NEW YORK – It is well known that reoperative carotid endarterectomy can be technically challenging because of the scarring left from the initial procedure, but an analysis of a large database presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation also revealed that the risk of complications, particularly stroke, is greater.

When “redo” carotid endarterectomies were compared with the index primary procedure collected in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, the odds ratio for stroke was several times greater (odds ratio, 3.71; P = .002) on univariate analysis, reported Jeffrey J. Siracuse, MD, associate professor of surgery and radiology at Boston University.

Previous single-center reports of redo endarterectomies “showed terrific results, really no perioperative stroke or morbidity, but this is older data from a different era,” said Dr. Siracuse, who undertook this study to determine whether “real-world” data would tell a different story.

In this study, 75,943 primary carotid endarterectomies and 140 redo procedures were identified in the ACS NSQIP database and compared. The redo population had a significantly higher incidence of end-stage renal disease (3.6% vs. 1.1%; P = .004), but history of stroke, whether with deficit (20.8% vs. 15.4%) or without (11.5% vs. 9.1%), was numerically higher among those undergoing a primary procedure even though these differences did not reach statistical significance. Baseline demographics and comorbidities were otherwise similar.

Presumably because of the difficulty of recanalizing scarred tissue, the mean procedure time for redos was longer than that for the primary procedures (137 vs. 49 minutes; P less than .001), but there were no significant differences in the rate of surgical site infections (0.7% vs. 0.3%; P = .482), return to the operating room (3.6% vs. 4%; P = .853), or 30-day readmissions (2.1% vs. 6.9%; P = .810) for the redo and index procedures, respectively.

Although perioperative MI rates were higher in the redo group (2.1%) than in the primary endarterectomy group (0.9%), this difference did not reach statistical significance (P = .125). However, a multivariate analysis associated redo carotid endarterectomy procedures with a nearly threefold increase in risk of a composite of major adverse cardiovascular events when compared on a multivariate analysis (OR, 2.76; P = .007), Dr. Siracuse reported.

For the surgeons considering a redo carotid endarterectomy, these data “inform a risk-benefit analysis,” according to Dr. Siracuse, but he also said that redo procedures still should be considered a viable strategy when considered in the context of other options.

Presenting a case he performed just prior to the VEITHsymposium, Dr. Siracuse displayed CT images that showed internal and common carotids with more than 75% stenosis in an 80-year-old women 7 years after a primary carotid endarterectomy. The tight stenoses and the evidence of substantial intra-arterial debris were concerns, but a decision to perform a redo endarterectomy was reached after other options, including stenting, were considered.

“She did great. She went home and has had no more symptoms,” Dr. Siracuse reported. “The point is you still have to take these [potential redo endarterectomies] on a case-by case basis.”

Dr. Siracuse reported he had no financial relationships relevant to this study.

NEW YORK – It is well known that reoperative carotid endarterectomy can be technically challenging because of the scarring left from the initial procedure, but an analysis of a large database presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation also revealed that the risk of complications, particularly stroke, is greater.

When “redo” carotid endarterectomies were compared with the index primary procedure collected in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, the odds ratio for stroke was several times greater (odds ratio, 3.71; P = .002) on univariate analysis, reported Jeffrey J. Siracuse, MD, associate professor of surgery and radiology at Boston University.

Previous single-center reports of redo endarterectomies “showed terrific results, really no perioperative stroke or morbidity, but this is older data from a different era,” said Dr. Siracuse, who undertook this study to determine whether “real-world” data would tell a different story.

In this study, 75,943 primary carotid endarterectomies and 140 redo procedures were identified in the ACS NSQIP database and compared. The redo population had a significantly higher incidence of end-stage renal disease (3.6% vs. 1.1%; P = .004), but history of stroke, whether with deficit (20.8% vs. 15.4%) or without (11.5% vs. 9.1%), was numerically higher among those undergoing a primary procedure even though these differences did not reach statistical significance. Baseline demographics and comorbidities were otherwise similar.

Presumably because of the difficulty of recanalizing scarred tissue, the mean procedure time for redos was longer than that for the primary procedures (137 vs. 49 minutes; P less than .001), but there were no significant differences in the rate of surgical site infections (0.7% vs. 0.3%; P = .482), return to the operating room (3.6% vs. 4%; P = .853), or 30-day readmissions (2.1% vs. 6.9%; P = .810) for the redo and index procedures, respectively.

Although perioperative MI rates were higher in the redo group (2.1%) than in the primary endarterectomy group (0.9%), this difference did not reach statistical significance (P = .125). However, a multivariate analysis associated redo carotid endarterectomy procedures with a nearly threefold increase in risk of a composite of major adverse cardiovascular events when compared on a multivariate analysis (OR, 2.76; P = .007), Dr. Siracuse reported.

For the surgeons considering a redo carotid endarterectomy, these data “inform a risk-benefit analysis,” according to Dr. Siracuse, but he also said that redo procedures still should be considered a viable strategy when considered in the context of other options.

Presenting a case he performed just prior to the VEITHsymposium, Dr. Siracuse displayed CT images that showed internal and common carotids with more than 75% stenosis in an 80-year-old women 7 years after a primary carotid endarterectomy. The tight stenoses and the evidence of substantial intra-arterial debris were concerns, but a decision to perform a redo endarterectomy was reached after other options, including stenting, were considered.

“She did great. She went home and has had no more symptoms,” Dr. Siracuse reported. “The point is you still have to take these [potential redo endarterectomies] on a case-by case basis.”

Dr. Siracuse reported he had no financial relationships relevant to this study.

NEW YORK – It is well known that reoperative carotid endarterectomy can be technically challenging because of the scarring left from the initial procedure, but an analysis of a large database presented at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation also revealed that the risk of complications, particularly stroke, is greater.

When “redo” carotid endarterectomies were compared with the index primary procedure collected in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, the odds ratio for stroke was several times greater (odds ratio, 3.71; P = .002) on univariate analysis, reported Jeffrey J. Siracuse, MD, associate professor of surgery and radiology at Boston University.

Previous single-center reports of redo endarterectomies “showed terrific results, really no perioperative stroke or morbidity, but this is older data from a different era,” said Dr. Siracuse, who undertook this study to determine whether “real-world” data would tell a different story.

In this study, 75,943 primary carotid endarterectomies and 140 redo procedures were identified in the ACS NSQIP database and compared. The redo population had a significantly higher incidence of end-stage renal disease (3.6% vs. 1.1%; P = .004), but history of stroke, whether with deficit (20.8% vs. 15.4%) or without (11.5% vs. 9.1%), was numerically higher among those undergoing a primary procedure even though these differences did not reach statistical significance. Baseline demographics and comorbidities were otherwise similar.

Presumably because of the difficulty of recanalizing scarred tissue, the mean procedure time for redos was longer than that for the primary procedures (137 vs. 49 minutes; P less than .001), but there were no significant differences in the rate of surgical site infections (0.7% vs. 0.3%; P = .482), return to the operating room (3.6% vs. 4%; P = .853), or 30-day readmissions (2.1% vs. 6.9%; P = .810) for the redo and index procedures, respectively.

Although perioperative MI rates were higher in the redo group (2.1%) than in the primary endarterectomy group (0.9%), this difference did not reach statistical significance (P = .125). However, a multivariate analysis associated redo carotid endarterectomy procedures with a nearly threefold increase in risk of a composite of major adverse cardiovascular events when compared on a multivariate analysis (OR, 2.76; P = .007), Dr. Siracuse reported.

For the surgeons considering a redo carotid endarterectomy, these data “inform a risk-benefit analysis,” according to Dr. Siracuse, but he also said that redo procedures still should be considered a viable strategy when considered in the context of other options.

Presenting a case he performed just prior to the VEITHsymposium, Dr. Siracuse displayed CT images that showed internal and common carotids with more than 75% stenosis in an 80-year-old women 7 years after a primary carotid endarterectomy. The tight stenoses and the evidence of substantial intra-arterial debris were concerns, but a decision to perform a redo endarterectomy was reached after other options, including stenting, were considered.

“She did great. She went home and has had no more symptoms,” Dr. Siracuse reported. “The point is you still have to take these [potential redo endarterectomies] on a case-by case basis.”

Dr. Siracuse reported he had no financial relationships relevant to this study.

Health care spending as a percentage of gross domestic product remained relatively stable in 2017, despite a slowdown in the growth of spending.

utah778/Thinkstock

Total health care spending in the United States was $3.5 trillion in 2017, an increase of 3.9% from 2016, according to data released Dec. 6 by the Centers for Medicare & Medicaid Services.

The growth rate was down from that of 2016 (4.8%) but similar to growth rates experienced during 2008-2013, according to the research article in Health Affairs.

“The slower growth in health care spending in 2017 resulted primarily from slower growth in hospital care, physician and clinical services, and retail prescription drugs, with residual use and intensity of these goods and services contributing substantially to the trend,” Anne B. Martin, an economist in the CMS Office of the Actuary’s National Health Statistics Group, and her colleagues wrote.

The report notes that slower growth in the use and intensity of health care goods and services in 2017 “may have been affected by slower growth in overall health insurance enrollment, as the insured share of the population fell from 91.1% in 2016 to 90.9% in 2017.”

Spending on hospital care increased 4.6% to $1.1 trillion in 2017 and accounted for 33% of total health care spending; however, growth was slower than in the previous year (5.6%). Ms. Martin and her colleagues noted that growth in outpatient visits slowed while growth in inpatient days increased at about the same rate and prices in hospital care grew in 2017 to 1.7% from 1.2% in the previous year.

Spending on physician and clinical services grew 4.2% in 2017 to $694.3 billion and accounted for 20% of total health care spending. The growth rate is down from the previous year (5.6%) and a recent peak of 6% in 2015.

“Although spending growth for both physician services and clinical services slowed in 2017, the growth rate for the latter (5.0%) continued to out pace the rate for the former (3.9%), as spending for most types of outpatient care centers contributed to the stronger growth in spending for clinical services,” Ms. Martin and her colleagues reported.

They attributed the slowdown to non-price factors, such as slower growth in the use and intensity of physician and clinical services, although price growth for physician and clinical services increased 0.4% in 2017, up from 0.2% in 2016.

Spending on retail prescription drugs grew 0.4% in 2017 to $333.4 billion and accounted for 10% of total national health spending. It is the slowest growth rate increase since 2012, a year that saw a number of blockbuster drugs lose patent protection. This was down from a growth rate of 2.3% in 2016 and down from recent rates of 12.4% in 2014 and 8.9% in 2015.

“Slower growth in non-price factors, such as the use and mix of retail prescription drugs – and, to a lesser extent, in retail prescription drug prices – contributed to the slower overall growth in retail prescription drug spending in 2017,” according to the authors. Key factors included slower growth in the number of prescriptions dispensed, the continued shift to lower-cost generics, and slower growth in the volume of high-cost drugs, particularly those used to treat hepatitis C. Price decreases in generics and lower increases for existing brand-name drugs also contributed to the lower spending growth in 2017.

Ms. Martin and her colleagues highlighted the slower growth rate in the number of prescriptions (1.8% in 2017, down from 2.3% in 2016) “resulted in large part from a decline in the number of prescriptions dispensed for drugs used to treat pain.”

Medicare spending, which represents 20% of all national health care spending in 2017 ($705.9 billion), grew 4.2%, a slight decline from the 4.3% growth in 2016. Enrollment growth slowed slightly to 2.5% in 2017 from 2.7% in the previous year, while in the same time frame, per-enrollee expenditures increased slightly to 1.7% from 1.6%. Slower growth in fee-for-service Medicare spending was offset by faster growth in spending by Medicare private health plans.

Medicaid spending reached $581.9 billion (17% of national health care spending), and the growth rate slowed for the third straight year, increasing 2.9% in 2017 versus 4.2% in 2016. The slower growth “was influenced by a deceleration in enrollment growth and a reduction in the Medicaid net cost of health insurance as the federal government recovered payments from managed care organizations based on their favorable prior-period experience,” the authors stated. Enrollment growth has been decelerating following a peak of growth of 11.9% in 2014 because of states that elected to expand Medicaid eligibility, which was followed by 3 years of slower growth rates of 4.9%, 3.0% and 2.0% in 2015, 2016, and 2017, respectively. Per-enrollee spending also slowed to 0.9% growth in 2017 from a rate of 1.2% in 2016, attributed to “the decline in government administration and the net cost of insurance.”

[email protected]

SOURCE: Martin A et al. Health Aff. 2018. doi: 10.1377/hlthaff.2018.05085.

Health care spending as a percentage of gross domestic product remained relatively stable in 2017, despite a slowdown in the growth of spending.

utah778/Thinkstock

Total health care spending in the United States was $3.5 trillion in 2017, an increase of 3.9% from 2016, according to data released Dec. 6 by the Centers for Medicare & Medicaid Services.

The growth rate was down from that of 2016 (4.8%) but similar to growth rates experienced during 2008-2013, according to the research article in Health Affairs.

“The slower growth in health care spending in 2017 resulted primarily from slower growth in hospital care, physician and clinical services, and retail prescription drugs, with residual use and intensity of these goods and services contributing substantially to the trend,” Anne B. Martin, an economist in the CMS Office of the Actuary’s National Health Statistics Group, and her colleagues wrote.

The report notes that slower growth in the use and intensity of health care goods and services in 2017 “may have been affected by slower growth in overall health insurance enrollment, as the insured share of the population fell from 91.1% in 2016 to 90.9% in 2017.”

Spending on hospital care increased 4.6% to $1.1 trillion in 2017 and accounted for 33% of total health care spending; however, growth was slower than in the previous year (5.6%). Ms. Martin and her colleagues noted that growth in outpatient visits slowed while growth in inpatient days increased at about the same rate and prices in hospital care grew in 2017 to 1.7% from 1.2% in the previous year.

Spending on physician and clinical services grew 4.2% in 2017 to $694.3 billion and accounted for 20% of total health care spending. The growth rate is down from the previous year (5.6%) and a recent peak of 6% in 2015.

“Although spending growth for both physician services and clinical services slowed in 2017, the growth rate for the latter (5.0%) continued to out pace the rate for the former (3.9%), as spending for most types of outpatient care centers contributed to the stronger growth in spending for clinical services,” Ms. Martin and her colleagues reported.

They attributed the slowdown to non-price factors, such as slower growth in the use and intensity of physician and clinical services, although price growth for physician and clinical services increased 0.4% in 2017, up from 0.2% in 2016.

Spending on retail prescription drugs grew 0.4% in 2017 to $333.4 billion and accounted for 10% of total national health spending. It is the slowest growth rate increase since 2012, a year that saw a number of blockbuster drugs lose patent protection. This was down from a growth rate of 2.3% in 2016 and down from recent rates of 12.4% in 2014 and 8.9% in 2015.

“Slower growth in non-price factors, such as the use and mix of retail prescription drugs – and, to a lesser extent, in retail prescription drug prices – contributed to the slower overall growth in retail prescription drug spending in 2017,” according to the authors. Key factors included slower growth in the number of prescriptions dispensed, the continued shift to lower-cost generics, and slower growth in the volume of high-cost drugs, particularly those used to treat hepatitis C. Price decreases in generics and lower increases for existing brand-name drugs also contributed to the lower spending growth in 2017.

Ms. Martin and her colleagues highlighted the slower growth rate in the number of prescriptions (1.8% in 2017, down from 2.3% in 2016) “resulted in large part from a decline in the number of prescriptions dispensed for drugs used to treat pain.”

Medicare spending, which represents 20% of all national health care spending in 2017 ($705.9 billion), grew 4.2%, a slight decline from the 4.3% growth in 2016. Enrollment growth slowed slightly to 2.5% in 2017 from 2.7% in the previous year, while in the same time frame, per-enrollee expenditures increased slightly to 1.7% from 1.6%. Slower growth in fee-for-service Medicare spending was offset by faster growth in spending by Medicare private health plans.

Medicaid spending reached $581.9 billion (17% of national health care spending), and the growth rate slowed for the third straight year, increasing 2.9% in 2017 versus 4.2% in 2016. The slower growth “was influenced by a deceleration in enrollment growth and a reduction in the Medicaid net cost of health insurance as the federal government recovered payments from managed care organizations based on their favorable prior-period experience,” the authors stated. Enrollment growth has been decelerating following a peak of growth of 11.9% in 2014 because of states that elected to expand Medicaid eligibility, which was followed by 3 years of slower growth rates of 4.9%, 3.0% and 2.0% in 2015, 2016, and 2017, respectively. Per-enrollee spending also slowed to 0.9% growth in 2017 from a rate of 1.2% in 2016, attributed to “the decline in government administration and the net cost of insurance.”

[email protected]

SOURCE: Martin A et al. Health Aff. 2018. doi: 10.1377/hlthaff.2018.05085.

Health care spending as a percentage of gross domestic product remained relatively stable in 2017, despite a slowdown in the growth of spending.

utah778/Thinkstock

Total health care spending in the United States was $3.5 trillion in 2017, an increase of 3.9% from 2016, according to data released Dec. 6 by the Centers for Medicare & Medicaid Services.

The growth rate was down from that of 2016 (4.8%) but similar to growth rates experienced during 2008-2013, according to the research article in Health Affairs.

“The slower growth in health care spending in 2017 resulted primarily from slower growth in hospital care, physician and clinical services, and retail prescription drugs, with residual use and intensity of these goods and services contributing substantially to the trend,” Anne B. Martin, an economist in the CMS Office of the Actuary’s National Health Statistics Group, and her colleagues wrote.

The report notes that slower growth in the use and intensity of health care goods and services in 2017 “may have been affected by slower growth in overall health insurance enrollment, as the insured share of the population fell from 91.1% in 2016 to 90.9% in 2017.”

Spending on hospital care increased 4.6% to $1.1 trillion in 2017 and accounted for 33% of total health care spending; however, growth was slower than in the previous year (5.6%). Ms. Martin and her colleagues noted that growth in outpatient visits slowed while growth in inpatient days increased at about the same rate and prices in hospital care grew in 2017 to 1.7% from 1.2% in the previous year.

Spending on physician and clinical services grew 4.2% in 2017 to $694.3 billion and accounted for 20% of total health care spending. The growth rate is down from the previous year (5.6%) and a recent peak of 6% in 2015.

“Although spending growth for both physician services and clinical services slowed in 2017, the growth rate for the latter (5.0%) continued to out pace the rate for the former (3.9%), as spending for most types of outpatient care centers contributed to the stronger growth in spending for clinical services,” Ms. Martin and her colleagues reported.

They attributed the slowdown to non-price factors, such as slower growth in the use and intensity of physician and clinical services, although price growth for physician and clinical services increased 0.4% in 2017, up from 0.2% in 2016.

Spending on retail prescription drugs grew 0.4% in 2017 to $333.4 billion and accounted for 10% of total national health spending. It is the slowest growth rate increase since 2012, a year that saw a number of blockbuster drugs lose patent protection. This was down from a growth rate of 2.3% in 2016 and down from recent rates of 12.4% in 2014 and 8.9% in 2015.

“Slower growth in non-price factors, such as the use and mix of retail prescription drugs – and, to a lesser extent, in retail prescription drug prices – contributed to the slower overall growth in retail prescription drug spending in 2017,” according to the authors. Key factors included slower growth in the number of prescriptions dispensed, the continued shift to lower-cost generics, and slower growth in the volume of high-cost drugs, particularly those used to treat hepatitis C. Price decreases in generics and lower increases for existing brand-name drugs also contributed to the lower spending growth in 2017.

Ms. Martin and her colleagues highlighted the slower growth rate in the number of prescriptions (1.8% in 2017, down from 2.3% in 2016) “resulted in large part from a decline in the number of prescriptions dispensed for drugs used to treat pain.”

Medicare spending, which represents 20% of all national health care spending in 2017 ($705.9 billion), grew 4.2%, a slight decline from the 4.3% growth in 2016. Enrollment growth slowed slightly to 2.5% in 2017 from 2.7% in the previous year, while in the same time frame, per-enrollee expenditures increased slightly to 1.7% from 1.6%. Slower growth in fee-for-service Medicare spending was offset by faster growth in spending by Medicare private health plans.

Medicaid spending reached $581.9 billion (17% of national health care spending), and the growth rate slowed for the third straight year, increasing 2.9% in 2017 versus 4.2% in 2016. The slower growth “was influenced by a deceleration in enrollment growth and a reduction in the Medicaid net cost of health insurance as the federal government recovered payments from managed care organizations based on their favorable prior-period experience,” the authors stated. Enrollment growth has been decelerating following a peak of growth of 11.9% in 2014 because of states that elected to expand Medicaid eligibility, which was followed by 3 years of slower growth rates of 4.9%, 3.0% and 2.0% in 2015, 2016, and 2017, respectively. Per-enrollee spending also slowed to 0.9% growth in 2017 from a rate of 1.2% in 2016, attributed to “the decline in government administration and the net cost of insurance.”

[email protected]

SOURCE: Martin A et al. Health Aff. 2018. doi: 10.1377/hlthaff.2018.05085.

Though lobectomy is the long-held standard of care for people with early stage non–small cell lung cancer, a noninferiority study shows little difference in perioperative morbidity and mortality outcomes when sublobar resections are performed instead.

The study, published online in The Lancet Respiratory Medicine, compared results from 697 functionally and physically fit patients with stage I cancer randomized over a 10-year period to lobar resection (n = 357) or sublobar resection (n = 340). Patients were analyzed for morbidity and mortality outcomes at 30 and 90 days post surgery. Nasser K. Altorki, MD, of Weill Cornell Medicine–New York Presbyterian Hospital, led the study as a post hoc, exploratory analysis of CALGB/Alliance 140503, a multinational phase 3 trial whose primary outcome – still pending – is disease-free survival associated with the two different surgeries.

Dr. Altorki and his colleagues found 30- and 90-day survival to be comparable between surgery types. At 30 days, six patients in the study had died; four in the lobar resection group and two in the sublobar group (1.1% and 0.6%). At 90 days, 10 patients had died, or 1.4% of the cohort; 6 following lobar resection and 4 following sublobar resection. The between-group difference at 30 days was 0.5% (95% confidence interval, –1.1 to 2.3) and at 90 days remained 0.5% (95% CI, –1.5 to 2.6).

Similar rates of serious (grade 3 or worse) adverse advents were seen between surgery groups at 15% and 14%, respectively, and no differences were seen for cardiac or pulmonary complications. In the study, the type of sublobar approach was left to the surgeon’s discretion, and a majority of the sublobar procedures (59%) were found to comprise wedge resections, with the rest segmentectomies. Dr. Altorki and colleagues noted the high rate of wedge resections as striking, because “conventional wisdom … holds that an anatomical segmentectomy, involving individual ligation of segmental vessels and bronchi and wider parenchymal resection, is oncologically superior to nonanatomical wedge resections.” In their analysis the researchers conceded that a three-arm trial allocating patients to lobectomy, segmentectomy, or wedge resection “would have answered more precisely the posited research question,” but said that the sample size needed would have been too large.

The study was funded by the National Cancer Institute. Dr. Altorki reported a research grant from AstraZeneca unrelated to the study; two more coauthors disclosed funding from pharmaceutical or device manufacturers, and an additional 17 coauthors listed no competing interests.

SOURCE: Altorki NK et al. Lancet Respir Med. 2018 Nov 12. doi: 10.1016/S2213-2600(18)30411-9 .

Though lobectomy is the long-held standard of care for people with early stage non–small cell lung cancer, a noninferiority study shows little difference in perioperative morbidity and mortality outcomes when sublobar resections are performed instead.

The study, published online in The Lancet Respiratory Medicine, compared results from 697 functionally and physically fit patients with stage I cancer randomized over a 10-year period to lobar resection (n = 357) or sublobar resection (n = 340). Patients were analyzed for morbidity and mortality outcomes at 30 and 90 days post surgery. Nasser K. Altorki, MD, of Weill Cornell Medicine–New York Presbyterian Hospital, led the study as a post hoc, exploratory analysis of CALGB/Alliance 140503, a multinational phase 3 trial whose primary outcome – still pending – is disease-free survival associated with the two different surgeries.

Dr. Altorki and his colleagues found 30- and 90-day survival to be comparable between surgery types. At 30 days, six patients in the study had died; four in the lobar resection group and two in the sublobar group (1.1% and 0.6%). At 90 days, 10 patients had died, or 1.4% of the cohort; 6 following lobar resection and 4 following sublobar resection. The between-group difference at 30 days was 0.5% (95% confidence interval, –1.1 to 2.3) and at 90 days remained 0.5% (95% CI, –1.5 to 2.6).

Similar rates of serious (grade 3 or worse) adverse advents were seen between surgery groups at 15% and 14%, respectively, and no differences were seen for cardiac or pulmonary complications. In the study, the type of sublobar approach was left to the surgeon’s discretion, and a majority of the sublobar procedures (59%) were found to comprise wedge resections, with the rest segmentectomies. Dr. Altorki and colleagues noted the high rate of wedge resections as striking, because “conventional wisdom … holds that an anatomical segmentectomy, involving individual ligation of segmental vessels and bronchi and wider parenchymal resection, is oncologically superior to nonanatomical wedge resections.” In their analysis the researchers conceded that a three-arm trial allocating patients to lobectomy, segmentectomy, or wedge resection “would have answered more precisely the posited research question,” but said that the sample size needed would have been too large.

The study was funded by the National Cancer Institute. Dr. Altorki reported a research grant from AstraZeneca unrelated to the study; two more coauthors disclosed funding from pharmaceutical or device manufacturers, and an additional 17 coauthors listed no competing interests.

SOURCE: Altorki NK et al. Lancet Respir Med. 2018 Nov 12. doi: 10.1016/S2213-2600(18)30411-9 .

Though lobectomy is the long-held standard of care for people with early stage non–small cell lung cancer, a noninferiority study shows little difference in perioperative morbidity and mortality outcomes when sublobar resections are performed instead.

The study, published online in The Lancet Respiratory Medicine, compared results from 697 functionally and physically fit patients with stage I cancer randomized over a 10-year period to lobar resection (n = 357) or sublobar resection (n = 340). Patients were analyzed for morbidity and mortality outcomes at 30 and 90 days post surgery. Nasser K. Altorki, MD, of Weill Cornell Medicine–New York Presbyterian Hospital, led the study as a post hoc, exploratory analysis of CALGB/Alliance 140503, a multinational phase 3 trial whose primary outcome – still pending – is disease-free survival associated with the two different surgeries.

Dr. Altorki and his colleagues found 30- and 90-day survival to be comparable between surgery types. At 30 days, six patients in the study had died; four in the lobar resection group and two in the sublobar group (1.1% and 0.6%). At 90 days, 10 patients had died, or 1.4% of the cohort; 6 following lobar resection and 4 following sublobar resection. The between-group difference at 30 days was 0.5% (95% confidence interval, –1.1 to 2.3) and at 90 days remained 0.5% (95% CI, –1.5 to 2.6).

Similar rates of serious (grade 3 or worse) adverse advents were seen between surgery groups at 15% and 14%, respectively, and no differences were seen for cardiac or pulmonary complications. In the study, the type of sublobar approach was left to the surgeon’s discretion, and a majority of the sublobar procedures (59%) were found to comprise wedge resections, with the rest segmentectomies. Dr. Altorki and colleagues noted the high rate of wedge resections as striking, because “conventional wisdom … holds that an anatomical segmentectomy, involving individual ligation of segmental vessels and bronchi and wider parenchymal resection, is oncologically superior to nonanatomical wedge resections.” In their analysis the researchers conceded that a three-arm trial allocating patients to lobectomy, segmentectomy, or wedge resection “would have answered more precisely the posited research question,” but said that the sample size needed would have been too large.

The study was funded by the National Cancer Institute. Dr. Altorki reported a research grant from AstraZeneca unrelated to the study; two more coauthors disclosed funding from pharmaceutical or device manufacturers, and an additional 17 coauthors listed no competing interests.

SOURCE: Altorki NK et al. Lancet Respir Med. 2018 Nov 12. doi: 10.1016/S2213-2600(18)30411-9 .

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic non-squamous, non-small cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations.

Approval was based on greater overall survival (OS) among patients receiving the four drug combination, compared with patients who did not receive the checkpoint inhibitor but received the other three drugs in the randomized IMpower150 trial.

For the trial, 1,202 patients with metastatic NSq NSCLC were randomized to three arms for first-line treatment:

• atezolizumab, carboplatin, paclitaxel, and bevacizumab (4-drug regimen);

• atezolizumab, carboplatin and paclitaxel (3-drug regimen); or

• carboplatin, paclitaxel, and bevacizumab (control arm).

Among patients with NSq NSCLC without an EGFR or ALK mutation (87%), the estimated median OS was 19.2 months for patients receiving the 4-drug regimen and 14.7 months for those in the control arm (hazard ratio [HR] 0.78; 95% CI: 0.64, 0.96; P = .016), the FDA said in a press statement announcing the approval.

The median progression-free survival was 8.5 months for patients receiving the 4-drug regimen and 7.0 months for those in the control arm (HR 0.71; 95% CI 0.59, 0.85; P = .0002). The overall response rates were 55% in the 4-drug arm and 42% in the control arm. There were no significant differences in OS or final progression-free survival between the 3-drug arm containing atezolizumab and the control arm.

The most common adverse reactions with atezolizumab were fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Treatment with atezolizumab was discontinued in 15% of patients due to adverse reactions, the most common reason being pneumonitis.

The recommended atezolizumab dose is 1,200 mg intravenously over 60 minutes every 3 weeks, the FDA said.

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic non-squamous, non-small cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations.

Approval was based on greater overall survival (OS) among patients receiving the four drug combination, compared with patients who did not receive the checkpoint inhibitor but received the other three drugs in the randomized IMpower150 trial.

For the trial, 1,202 patients with metastatic NSq NSCLC were randomized to three arms for first-line treatment:

• atezolizumab, carboplatin, paclitaxel, and bevacizumab (4-drug regimen);

• atezolizumab, carboplatin and paclitaxel (3-drug regimen); or

• carboplatin, paclitaxel, and bevacizumab (control arm).

Among patients with NSq NSCLC without an EGFR or ALK mutation (87%), the estimated median OS was 19.2 months for patients receiving the 4-drug regimen and 14.7 months for those in the control arm (hazard ratio [HR] 0.78; 95% CI: 0.64, 0.96; P = .016), the FDA said in a press statement announcing the approval.

The median progression-free survival was 8.5 months for patients receiving the 4-drug regimen and 7.0 months for those in the control arm (HR 0.71; 95% CI 0.59, 0.85; P = .0002). The overall response rates were 55% in the 4-drug arm and 42% in the control arm. There were no significant differences in OS or final progression-free survival between the 3-drug arm containing atezolizumab and the control arm.

The most common adverse reactions with atezolizumab were fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Treatment with atezolizumab was discontinued in 15% of patients due to adverse reactions, the most common reason being pneumonitis.

The recommended atezolizumab dose is 1,200 mg intravenously over 60 minutes every 3 weeks, the FDA said.

The Food and Drug Administration has approved atezolizumab (Tecentriq) in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic non-squamous, non-small cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations.

Approval was based on greater overall survival (OS) among patients receiving the four drug combination, compared with patients who did not receive the checkpoint inhibitor but received the other three drugs in the randomized IMpower150 trial.

For the trial, 1,202 patients with metastatic NSq NSCLC were randomized to three arms for first-line treatment:

• atezolizumab, carboplatin, paclitaxel, and bevacizumab (4-drug regimen);

• atezolizumab, carboplatin and paclitaxel (3-drug regimen); or

• carboplatin, paclitaxel, and bevacizumab (control arm).

Among patients with NSq NSCLC without an EGFR or ALK mutation (87%), the estimated median OS was 19.2 months for patients receiving the 4-drug regimen and 14.7 months for those in the control arm (hazard ratio [HR] 0.78; 95% CI: 0.64, 0.96; P = .016), the FDA said in a press statement announcing the approval.

The median progression-free survival was 8.5 months for patients receiving the 4-drug regimen and 7.0 months for those in the control arm (HR 0.71; 95% CI 0.59, 0.85; P = .0002). The overall response rates were 55% in the 4-drug arm and 42% in the control arm. There were no significant differences in OS or final progression-free survival between the 3-drug arm containing atezolizumab and the control arm.

The most common adverse reactions with atezolizumab were fatigue/asthenia, alopecia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Treatment with atezolizumab was discontinued in 15% of patients due to adverse reactions, the most common reason being pneumonitis.

The recommended atezolizumab dose is 1,200 mg intravenously over 60 minutes every 3 weeks, the FDA said.

SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).

After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.

The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.

“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).

Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.

Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.

Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.

The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.

Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.

SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.

SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).

After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.

The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.

“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).

Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.

Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.

Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.

The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.

Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.

SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.

SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).

After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.

The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.

“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).

Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.

Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.

Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.

The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.

Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.

SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.

SAN ANTONIO – Good old tamoxifen, there’s life in the old girl yet: A 3-year course of low-dose tamoxifen – one-fourth of the standard dose – reduced the risk of breast intraepithelial neoplasia (IEN) recurrence by half, compared with placebo.

And although the patient numbers were relatively small, tamoxifen at 5 mg/day also reduced the risk of contralateral breast cancer by 75%, results of the TAM01 study showed.

Among 500 patients with either atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) randomized either to tamoxifen 5 mg/day for 3 years or placebo, there were 28 cases of either invasive breast cancer or recurrent DCIS in patients after a median follow-up of 5.1 years for patients assigned to placebo, compared with 14 events for patients assigned to tamoxifen, translating into a hazard ratio of 0.48 (P = .024), reported Andrea De Censi, MD, from Ospidali Galliera in Genoa, Italy, at the San Antonio Breast Cancer Symposium.

“We think our results have external validity because of the pragmatic nature of the study and the easy accessibility of the drug, and so they are generalizable,” he said, adding that “our findings are applicable in clinical practice from tomorrow [on].”

Despite concerns about the known carcinogenic and cardiovascular side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis (DVT)/pulmonary embolism between the groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen.

IEN accounts for approximately 15%-25% of all breast neoplasms. Although tamoxifen has a long track record of efficacy in prevention of recurrence, its side effects, including increased risk of endometrial cancer and thrombotic events as well as menopausal-type symptoms, have dissuaded some clinicians from prescribing it and scared some patients away from taking it.

Dr. De Censi and his colleagues conducted a phase 3 trial comparing tamoxifen 5 mg daily with placebo in 500 women with hormone-sensitive breast IEN following surgery. Women with grade 3 disease, positive margins, or comedo/necrosis DCIS received radiotherapy.

The patients were followed every 6 months, and had annual mammograms for at least 5 years after randomization.

As noted before, after 5.1 years median follow-up the primary endpoint of invasive breast cancer or DCIS had occurred in 28 patients on placebo versus 14 on tamoxifen, for an HR of 0.48. The respective incidences of contralateral breast cancer were 12 and 3, translating into a HR for tamoxifen at 0.24 (P = .018).

There were no statistically significant differences in serious adverse events between groups, including endometrial cancer (one in the tamoxifen group vs. one in the placebo group), DVT/PE (one in each group), other neoplasms (four vs. six cases, respectively), coronary heart disease (two cases each), other nonfatal events (three vs. five), or deaths (one vs. two).

“If we compare these findings with the NSABP-P1 prevention trial with a dose of 20 mg per day we would expect 2.7 endometrial cancers on tamoxifen, and 2.4 DVT or pulmonary emboli,” Dr. De Censi said in a briefing prior to his presentation of the data in a general session.

Patient-reported daily hot flashes occurred slightly but significantly more often with tamoxifen (P = .05). But when the frequency of reported hot flashes was multiplied by the intensity, the difference between the arms was not significant.

There were no significant differences between the groups for the patient-reported outcomes of vaginal dryness or pain at intercourse, or of musculoskeletal pain/arthralgia. Treatment adherence over 3 years did not differ between the groups.

Dr. De Censi noted that because 5 mg tablets of tamoxifen are not currently available, investigators recommend either cutting 10 mg tablets in half or taking the 10-mg dose every other day.

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated the briefing, commented that the study provides valuable information about the dosing of this time-tested drug.

“When you look at drug development, in many cases we rush these drugs out and we don’t pay attention to the dose that’s needed – we pay attention to the dose that’s not very toxic, and so many of the drugs that we use we end up using them at higher doses than we need to use them,” she said.

“A drug doesn’t work if you don’t take it, and so if you can find ways to take the drug, like in giving it at lower doses, then these women are going to benefit,” Dr. Kaklamani added.

She said that based on these data she would “definitely” give patients with ADH and LCIS lower doses of tamoxifen, and while she wants to see more data on DCIS patients with further follow-up, “if I have a DCIS patient who’s not tolerating tamoxifen at the 20 mg dose, I’d be extremely happy lowering to 5 mg.”

Sandhya Pruthi, MD, from the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, said in an interview that, while she was impressed by both the reduction in risk and the favorable side effect profile, the patient sample was too small to draw firm conclusions.

“Could I go back to the clinic and tell all my patients who are taking 20 mg of tamoxifen that you can now cut your dose in half to 10 mg or even to the 5-mg dose based on this trial? That would I think be a little premature,” she said.

“Where I would like to go with this is that we do a larger trial – a randomized, controlled trial,” Dr. Pruthi added.

The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest. Dr. Kaklamani and Dr. Pruthi reported no relevant conflicts of interest.

SOURCE: De Censi A et al. SABCS 2018, Abstract GS3-01.

SAN ANTONIO – Good old tamoxifen, there’s life in the old girl yet: A 3-year course of low-dose tamoxifen – one-fourth of the standard dose – reduced the risk of breast intraepithelial neoplasia (IEN) recurrence by half, compared with placebo.

And although the patient numbers were relatively small, tamoxifen at 5 mg/day also reduced the risk of contralateral breast cancer by 75%, results of the TAM01 study showed.

Among 500 patients with either atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) randomized either to tamoxifen 5 mg/day for 3 years or placebo, there were 28 cases of either invasive breast cancer or recurrent DCIS in patients after a median follow-up of 5.1 years for patients assigned to placebo, compared with 14 events for patients assigned to tamoxifen, translating into a hazard ratio of 0.48 (P = .024), reported Andrea De Censi, MD, from Ospidali Galliera in Genoa, Italy, at the San Antonio Breast Cancer Symposium.

“We think our results have external validity because of the pragmatic nature of the study and the easy accessibility of the drug, and so they are generalizable,” he said, adding that “our findings are applicable in clinical practice from tomorrow [on].”

Despite concerns about the known carcinogenic and cardiovascular side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis (DVT)/pulmonary embolism between the groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen.

IEN accounts for approximately 15%-25% of all breast neoplasms. Although tamoxifen has a long track record of efficacy in prevention of recurrence, its side effects, including increased risk of endometrial cancer and thrombotic events as well as menopausal-type symptoms, have dissuaded some clinicians from prescribing it and scared some patients away from taking it.

Dr. De Censi and his colleagues conducted a phase 3 trial comparing tamoxifen 5 mg daily with placebo in 500 women with hormone-sensitive breast IEN following surgery. Women with grade 3 disease, positive margins, or comedo/necrosis DCIS received radiotherapy.

The patients were followed every 6 months, and had annual mammograms for at least 5 years after randomization.

As noted before, after 5.1 years median follow-up the primary endpoint of invasive breast cancer or DCIS had occurred in 28 patients on placebo versus 14 on tamoxifen, for an HR of 0.48. The respective incidences of contralateral breast cancer were 12 and 3, translating into a HR for tamoxifen at 0.24 (P = .018).

There were no statistically significant differences in serious adverse events between groups, including endometrial cancer (one in the tamoxifen group vs. one in the placebo group), DVT/PE (one in each group), other neoplasms (four vs. six cases, respectively), coronary heart disease (two cases each), other nonfatal events (three vs. five), or deaths (one vs. two).

“If we compare these findings with the NSABP-P1 prevention trial with a dose of 20 mg per day we would expect 2.7 endometrial cancers on tamoxifen, and 2.4 DVT or pulmonary emboli,” Dr. De Censi said in a briefing prior to his presentation of the data in a general session.

Patient-reported daily hot flashes occurred slightly but significantly more often with tamoxifen (P = .05). But when the frequency of reported hot flashes was multiplied by the intensity, the difference between the arms was not significant.

There were no significant differences between the groups for the patient-reported outcomes of vaginal dryness or pain at intercourse, or of musculoskeletal pain/arthralgia. Treatment adherence over 3 years did not differ between the groups.

Dr. De Censi noted that because 5 mg tablets of tamoxifen are not currently available, investigators recommend either cutting 10 mg tablets in half or taking the 10-mg dose every other day.

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated the briefing, commented that the study provides valuable information about the dosing of this time-tested drug.

“When you look at drug development, in many cases we rush these drugs out and we don’t pay attention to the dose that’s needed – we pay attention to the dose that’s not very toxic, and so many of the drugs that we use we end up using them at higher doses than we need to use them,” she said.

“A drug doesn’t work if you don’t take it, and so if you can find ways to take the drug, like in giving it at lower doses, then these women are going to benefit,” Dr. Kaklamani added.

She said that based on these data she would “definitely” give patients with ADH and LCIS lower doses of tamoxifen, and while she wants to see more data on DCIS patients with further follow-up, “if I have a DCIS patient who’s not tolerating tamoxifen at the 20 mg dose, I’d be extremely happy lowering to 5 mg.”

Sandhya Pruthi, MD, from the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, said in an interview that, while she was impressed by both the reduction in risk and the favorable side effect profile, the patient sample was too small to draw firm conclusions.

“Could I go back to the clinic and tell all my patients who are taking 20 mg of tamoxifen that you can now cut your dose in half to 10 mg or even to the 5-mg dose based on this trial? That would I think be a little premature,” she said.

“Where I would like to go with this is that we do a larger trial – a randomized, controlled trial,” Dr. Pruthi added.

The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest. Dr. Kaklamani and Dr. Pruthi reported no relevant conflicts of interest.

SOURCE: De Censi A et al. SABCS 2018, Abstract GS3-01.

SAN ANTONIO – Good old tamoxifen, there’s life in the old girl yet: A 3-year course of low-dose tamoxifen – one-fourth of the standard dose – reduced the risk of breast intraepithelial neoplasia (IEN) recurrence by half, compared with placebo.

And although the patient numbers were relatively small, tamoxifen at 5 mg/day also reduced the risk of contralateral breast cancer by 75%, results of the TAM01 study showed.

Among 500 patients with either atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) randomized either to tamoxifen 5 mg/day for 3 years or placebo, there were 28 cases of either invasive breast cancer or recurrent DCIS in patients after a median follow-up of 5.1 years for patients assigned to placebo, compared with 14 events for patients assigned to tamoxifen, translating into a hazard ratio of 0.48 (P = .024), reported Andrea De Censi, MD, from Ospidali Galliera in Genoa, Italy, at the San Antonio Breast Cancer Symposium.

“We think our results have external validity because of the pragmatic nature of the study and the easy accessibility of the drug, and so they are generalizable,” he said, adding that “our findings are applicable in clinical practice from tomorrow [on].”

Despite concerns about the known carcinogenic and cardiovascular side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis (DVT)/pulmonary embolism between the groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen.

IEN accounts for approximately 15%-25% of all breast neoplasms. Although tamoxifen has a long track record of efficacy in prevention of recurrence, its side effects, including increased risk of endometrial cancer and thrombotic events as well as menopausal-type symptoms, have dissuaded some clinicians from prescribing it and scared some patients away from taking it.

Dr. De Censi and his colleagues conducted a phase 3 trial comparing tamoxifen 5 mg daily with placebo in 500 women with hormone-sensitive breast IEN following surgery. Women with grade 3 disease, positive margins, or comedo/necrosis DCIS received radiotherapy.

The patients were followed every 6 months, and had annual mammograms for at least 5 years after randomization.

As noted before, after 5.1 years median follow-up the primary endpoint of invasive breast cancer or DCIS had occurred in 28 patients on placebo versus 14 on tamoxifen, for an HR of 0.48. The respective incidences of contralateral breast cancer were 12 and 3, translating into a HR for tamoxifen at 0.24 (P = .018).

There were no statistically significant differences in serious adverse events between groups, including endometrial cancer (one in the tamoxifen group vs. one in the placebo group), DVT/PE (one in each group), other neoplasms (four vs. six cases, respectively), coronary heart disease (two cases each), other nonfatal events (three vs. five), or deaths (one vs. two).

“If we compare these findings with the NSABP-P1 prevention trial with a dose of 20 mg per day we would expect 2.7 endometrial cancers on tamoxifen, and 2.4 DVT or pulmonary emboli,” Dr. De Censi said in a briefing prior to his presentation of the data in a general session.

Patient-reported daily hot flashes occurred slightly but significantly more often with tamoxifen (P = .05). But when the frequency of reported hot flashes was multiplied by the intensity, the difference between the arms was not significant.

There were no significant differences between the groups for the patient-reported outcomes of vaginal dryness or pain at intercourse, or of musculoskeletal pain/arthralgia. Treatment adherence over 3 years did not differ between the groups.

Dr. De Censi noted that because 5 mg tablets of tamoxifen are not currently available, investigators recommend either cutting 10 mg tablets in half or taking the 10-mg dose every other day.

Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated the briefing, commented that the study provides valuable information about the dosing of this time-tested drug.

“When you look at drug development, in many cases we rush these drugs out and we don’t pay attention to the dose that’s needed – we pay attention to the dose that’s not very toxic, and so many of the drugs that we use we end up using them at higher doses than we need to use them,” she said.

“A drug doesn’t work if you don’t take it, and so if you can find ways to take the drug, like in giving it at lower doses, then these women are going to benefit,” Dr. Kaklamani added.

She said that based on these data she would “definitely” give patients with ADH and LCIS lower doses of tamoxifen, and while she wants to see more data on DCIS patients with further follow-up, “if I have a DCIS patient who’s not tolerating tamoxifen at the 20 mg dose, I’d be extremely happy lowering to 5 mg.”

Sandhya Pruthi, MD, from the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, said in an interview that, while she was impressed by both the reduction in risk and the favorable side effect profile, the patient sample was too small to draw firm conclusions.

“Could I go back to the clinic and tell all my patients who are taking 20 mg of tamoxifen that you can now cut your dose in half to 10 mg or even to the 5-mg dose based on this trial? That would I think be a little premature,” she said.

“Where I would like to go with this is that we do a larger trial – a randomized, controlled trial,” Dr. Pruthi added.

The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest. Dr. Kaklamani and Dr. Pruthi reported no relevant conflicts of interest.

SOURCE: De Censi A et al. SABCS 2018, Abstract GS3-01.

MONTREAL – A randomized trial designed to definitively test the efficacy of mechanical thrombectomy for treating acute ischemic strokes caused by basilar artery occlusion fell victim to slow recruitment and crossovers that muddied the intention-to-treat results, but the per-protocol and as-treated analyses both showed that thrombectomy was superior to best medical therapy in a multicenter, randomized study with 131 Chinese patients.

Mitchel L. Zoler/MDedge News

“Our findings should be considered in the context of the best evidence currently available, and progressive loss of equipoise for endovascular therapy for severe, large-vessel occlusion strokes,” Raul G. Nogueira, MD, said at the World Stroke Congress. “This was not a perfect trial, but it’s the best data we have, by far, at least for now” on the value of mechanical thrombectomy for treating acute ischemic stroke caused by a basilar artery occlusion, added Dr. Nogueira, professor of neurology and director of the neuroendovascular service at Emory University, Atlanta.

In the study’s per-protocol analysis, which considered patients who received their randomized treatment, the study’s primary endpoint of a modified Rankin Scale (mRS) score of 0-3 at 90 days after treatment was 44% in 63 patients who underwent thrombectomy and 26% in 51 patients randomized to best medical therapy who remained on that regimen, a statistically significant difference, Dr. Nogueira reported. In the as-treated analysis, which considered all enrolled patients based on the treatment they actually received regardless of randomization group, 77 patients treated with thrombectomy had a 47% rate of achieving the primary outcome, compared with 24% of 54 controls, also a statistically significant difference.

In contrast, the prespecified primary analysis for the study, the intention-to-treat analysis that considered patients based on their randomization assignment regardless of the treatment they actually received, showed that after 90 days the rate of patients with a mRS score of 0-3 was 42% in 66 thrombectomy patients and 32% among 65 controls, a difference that was not significant; this is a finding that, from a purist’s standpoint, makes the trial’s result neutral. The per-protocol and as-treated analyses were also prespecified steps in the study’s design, but not primary endpoints.

Despite the shortcoming for the primary analysis, Dr. Nogueira said that he found the per-protocol and as-treated findings very persuasive. “I personally could not randomize these patients” in the future to not receive mechanical thrombectomy, he confessed from the podium.

The BEST trial randomized 131 patients at any of 28 Chinese sites between April 2015 and September 2017. Patients had to enter within 8 hours of stroke onset. The original trial design called for enrolling 344 patients, but the steering committee decided in 2017 to prematurely stop the study because of a progressive drop in enrollment of patients, and “excessive” crossovers from the control arm to thrombectomy, a total of 14 patients. During the final month of the trial, 6 of 10 patients assigned by randomization to receive best medical care instead underwent thrombectomy. “At that point, we pretty much had to stop,” Dr. Nogueira said. Enrolled patients averaged about 65 years old, about 90% had a basilar artery occlusion and about 10% a vertebral artery occlusion, about 30% received intravenous alteplase, and the median National Institutes of Health Stroke Scale score at entry was about 30.

The major adverse effect from thrombectomy seen in the study was symptomatic intracranial hemorrhage, which occurred in 5 of the 77 patients (6%) actually treated with thrombectomy, compared with none of the 54 patients not treated with thrombectomy. This modest rate of intracranial hemorrhages was “not unexpected,” Dr. Nogueira noted.

Acute ischemic strokes caused by a basilar artery occlusion are relatively uncommon, accounting for about 1% of all acute ischemic strokes and 5%-10% of acute ischemic strokes caused by occlusion of a proximal intracranial artery. But when these strokes occur, they are a “neurological catastrophe,” Dr. Nogueira said, causing severe disability or mortality in about 70% of patients.

BEST had no commercial funding. Dr. Nogueira reported no disclosures.

[email protected]

SOURCE: Nogueira RG et al. Int J Stroke. 2018;13(2_suppl):227, Abstract 978.


 

MONTREAL – A randomized trial designed to definitively test the efficacy of mechanical thrombectomy for treating acute ischemic strokes caused by basilar artery occlusion fell victim to slow recruitment and crossovers that muddied the intention-to-treat results, but the per-protocol and as-treated analyses both showed that thrombectomy was superior to best medical therapy in a multicenter, randomized study with 131 Chinese patients.

Mitchel L. Zoler/MDedge News

“Our findings should be considered in the context of the best evidence currently available, and progressive loss of equipoise for endovascular therapy for severe, large-vessel occlusion strokes,” Raul G. Nogueira, MD, said at the World Stroke Congress. “This was not a perfect trial, but it’s the best data we have, by far, at least for now” on the value of mechanical thrombectomy for treating acute ischemic stroke caused by a basilar artery occlusion, added Dr. Nogueira, professor of neurology and director of the neuroendovascular service at Emory University, Atlanta.

In the study’s per-protocol analysis, which considered patients who received their randomized treatment, the study’s primary endpoint of a modified Rankin Scale (mRS) score of 0-3 at 90 days after treatment was 44% in 63 patients who underwent thrombectomy and 26% in 51 patients randomized to best medical therapy who remained on that regimen, a statistically significant difference, Dr. Nogueira reported. In the as-treated analysis, which considered all enrolled patients based on the treatment they actually received regardless of randomization group, 77 patients treated with thrombectomy had a 47% rate of achieving the primary outcome, compared with 24% of 54 controls, also a statistically significant difference.

In contrast, the prespecified primary analysis for the study, the intention-to-treat analysis that considered patients based on their randomization assignment regardless of the treatment they actually received, showed that after 90 days the rate of patients with a mRS score of 0-3 was 42% in 66 thrombectomy patients and 32% among 65 controls, a difference that was not significant; this is a finding that, from a purist’s standpoint, makes the trial’s result neutral. The per-protocol and as-treated analyses were also prespecified steps in the study’s design, but not primary endpoints.

Despite the shortcoming for the primary analysis, Dr. Nogueira said that he found the per-protocol and as-treated findings very persuasive. “I personally could not randomize these patients” in the future to not receive mechanical thrombectomy, he confessed from the podium.

The BEST trial randomized 131 patients at any of 28 Chinese sites between April 2015 and September 2017. Patients had to enter within 8 hours of stroke onset. The original trial design called for enrolling 344 patients, but the steering committee decided in 2017 to prematurely stop the study because of a progressive drop in enrollment of patients, and “excessive” crossovers from the control arm to thrombectomy, a total of 14 patients. During the final month of the trial, 6 of 10 patients assigned by randomization to receive best medical care instead underwent thrombectomy. “At that point, we pretty much had to stop,” Dr. Nogueira said. Enrolled patients averaged about 65 years old, about 90% had a basilar artery occlusion and about 10% a vertebral artery occlusion, about 30% received intravenous alteplase, and the median National Institutes of Health Stroke Scale score at entry was about 30.

The major adverse effect from thrombectomy seen in the study was symptomatic intracranial hemorrhage, which occurred in 5 of the 77 patients (6%) actually treated with thrombectomy, compared with none of the 54 patients not treated with thrombectomy. This modest rate of intracranial hemorrhages was “not unexpected,” Dr. Nogueira noted.

Acute ischemic strokes caused by a basilar artery occlusion are relatively uncommon, accounting for about 1% of all acute ischemic strokes and 5%-10% of acute ischemic strokes caused by occlusion of a proximal intracranial artery. But when these strokes occur, they are a “neurological catastrophe,” Dr. Nogueira said, causing severe disability or mortality in about 70% of patients.

BEST had no commercial funding. Dr. Nogueira reported no disclosures.

[email protected]

SOURCE: Nogueira RG et al. Int J Stroke. 2018;13(2_suppl):227, Abstract 978.


 

MONTREAL – A randomized trial designed to definitively test the efficacy of mechanical thrombectomy for treating acute ischemic strokes caused by basilar artery occlusion fell victim to slow recruitment and crossovers that muddied the intention-to-treat results, but the per-protocol and as-treated analyses both showed that thrombectomy was superior to best medical therapy in a multicenter, randomized study with 131 Chinese patients.

Mitchel L. Zoler/MDedge News

“Our findings should be considered in the context of the best evidence currently available, and progressive loss of equipoise for endovascular therapy for severe, large-vessel occlusion strokes,” Raul G. Nogueira, MD, said at the World Stroke Congress. “This was not a perfect trial, but it’s the best data we have, by far, at least for now” on the value of mechanical thrombectomy for treating acute ischemic stroke caused by a basilar artery occlusion, added Dr. Nogueira, professor of neurology and director of the neuroendovascular service at Emory University, Atlanta.

In the study’s per-protocol analysis, which considered patients who received their randomized treatment, the study’s primary endpoint of a modified Rankin Scale (mRS) score of 0-3 at 90 days after treatment was 44% in 63 patients who underwent thrombectomy and 26% in 51 patients randomized to best medical therapy who remained on that regimen, a statistically significant difference, Dr. Nogueira reported. In the as-treated analysis, which considered all enrolled patients based on the treatment they actually received regardless of randomization group, 77 patients treated with thrombectomy had a 47% rate of achieving the primary outcome, compared with 24% of 54 controls, also a statistically significant difference.

In contrast, the prespecified primary analysis for the study, the intention-to-treat analysis that considered patients based on their randomization assignment regardless of the treatment they actually received, showed that after 90 days the rate of patients with a mRS score of 0-3 was 42% in 66 thrombectomy patients and 32% among 65 controls, a difference that was not significant; this is a finding that, from a purist’s standpoint, makes the trial’s result neutral. The per-protocol and as-treated analyses were also prespecified steps in the study’s design, but not primary endpoints.

Despite the shortcoming for the primary analysis, Dr. Nogueira said that he found the per-protocol and as-treated findings very persuasive. “I personally could not randomize these patients” in the future to not receive mechanical thrombectomy, he confessed from the podium.

The BEST trial randomized 131 patients at any of 28 Chinese sites between April 2015 and September 2017. Patients had to enter within 8 hours of stroke onset. The original trial design called for enrolling 344 patients, but the steering committee decided in 2017 to prematurely stop the study because of a progressive drop in enrollment of patients, and “excessive” crossovers from the control arm to thrombectomy, a total of 14 patients. During the final month of the trial, 6 of 10 patients assigned by randomization to receive best medical care instead underwent thrombectomy. “At that point, we pretty much had to stop,” Dr. Nogueira said. Enrolled patients averaged about 65 years old, about 90% had a basilar artery occlusion and about 10% a vertebral artery occlusion, about 30% received intravenous alteplase, and the median National Institutes of Health Stroke Scale score at entry was about 30.

The major adverse effect from thrombectomy seen in the study was symptomatic intracranial hemorrhage, which occurred in 5 of the 77 patients (6%) actually treated with thrombectomy, compared with none of the 54 patients not treated with thrombectomy. This modest rate of intracranial hemorrhages was “not unexpected,” Dr. Nogueira noted.

Acute ischemic strokes caused by a basilar artery occlusion are relatively uncommon, accounting for about 1% of all acute ischemic strokes and 5%-10% of acute ischemic strokes caused by occlusion of a proximal intracranial artery. But when these strokes occur, they are a “neurological catastrophe,” Dr. Nogueira said, causing severe disability or mortality in about 70% of patients.

BEST had no commercial funding. Dr. Nogueira reported no disclosures.

[email protected]

SOURCE: Nogueira RG et al. Int J Stroke. 2018;13(2_suppl):227, Abstract 978.


 

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

[email protected]

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

[email protected]

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

CHICAGO – A recent history of GI bleeding or malignancy may not be a valid contraindication to thrombolytic therapy in patients with an acute ischemic stroke, based on a review of outcomes from more than 40,000 U.S. stroke patients.

The analysis showed that, among 40,396 U.S. patients who had an acute ischemic stroke during 2009-2015 and received timely treatment with alteplase, “we did not find statistically significant increased rates of in-hospital mortality or bleeding” in the small number of patients who received alteplase (Activase) despite a recent GI bleed or diagnosed GI malignancy, Taku Inohara, MD, said at the American Heart Association scientific sessions. The 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke deemed thrombolytic therapy with alteplase in these types of patients contraindicated, based on consensus expert opinion (Stroke. 2018 March;49[3]:e66-e110).

“Further study is needed to evaluate the safety of recombinant tissue–type plasminogen activator [alteplase] in this specific population,” suggested Dr. Inohara, a cardiologist and research fellow at Duke University, Durham, N.C.

His analysis used data collected by the Get With the Guidelines–Stroke program, a voluntary quality promotion and improvement program that during 2009-2015 included records for more than 633,000 U.S. stroke patients that could be linked with records kept by the Centers for Medicare & Medicaid Services. From this database, 40,396 patients (6%) treated with alteplase within 4.5 hours of stroke onset were identified. The alteplase-treated patients included 93 with a diagnosis code during the prior year for a GI malignancy and 43 with a diagnostic code within the prior 21 days for a GI bleed.


Dr. Inohara and his associates determined patients’ mortality during their stroke hospitalization, as well as several measures of functional recovery at hospital discharge and thrombolysis-related complications. For each of these endpoints, the rate among patients with a GI malignancy, a GI bleed, or the rate among a combined group of both patients showed no statistically significant differences, compared with the more than 40,000 other patients without a GI complication after adjustment for several demographic and clinical between-group differences. However, Dr. Inohara cautioned that residual or unmeasured confounding may exist that distorts these findings. The rate of in-hospital mortality, the prespecified primary endpoint for the analysis, was 10% among patients with either type of GI complication and 9% in those without. The rate of serious thrombolysis-related complications was 7% in the patients with GI disease and 9% in those without.

In a separate analysis of the complete database of more than 633,000 patients, Dr. Inohara and his associates found 148 patients who had either a GI bleed or malignancy and otherwise qualified for thrombolytic therapy but did not receive this treatment. This meant that overall, in this large U.S. experience, 136 of 284 (48%) acute ischemic stroke patients who qualified for thrombolysis but had a GI complication nonetheless received thrombolysis. Further analysis showed that the patients not treated with thrombolysis had at admission an average National Institutes of Health Stroke Scale score of 11, compared with an average score of 14 among patients who received thrombolysis.

This apparent selection for thrombolytic treatment of patients with more severe strokes “may have overestimated risk in the patients with GI disease,” Dr. Inohara said.

Dr. Inohara reported receiving research funding from Boston Scientific.

[email protected]

SOURCE: Inohara T et al. Circulation. 2018 Nov 6;138[suppl 1], Abstract 12291.

Carol Bernstein, MD, joins Nick Andrews to talk about the difference between physician burnout and depression. Dr. Bernstein is a professor at NYU Langone in New York City and has been a guest on the MDedge Psychcast.
Apple Podcasts
Google Podcasts


 

Carol Bernstein, MD, joins Nick Andrews to talk about the difference between physician burnout and depression. Dr. Bernstein is a professor at NYU Langone in New York City and has been a guest on the MDedge Psychcast.
Apple Podcasts
Google Podcasts


 

Carol Bernstein, MD, joins Nick Andrews to talk about the difference between physician burnout and depression. Dr. Bernstein is a professor at NYU Langone in New York City and has been a guest on the MDedge Psychcast.
Apple Podcasts
Google Podcasts


 

A new proposal aims to move clinicians away from the keyboard and back to face time with patients. Also today, diuretics are linked to diabetic amputations in type 2 diabetes, pausing direct acting oral anticoagulants show favorable outcomes for atrial fibrillation, and while therapy has matured for patients with HCV, there are still issues with access.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

A new proposal aims to move clinicians away from the keyboard and back to face time with patients. Also today, diuretics are linked to diabetic amputations in type 2 diabetes, pausing direct acting oral anticoagulants show favorable outcomes for atrial fibrillation, and while therapy has matured for patients with HCV, there are still issues with access.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

A new proposal aims to move clinicians away from the keyboard and back to face time with patients. Also today, diuretics are linked to diabetic amputations in type 2 diabetes, pausing direct acting oral anticoagulants show favorable outcomes for atrial fibrillation, and while therapy has matured for patients with HCV, there are still issues with access.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify