of diverticula (or “tics”) increased with age. Younger than age 50, the prevalence was higher in men than in women, after which prevalence equalized with age.

In the study population, 124 men had diverticula and 150 did not; 136 women had diverticula and 214 did not. Women with diverticula were more likely to be older, white, and have a higher body mass index (BMI).

The investigators looked at several measures of obesity, including BMI, waist circumference, and waist-to-height ratio. Women with greater BMI were at increased risk for diverticula, a risk relationship that was not seen in men. The risk of developing six or more diverticula was more than twofold greater in obese women.

Men with a greater waist circumference (more than 102 cm) had no increased risk for diverticula, while women with a greater waist circumference (more than 88 cm) were at increased risk of any diverticula, as well as having six or more diverticula.

A similar pattern was observed for waist-to-height ratio, which some experts believe is related to obesity, according to Dr. Peery. No association was found in men. But for women, a high-risk waist-to-height ratio increased the risk of diverticula, and the risk of having six or more diverticula was almost twice as great in these women, compared with men.

The investigators then measured the association between dietary fiber and physical activity with diverticula. No associations with diverticula were found in any quartile (lowest to highest) for both physical activity and dietary fiber intake.

In an interview, Dr. Peery speculated on why women have a lower prevalence of “tics,” compared with men younger than age 50. She said there are gender-related differences in the way fat is stored and metabolized.

“Obese women have more visceral adiposity that men, and they tend to eat more carbohydrates, while obese men have higher alcohol and meat intake. These differences will be studied in greater depth as they relate to diverticula and complications,” she noted.

People with chronic hepatitis C infection were nearly four times more likely than other health system patients to be hospitalized, and not only with liver-related problems.

An observational cohort study of 10,131 patients with chronic hepatitis C infection (the Chronic Hepatitis Cohort Study) and 20,262 health system patients showed the overall hospitalization rate was 3.7 times higher in patients with chronic hepatitis C.

The study, published online May 15 in the Journal of Viral Hepatitis, found patients with chronic hepatitis C experienced an average of 3.5 hospitalizations over a mean of 5.5 years follow-up, compared with 1.9 hospitalizations in other patients over an average of 4.8 years. Investigators excluded HCV patients with HIV or hepatitis B coinfection, or who had received a liver transplant.

©s-c-s/Thinkstock

Hospitalization rates in both groups were significantly higher among patients who were older than 65 years, black, or who had a household income less than $15,000 per year (J Viral Hepat. 2016 May 15. doi: 10.1111/jvh.12548).

Patients with chronic hepatitis C had a nearly 25-fold greater risk of being hospitalized with liver-related conditions, compared with other health system patients.

“Liver-related conditions are the third leading cause of nonsurgical hospitalizations of chronic HCV patients after cardiovascular diseases and infections,” wrote Dr. E. H. Teshale, from the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta, and coauthors.

However liver-related complications only accounted for 9.1% of all hospitalizations in this group, compared with 1.3% of hospitalizations in the control group.

The analysis also revealed a sixfold greater risk of hospitalization for infection, a sevenfold greater risk for dermatologic and hematologic problems, a 10-fold greater risk of hospitalization for substance abuse, and a nearly threefold greater risk of being hospitalized for cardiovascular disease, compared with other health system patients.

Hospitalizations were significantly lower among patients receiving treatment for hepatitis C and who had achieved a sustained virologic response, the authors noted.

“Initiation of treatment prior to progression to advanced liver disease can reduce the cost of hospitalization, which in many cases may include repeated hospitalizations and other costly interventions,” the investigators reported. “Some studies have found a significant health care cost alleviation following HCV therapy, which [was] primarily due to costs associated with hospitalizations for non-HCV–related comorbidities.”

The Chronic Hepatitis Cohort Study was funded by the CDC Foundation, which receives grants from a range of pharmaceutical companies. No other conflicts of interest were declared.

People with chronic hepatitis C infection were nearly four times more likely than other health system patients to be hospitalized, and not only with liver-related problems.

An observational cohort study of 10,131 patients with chronic hepatitis C infection (the Chronic Hepatitis Cohort Study) and 20,262 health system patients showed the overall hospitalization rate was 3.7 times higher in patients with chronic hepatitis C.

The study, published online May 15 in the Journal of Viral Hepatitis, found patients with chronic hepatitis C experienced an average of 3.5 hospitalizations over a mean of 5.5 years follow-up, compared with 1.9 hospitalizations in other patients over an average of 4.8 years. Investigators excluded HCV patients with HIV or hepatitis B coinfection, or who had received a liver transplant.

©s-c-s/Thinkstock

Hospitalization rates in both groups were significantly higher among patients who were older than 65 years, black, or who had a household income less than $15,000 per year (J Viral Hepat. 2016 May 15. doi: 10.1111/jvh.12548).

Patients with chronic hepatitis C had a nearly 25-fold greater risk of being hospitalized with liver-related conditions, compared with other health system patients.

“Liver-related conditions are the third leading cause of nonsurgical hospitalizations of chronic HCV patients after cardiovascular diseases and infections,” wrote Dr. E. H. Teshale, from the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta, and coauthors.

However liver-related complications only accounted for 9.1% of all hospitalizations in this group, compared with 1.3% of hospitalizations in the control group.

The analysis also revealed a sixfold greater risk of hospitalization for infection, a sevenfold greater risk for dermatologic and hematologic problems, a 10-fold greater risk of hospitalization for substance abuse, and a nearly threefold greater risk of being hospitalized for cardiovascular disease, compared with other health system patients.

Hospitalizations were significantly lower among patients receiving treatment for hepatitis C and who had achieved a sustained virologic response, the authors noted.

“Initiation of treatment prior to progression to advanced liver disease can reduce the cost of hospitalization, which in many cases may include repeated hospitalizations and other costly interventions,” the investigators reported. “Some studies have found a significant health care cost alleviation following HCV therapy, which [was] primarily due to costs associated with hospitalizations for non-HCV–related comorbidities.”

The Chronic Hepatitis Cohort Study was funded by the CDC Foundation, which receives grants from a range of pharmaceutical companies. No other conflicts of interest were declared.

People with chronic hepatitis C infection were nearly four times more likely than other health system patients to be hospitalized, and not only with liver-related problems.

An observational cohort study of 10,131 patients with chronic hepatitis C infection (the Chronic Hepatitis Cohort Study) and 20,262 health system patients showed the overall hospitalization rate was 3.7 times higher in patients with chronic hepatitis C.

The study, published online May 15 in the Journal of Viral Hepatitis, found patients with chronic hepatitis C experienced an average of 3.5 hospitalizations over a mean of 5.5 years follow-up, compared with 1.9 hospitalizations in other patients over an average of 4.8 years. Investigators excluded HCV patients with HIV or hepatitis B coinfection, or who had received a liver transplant.

©s-c-s/Thinkstock

Hospitalization rates in both groups were significantly higher among patients who were older than 65 years, black, or who had a household income less than $15,000 per year (J Viral Hepat. 2016 May 15. doi: 10.1111/jvh.12548).

Patients with chronic hepatitis C had a nearly 25-fold greater risk of being hospitalized with liver-related conditions, compared with other health system patients.

“Liver-related conditions are the third leading cause of nonsurgical hospitalizations of chronic HCV patients after cardiovascular diseases and infections,” wrote Dr. E. H. Teshale, from the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta, and coauthors.

However liver-related complications only accounted for 9.1% of all hospitalizations in this group, compared with 1.3% of hospitalizations in the control group.

The analysis also revealed a sixfold greater risk of hospitalization for infection, a sevenfold greater risk for dermatologic and hematologic problems, a 10-fold greater risk of hospitalization for substance abuse, and a nearly threefold greater risk of being hospitalized for cardiovascular disease, compared with other health system patients.

Hospitalizations were significantly lower among patients receiving treatment for hepatitis C and who had achieved a sustained virologic response, the authors noted.

“Initiation of treatment prior to progression to advanced liver disease can reduce the cost of hospitalization, which in many cases may include repeated hospitalizations and other costly interventions,” the investigators reported. “Some studies have found a significant health care cost alleviation following HCV therapy, which [was] primarily due to costs associated with hospitalizations for non-HCV–related comorbidities.”

The Chronic Hepatitis Cohort Study was funded by the CDC Foundation, which receives grants from a range of pharmaceutical companies. No other conflicts of interest were declared.

SCOTTSDALE – Stevens-Johnson syndrome and toxic epidermal necrolysis are not quite as rare as previously thought, according to one of the first population-based epidemiologic studies of the disorders.

“The incidence of Stevens-Johnson syndrome appears to be higher than previously reported, though mortality rates are lower,” said Derek Hsu of Northwestern University in Chicago, together with his associates. Both diagnoses were linked to a number of immune system disorders, “suggesting that immune dysregulation contributes to these diseases,” the investigators added.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening mucocutaneous conditions that are usually triggered by medications or infections. In 1991, a population-based study in three U.S. states reported annual incidence rates of 7.1, 2.6, and 6.8 cases per million individuals for SJS, SJS/TEN, and TEN, respectively.

More recent studies have been limited mostly to case series, and the current incidence, mortality, and health care costs of those conditions among adults in the United States were unknown, Mr. Hsu and his coinvestigators noted.

Therefore, they analyzed data for 2009 through 2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the country. Using validated ICD-9 codes, the researchers extracted information on patients with Stevens-Johnson syndrome and/or toxic epidermal necrolysis. To improve the positive predictive value of the diagnostic codes, they excluded patients with concurrent diagnoses of bullous dermatoses or erythema multiforme major.

The estimated annual incidence of SJS ranged from 8.6 to 9.8 cases per million adults per year, with a mean of 9.3 cases per million population, Mr. Hsu and his coinvestigators reported at the annual meeting of the Society for Investigative Dermatology.

Rates of combined SJS/TEN and TEN were substantially lower, with means of 1.6 and 1.9 cases per million per year, respectively.

Inpatients who were black, Hispanic, Asian, Native American, or of mixed race or ethnicity were more likely to have those diagnoses than were white inpatients, as were Medicare and self-pay patients and patients with relatively more comorbidities.

Patients diagnosed with SJS stayed in the hospital an average of 9.8 days, incurring $21,407 in mean inflation-adjusted treatment costs, while patients with SJS/TEN or TEN stayed an average of more than 16 days, with associated costs of nearly $59,00 and $53,700, respectively. For all three diagnostic categories, length of stay and costs were significantly greater than among inpatients as a whole, Mr. Hsu and his associates noted.

Age- and sex-adjusted case-fatality rates were lower than previously reported, ranging from 3.7% to 7.5% for SJS (average, 4.7%), from 15.7% to 22.3% for SJS/TEN, and from 7.7% to 19% (average, 14.8%) for TEN. The risk of mortality increased very little after the affected body surface exceeded 10%, the researchers noted. Septicemia, other infections, renal failure, cancers, and older age all increased the risk of mortality.

After accounting for race, age, and sex, SJS/TEN were significantly associated with a number of comorbidities, including systemic lupus erythematosus, renal failure, liver disease, epilepsy, and HIV disease, as well as mycoplasma, tuberculosis, and other serious infections, the researchers also found.

In addition, SJS and TEN were significantly more likely among inpatients with non-Hodgkin lymphoma, multiple myeloma, and leukemia. “Further studies are needed to understand the mechanism of these associations,” the investigators said.

The Dermatology Foundation and the Agency for Healthcare Research and Quality funded the study. Mr. Hsu had no disclosures.

SCOTTSDALE – Stevens-Johnson syndrome and toxic epidermal necrolysis are not quite as rare as previously thought, according to one of the first population-based epidemiologic studies of the disorders.

“The incidence of Stevens-Johnson syndrome appears to be higher than previously reported, though mortality rates are lower,” said Derek Hsu of Northwestern University in Chicago, together with his associates. Both diagnoses were linked to a number of immune system disorders, “suggesting that immune dysregulation contributes to these diseases,” the investigators added.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening mucocutaneous conditions that are usually triggered by medications or infections. In 1991, a population-based study in three U.S. states reported annual incidence rates of 7.1, 2.6, and 6.8 cases per million individuals for SJS, SJS/TEN, and TEN, respectively.

More recent studies have been limited mostly to case series, and the current incidence, mortality, and health care costs of those conditions among adults in the United States were unknown, Mr. Hsu and his coinvestigators noted.

Therefore, they analyzed data for 2009 through 2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the country. Using validated ICD-9 codes, the researchers extracted information on patients with Stevens-Johnson syndrome and/or toxic epidermal necrolysis. To improve the positive predictive value of the diagnostic codes, they excluded patients with concurrent diagnoses of bullous dermatoses or erythema multiforme major.

The estimated annual incidence of SJS ranged from 8.6 to 9.8 cases per million adults per year, with a mean of 9.3 cases per million population, Mr. Hsu and his coinvestigators reported at the annual meeting of the Society for Investigative Dermatology.

Rates of combined SJS/TEN and TEN were substantially lower, with means of 1.6 and 1.9 cases per million per year, respectively.

Inpatients who were black, Hispanic, Asian, Native American, or of mixed race or ethnicity were more likely to have those diagnoses than were white inpatients, as were Medicare and self-pay patients and patients with relatively more comorbidities.

Patients diagnosed with SJS stayed in the hospital an average of 9.8 days, incurring $21,407 in mean inflation-adjusted treatment costs, while patients with SJS/TEN or TEN stayed an average of more than 16 days, with associated costs of nearly $59,00 and $53,700, respectively. For all three diagnostic categories, length of stay and costs were significantly greater than among inpatients as a whole, Mr. Hsu and his associates noted.

Age- and sex-adjusted case-fatality rates were lower than previously reported, ranging from 3.7% to 7.5% for SJS (average, 4.7%), from 15.7% to 22.3% for SJS/TEN, and from 7.7% to 19% (average, 14.8%) for TEN. The risk of mortality increased very little after the affected body surface exceeded 10%, the researchers noted. Septicemia, other infections, renal failure, cancers, and older age all increased the risk of mortality.

After accounting for race, age, and sex, SJS/TEN were significantly associated with a number of comorbidities, including systemic lupus erythematosus, renal failure, liver disease, epilepsy, and HIV disease, as well as mycoplasma, tuberculosis, and other serious infections, the researchers also found.

In addition, SJS and TEN were significantly more likely among inpatients with non-Hodgkin lymphoma, multiple myeloma, and leukemia. “Further studies are needed to understand the mechanism of these associations,” the investigators said.

The Dermatology Foundation and the Agency for Healthcare Research and Quality funded the study. Mr. Hsu had no disclosures.

SCOTTSDALE – Stevens-Johnson syndrome and toxic epidermal necrolysis are not quite as rare as previously thought, according to one of the first population-based epidemiologic studies of the disorders.

“The incidence of Stevens-Johnson syndrome appears to be higher than previously reported, though mortality rates are lower,” said Derek Hsu of Northwestern University in Chicago, together with his associates. Both diagnoses were linked to a number of immune system disorders, “suggesting that immune dysregulation contributes to these diseases,” the investigators added.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening mucocutaneous conditions that are usually triggered by medications or infections. In 1991, a population-based study in three U.S. states reported annual incidence rates of 7.1, 2.6, and 6.8 cases per million individuals for SJS, SJS/TEN, and TEN, respectively.

More recent studies have been limited mostly to case series, and the current incidence, mortality, and health care costs of those conditions among adults in the United States were unknown, Mr. Hsu and his coinvestigators noted.

Therefore, they analyzed data for 2009 through 2012 from the Nationwide Inpatient Sample, which covers 20% of hospitalizations in the country. Using validated ICD-9 codes, the researchers extracted information on patients with Stevens-Johnson syndrome and/or toxic epidermal necrolysis. To improve the positive predictive value of the diagnostic codes, they excluded patients with concurrent diagnoses of bullous dermatoses or erythema multiforme major.

The estimated annual incidence of SJS ranged from 8.6 to 9.8 cases per million adults per year, with a mean of 9.3 cases per million population, Mr. Hsu and his coinvestigators reported at the annual meeting of the Society for Investigative Dermatology.

Rates of combined SJS/TEN and TEN were substantially lower, with means of 1.6 and 1.9 cases per million per year, respectively.

Inpatients who were black, Hispanic, Asian, Native American, or of mixed race or ethnicity were more likely to have those diagnoses than were white inpatients, as were Medicare and self-pay patients and patients with relatively more comorbidities.

Patients diagnosed with SJS stayed in the hospital an average of 9.8 days, incurring $21,407 in mean inflation-adjusted treatment costs, while patients with SJS/TEN or TEN stayed an average of more than 16 days, with associated costs of nearly $59,00 and $53,700, respectively. For all three diagnostic categories, length of stay and costs were significantly greater than among inpatients as a whole, Mr. Hsu and his associates noted.

Age- and sex-adjusted case-fatality rates were lower than previously reported, ranging from 3.7% to 7.5% for SJS (average, 4.7%), from 15.7% to 22.3% for SJS/TEN, and from 7.7% to 19% (average, 14.8%) for TEN. The risk of mortality increased very little after the affected body surface exceeded 10%, the researchers noted. Septicemia, other infections, renal failure, cancers, and older age all increased the risk of mortality.

After accounting for race, age, and sex, SJS/TEN were significantly associated with a number of comorbidities, including systemic lupus erythematosus, renal failure, liver disease, epilepsy, and HIV disease, as well as mycoplasma, tuberculosis, and other serious infections, the researchers also found.

In addition, SJS and TEN were significantly more likely among inpatients with non-Hodgkin lymphoma, multiple myeloma, and leukemia. “Further studies are needed to understand the mechanism of these associations,” the investigators said.

The Dermatology Foundation and the Agency for Healthcare Research and Quality funded the study. Mr. Hsu had no disclosures.

WASHINGTON – Intraperitoneal chemotherapy may be unpleasant and interfere with daily life, but the large majority of women who received it for ovarian cancer agreed that it was the right choice for them.

A small survey of women who completed up to six cycles of the treatment found that most women did experience side effects, including fatigue, pain, and gastrointestinal issues. Despite those problems, more than 80% said they felt the regimen was “worth it,” and more than 90% said they would recommend it to another woman.

“Outpatient administration of chemotherapy appears to be feasible with acceptable toxicities and high completion rates,” Dr. Kristin Gotimer said at the annual meeting of the American College of Obstetricians and Gynecologists. “Toxicities were troublesome, and they did definitely affect quality of life; but almost none of our patients regretted being treated – even the ones who experienced recurrent disease.”

Dr. Gotimer of the Winthrop University Hospital, Mineola, N.Y., discussed a retrospective study of 98 women who underwent intraperitoneal chemotherapy for a gynecologic cancer from 2006 to 2014. Mean age of the patients was 58 years. Most women (71%) had ovarian cancer, and most cancer (70%) was stage IIIC or higher. All patients underwent cytoreductive surgery before starting chemotherapy.

Almost all women were prescribed six cycles of the regimen, which consisted of IV paclitaxel on day 1, intraperitoneal cisplatin on day 2, and intraperitoneal paclitaxel on day 8. Overall, 73% of patients completed their prescribed treatment. Among those prescribed six cycles, 71% completed all of them. Of the 26 patients who discontinued, 12 did so because of port complications, and 14 did so because of toxicities.

The most commonly reported side effects were gastrointestinal effects, fatigue, and neuropathy. Grade 3/4 toxicities were most often fatigue, neuropathy, and pain; those occurred in about 6% of patients per cycle. There were four cases of neutropenic fever; two of those resulted in treatment delays.

Seven patients had to change treatment, Dr. Gotimer said. Six switched from intraperitoneal cisplatin to intraperitoneal carboplatin, and one patient switched from IV paclitaxel to IV Abraxane. Toxicities were more likely to appear in later cycles. “The probability of starting each cycle was lower if the patient had experienced a severe toxicity in the prior cycle,” Dr. Gotimer explained.

A subset of patients (48) completed a survey about the treatment at a mean of 31 months after treatment. Of those, 92% had completed all their prescribed cycles. Disease had recurred in 21%. The three-domain survey queried the mental, physical, and social impact of the treatment.

On the physical health domain, half the group reported fatigue associated with the treatment. Others complained of pain (40%), gastrointestinal effects (37%), “chemo brain” cognitive dysfunction (29%), and alopecia (25%). A few patients experienced infections and dermatologic problems (less than 10% each).

In the mental health domain, patients most often noted stress (25%), anxiety (21%), and depression (15%) during treatment. They also said the therapy interfered with their social health, affecting work attendance (27%), housework (29%), and social interactions (19%). It also imposed a substantial time commitment, 17% of patients noted.

Despite those issues, 83% of patients endorsed intraperitoneal chemotherapy as “worth it,” and almost 90% said they would recommend it to a friend or family member considering it. Only about 5% of patients said they regretted using the treatment, although Dr. Gotimer didn’t specify what those regrets were.

Despite its small size and retrospective nature, the survey offers some clinically useful information, Dr. Gotimer noted. “We can identify modifiable side effects and develop specific interventions aimed at increasing tolerability.”

The results could also be used to “improve physician and patient understanding of realistic short- and long-term expectations to improve patient counseling,” she added.

Dr. Gotimer had no financial declarations.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Intraperitoneal chemotherapy may be unpleasant and interfere with daily life, but the large majority of women who received it for ovarian cancer agreed that it was the right choice for them.

A small survey of women who completed up to six cycles of the treatment found that most women did experience side effects, including fatigue, pain, and gastrointestinal issues. Despite those problems, more than 80% said they felt the regimen was “worth it,” and more than 90% said they would recommend it to another woman.

“Outpatient administration of chemotherapy appears to be feasible with acceptable toxicities and high completion rates,” Dr. Kristin Gotimer said at the annual meeting of the American College of Obstetricians and Gynecologists. “Toxicities were troublesome, and they did definitely affect quality of life; but almost none of our patients regretted being treated – even the ones who experienced recurrent disease.”

Dr. Gotimer of the Winthrop University Hospital, Mineola, N.Y., discussed a retrospective study of 98 women who underwent intraperitoneal chemotherapy for a gynecologic cancer from 2006 to 2014. Mean age of the patients was 58 years. Most women (71%) had ovarian cancer, and most cancer (70%) was stage IIIC or higher. All patients underwent cytoreductive surgery before starting chemotherapy.

Almost all women were prescribed six cycles of the regimen, which consisted of IV paclitaxel on day 1, intraperitoneal cisplatin on day 2, and intraperitoneal paclitaxel on day 8. Overall, 73% of patients completed their prescribed treatment. Among those prescribed six cycles, 71% completed all of them. Of the 26 patients who discontinued, 12 did so because of port complications, and 14 did so because of toxicities.

The most commonly reported side effects were gastrointestinal effects, fatigue, and neuropathy. Grade 3/4 toxicities were most often fatigue, neuropathy, and pain; those occurred in about 6% of patients per cycle. There were four cases of neutropenic fever; two of those resulted in treatment delays.

Seven patients had to change treatment, Dr. Gotimer said. Six switched from intraperitoneal cisplatin to intraperitoneal carboplatin, and one patient switched from IV paclitaxel to IV Abraxane. Toxicities were more likely to appear in later cycles. “The probability of starting each cycle was lower if the patient had experienced a severe toxicity in the prior cycle,” Dr. Gotimer explained.

A subset of patients (48) completed a survey about the treatment at a mean of 31 months after treatment. Of those, 92% had completed all their prescribed cycles. Disease had recurred in 21%. The three-domain survey queried the mental, physical, and social impact of the treatment.

On the physical health domain, half the group reported fatigue associated with the treatment. Others complained of pain (40%), gastrointestinal effects (37%), “chemo brain” cognitive dysfunction (29%), and alopecia (25%). A few patients experienced infections and dermatologic problems (less than 10% each).

In the mental health domain, patients most often noted stress (25%), anxiety (21%), and depression (15%) during treatment. They also said the therapy interfered with their social health, affecting work attendance (27%), housework (29%), and social interactions (19%). It also imposed a substantial time commitment, 17% of patients noted.

Despite those issues, 83% of patients endorsed intraperitoneal chemotherapy as “worth it,” and almost 90% said they would recommend it to a friend or family member considering it. Only about 5% of patients said they regretted using the treatment, although Dr. Gotimer didn’t specify what those regrets were.

Despite its small size and retrospective nature, the survey offers some clinically useful information, Dr. Gotimer noted. “We can identify modifiable side effects and develop specific interventions aimed at increasing tolerability.”

The results could also be used to “improve physician and patient understanding of realistic short- and long-term expectations to improve patient counseling,” she added.

Dr. Gotimer had no financial declarations.

[email protected]

On Twitter @Alz_Gal

WASHINGTON – Intraperitoneal chemotherapy may be unpleasant and interfere with daily life, but the large majority of women who received it for ovarian cancer agreed that it was the right choice for them.

A small survey of women who completed up to six cycles of the treatment found that most women did experience side effects, including fatigue, pain, and gastrointestinal issues. Despite those problems, more than 80% said they felt the regimen was “worth it,” and more than 90% said they would recommend it to another woman.

“Outpatient administration of chemotherapy appears to be feasible with acceptable toxicities and high completion rates,” Dr. Kristin Gotimer said at the annual meeting of the American College of Obstetricians and Gynecologists. “Toxicities were troublesome, and they did definitely affect quality of life; but almost none of our patients regretted being treated – even the ones who experienced recurrent disease.”

Dr. Gotimer of the Winthrop University Hospital, Mineola, N.Y., discussed a retrospective study of 98 women who underwent intraperitoneal chemotherapy for a gynecologic cancer from 2006 to 2014. Mean age of the patients was 58 years. Most women (71%) had ovarian cancer, and most cancer (70%) was stage IIIC or higher. All patients underwent cytoreductive surgery before starting chemotherapy.

Almost all women were prescribed six cycles of the regimen, which consisted of IV paclitaxel on day 1, intraperitoneal cisplatin on day 2, and intraperitoneal paclitaxel on day 8. Overall, 73% of patients completed their prescribed treatment. Among those prescribed six cycles, 71% completed all of them. Of the 26 patients who discontinued, 12 did so because of port complications, and 14 did so because of toxicities.

The most commonly reported side effects were gastrointestinal effects, fatigue, and neuropathy. Grade 3/4 toxicities were most often fatigue, neuropathy, and pain; those occurred in about 6% of patients per cycle. There were four cases of neutropenic fever; two of those resulted in treatment delays.

Seven patients had to change treatment, Dr. Gotimer said. Six switched from intraperitoneal cisplatin to intraperitoneal carboplatin, and one patient switched from IV paclitaxel to IV Abraxane. Toxicities were more likely to appear in later cycles. “The probability of starting each cycle was lower if the patient had experienced a severe toxicity in the prior cycle,” Dr. Gotimer explained.

A subset of patients (48) completed a survey about the treatment at a mean of 31 months after treatment. Of those, 92% had completed all their prescribed cycles. Disease had recurred in 21%. The three-domain survey queried the mental, physical, and social impact of the treatment.

On the physical health domain, half the group reported fatigue associated with the treatment. Others complained of pain (40%), gastrointestinal effects (37%), “chemo brain” cognitive dysfunction (29%), and alopecia (25%). A few patients experienced infections and dermatologic problems (less than 10% each).

In the mental health domain, patients most often noted stress (25%), anxiety (21%), and depression (15%) during treatment. They also said the therapy interfered with their social health, affecting work attendance (27%), housework (29%), and social interactions (19%). It also imposed a substantial time commitment, 17% of patients noted.

Despite those issues, 83% of patients endorsed intraperitoneal chemotherapy as “worth it,” and almost 90% said they would recommend it to a friend or family member considering it. Only about 5% of patients said they regretted using the treatment, although Dr. Gotimer didn’t specify what those regrets were.

Despite its small size and retrospective nature, the survey offers some clinically useful information, Dr. Gotimer noted. “We can identify modifiable side effects and develop specific interventions aimed at increasing tolerability.”

The results could also be used to “improve physician and patient understanding of realistic short- and long-term expectations to improve patient counseling,” she added.

Dr. Gotimer had no financial declarations.

[email protected]

On Twitter @Alz_Gal

SAN FRANCISCO – Catheter ablation is a better option than antiarrhythmic drug escalation when patients with ventricular tachycardia (VT) fail standard first-line medical therapy, according to a 259-patient trial.

During a mean follow-up of 27.9 months, 59.1% (78) of patients randomized to ablation, but 68.5% (87) randomized to escalation, met the combined primary endpoint of death, ventricular tachycardia (VT) storm, or appropriate implantable cardioverter defibrillator shock (hazard ratio favoring ablation, 0.72; P = 0.04).

All the patients had ischemic cardiomyopathy secondary to myocardial infarct, as well as an implantable cardioverter defibrillator (ICD) and recurrent VT despite amiodarone in two-thirds and sotalol in the rest. “In this situation with the options we have available, catheter ablation is preferable,” lead investigator Dr. John Sapp, a cardiology professor at Dalhousie University in Halifax, N.S., said at the annual scientific sessions of the Heart Rhythm Society.

Guidelines already recommend ablation when antiarrhythmic drugs don’t do the job, but many clinicians opt for caution and escalate drug therapy instead; the two approaches have never been compared head to head. “This trial provides evidence that catheter ablation should be preferred over escalation of AAD [antiarrhythmic drug] therapy” to reduce “recurrent ventricular tachycardia,” Dr. Sapp and his colleagues concluded in their report, which was published online at the time of presentation (N Engl J Med. 2016 May 5. doi: 10.1056/NEJMoa1513614).

The benefit of ablation was seen only in patients on baseline amiodarone and was due entirely to fewer shocks and VT storms. There was no significant between-group difference in mortality, which was about 27% in both arms and mostly from cardiovascular causes. Dr. Sapp noted that the study wasn’t powered to detect a difference in mortality.

Three deaths were attributed to AAD in the escalation arm, two from pulmonary and one from hepatic complications. The authors didn’t attribute any deaths directly to ablation, but noted that there were two cardiac perforations and three cases of major bleeding in the ablation arm. Even so, treatment-related adverse events were significantly more common with escalation (51 vs. 22 in ablation patients) and occurred in more patients (39 and 20, respectively). VT that was undetectable by ICD persisted in 10.2% (13) of drug-escalated patient and 3% (4) of ablation patients.

In the patients randomly assigned to escalation, those on sotalol were switched to amiodarone 200 mg/day; amiodarone patients were either increased to more than 300 mg/day or, if already at that level, had mexiletine 600 mg/day added to their regimen.

The work was funded by the Canadian Institutes of Health Research, St. Jude Medical, and Biosense Webster. Dr. Sapp reported research grants from St. Jude, Biosense, Medtronic, and Philips.

[email protected]

SAN FRANCISCO – Catheter ablation is a better option than antiarrhythmic drug escalation when patients with ventricular tachycardia (VT) fail standard first-line medical therapy, according to a 259-patient trial.

During a mean follow-up of 27.9 months, 59.1% (78) of patients randomized to ablation, but 68.5% (87) randomized to escalation, met the combined primary endpoint of death, ventricular tachycardia (VT) storm, or appropriate implantable cardioverter defibrillator shock (hazard ratio favoring ablation, 0.72; P = 0.04).

All the patients had ischemic cardiomyopathy secondary to myocardial infarct, as well as an implantable cardioverter defibrillator (ICD) and recurrent VT despite amiodarone in two-thirds and sotalol in the rest. “In this situation with the options we have available, catheter ablation is preferable,” lead investigator Dr. John Sapp, a cardiology professor at Dalhousie University in Halifax, N.S., said at the annual scientific sessions of the Heart Rhythm Society.

Guidelines already recommend ablation when antiarrhythmic drugs don’t do the job, but many clinicians opt for caution and escalate drug therapy instead; the two approaches have never been compared head to head. “This trial provides evidence that catheter ablation should be preferred over escalation of AAD [antiarrhythmic drug] therapy” to reduce “recurrent ventricular tachycardia,” Dr. Sapp and his colleagues concluded in their report, which was published online at the time of presentation (N Engl J Med. 2016 May 5. doi: 10.1056/NEJMoa1513614).

The benefit of ablation was seen only in patients on baseline amiodarone and was due entirely to fewer shocks and VT storms. There was no significant between-group difference in mortality, which was about 27% in both arms and mostly from cardiovascular causes. Dr. Sapp noted that the study wasn’t powered to detect a difference in mortality.

Three deaths were attributed to AAD in the escalation arm, two from pulmonary and one from hepatic complications. The authors didn’t attribute any deaths directly to ablation, but noted that there were two cardiac perforations and three cases of major bleeding in the ablation arm. Even so, treatment-related adverse events were significantly more common with escalation (51 vs. 22 in ablation patients) and occurred in more patients (39 and 20, respectively). VT that was undetectable by ICD persisted in 10.2% (13) of drug-escalated patient and 3% (4) of ablation patients.

In the patients randomly assigned to escalation, those on sotalol were switched to amiodarone 200 mg/day; amiodarone patients were either increased to more than 300 mg/day or, if already at that level, had mexiletine 600 mg/day added to their regimen.

The work was funded by the Canadian Institutes of Health Research, St. Jude Medical, and Biosense Webster. Dr. Sapp reported research grants from St. Jude, Biosense, Medtronic, and Philips.

[email protected]

SAN FRANCISCO – Catheter ablation is a better option than antiarrhythmic drug escalation when patients with ventricular tachycardia (VT) fail standard first-line medical therapy, according to a 259-patient trial.

During a mean follow-up of 27.9 months, 59.1% (78) of patients randomized to ablation, but 68.5% (87) randomized to escalation, met the combined primary endpoint of death, ventricular tachycardia (VT) storm, or appropriate implantable cardioverter defibrillator shock (hazard ratio favoring ablation, 0.72; P = 0.04).

All the patients had ischemic cardiomyopathy secondary to myocardial infarct, as well as an implantable cardioverter defibrillator (ICD) and recurrent VT despite amiodarone in two-thirds and sotalol in the rest. “In this situation with the options we have available, catheter ablation is preferable,” lead investigator Dr. John Sapp, a cardiology professor at Dalhousie University in Halifax, N.S., said at the annual scientific sessions of the Heart Rhythm Society.

Guidelines already recommend ablation when antiarrhythmic drugs don’t do the job, but many clinicians opt for caution and escalate drug therapy instead; the two approaches have never been compared head to head. “This trial provides evidence that catheter ablation should be preferred over escalation of AAD [antiarrhythmic drug] therapy” to reduce “recurrent ventricular tachycardia,” Dr. Sapp and his colleagues concluded in their report, which was published online at the time of presentation (N Engl J Med. 2016 May 5. doi: 10.1056/NEJMoa1513614).

The benefit of ablation was seen only in patients on baseline amiodarone and was due entirely to fewer shocks and VT storms. There was no significant between-group difference in mortality, which was about 27% in both arms and mostly from cardiovascular causes. Dr. Sapp noted that the study wasn’t powered to detect a difference in mortality.

Three deaths were attributed to AAD in the escalation arm, two from pulmonary and one from hepatic complications. The authors didn’t attribute any deaths directly to ablation, but noted that there were two cardiac perforations and three cases of major bleeding in the ablation arm. Even so, treatment-related adverse events were significantly more common with escalation (51 vs. 22 in ablation patients) and occurred in more patients (39 and 20, respectively). VT that was undetectable by ICD persisted in 10.2% (13) of drug-escalated patient and 3% (4) of ablation patients.

In the patients randomly assigned to escalation, those on sotalol were switched to amiodarone 200 mg/day; amiodarone patients were either increased to more than 300 mg/day or, if already at that level, had mexiletine 600 mg/day added to their regimen.

The work was funded by the Canadian Institutes of Health Research, St. Jude Medical, and Biosense Webster. Dr. Sapp reported research grants from St. Jude, Biosense, Medtronic, and Philips.

[email protected]

PARIS – In patients at high bleeding risk undergoing percutaneous coronary intervention for acute coronary syndrome, a unique drug-coated, polymer-free stent backed by just a single month of dual-antiplatelet therapy (DAPT) trounced a bare metal stent in both efficacy and safety at 1 year in a large randomized trial, Dr. Christoph K. Naber reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

The BioFreedom stent, coated with a proprietary sirolimus analogue called Biolimus-A9, rapidly transfers the drug to the vessel wall, leaving in place a metallic stent. This drug-coated stent (DCS) provides the antirestenotic benefits of a drug-eluting stent with the advantages of a shorter DAPT requirement and no potential polymer-related adverse events. The device’s performance in this prespecified subgroup analysis of the Leaders Free trial will be practice altering, predicted Dr. Naber of Elisabeth University Hospital in Essen, Germany.

Bruce Jancin/Frontline Medical News

“We believe that current guidelines and clinical practice need to change. Bare-metal stents can no longer be recommended for high–bleeding risk patients presenting with ACS. The Biolimus-A9–coated stent currently has the best supporting evidence for this indication,” he said.

“This was the last chance for bare metal stents to show a good indication. They were thought to be good only in high–bleeding risk patients. Now we see that a drug-coated stent provides better efficacy and is even safer,” the cardiologist continued.

Leaders Free was a randomized double-blind clinical trial in which 2,499 patients at high risk of bleeding who underwent PCI received either the DCS or the Gazelle bare-metal stent (BMS) and 1 month of dual-antiplatelet therapy. The main results, in which the DCS showed superior safety and efficacy at 12 months of follow-up, have been published (N Engl J Med. 2015 Nov 19;373[21]:2038-47).

Dr. Naber presented a prespecified subgroup analysis that included the 659 Leaders Free participants who presented with ACS.

The primary efficacy endpoint – the 12-month rate of clinically driven target lesion revascularization – was 3.9% in the DCS group, compared with 9% in patients randomized to the BMS, for an adjusted 59% relative risk reduction.

The composite safety endpoint was composed of the 1-year rate of cardiac death, acute MI, and definite or probable stent thrombosis. This occurred in 9.3% of the DCS- and 18.5% of the BMS-treated patients, for a relative risk reduction of 52%.

The BioFreedom stent has a selectively microstructured surface coated with Biolimus-A9, a drug that’s far more lipophilic than sirolimus, everolimus, or zotarolimus. As a result, 98% of the drug is transferred to the plaque-laden vessel within 30 days, which is why it’s safe to shorten DAPT to 1 month, Dr. Naber explained.

It’s estimated that up to 20% of patients undergoing PCI are at high bleeding risk for various reasons.

The DCS is marketed in Europe and in clinical trials in the United States aimed at getting Food and Drug Administration approval.

Discussant Dr. Thomas Cuisset of Timone Hospital in Marseille, France, agreed that “in 2016, bare-metal stents are no longer the gold standard in patients at high bleeding risk.”

He added that the Leaders Free ACS substudy leaves unanswered two major remaining questions: What’s the optimal duration of DAPT for DCS in non-ACS patients at high bleeding risk – is 1 month of DAPT as safe as 6 months? And how do contemporary drug-eluting, polymer-based stents compare to the BioFreedom stent for PCI in the setting of high bleeding risk?

In an interview, Dr. Naber said that before a head-to-head comparative clinical trial can even be considered, there will need to be evidence that drug-eluting stents are safe with shortened DAPT. That has yet to be shown.

The study was funded by Biosensors. Dr. Naber reported receiving consultant’s fees from that medical device company and several others. Dr. Cuisset serves as a consultant to or paid lecturer for more than a dozen medical companies.

Simultaneous with Dr. Naber’s presentation at EuroPCR in Paris, the Leaders Free ACS substudy results were published online (Eur Heart J. doi:10.1093/eurheartj/ehw203).

[email protected]

PARIS – In patients at high bleeding risk undergoing percutaneous coronary intervention for acute coronary syndrome, a unique drug-coated, polymer-free stent backed by just a single month of dual-antiplatelet therapy (DAPT) trounced a bare metal stent in both efficacy and safety at 1 year in a large randomized trial, Dr. Christoph K. Naber reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

The BioFreedom stent, coated with a proprietary sirolimus analogue called Biolimus-A9, rapidly transfers the drug to the vessel wall, leaving in place a metallic stent. This drug-coated stent (DCS) provides the antirestenotic benefits of a drug-eluting stent with the advantages of a shorter DAPT requirement and no potential polymer-related adverse events. The device’s performance in this prespecified subgroup analysis of the Leaders Free trial will be practice altering, predicted Dr. Naber of Elisabeth University Hospital in Essen, Germany.

Bruce Jancin/Frontline Medical News

“We believe that current guidelines and clinical practice need to change. Bare-metal stents can no longer be recommended for high–bleeding risk patients presenting with ACS. The Biolimus-A9–coated stent currently has the best supporting evidence for this indication,” he said.

“This was the last chance for bare metal stents to show a good indication. They were thought to be good only in high–bleeding risk patients. Now we see that a drug-coated stent provides better efficacy and is even safer,” the cardiologist continued.

Leaders Free was a randomized double-blind clinical trial in which 2,499 patients at high risk of bleeding who underwent PCI received either the DCS or the Gazelle bare-metal stent (BMS) and 1 month of dual-antiplatelet therapy. The main results, in which the DCS showed superior safety and efficacy at 12 months of follow-up, have been published (N Engl J Med. 2015 Nov 19;373[21]:2038-47).

Dr. Naber presented a prespecified subgroup analysis that included the 659 Leaders Free participants who presented with ACS.

The primary efficacy endpoint – the 12-month rate of clinically driven target lesion revascularization – was 3.9% in the DCS group, compared with 9% in patients randomized to the BMS, for an adjusted 59% relative risk reduction.

The composite safety endpoint was composed of the 1-year rate of cardiac death, acute MI, and definite or probable stent thrombosis. This occurred in 9.3% of the DCS- and 18.5% of the BMS-treated patients, for a relative risk reduction of 52%.

The BioFreedom stent has a selectively microstructured surface coated with Biolimus-A9, a drug that’s far more lipophilic than sirolimus, everolimus, or zotarolimus. As a result, 98% of the drug is transferred to the plaque-laden vessel within 30 days, which is why it’s safe to shorten DAPT to 1 month, Dr. Naber explained.

It’s estimated that up to 20% of patients undergoing PCI are at high bleeding risk for various reasons.

The DCS is marketed in Europe and in clinical trials in the United States aimed at getting Food and Drug Administration approval.

Discussant Dr. Thomas Cuisset of Timone Hospital in Marseille, France, agreed that “in 2016, bare-metal stents are no longer the gold standard in patients at high bleeding risk.”

He added that the Leaders Free ACS substudy leaves unanswered two major remaining questions: What’s the optimal duration of DAPT for DCS in non-ACS patients at high bleeding risk – is 1 month of DAPT as safe as 6 months? And how do contemporary drug-eluting, polymer-based stents compare to the BioFreedom stent for PCI in the setting of high bleeding risk?

In an interview, Dr. Naber said that before a head-to-head comparative clinical trial can even be considered, there will need to be evidence that drug-eluting stents are safe with shortened DAPT. That has yet to be shown.

The study was funded by Biosensors. Dr. Naber reported receiving consultant’s fees from that medical device company and several others. Dr. Cuisset serves as a consultant to or paid lecturer for more than a dozen medical companies.

Simultaneous with Dr. Naber’s presentation at EuroPCR in Paris, the Leaders Free ACS substudy results were published online (Eur Heart J. doi:10.1093/eurheartj/ehw203).

[email protected]

PARIS – In patients at high bleeding risk undergoing percutaneous coronary intervention for acute coronary syndrome, a unique drug-coated, polymer-free stent backed by just a single month of dual-antiplatelet therapy (DAPT) trounced a bare metal stent in both efficacy and safety at 1 year in a large randomized trial, Dr. Christoph K. Naber reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

The BioFreedom stent, coated with a proprietary sirolimus analogue called Biolimus-A9, rapidly transfers the drug to the vessel wall, leaving in place a metallic stent. This drug-coated stent (DCS) provides the antirestenotic benefits of a drug-eluting stent with the advantages of a shorter DAPT requirement and no potential polymer-related adverse events. The device’s performance in this prespecified subgroup analysis of the Leaders Free trial will be practice altering, predicted Dr. Naber of Elisabeth University Hospital in Essen, Germany.

Bruce Jancin/Frontline Medical News

“We believe that current guidelines and clinical practice need to change. Bare-metal stents can no longer be recommended for high–bleeding risk patients presenting with ACS. The Biolimus-A9–coated stent currently has the best supporting evidence for this indication,” he said.

“This was the last chance for bare metal stents to show a good indication. They were thought to be good only in high–bleeding risk patients. Now we see that a drug-coated stent provides better efficacy and is even safer,” the cardiologist continued.

Leaders Free was a randomized double-blind clinical trial in which 2,499 patients at high risk of bleeding who underwent PCI received either the DCS or the Gazelle bare-metal stent (BMS) and 1 month of dual-antiplatelet therapy. The main results, in which the DCS showed superior safety and efficacy at 12 months of follow-up, have been published (N Engl J Med. 2015 Nov 19;373[21]:2038-47).

Dr. Naber presented a prespecified subgroup analysis that included the 659 Leaders Free participants who presented with ACS.

The primary efficacy endpoint – the 12-month rate of clinically driven target lesion revascularization – was 3.9% in the DCS group, compared with 9% in patients randomized to the BMS, for an adjusted 59% relative risk reduction.

The composite safety endpoint was composed of the 1-year rate of cardiac death, acute MI, and definite or probable stent thrombosis. This occurred in 9.3% of the DCS- and 18.5% of the BMS-treated patients, for a relative risk reduction of 52%.

The BioFreedom stent has a selectively microstructured surface coated with Biolimus-A9, a drug that’s far more lipophilic than sirolimus, everolimus, or zotarolimus. As a result, 98% of the drug is transferred to the plaque-laden vessel within 30 days, which is why it’s safe to shorten DAPT to 1 month, Dr. Naber explained.

It’s estimated that up to 20% of patients undergoing PCI are at high bleeding risk for various reasons.

The DCS is marketed in Europe and in clinical trials in the United States aimed at getting Food and Drug Administration approval.

Discussant Dr. Thomas Cuisset of Timone Hospital in Marseille, France, agreed that “in 2016, bare-metal stents are no longer the gold standard in patients at high bleeding risk.”

He added that the Leaders Free ACS substudy leaves unanswered two major remaining questions: What’s the optimal duration of DAPT for DCS in non-ACS patients at high bleeding risk – is 1 month of DAPT as safe as 6 months? And how do contemporary drug-eluting, polymer-based stents compare to the BioFreedom stent for PCI in the setting of high bleeding risk?

In an interview, Dr. Naber said that before a head-to-head comparative clinical trial can even be considered, there will need to be evidence that drug-eluting stents are safe with shortened DAPT. That has yet to be shown.

The study was funded by Biosensors. Dr. Naber reported receiving consultant’s fees from that medical device company and several others. Dr. Cuisset serves as a consultant to or paid lecturer for more than a dozen medical companies.

Simultaneous with Dr. Naber’s presentation at EuroPCR in Paris, the Leaders Free ACS substudy results were published online (Eur Heart J. doi:10.1093/eurheartj/ehw203).

[email protected]

CHICAGO – Patients who reported using marijuana prior to experiencing an acute MI had significantly lower in-hospital mortality and were less likely to have cardiogenic shock or require an intra-aortic balloon pump than marijuana nonusers with an MI in an eight-state hospital records study, Dr. Cecelia P. Johnson-Sasso reported at the annual meeting of the American College of Cardiology.

“If this observation is confirmed in independent studies, further investigation into the possible therapeutic benefit of cannabinoid receptor agonists in acute MI may be warranted,” declared Dr. Johnson-Sasso of the University of Colorado Denver.

Smithore

She and her coinvestigators obtained hospital records with identity information removed for more than 3 million patients admitted for acute MI during 1994-2013 in eight states: California, Colorado, New Hampshire, New Jersey, New York, Texas, Vermont, and West Virginia.

After excluding concomitant users of cocaine, methamphetamine, or alcohol due to the potential for confounding cardiotoxic effects; MI patients under age 19 because of the likelihood of congenital heart disease; and patients over age 70 because only 0.01% of them admitted to marijuana use, the investigators were left with a study population of 3,854 marijuana users and 1.27 million MI patients who hadn’t used marijuana.

In a multivariate regression analysis adjusted for potential confounders including baseline comorbid conditions, patient demographics, and payer status, the marijuana users prior to MI had a 17% reduction in in-hospital mortality, were 20% less likely to undergo intra-aortic balloon pump placement, and had a 26% reduction in shock. On the other hand, they were also 19% more likely than marijuana nonusers to be placed on mechanical ventilation. And even though they were equally likely to undergo diagnostic coronary angiography, they were 28% less likely than marijuana nonusers to undergo percutaneous coronary intervention. All of these differences were statistically significant and clinically meaningful.

She was quick to note the limitations of her study: No data were available on readmissions or late mortality, and it’s highly likely that marijuana use by patients with acute MI was significantly underreported during the study period, which was largely before the legalization movement took off.

With state marijuana laws rapidly changing and the legal pot industry becoming a big business, the lack of research into the health consequences of marijuana by disinterested parties has become glaringly obvious, according to Dr. Johnson-Sasso. Cannabinoid receptors are found not only in the brain, but in cardiac muscle, the kidney, liver, vascular and visceral muscle, aorta, bladder, and immune cells.

She reported having no financial conflicts of interest regarding this study.

[email protected]

CHICAGO – Patients who reported using marijuana prior to experiencing an acute MI had significantly lower in-hospital mortality and were less likely to have cardiogenic shock or require an intra-aortic balloon pump than marijuana nonusers with an MI in an eight-state hospital records study, Dr. Cecelia P. Johnson-Sasso reported at the annual meeting of the American College of Cardiology.

“If this observation is confirmed in independent studies, further investigation into the possible therapeutic benefit of cannabinoid receptor agonists in acute MI may be warranted,” declared Dr. Johnson-Sasso of the University of Colorado Denver.

Smithore

She and her coinvestigators obtained hospital records with identity information removed for more than 3 million patients admitted for acute MI during 1994-2013 in eight states: California, Colorado, New Hampshire, New Jersey, New York, Texas, Vermont, and West Virginia.

After excluding concomitant users of cocaine, methamphetamine, or alcohol due to the potential for confounding cardiotoxic effects; MI patients under age 19 because of the likelihood of congenital heart disease; and patients over age 70 because only 0.01% of them admitted to marijuana use, the investigators were left with a study population of 3,854 marijuana users and 1.27 million MI patients who hadn’t used marijuana.

In a multivariate regression analysis adjusted for potential confounders including baseline comorbid conditions, patient demographics, and payer status, the marijuana users prior to MI had a 17% reduction in in-hospital mortality, were 20% less likely to undergo intra-aortic balloon pump placement, and had a 26% reduction in shock. On the other hand, they were also 19% more likely than marijuana nonusers to be placed on mechanical ventilation. And even though they were equally likely to undergo diagnostic coronary angiography, they were 28% less likely than marijuana nonusers to undergo percutaneous coronary intervention. All of these differences were statistically significant and clinically meaningful.

She was quick to note the limitations of her study: No data were available on readmissions or late mortality, and it’s highly likely that marijuana use by patients with acute MI was significantly underreported during the study period, which was largely before the legalization movement took off.

With state marijuana laws rapidly changing and the legal pot industry becoming a big business, the lack of research into the health consequences of marijuana by disinterested parties has become glaringly obvious, according to Dr. Johnson-Sasso. Cannabinoid receptors are found not only in the brain, but in cardiac muscle, the kidney, liver, vascular and visceral muscle, aorta, bladder, and immune cells.

She reported having no financial conflicts of interest regarding this study.

[email protected]

CHICAGO – Patients who reported using marijuana prior to experiencing an acute MI had significantly lower in-hospital mortality and were less likely to have cardiogenic shock or require an intra-aortic balloon pump than marijuana nonusers with an MI in an eight-state hospital records study, Dr. Cecelia P. Johnson-Sasso reported at the annual meeting of the American College of Cardiology.

“If this observation is confirmed in independent studies, further investigation into the possible therapeutic benefit of cannabinoid receptor agonists in acute MI may be warranted,” declared Dr. Johnson-Sasso of the University of Colorado Denver.

Smithore

She and her coinvestigators obtained hospital records with identity information removed for more than 3 million patients admitted for acute MI during 1994-2013 in eight states: California, Colorado, New Hampshire, New Jersey, New York, Texas, Vermont, and West Virginia.

After excluding concomitant users of cocaine, methamphetamine, or alcohol due to the potential for confounding cardiotoxic effects; MI patients under age 19 because of the likelihood of congenital heart disease; and patients over age 70 because only 0.01% of them admitted to marijuana use, the investigators were left with a study population of 3,854 marijuana users and 1.27 million MI patients who hadn’t used marijuana.

In a multivariate regression analysis adjusted for potential confounders including baseline comorbid conditions, patient demographics, and payer status, the marijuana users prior to MI had a 17% reduction in in-hospital mortality, were 20% less likely to undergo intra-aortic balloon pump placement, and had a 26% reduction in shock. On the other hand, they were also 19% more likely than marijuana nonusers to be placed on mechanical ventilation. And even though they were equally likely to undergo diagnostic coronary angiography, they were 28% less likely than marijuana nonusers to undergo percutaneous coronary intervention. All of these differences were statistically significant and clinically meaningful.

She was quick to note the limitations of her study: No data were available on readmissions or late mortality, and it’s highly likely that marijuana use by patients with acute MI was significantly underreported during the study period, which was largely before the legalization movement took off.

With state marijuana laws rapidly changing and the legal pot industry becoming a big business, the lack of research into the health consequences of marijuana by disinterested parties has become glaringly obvious, according to Dr. Johnson-Sasso. Cannabinoid receptors are found not only in the brain, but in cardiac muscle, the kidney, liver, vascular and visceral muscle, aorta, bladder, and immune cells.

She reported having no financial conflicts of interest regarding this study.

[email protected]

Dear Dr. Hospitalist:

I am a seasoned hospitalist at a large academic medical center in the Northeast and have recently become more bothered by how our group is being coerced to aggressively bill for our services. It seems the current reimbursement environment has pushed some of our leaders to demand more aggressive billing from our hospitalists. How should I respond?

Sincerely,

A Seasoned Hospitalist

 

Dr. Hospitalist responds:

By “aggressive billing,” I assume you mean billing that may not be entirely ethical and approaching or outright fraudulent. The short answer is you should always bill only for the services you perform. I know—if only it was that simple.

As another “seasoned” hospitalist, I, too, have seen the wide pendulum swing from when internist inpatient billing was an afterthought and done by others to the current system of billing classes, RVU enticement, and reminders of how to construct the note. Enter the electronic health record, and now instead of clinical notes being used as a form of communication among clinicians, it does seem today to be created more for billing purposes.

How did we get here?

Physicians have to accept some of the blame. I can recall when I was an orderly at our local hospital in the mid 1970s and some physician “rounds” consisted of standing in a patient’s doorway and calling out, “How are you doing today, Mrs. Smith?” I must admit to having no idea how these docs were billing, but I do know that Medicare allowed for twice-daily billing for hospital visits back then. I also recall some of the paltry progress notes that consisted of one-liners like “pt doing well today.”

Like most corrective actions, the response has overshot the intended mark and made the daily progress note more ritualistic than informative. When the first attempts by the American Medical Association and the Centers for Medicare & Medicaid Services were released in the early 1990s, I’m sure most docs had no idea it would morph into its current level of significance for reimbursement—and that one day docs would be asked to implement, keep up with changes and modifications (think ICD-10), and use daily. Don’t get me wrong: I, like most hospitalists, recognize the clinical utility of a concise and well-written note. But when an otherwise complete H&P gets down-coded from a level 99223 to a 99221 because I leave off the family history of a 95-year-old man, of course I believe something is wrong with the system.

Also, human nature being what it is, I have always felt that if you incentivize people to increase production of an item, whether it’s a widget or an RVU, you will have some who will learn to game the system, consciously or subconsciously. With healthcare spending in the U.S. approaching 20% of gross domestic product, we as physicians should not be placed in positions of increased financial gain at the expense of our country’s economic health and viability. After all, we’re citizens first and physicians second.

You should recognize the need for proper coding and billing as inherent to the hospital’s financial viability, and if done correctly, it should not create an ethical or legal conflict for you. In the vast majority of cases, a well-written note can be properly billed and coded without creating angst.

Good luck! TH

Dear Dr. Hospitalist:

I am a seasoned hospitalist at a large academic medical center in the Northeast and have recently become more bothered by how our group is being coerced to aggressively bill for our services. It seems the current reimbursement environment has pushed some of our leaders to demand more aggressive billing from our hospitalists. How should I respond?

Sincerely,

A Seasoned Hospitalist

 

Dr. Hospitalist responds:

By “aggressive billing,” I assume you mean billing that may not be entirely ethical and approaching or outright fraudulent. The short answer is you should always bill only for the services you perform. I know—if only it was that simple.

As another “seasoned” hospitalist, I, too, have seen the wide pendulum swing from when internist inpatient billing was an afterthought and done by others to the current system of billing classes, RVU enticement, and reminders of how to construct the note. Enter the electronic health record, and now instead of clinical notes being used as a form of communication among clinicians, it does seem today to be created more for billing purposes.

How did we get here?

Physicians have to accept some of the blame. I can recall when I was an orderly at our local hospital in the mid 1970s and some physician “rounds” consisted of standing in a patient’s doorway and calling out, “How are you doing today, Mrs. Smith?” I must admit to having no idea how these docs were billing, but I do know that Medicare allowed for twice-daily billing for hospital visits back then. I also recall some of the paltry progress notes that consisted of one-liners like “pt doing well today.”

Like most corrective actions, the response has overshot the intended mark and made the daily progress note more ritualistic than informative. When the first attempts by the American Medical Association and the Centers for Medicare & Medicaid Services were released in the early 1990s, I’m sure most docs had no idea it would morph into its current level of significance for reimbursement—and that one day docs would be asked to implement, keep up with changes and modifications (think ICD-10), and use daily. Don’t get me wrong: I, like most hospitalists, recognize the clinical utility of a concise and well-written note. But when an otherwise complete H&P gets down-coded from a level 99223 to a 99221 because I leave off the family history of a 95-year-old man, of course I believe something is wrong with the system.

Also, human nature being what it is, I have always felt that if you incentivize people to increase production of an item, whether it’s a widget or an RVU, you will have some who will learn to game the system, consciously or subconsciously. With healthcare spending in the U.S. approaching 20% of gross domestic product, we as physicians should not be placed in positions of increased financial gain at the expense of our country’s economic health and viability. After all, we’re citizens first and physicians second.

You should recognize the need for proper coding and billing as inherent to the hospital’s financial viability, and if done correctly, it should not create an ethical or legal conflict for you. In the vast majority of cases, a well-written note can be properly billed and coded without creating angst.

Good luck! TH

Dear Dr. Hospitalist:

I am a seasoned hospitalist at a large academic medical center in the Northeast and have recently become more bothered by how our group is being coerced to aggressively bill for our services. It seems the current reimbursement environment has pushed some of our leaders to demand more aggressive billing from our hospitalists. How should I respond?

Sincerely,

A Seasoned Hospitalist

 

Dr. Hospitalist responds:

By “aggressive billing,” I assume you mean billing that may not be entirely ethical and approaching or outright fraudulent. The short answer is you should always bill only for the services you perform. I know—if only it was that simple.

As another “seasoned” hospitalist, I, too, have seen the wide pendulum swing from when internist inpatient billing was an afterthought and done by others to the current system of billing classes, RVU enticement, and reminders of how to construct the note. Enter the electronic health record, and now instead of clinical notes being used as a form of communication among clinicians, it does seem today to be created more for billing purposes.

How did we get here?

Physicians have to accept some of the blame. I can recall when I was an orderly at our local hospital in the mid 1970s and some physician “rounds” consisted of standing in a patient’s doorway and calling out, “How are you doing today, Mrs. Smith?” I must admit to having no idea how these docs were billing, but I do know that Medicare allowed for twice-daily billing for hospital visits back then. I also recall some of the paltry progress notes that consisted of one-liners like “pt doing well today.”

Like most corrective actions, the response has overshot the intended mark and made the daily progress note more ritualistic than informative. When the first attempts by the American Medical Association and the Centers for Medicare & Medicaid Services were released in the early 1990s, I’m sure most docs had no idea it would morph into its current level of significance for reimbursement—and that one day docs would be asked to implement, keep up with changes and modifications (think ICD-10), and use daily. Don’t get me wrong: I, like most hospitalists, recognize the clinical utility of a concise and well-written note. But when an otherwise complete H&P gets down-coded from a level 99223 to a 99221 because I leave off the family history of a 95-year-old man, of course I believe something is wrong with the system.

Also, human nature being what it is, I have always felt that if you incentivize people to increase production of an item, whether it’s a widget or an RVU, you will have some who will learn to game the system, consciously or subconsciously. With healthcare spending in the U.S. approaching 20% of gross domestic product, we as physicians should not be placed in positions of increased financial gain at the expense of our country’s economic health and viability. After all, we’re citizens first and physicians second.

You should recognize the need for proper coding and billing as inherent to the hospital’s financial viability, and if done correctly, it should not create an ethical or legal conflict for you. In the vast majority of cases, a well-written note can be properly billed and coded without creating angst.

Good luck! TH

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for CPX-351 (Vyxeos), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle, to treat adults with therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 3 trial

The breakthrough designation for CPX-351 is primarily based on positive results from a phase 3 trial in older patients with previously untreated, high-risk, secondary AML.

The trial was sponsored by Celator Pharmaceuticals, Inc., the company developing CPX-351.

The company has released some results from the trial, and additional data are scheduled to be presented at the 2016 ASCO Annual Meeting (abstract 7000).

The trial enrolled 309 patients, ages 60 to 75, with one of the following:

• Untreated AML and a history of prior cytotoxic treatment
• Antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia, with or without prior hypomethylating therapy
• AML with WHO-defined, MDS-related cytogenetic abnormalities.

One hundred and fifty-three patients were randomized to receive CPX-351, and 156 were randomized to 7+3 (cytarabine continuously for 7 days and a single dose of daunorubicin for the first 3 days).

The treatment arms were well-balanced for sex, race, age, performance status, AML subtype, MDS-related cytogenetics, and prior hypomethylating therapy.

The trial met its primary endpoint, demonstrating a significant improvement in overall survival with CPX-351. The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm. The hazard ratio was 0.69 (P=0.005).

According to researchers, there was no substantial difference between the treatment arms with regard to grade 3-5 adverse events.

About CPX-351

CPX-351 is a liposomal formulation of a 5:1 molar ratio of cytarabine and daunorubicin.

In one phase 2 trial, CPX-351 conferred a significant improvement in survival—over investigator’s choice of therapy—when used as salvage therapy in poor-risk patients with AML.

In another phase 2 trial, CPX-351 conferred a significant survival benefit—over 7+3—in patients with secondary AML.

The FDA previously granted CPX-351 fast track designation to treat elderly patients with secondary AML. The agency established the fast track designation process to expedite the review of drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

The designation allows a drug’s developer to submit sections of a new drug application (NDA) on a rolling basis, so the FDA can review portions of the NDA as they are received instead of waiting for the entire NDA submission. A fast-track-designated product could be eligible for priority review if supported by clinical data at the time of NDA submission.

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for CPX-351 (Vyxeos), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle, to treat adults with therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 3 trial

The breakthrough designation for CPX-351 is primarily based on positive results from a phase 3 trial in older patients with previously untreated, high-risk, secondary AML.

The trial was sponsored by Celator Pharmaceuticals, Inc., the company developing CPX-351.

The company has released some results from the trial, and additional data are scheduled to be presented at the 2016 ASCO Annual Meeting (abstract 7000).

The trial enrolled 309 patients, ages 60 to 75, with one of the following:

• Untreated AML and a history of prior cytotoxic treatment
• Antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia, with or without prior hypomethylating therapy
• AML with WHO-defined, MDS-related cytogenetic abnormalities.

One hundred and fifty-three patients were randomized to receive CPX-351, and 156 were randomized to 7+3 (cytarabine continuously for 7 days and a single dose of daunorubicin for the first 3 days).

The treatment arms were well-balanced for sex, race, age, performance status, AML subtype, MDS-related cytogenetics, and prior hypomethylating therapy.

The trial met its primary endpoint, demonstrating a significant improvement in overall survival with CPX-351. The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm. The hazard ratio was 0.69 (P=0.005).

According to researchers, there was no substantial difference between the treatment arms with regard to grade 3-5 adverse events.

About CPX-351

CPX-351 is a liposomal formulation of a 5:1 molar ratio of cytarabine and daunorubicin.

In one phase 2 trial, CPX-351 conferred a significant improvement in survival—over investigator’s choice of therapy—when used as salvage therapy in poor-risk patients with AML.

In another phase 2 trial, CPX-351 conferred a significant survival benefit—over 7+3—in patients with secondary AML.

The FDA previously granted CPX-351 fast track designation to treat elderly patients with secondary AML. The agency established the fast track designation process to expedite the review of drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

The designation allows a drug’s developer to submit sections of a new drug application (NDA) on a rolling basis, so the FDA can review portions of the NDA as they are received instead of waiting for the entire NDA submission. A fast-track-designated product could be eligible for priority review if supported by clinical data at the time of NDA submission.

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for CPX-351 (Vyxeos), a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle, to treat adults with therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 3 trial

The breakthrough designation for CPX-351 is primarily based on positive results from a phase 3 trial in older patients with previously untreated, high-risk, secondary AML.

The trial was sponsored by Celator Pharmaceuticals, Inc., the company developing CPX-351.

The company has released some results from the trial, and additional data are scheduled to be presented at the 2016 ASCO Annual Meeting (abstract 7000).

The trial enrolled 309 patients, ages 60 to 75, with one of the following:

• Untreated AML and a history of prior cytotoxic treatment
• Antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia, with or without prior hypomethylating therapy
• AML with WHO-defined, MDS-related cytogenetic abnormalities.

One hundred and fifty-three patients were randomized to receive CPX-351, and 156 were randomized to 7+3 (cytarabine continuously for 7 days and a single dose of daunorubicin for the first 3 days).

The treatment arms were well-balanced for sex, race, age, performance status, AML subtype, MDS-related cytogenetics, and prior hypomethylating therapy.

The trial met its primary endpoint, demonstrating a significant improvement in overall survival with CPX-351. The median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm. The hazard ratio was 0.69 (P=0.005).

According to researchers, there was no substantial difference between the treatment arms with regard to grade 3-5 adverse events.

About CPX-351

CPX-351 is a liposomal formulation of a 5:1 molar ratio of cytarabine and daunorubicin.

In one phase 2 trial, CPX-351 conferred a significant improvement in survival—over investigator’s choice of therapy—when used as salvage therapy in poor-risk patients with AML.

In another phase 2 trial, CPX-351 conferred a significant survival benefit—over 7+3—in patients with secondary AML.

The FDA previously granted CPX-351 fast track designation to treat elderly patients with secondary AML. The agency established the fast track designation process to expedite the review of drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.

The designation allows a drug’s developer to submit sections of a new drug application (NDA) on a rolling basis, so the FDA can review portions of the NDA as they are received instead of waiting for the entire NDA submission. A fast-track-designated product could be eligible for priority review if supported by clinical data at the time of NDA submission.

Optimal use of two recently approved medications for heart failure has been detailed by the major heart societies in a guideline update.

The American College of Cardiology, the American Heart Association, and the Heart Failure Society of America issued joint recommendations May 20 on the two new medicines for stage C heart failure patients with a reduced ejection fraction.

Mitchel L. Zoler/Frontline Medical News

Valsartan/sacubitril (Entresto, Novartis), is a combination angiotensin receptor–neprilysin inhibitor, the first in a novel class of drugs slugged ARNIs. Ivabradine (Corlanor, Amgen), is a sinoatrial node modulator. Both medicines were approved by the Food and Drug Administration in 2015, though ivabradine has been licensed for a decade in Europe.

Although a comprehensive update to ACC/AHA/HSFA heart failure guidelines is still being developed, the focused update is intended to coincide with the release of new European Society of Cardiology heart failure guidelines, “in order to minimize confusion and improve the care of patients with heart failure,” the societies said in a statement May 20. The recommendations were published online simultaneously in Circulation and the Journal of Cardiac Failure.

The guideline authors, led by Dr. Clyde W. Yancy of Northwestern University in Chicago, recommend that the ARNI replace an ACE inhibitor or an angiotensin II receptor blocker (ARB) for patients who have been tolerating these therapies alongside standard care with a beta-blocker and, for some patients, an aldosterone antagonist as well. The guidelines caution against combining an ARNI with an ACE inhibitor, and against using ARNIs in patients with a history of angioedema.

For patients not suited to treatment with an ARNI, continued use of an ACE inhibitor is recommended. In patients for whom an ACE inhibitor or an ARNI is inappropriate, use of an ARB remains advised. The authors noted that head-to-head comparisons of an ARB versus an ARNI for heart failure do not exist; however, in a randomized, controlled trial in heart failure patients, treatment with valsartan/sacubitril plus standard care reduced cardiovascular death or heart failure hospitalization by 20%, compared with treatment with an ACE inhibitor plus standard care.

Ivabradine, meanwhile, has shown benefit in reducing heart failure hospitalizations in patients with symptomatic, stable, chronic heart failure with reduced ejection fraction who are receiving standard treatment including a beta-blocker, and who are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest.

The new therapies, “when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure,” wrote Dr. Elliott M. Antman of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass., in an editorial accompanying the guidelines.

About half the guideline writing committee members and guideline reviewers disclosed financial relationships with pharmaceutical companies or device manufacturers. Dr. Yancy disclosed no conflicts of interest.

Optimal use of two recently approved medications for heart failure has been detailed by the major heart societies in a guideline update.

The American College of Cardiology, the American Heart Association, and the Heart Failure Society of America issued joint recommendations May 20 on the two new medicines for stage C heart failure patients with a reduced ejection fraction.

Mitchel L. Zoler/Frontline Medical News

Valsartan/sacubitril (Entresto, Novartis), is a combination angiotensin receptor–neprilysin inhibitor, the first in a novel class of drugs slugged ARNIs. Ivabradine (Corlanor, Amgen), is a sinoatrial node modulator. Both medicines were approved by the Food and Drug Administration in 2015, though ivabradine has been licensed for a decade in Europe.

Although a comprehensive update to ACC/AHA/HSFA heart failure guidelines is still being developed, the focused update is intended to coincide with the release of new European Society of Cardiology heart failure guidelines, “in order to minimize confusion and improve the care of patients with heart failure,” the societies said in a statement May 20. The recommendations were published online simultaneously in Circulation and the Journal of Cardiac Failure.

The guideline authors, led by Dr. Clyde W. Yancy of Northwestern University in Chicago, recommend that the ARNI replace an ACE inhibitor or an angiotensin II receptor blocker (ARB) for patients who have been tolerating these therapies alongside standard care with a beta-blocker and, for some patients, an aldosterone antagonist as well. The guidelines caution against combining an ARNI with an ACE inhibitor, and against using ARNIs in patients with a history of angioedema.

For patients not suited to treatment with an ARNI, continued use of an ACE inhibitor is recommended. In patients for whom an ACE inhibitor or an ARNI is inappropriate, use of an ARB remains advised. The authors noted that head-to-head comparisons of an ARB versus an ARNI for heart failure do not exist; however, in a randomized, controlled trial in heart failure patients, treatment with valsartan/sacubitril plus standard care reduced cardiovascular death or heart failure hospitalization by 20%, compared with treatment with an ACE inhibitor plus standard care.

Ivabradine, meanwhile, has shown benefit in reducing heart failure hospitalizations in patients with symptomatic, stable, chronic heart failure with reduced ejection fraction who are receiving standard treatment including a beta-blocker, and who are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest.

The new therapies, “when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure,” wrote Dr. Elliott M. Antman of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass., in an editorial accompanying the guidelines.

About half the guideline writing committee members and guideline reviewers disclosed financial relationships with pharmaceutical companies or device manufacturers. Dr. Yancy disclosed no conflicts of interest.

Optimal use of two recently approved medications for heart failure has been detailed by the major heart societies in a guideline update.

The American College of Cardiology, the American Heart Association, and the Heart Failure Society of America issued joint recommendations May 20 on the two new medicines for stage C heart failure patients with a reduced ejection fraction.

Mitchel L. Zoler/Frontline Medical News

Valsartan/sacubitril (Entresto, Novartis), is a combination angiotensin receptor–neprilysin inhibitor, the first in a novel class of drugs slugged ARNIs. Ivabradine (Corlanor, Amgen), is a sinoatrial node modulator. Both medicines were approved by the Food and Drug Administration in 2015, though ivabradine has been licensed for a decade in Europe.

Although a comprehensive update to ACC/AHA/HSFA heart failure guidelines is still being developed, the focused update is intended to coincide with the release of new European Society of Cardiology heart failure guidelines, “in order to minimize confusion and improve the care of patients with heart failure,” the societies said in a statement May 20. The recommendations were published online simultaneously in Circulation and the Journal of Cardiac Failure.

The guideline authors, led by Dr. Clyde W. Yancy of Northwestern University in Chicago, recommend that the ARNI replace an ACE inhibitor or an angiotensin II receptor blocker (ARB) for patients who have been tolerating these therapies alongside standard care with a beta-blocker and, for some patients, an aldosterone antagonist as well. The guidelines caution against combining an ARNI with an ACE inhibitor, and against using ARNIs in patients with a history of angioedema.

For patients not suited to treatment with an ARNI, continued use of an ACE inhibitor is recommended. In patients for whom an ACE inhibitor or an ARNI is inappropriate, use of an ARB remains advised. The authors noted that head-to-head comparisons of an ARB versus an ARNI for heart failure do not exist; however, in a randomized, controlled trial in heart failure patients, treatment with valsartan/sacubitril plus standard care reduced cardiovascular death or heart failure hospitalization by 20%, compared with treatment with an ACE inhibitor plus standard care.

Ivabradine, meanwhile, has shown benefit in reducing heart failure hospitalizations in patients with symptomatic, stable, chronic heart failure with reduced ejection fraction who are receiving standard treatment including a beta-blocker, and who are in sinus rhythm with a heart rate of 70 beats per minute or greater at rest.

The new therapies, “when applied judiciously, complement established pharmacological and device-based therapies, representing milestones in the evolution of care for patients with heart failure,” wrote Dr. Elliott M. Antman of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass., in an editorial accompanying the guidelines.

About half the guideline writing committee members and guideline reviewers disclosed financial relationships with pharmaceutical companies or device manufacturers. Dr. Yancy disclosed no conflicts of interest.