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Official Newspaper of the American College of Surgeons
Mitral valve repair no better than replacement
Mitral valve repair was no better than chordal-sparing mitral valve replacement in the first randomized clinical trial attempting to settle the controversy over which procedure is superior for treating functional ischemic mitral regurgitation, which was simultaneously reported at the annual scientific sessions of the American Heart Association and online Nov. 18 in the New England Journal of Medicine.
In the past few years, the use of mitral valve repair has far exceeded that of mitral valve replacement for this indication, largely on the basis of reports that the repair procedure yields lower operative mortality, improved left ventricular function, and higher long-term survival rates. In particular, a 2011 meta-analysis found a 35% lower relative risk of death in the long term with mitral valve repair, compared with replacement, said Dr. Michael A. Acker and his associates in the Cardiothoracic Surgical Trials Network (CTSN).
But in their multicenter study directly comparing the two procedures in 251 patients with severe functional ischemic mitral regurgitation, there was no significant difference between the surgeries in left ventricular end-systolic volume index at 1 year, nor in mortality at either 1 month or 1 year.
Moreover, study participants who underwent mitral valve repair showed a disturbing excess in the rate of recurrence of mitral regurgitation at 1 year, with a rate that was 30 percentage points higher than that among patients who underwent mitral valve replacement. "This lack of durability in correction of mitral regurgitation is disconcerting, given its reported association with further progression and long-term negative outcomes," said Dr. Acker of the division of cardiovascular surgery, University of Pennsylvania, Philadelphia, and his associates.
Functional ischemic mitral regurgitation, a "high-prevalence" condition affecting an estimated 2-3 million Americans, differs from primary degenerative mitral regurgitation in that the valve leaflets themselves remain normal while the defect occurs in the myocardium. "Ischemic mitral regurgitation is a consequence of adverse left ventricular remodeling after myocardial injury, with enlargement of the left ventricular chamber and mitral annulus, apical and lateral migration of the papillary muscles, leaflet retethering, and reduced closing forces.
"These processes lead to malcoaptation of the leaflets and variable degrees of mitral regurgitation that can fluctuate dynamically as a function of volume status, afterload, heart rhythm, and residual ischemia," the researchers said.
Current practice guidelines recommend mitral valve repair or chordal-sparing mitral valve replacement for severe regurgitation unresponsive to medical therapy, but do not specify which procedure is preferred because there is no conclusive evidence demonstrating the superiority of one over the other. "Recently, the field has embraced mitral valve repair over replacement," even without such evidence, Dr. Acker and his colleagues said.
The CTSN performed this study at 22 medical centers to assess the relative benefits of the two surgeries, with 126 patients randomized to undergo mitral valve repair and 125 to undergo replacement that included complete preservation of the subvalvular apparatus.
The primary endpoint was the degree of LV reverse remodeling, as measured by the left ventricular end-systolic volume index (LVESVI) on transthoracic echocardiography, at 1 year. The mean LVESVI was not significantly different between the repair group (54.6 mL per square meter) and the replacement group (60.7 mL per square meter), reflecting decreases of 6.6 mL per square meter and 6.8 mL per square meter, respectively, the investigators said (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1312808]).
The median between group difference in the change in LVESVI score after surgery also was not clinically significant.
However, 32.6% of patients who underwent mitral valve repair had a recurrence of regurgitation within 1 year, compared with only 2.3% of those who had mitral valve replacement. Three patients in the repair group required reoperation, compared with none in the replacement group.
There were no significant differences in cumulative mortality, 30-day postoperative mortality, or 1-year mortality between the two study groups, and no significant difference in a composite endpoint of major adverse cardiac or cerebrovascular events.
Rates of serious adverse events were similar, and the durations of hospitalization were similar between the two study groups, as were rates of readmission. All measures of quality of life and functional status on two different assessment tools also were similar.
"Our findings contradict much of the published literature on this topic, which reports several advantages to mitral valve repair over replacement, including lower operative mortality, improved left ventricular function, and higher rates of long-term survival," Dr. Acker and his associates noted.
The evolution of the valve replacement procedure, which now includes chordal sparing, "may account for the improved results we observed, as compared with previous studies, since the retention of the internal architectural support of the left ventricle may preserve contractile efficiency and reduce left ventricular dilatation and dysfunction," they said.
This study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Diseases and Stroke, and the Canadian Institutes of Health Research. Dr. Acker and his associates reported no financial conflicts of interest.
Mitral valve repair was no better than chordal-sparing mitral valve replacement in the first randomized clinical trial attempting to settle the controversy over which procedure is superior for treating functional ischemic mitral regurgitation, which was simultaneously reported at the annual scientific sessions of the American Heart Association and online Nov. 18 in the New England Journal of Medicine.
In the past few years, the use of mitral valve repair has far exceeded that of mitral valve replacement for this indication, largely on the basis of reports that the repair procedure yields lower operative mortality, improved left ventricular function, and higher long-term survival rates. In particular, a 2011 meta-analysis found a 35% lower relative risk of death in the long term with mitral valve repair, compared with replacement, said Dr. Michael A. Acker and his associates in the Cardiothoracic Surgical Trials Network (CTSN).
But in their multicenter study directly comparing the two procedures in 251 patients with severe functional ischemic mitral regurgitation, there was no significant difference between the surgeries in left ventricular end-systolic volume index at 1 year, nor in mortality at either 1 month or 1 year.
Moreover, study participants who underwent mitral valve repair showed a disturbing excess in the rate of recurrence of mitral regurgitation at 1 year, with a rate that was 30 percentage points higher than that among patients who underwent mitral valve replacement. "This lack of durability in correction of mitral regurgitation is disconcerting, given its reported association with further progression and long-term negative outcomes," said Dr. Acker of the division of cardiovascular surgery, University of Pennsylvania, Philadelphia, and his associates.
Functional ischemic mitral regurgitation, a "high-prevalence" condition affecting an estimated 2-3 million Americans, differs from primary degenerative mitral regurgitation in that the valve leaflets themselves remain normal while the defect occurs in the myocardium. "Ischemic mitral regurgitation is a consequence of adverse left ventricular remodeling after myocardial injury, with enlargement of the left ventricular chamber and mitral annulus, apical and lateral migration of the papillary muscles, leaflet retethering, and reduced closing forces.
"These processes lead to malcoaptation of the leaflets and variable degrees of mitral regurgitation that can fluctuate dynamically as a function of volume status, afterload, heart rhythm, and residual ischemia," the researchers said.
Current practice guidelines recommend mitral valve repair or chordal-sparing mitral valve replacement for severe regurgitation unresponsive to medical therapy, but do not specify which procedure is preferred because there is no conclusive evidence demonstrating the superiority of one over the other. "Recently, the field has embraced mitral valve repair over replacement," even without such evidence, Dr. Acker and his colleagues said.
The CTSN performed this study at 22 medical centers to assess the relative benefits of the two surgeries, with 126 patients randomized to undergo mitral valve repair and 125 to undergo replacement that included complete preservation of the subvalvular apparatus.
The primary endpoint was the degree of LV reverse remodeling, as measured by the left ventricular end-systolic volume index (LVESVI) on transthoracic echocardiography, at 1 year. The mean LVESVI was not significantly different between the repair group (54.6 mL per square meter) and the replacement group (60.7 mL per square meter), reflecting decreases of 6.6 mL per square meter and 6.8 mL per square meter, respectively, the investigators said (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1312808]).
The median between group difference in the change in LVESVI score after surgery also was not clinically significant.
However, 32.6% of patients who underwent mitral valve repair had a recurrence of regurgitation within 1 year, compared with only 2.3% of those who had mitral valve replacement. Three patients in the repair group required reoperation, compared with none in the replacement group.
There were no significant differences in cumulative mortality, 30-day postoperative mortality, or 1-year mortality between the two study groups, and no significant difference in a composite endpoint of major adverse cardiac or cerebrovascular events.
Rates of serious adverse events were similar, and the durations of hospitalization were similar between the two study groups, as were rates of readmission. All measures of quality of life and functional status on two different assessment tools also were similar.
"Our findings contradict much of the published literature on this topic, which reports several advantages to mitral valve repair over replacement, including lower operative mortality, improved left ventricular function, and higher rates of long-term survival," Dr. Acker and his associates noted.
The evolution of the valve replacement procedure, which now includes chordal sparing, "may account for the improved results we observed, as compared with previous studies, since the retention of the internal architectural support of the left ventricle may preserve contractile efficiency and reduce left ventricular dilatation and dysfunction," they said.
This study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Diseases and Stroke, and the Canadian Institutes of Health Research. Dr. Acker and his associates reported no financial conflicts of interest.
Mitral valve repair was no better than chordal-sparing mitral valve replacement in the first randomized clinical trial attempting to settle the controversy over which procedure is superior for treating functional ischemic mitral regurgitation, which was simultaneously reported at the annual scientific sessions of the American Heart Association and online Nov. 18 in the New England Journal of Medicine.
In the past few years, the use of mitral valve repair has far exceeded that of mitral valve replacement for this indication, largely on the basis of reports that the repair procedure yields lower operative mortality, improved left ventricular function, and higher long-term survival rates. In particular, a 2011 meta-analysis found a 35% lower relative risk of death in the long term with mitral valve repair, compared with replacement, said Dr. Michael A. Acker and his associates in the Cardiothoracic Surgical Trials Network (CTSN).
But in their multicenter study directly comparing the two procedures in 251 patients with severe functional ischemic mitral regurgitation, there was no significant difference between the surgeries in left ventricular end-systolic volume index at 1 year, nor in mortality at either 1 month or 1 year.
Moreover, study participants who underwent mitral valve repair showed a disturbing excess in the rate of recurrence of mitral regurgitation at 1 year, with a rate that was 30 percentage points higher than that among patients who underwent mitral valve replacement. "This lack of durability in correction of mitral regurgitation is disconcerting, given its reported association with further progression and long-term negative outcomes," said Dr. Acker of the division of cardiovascular surgery, University of Pennsylvania, Philadelphia, and his associates.
Functional ischemic mitral regurgitation, a "high-prevalence" condition affecting an estimated 2-3 million Americans, differs from primary degenerative mitral regurgitation in that the valve leaflets themselves remain normal while the defect occurs in the myocardium. "Ischemic mitral regurgitation is a consequence of adverse left ventricular remodeling after myocardial injury, with enlargement of the left ventricular chamber and mitral annulus, apical and lateral migration of the papillary muscles, leaflet retethering, and reduced closing forces.
"These processes lead to malcoaptation of the leaflets and variable degrees of mitral regurgitation that can fluctuate dynamically as a function of volume status, afterload, heart rhythm, and residual ischemia," the researchers said.
Current practice guidelines recommend mitral valve repair or chordal-sparing mitral valve replacement for severe regurgitation unresponsive to medical therapy, but do not specify which procedure is preferred because there is no conclusive evidence demonstrating the superiority of one over the other. "Recently, the field has embraced mitral valve repair over replacement," even without such evidence, Dr. Acker and his colleagues said.
The CTSN performed this study at 22 medical centers to assess the relative benefits of the two surgeries, with 126 patients randomized to undergo mitral valve repair and 125 to undergo replacement that included complete preservation of the subvalvular apparatus.
The primary endpoint was the degree of LV reverse remodeling, as measured by the left ventricular end-systolic volume index (LVESVI) on transthoracic echocardiography, at 1 year. The mean LVESVI was not significantly different between the repair group (54.6 mL per square meter) and the replacement group (60.7 mL per square meter), reflecting decreases of 6.6 mL per square meter and 6.8 mL per square meter, respectively, the investigators said (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1312808]).
The median between group difference in the change in LVESVI score after surgery also was not clinically significant.
However, 32.6% of patients who underwent mitral valve repair had a recurrence of regurgitation within 1 year, compared with only 2.3% of those who had mitral valve replacement. Three patients in the repair group required reoperation, compared with none in the replacement group.
There were no significant differences in cumulative mortality, 30-day postoperative mortality, or 1-year mortality between the two study groups, and no significant difference in a composite endpoint of major adverse cardiac or cerebrovascular events.
Rates of serious adverse events were similar, and the durations of hospitalization were similar between the two study groups, as were rates of readmission. All measures of quality of life and functional status on two different assessment tools also were similar.
"Our findings contradict much of the published literature on this topic, which reports several advantages to mitral valve repair over replacement, including lower operative mortality, improved left ventricular function, and higher rates of long-term survival," Dr. Acker and his associates noted.
The evolution of the valve replacement procedure, which now includes chordal sparing, "may account for the improved results we observed, as compared with previous studies, since the retention of the internal architectural support of the left ventricle may preserve contractile efficiency and reduce left ventricular dilatation and dysfunction," they said.
This study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Diseases and Stroke, and the Canadian Institutes of Health Research. Dr. Acker and his associates reported no financial conflicts of interest.
FROM THE AHA SCIENTIFIC SESSIONS
Major Finding: The primary end point – the degree of LV reverse remodeling, as measured by the left ventricular end-systolic volume index on transthoracic echocardiography at 1 year – was not significantly different between the repair group (54.6 mL per square meter) and the replacement group (60.7 mL per square meter).
Data Source: A randomized clinical trial involving 126 patients with severe functional ischemic mitral regurgitation who underwent mitral valve repair and 125 who underwent chordal-sparing mitral valve replacement, and who were followed for 1 year.
Disclosures: This study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Diseases and Stroke, and the Canadian Institutes of Health Research. Dr. Acker and his associates reported no financial conflicts of interest.
No greater risk of lymph node involvement in triple-negative breast cancer
SAN FRANCISCO – Patients with triple-negative breast cancer had no higher risk for metastases in the lymph nodes as compared with patients whose breast cancer was not triple-negative, a review of 2,957 cases found.
The study included patients with invasive breast cancer treated surgically between January 2000 and May 2012. Immunohistochemical identification of markers showed that 2,201 (74%) had luminal A subtype breast cancer (estrogen receptor– and progesterone receptor–positive and HER2 negative), 344 (12%) had luminal B subtype (all three markers positive), 144 (5%) were HER2 positive but estrogen and progesterone receptors–negative, and 278 (9%) were negative for all three markers (the triple-negative group). The study excluded men, patients treated with neoadjuvant therapy, patients with distant metastases, and those who did not undergo nodal sampling.
At least one positive lymph node was found in 35% of patients, and four or more positive nodes were found in 10% of patients.
Patients in the triple-negative group were significantly younger at diagnosis and significantly more likely to have higher-grade tumors, compared with patients with other subtypes of breast cancer. Grade 3 cancer was seen in 87% of the triple-negative group and in 27% of the luminal A group, 51% of the luminal B group, and 80% of the HER2-positive group, Dr. Alexandra Gangi and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
In multivariant analyses, younger age, higher tumor grade, larger tumor size, and lymphovascular invasion predicted increased likelihood of lymph node metastases. The triple-negative phenotype predicted neither a higher risk for lymph node positivity nor a greater likelihood of having four or more positive lymph nodes, which was found in 9% of the triple-negative group, 9% of the luminal A group, 14% of the luminal B group, and 19% of the HER2-positive group, reported Dr. Gangi of Cedars-Sinai Hospital, Los Angeles.
The likelihood of lymph node metastases was 50% higher in patients younger than 50 years as compared with older patients, 70% higher with grade 2 cancer as compared with grade 1 cancer, and 90% higher with grade 3 cancer as compared with grade 1 cancer. Lymphovascular invasion increased the likelihood of lymph node involvement four-fold. The risk of lymph node metastases was three times higher in patients with stage T2 breast cancer and 11 times higher in patients with stage T3 disease as compared with those with stage T1 breast cancer. All of these differences were statistically significant.
The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.
Dr. Gangi reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Patients with triple-negative breast cancer had no higher risk for metastases in the lymph nodes as compared with patients whose breast cancer was not triple-negative, a review of 2,957 cases found.
The study included patients with invasive breast cancer treated surgically between January 2000 and May 2012. Immunohistochemical identification of markers showed that 2,201 (74%) had luminal A subtype breast cancer (estrogen receptor– and progesterone receptor–positive and HER2 negative), 344 (12%) had luminal B subtype (all three markers positive), 144 (5%) were HER2 positive but estrogen and progesterone receptors–negative, and 278 (9%) were negative for all three markers (the triple-negative group). The study excluded men, patients treated with neoadjuvant therapy, patients with distant metastases, and those who did not undergo nodal sampling.
At least one positive lymph node was found in 35% of patients, and four or more positive nodes were found in 10% of patients.
Patients in the triple-negative group were significantly younger at diagnosis and significantly more likely to have higher-grade tumors, compared with patients with other subtypes of breast cancer. Grade 3 cancer was seen in 87% of the triple-negative group and in 27% of the luminal A group, 51% of the luminal B group, and 80% of the HER2-positive group, Dr. Alexandra Gangi and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
In multivariant analyses, younger age, higher tumor grade, larger tumor size, and lymphovascular invasion predicted increased likelihood of lymph node metastases. The triple-negative phenotype predicted neither a higher risk for lymph node positivity nor a greater likelihood of having four or more positive lymph nodes, which was found in 9% of the triple-negative group, 9% of the luminal A group, 14% of the luminal B group, and 19% of the HER2-positive group, reported Dr. Gangi of Cedars-Sinai Hospital, Los Angeles.
The likelihood of lymph node metastases was 50% higher in patients younger than 50 years as compared with older patients, 70% higher with grade 2 cancer as compared with grade 1 cancer, and 90% higher with grade 3 cancer as compared with grade 1 cancer. Lymphovascular invasion increased the likelihood of lymph node involvement four-fold. The risk of lymph node metastases was three times higher in patients with stage T2 breast cancer and 11 times higher in patients with stage T3 disease as compared with those with stage T1 breast cancer. All of these differences were statistically significant.
The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.
Dr. Gangi reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Patients with triple-negative breast cancer had no higher risk for metastases in the lymph nodes as compared with patients whose breast cancer was not triple-negative, a review of 2,957 cases found.
The study included patients with invasive breast cancer treated surgically between January 2000 and May 2012. Immunohistochemical identification of markers showed that 2,201 (74%) had luminal A subtype breast cancer (estrogen receptor– and progesterone receptor–positive and HER2 negative), 344 (12%) had luminal B subtype (all three markers positive), 144 (5%) were HER2 positive but estrogen and progesterone receptors–negative, and 278 (9%) were negative for all three markers (the triple-negative group). The study excluded men, patients treated with neoadjuvant therapy, patients with distant metastases, and those who did not undergo nodal sampling.
At least one positive lymph node was found in 35% of patients, and four or more positive nodes were found in 10% of patients.
Patients in the triple-negative group were significantly younger at diagnosis and significantly more likely to have higher-grade tumors, compared with patients with other subtypes of breast cancer. Grade 3 cancer was seen in 87% of the triple-negative group and in 27% of the luminal A group, 51% of the luminal B group, and 80% of the HER2-positive group, Dr. Alexandra Gangi and her associates reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
In multivariant analyses, younger age, higher tumor grade, larger tumor size, and lymphovascular invasion predicted increased likelihood of lymph node metastases. The triple-negative phenotype predicted neither a higher risk for lymph node positivity nor a greater likelihood of having four or more positive lymph nodes, which was found in 9% of the triple-negative group, 9% of the luminal A group, 14% of the luminal B group, and 19% of the HER2-positive group, reported Dr. Gangi of Cedars-Sinai Hospital, Los Angeles.
The likelihood of lymph node metastases was 50% higher in patients younger than 50 years as compared with older patients, 70% higher with grade 2 cancer as compared with grade 1 cancer, and 90% higher with grade 3 cancer as compared with grade 1 cancer. Lymphovascular invasion increased the likelihood of lymph node involvement four-fold. The risk of lymph node metastases was three times higher in patients with stage T2 breast cancer and 11 times higher in patients with stage T3 disease as compared with those with stage T1 breast cancer. All of these differences were statistically significant.
The symposium was cosponsored by the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Centers, the Society of Surgical Oncology, and the American Society for Radiation Oncology.
Dr. Gangi reported having no financial disclosures.
On Twitter @sherryboschert
AT THE ASCO BREAST CANCER SYMPOSIUM
Major finding: The likelihood of lymph node metastases was 50% higher in patients younger than 50 years as compared with older patients, 70% higher with grade 2 cancer as compared with grade 1 cancer, and 90% higher with grade 3 cancer as compared with grade 1 cancer.
Data source: A prospect review of 2,957 women treated surgically for breast cancer between January 2000 and May 2012.
Disclosures: Dr. Gangi reported having no financial disclosures.
Antimalarials prove protective against long-term lupus damage
SAN DIEGO – Potentially modifiable risk factors for future irreversible organ damage in lupus patients include hypertension, the use of corticosteroids, and higher levels of inflammation early on, according to findings from the SLICC (Systemic Lupus International Collaborating Clinics) Inception Cohort Study.
In addition, the study identified the use of antimalarial drugs as the one significant protective factor against steady accrual of irreversible organ damage in lupus patients.
"These findings help us pave the way to consider whether, firstly, one could use damage as a primary endpoint in future clinical trials in lupus – somewhat akin to how the erosion score is used in rheumatoid arthritis – and secondly, the results suggest particular interventions that might be important in reducing the risk of damage over time," Dr. Ian N. Bruce said at the annual meeting of the American College of Rheumatology.
The study also identified several fixed and unmodifiable risk factors for irreversible damage in lupus patients: older age at diagnosis, male gender, and being black or white Americans, added Dr. Bruce, professor of rheumatology at the University of Manchester (U.K.) and chair of the SLICC research group.
The SLICC Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries in North America, Europe, and Asia who enrolled within 15 months after being formally diagnosed with systemic lupus erythematosus based upon the 1997 ACR criteria. They averaged 35 years of age and had an average of 4.25 comprehensive annual follow-up visits during the study period.
Irreversible organ damage was assessed using the SLICC/ACR Damage Index, or SDI. At baseline, 35% of patients had at least one item of damage as indicated by an SDI score of 1 or more. Over time, damage rates slowly and steadily increased such that by 6 years of follow-up 51% of participants had an SDI of at least 1.
In a multivariate analysis, patients with an SDI score of 1 at baseline had a highly significant 37% reduction in the risk of increasing their score during follow-up if they were taking antimalarials, compared with those not taking antimalarials.
On the other hand, patients with a baseline SDI of 1 were 61% more likely to experience an increase in their damage score during follow-up if they had hypertension and 43% more likely to do so if they were on corticosteroids than if they weren’t. Moreover, their risk of going from an SDI of 1 to a higher SDI indicative of mounting damage increased by 10% for every 3-point increase on the SLE Disease Activity Index (SLEDAI).
Patients with a baseline SDI of 0 were 64% more likely to progress to a score of 1 or more during follow-up if they were taking corticosteroids and 71% more likely to do so if they were hypertensive. Their risk also increased by 17% for each 3-point increase in SLEDAI. Men had a 48% greater risk of going from an SDI of 0 to 1 or more than women. Asians were 40% less likely to develop irreversible damage.
Each 1-point increase in SDI score was associated with a 46% increased risk of mortality, as well as with poorer health-related quality of life, especially as reflected in SF-36 physical component scores.
Session chair Dr. Roberto Caricchio of Temple University, Philadelphia, called the SLICC study "very important work."
"It teaches us to be aggressive up-front with our lupus patients, which we often aren’t. We tend to spare ourselves because it’s a chronic disease, and we know we’ll see these patients for the next 20 years, so we try to spare them from certain therapies," said Dr. Caricchio.
Dr. Bruce concurred. "I think a concerted effort to switch the disease off in almost a treat-to-target way, getting people into remission, may well be very important with regard to avoiding long-term damage. If we could do that without using steroids, that would be ideal," he commented.
"SLICC is interested in the fact that most clinical trials in lupus to date have taken a very small subsection of the population, those with high disease activity, and used a particular biologic agent or new molecule to show that it improved disease activity. But actually the majority of people with lupus – around 60% have low-grade, grumbling disease and are on low-dose steroids. And those are the ones who accumulate damage. I think we need to have a paradigm shift in how we do clinical trials in lupus and think about doing lupus trials against a damage endpoint," the rheumatologist continued.
Power calculations based upon the SLICC Inception Cohort Study suggest such trials could be relatively modest in size, he added.
SLICC receives financial support from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. Dr. Bruce reported receiving research funding from GlaxoSmithKline, Bristol-Myers Squibb, Roche, and UCB.
SAN DIEGO – Potentially modifiable risk factors for future irreversible organ damage in lupus patients include hypertension, the use of corticosteroids, and higher levels of inflammation early on, according to findings from the SLICC (Systemic Lupus International Collaborating Clinics) Inception Cohort Study.
In addition, the study identified the use of antimalarial drugs as the one significant protective factor against steady accrual of irreversible organ damage in lupus patients.
"These findings help us pave the way to consider whether, firstly, one could use damage as a primary endpoint in future clinical trials in lupus – somewhat akin to how the erosion score is used in rheumatoid arthritis – and secondly, the results suggest particular interventions that might be important in reducing the risk of damage over time," Dr. Ian N. Bruce said at the annual meeting of the American College of Rheumatology.
The study also identified several fixed and unmodifiable risk factors for irreversible damage in lupus patients: older age at diagnosis, male gender, and being black or white Americans, added Dr. Bruce, professor of rheumatology at the University of Manchester (U.K.) and chair of the SLICC research group.
The SLICC Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries in North America, Europe, and Asia who enrolled within 15 months after being formally diagnosed with systemic lupus erythematosus based upon the 1997 ACR criteria. They averaged 35 years of age and had an average of 4.25 comprehensive annual follow-up visits during the study period.
Irreversible organ damage was assessed using the SLICC/ACR Damage Index, or SDI. At baseline, 35% of patients had at least one item of damage as indicated by an SDI score of 1 or more. Over time, damage rates slowly and steadily increased such that by 6 years of follow-up 51% of participants had an SDI of at least 1.
In a multivariate analysis, patients with an SDI score of 1 at baseline had a highly significant 37% reduction in the risk of increasing their score during follow-up if they were taking antimalarials, compared with those not taking antimalarials.
On the other hand, patients with a baseline SDI of 1 were 61% more likely to experience an increase in their damage score during follow-up if they had hypertension and 43% more likely to do so if they were on corticosteroids than if they weren’t. Moreover, their risk of going from an SDI of 1 to a higher SDI indicative of mounting damage increased by 10% for every 3-point increase on the SLE Disease Activity Index (SLEDAI).
Patients with a baseline SDI of 0 were 64% more likely to progress to a score of 1 or more during follow-up if they were taking corticosteroids and 71% more likely to do so if they were hypertensive. Their risk also increased by 17% for each 3-point increase in SLEDAI. Men had a 48% greater risk of going from an SDI of 0 to 1 or more than women. Asians were 40% less likely to develop irreversible damage.
Each 1-point increase in SDI score was associated with a 46% increased risk of mortality, as well as with poorer health-related quality of life, especially as reflected in SF-36 physical component scores.
Session chair Dr. Roberto Caricchio of Temple University, Philadelphia, called the SLICC study "very important work."
"It teaches us to be aggressive up-front with our lupus patients, which we often aren’t. We tend to spare ourselves because it’s a chronic disease, and we know we’ll see these patients for the next 20 years, so we try to spare them from certain therapies," said Dr. Caricchio.
Dr. Bruce concurred. "I think a concerted effort to switch the disease off in almost a treat-to-target way, getting people into remission, may well be very important with regard to avoiding long-term damage. If we could do that without using steroids, that would be ideal," he commented.
"SLICC is interested in the fact that most clinical trials in lupus to date have taken a very small subsection of the population, those with high disease activity, and used a particular biologic agent or new molecule to show that it improved disease activity. But actually the majority of people with lupus – around 60% have low-grade, grumbling disease and are on low-dose steroids. And those are the ones who accumulate damage. I think we need to have a paradigm shift in how we do clinical trials in lupus and think about doing lupus trials against a damage endpoint," the rheumatologist continued.
Power calculations based upon the SLICC Inception Cohort Study suggest such trials could be relatively modest in size, he added.
SLICC receives financial support from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. Dr. Bruce reported receiving research funding from GlaxoSmithKline, Bristol-Myers Squibb, Roche, and UCB.
SAN DIEGO – Potentially modifiable risk factors for future irreversible organ damage in lupus patients include hypertension, the use of corticosteroids, and higher levels of inflammation early on, according to findings from the SLICC (Systemic Lupus International Collaborating Clinics) Inception Cohort Study.
In addition, the study identified the use of antimalarial drugs as the one significant protective factor against steady accrual of irreversible organ damage in lupus patients.
"These findings help us pave the way to consider whether, firstly, one could use damage as a primary endpoint in future clinical trials in lupus – somewhat akin to how the erosion score is used in rheumatoid arthritis – and secondly, the results suggest particular interventions that might be important in reducing the risk of damage over time," Dr. Ian N. Bruce said at the annual meeting of the American College of Rheumatology.
The study also identified several fixed and unmodifiable risk factors for irreversible damage in lupus patients: older age at diagnosis, male gender, and being black or white Americans, added Dr. Bruce, professor of rheumatology at the University of Manchester (U.K.) and chair of the SLICC research group.
The SLICC Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries in North America, Europe, and Asia who enrolled within 15 months after being formally diagnosed with systemic lupus erythematosus based upon the 1997 ACR criteria. They averaged 35 years of age and had an average of 4.25 comprehensive annual follow-up visits during the study period.
Irreversible organ damage was assessed using the SLICC/ACR Damage Index, or SDI. At baseline, 35% of patients had at least one item of damage as indicated by an SDI score of 1 or more. Over time, damage rates slowly and steadily increased such that by 6 years of follow-up 51% of participants had an SDI of at least 1.
In a multivariate analysis, patients with an SDI score of 1 at baseline had a highly significant 37% reduction in the risk of increasing their score during follow-up if they were taking antimalarials, compared with those not taking antimalarials.
On the other hand, patients with a baseline SDI of 1 were 61% more likely to experience an increase in their damage score during follow-up if they had hypertension and 43% more likely to do so if they were on corticosteroids than if they weren’t. Moreover, their risk of going from an SDI of 1 to a higher SDI indicative of mounting damage increased by 10% for every 3-point increase on the SLE Disease Activity Index (SLEDAI).
Patients with a baseline SDI of 0 were 64% more likely to progress to a score of 1 or more during follow-up if they were taking corticosteroids and 71% more likely to do so if they were hypertensive. Their risk also increased by 17% for each 3-point increase in SLEDAI. Men had a 48% greater risk of going from an SDI of 0 to 1 or more than women. Asians were 40% less likely to develop irreversible damage.
Each 1-point increase in SDI score was associated with a 46% increased risk of mortality, as well as with poorer health-related quality of life, especially as reflected in SF-36 physical component scores.
Session chair Dr. Roberto Caricchio of Temple University, Philadelphia, called the SLICC study "very important work."
"It teaches us to be aggressive up-front with our lupus patients, which we often aren’t. We tend to spare ourselves because it’s a chronic disease, and we know we’ll see these patients for the next 20 years, so we try to spare them from certain therapies," said Dr. Caricchio.
Dr. Bruce concurred. "I think a concerted effort to switch the disease off in almost a treat-to-target way, getting people into remission, may well be very important with regard to avoiding long-term damage. If we could do that without using steroids, that would be ideal," he commented.
"SLICC is interested in the fact that most clinical trials in lupus to date have taken a very small subsection of the population, those with high disease activity, and used a particular biologic agent or new molecule to show that it improved disease activity. But actually the majority of people with lupus – around 60% have low-grade, grumbling disease and are on low-dose steroids. And those are the ones who accumulate damage. I think we need to have a paradigm shift in how we do clinical trials in lupus and think about doing lupus trials against a damage endpoint," the rheumatologist continued.
Power calculations based upon the SLICC Inception Cohort Study suggest such trials could be relatively modest in size, he added.
SLICC receives financial support from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. Dr. Bruce reported receiving research funding from GlaxoSmithKline, Bristol-Myers Squibb, Roche, and UCB.
AT THE ACR ANNUAL MEETING
Major finding: Patients with recently diagnosed SLE and no significant organ damage at baseline were 71% more likely to develop irreversible organ damage during follow-up if they were hypertensive and 64% more likely to do so if they were taking corticosteroids. Antimalarial drugs showed a protective effect against accrual of damage.
Data source: The Systemic Lupus International Collaborating Clinics Inception Cohort Study involves 1,722 patients at 31 centers in 11 countries, all recruited within 15 months after diagnosis.
Disclosures: The study group receives funding from GlaxoSmithKline, Bristol-Myers Squibb, and Human Genome Sciences. The presenter receives research grants from GlaxoSmithKline, Bristol-Myers Squibb, and several other pharmaceutical companies.
Discharge protocols cut 30-day bariatric surgery readmissions
ATLANTA – The addition of a comprehensive discharge protocol checklist and follow-up contact for bariatric surgery patients resulted in slightly longer hospital lengths of stay but significant reductions in readmissions.
"I feel the small amount of extra length of stay really supports the 46% overall decrease in readmissions. That’s pretty good," Sharon A. Krzyzanowski, RN, said at Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
To determine if the addition of discharge protocols had helped their bariatric surgery facility reduce the rate of 30-day readmissions, Ms. Krzyzanowski and her colleagues at the Celebration Health Florida Hospital in Orlando retrospectively analyzed patient data both pre- and post-implementation.
They compared the data of 224 Roux-en-Y gastric bypass (RYGB) patients before implementation of the protocols to 242 post-protocol RYGB patients; 125 pre-protocol laparoscopic gastric sleeve (LGS) patients to 178 post-protocol patients; and 100 gastric band patients admitted before the center had the protocols in place, vs. 50 such patients after the protocols.
Discharge protocols stipulated that patients must not be in extreme pain and were able to tolerate their pain medication; that they were not nauseous and were able to tolerate their nausea medication; and that they were able to comfortably drink a minimum of 30 ounces on the day of discharge. Respiratory values also had to be at "status quo," said Ms. Krzyzanowski. If patients did not meet any of those protocols, they were not discharged that day.
The second portion of the protocol that the researchers examined was post-discharge patient follow-up, either by phone or by e-mail. Under the protocol, a nurse contacted patients to discuss mental status, medications, postoperative regime, and any other questions the patients might have.
Patient readmissions were sorted according to reasons of technical concern, such as organ injury or leak; physical issues, such as an infection or a thromboembolic event; or general malaise, such as dehydration or benign abdominal pain.
The investigators determined that readmission rates in RYGB patients declined by 38.3%; 34.7% in LGS patients; and 100% in gastric banding patients.
The hospital length of stay in the RYGB group went from a pre-protocol average of 2.12 days to 2.50 days post protocol; in the LGS group, the average length of stay went from 1.93 to 2.10 average days.
The investigators found there was an overall reduction in readmissions of 46%. Readmissions associated with malaise were reduced from 6.5% to 2.9%; those associated with physical concerns were reduced from 2.9% to 2.1%, said Ms. Krzyzanowski. Technical readmissions did not change significantly.
During the question-and-answer portion of the presentation, Ms. Krzyzanowski said in response to a query about reimbursements for keeping patients an extra day, "As long as it’s documented why the patient is staying, insurance will review that and they will be fine. We have not had anybody denied for a third day."
Ms. Krzyzanowski, Dr. Kim, and Dr. Buffington reported no relevant disclosures.
ATLANTA – The addition of a comprehensive discharge protocol checklist and follow-up contact for bariatric surgery patients resulted in slightly longer hospital lengths of stay but significant reductions in readmissions.
"I feel the small amount of extra length of stay really supports the 46% overall decrease in readmissions. That’s pretty good," Sharon A. Krzyzanowski, RN, said at Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
To determine if the addition of discharge protocols had helped their bariatric surgery facility reduce the rate of 30-day readmissions, Ms. Krzyzanowski and her colleagues at the Celebration Health Florida Hospital in Orlando retrospectively analyzed patient data both pre- and post-implementation.
They compared the data of 224 Roux-en-Y gastric bypass (RYGB) patients before implementation of the protocols to 242 post-protocol RYGB patients; 125 pre-protocol laparoscopic gastric sleeve (LGS) patients to 178 post-protocol patients; and 100 gastric band patients admitted before the center had the protocols in place, vs. 50 such patients after the protocols.
Discharge protocols stipulated that patients must not be in extreme pain and were able to tolerate their pain medication; that they were not nauseous and were able to tolerate their nausea medication; and that they were able to comfortably drink a minimum of 30 ounces on the day of discharge. Respiratory values also had to be at "status quo," said Ms. Krzyzanowski. If patients did not meet any of those protocols, they were not discharged that day.
The second portion of the protocol that the researchers examined was post-discharge patient follow-up, either by phone or by e-mail. Under the protocol, a nurse contacted patients to discuss mental status, medications, postoperative regime, and any other questions the patients might have.
Patient readmissions were sorted according to reasons of technical concern, such as organ injury or leak; physical issues, such as an infection or a thromboembolic event; or general malaise, such as dehydration or benign abdominal pain.
The investigators determined that readmission rates in RYGB patients declined by 38.3%; 34.7% in LGS patients; and 100% in gastric banding patients.
The hospital length of stay in the RYGB group went from a pre-protocol average of 2.12 days to 2.50 days post protocol; in the LGS group, the average length of stay went from 1.93 to 2.10 average days.
The investigators found there was an overall reduction in readmissions of 46%. Readmissions associated with malaise were reduced from 6.5% to 2.9%; those associated with physical concerns were reduced from 2.9% to 2.1%, said Ms. Krzyzanowski. Technical readmissions did not change significantly.
During the question-and-answer portion of the presentation, Ms. Krzyzanowski said in response to a query about reimbursements for keeping patients an extra day, "As long as it’s documented why the patient is staying, insurance will review that and they will be fine. We have not had anybody denied for a third day."
Ms. Krzyzanowski, Dr. Kim, and Dr. Buffington reported no relevant disclosures.
ATLANTA – The addition of a comprehensive discharge protocol checklist and follow-up contact for bariatric surgery patients resulted in slightly longer hospital lengths of stay but significant reductions in readmissions.
"I feel the small amount of extra length of stay really supports the 46% overall decrease in readmissions. That’s pretty good," Sharon A. Krzyzanowski, RN, said at Obesity Week, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
To determine if the addition of discharge protocols had helped their bariatric surgery facility reduce the rate of 30-day readmissions, Ms. Krzyzanowski and her colleagues at the Celebration Health Florida Hospital in Orlando retrospectively analyzed patient data both pre- and post-implementation.
They compared the data of 224 Roux-en-Y gastric bypass (RYGB) patients before implementation of the protocols to 242 post-protocol RYGB patients; 125 pre-protocol laparoscopic gastric sleeve (LGS) patients to 178 post-protocol patients; and 100 gastric band patients admitted before the center had the protocols in place, vs. 50 such patients after the protocols.
Discharge protocols stipulated that patients must not be in extreme pain and were able to tolerate their pain medication; that they were not nauseous and were able to tolerate their nausea medication; and that they were able to comfortably drink a minimum of 30 ounces on the day of discharge. Respiratory values also had to be at "status quo," said Ms. Krzyzanowski. If patients did not meet any of those protocols, they were not discharged that day.
The second portion of the protocol that the researchers examined was post-discharge patient follow-up, either by phone or by e-mail. Under the protocol, a nurse contacted patients to discuss mental status, medications, postoperative regime, and any other questions the patients might have.
Patient readmissions were sorted according to reasons of technical concern, such as organ injury or leak; physical issues, such as an infection or a thromboembolic event; or general malaise, such as dehydration or benign abdominal pain.
The investigators determined that readmission rates in RYGB patients declined by 38.3%; 34.7% in LGS patients; and 100% in gastric banding patients.
The hospital length of stay in the RYGB group went from a pre-protocol average of 2.12 days to 2.50 days post protocol; in the LGS group, the average length of stay went from 1.93 to 2.10 average days.
The investigators found there was an overall reduction in readmissions of 46%. Readmissions associated with malaise were reduced from 6.5% to 2.9%; those associated with physical concerns were reduced from 2.9% to 2.1%, said Ms. Krzyzanowski. Technical readmissions did not change significantly.
During the question-and-answer portion of the presentation, Ms. Krzyzanowski said in response to a query about reimbursements for keeping patients an extra day, "As long as it’s documented why the patient is staying, insurance will review that and they will be fine. We have not had anybody denied for a third day."
Ms. Krzyzanowski, Dr. Kim, and Dr. Buffington reported no relevant disclosures.
AT OBESITY WEEK
Major finding: 30-day readmissions after bariatric surgery fell 46% after implementation of discharge protocols.
Data source: Review of single surgery site patient data pre- and post-protocol implementation.
Disclosures: Ms. Krzyzanowski, Dr. Kim, and Dr. Buffington reported no relevant disclosures.
First U.S. TAVR experience fares well post-market
Postmarket outcomes with the first commercially available U.S. transcatheter aortic valve replacement device are comparable with randomized trial and international registry experience, national registry results suggest.
The Edwards LifeSciences Sapien XT valve was successfully implanted in 92% of 7,710 TAVR patients, two-thirds with a transfemoral approach.
The primary outcomes of in-hospital all-cause mortality and stroke were 5.5% and 2%, respectively, Dr. Michael J. Mack reported at the American Heart Association scientific sessions.
Conversion to open-heart surgery was needed in only 1% of patients, but associated with a 49% incidence of in-hospital mortality.
Major bleeding and vascular complications were relatively low, at 3.5% and 6.4%, respectively, despite the overall lack of experience and use of larger sheath delivery systems. Acute renal insufficiency occurred in 5.5% of patients.
The 30-day death and stroke rates were 7.6% and 2.8% among 3,113 patients with sufficient follow-up. Most deaths were due to noncardiovascular causes, he noted.
This is the first public report from the national Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry, and comes amid calls for increased postmarket surveillance of high-risk medical devices.
The results also help address whether outcomes after a controlled commercial rollout of the first-generation valve hold up to those from clinical trials and the global TAVR experience, now based on second- and third-generation devices, according to Dr. Mack, past STS president and director of cardiovascular research and medicine at the Heart Hospital Baylor Plano in Plano, Texas.
The Food and Drug Administration initially approved the Edwards valve for severe, symptomatic aortic stenosis in inoperable patients in 2011 and expanded its label in September 2012 to include operable, high-risk patients using either a transfemoral or transapical approach.
The TVT analysis comprised 1,559 inoperable and 6,151 high-risk, operable patients who underwent TAVR at 224 participating registry hospitals from November 2011 to May 2013. Their median STS predicted risk of operative mortality (PROM) was 7%, but varied widely from 1.2% to 17.4%. Their median age was 84 years.
The risk profile of patients was generally lower in the registry than in randomized trials and European reports, and may have contributed to the good outcomes, Dr. Mack acknowledged. The mean PROM was 11.2% among inoperable patients and 11.8% among high-risk, operable patients in the pivotal PARTNER trial, which was used for the device’s approval.
Although incomplete data may have been entered into the risk calculator, the other plausible explanation is "risk creep," or that patients with lower surgical risk are being treated with the less-invasive procedure, leading to better outcomes, he noted.
Other possible contributors to the registry outcomes include a shorter U.S. learning curve due to international collaboration, inclusion of at least 35 highly experienced PARTNER study centers in the registry, and mandated training by the manufacturer including a company employed clinical specialist during all procedures.
Still, the results stack up well. Germany, which has led the TAVR revolution, had an in-hospital mortality of 5.1% with a transfemoral approach and 7.7% with a transapical approach in 2011 in the German Aortic Valve Registry.
In the PARTNER trial, 30-day mortality was 5% among inoperable patients, 3.7% among high-risk, operable patients by a transfemoral approach, and 8.7% among high-risk, operable patients by a transapical approach.
This compares with 30-day mortality rates of 6.1%, 4.6%, and 9.8%, respectively, in the TVT registry, Dr. Mack reported.
The TVT registry captured an estimated 88% of TAVR procedures performed between May 2012, when the Centers for Medicare and Medicaid Services issued its national coverage determination, and the end of the study. Notably, 30-day outcomes were reported from only 114 hospitals or 51% of the 244 hospitals in the registry. The results were published simultaneously with Dr. Mack’s presentation (JAMA 2013;310:2069-77. doi:10.1001/jama/2013.282043).
More complete long-term outcomes at 30 days and 1 year are needed to have a more comprehensive assessment of TAVR outcomes in the United States, Dr. Mack cautioned. Patient health status and quality of life outcomes will also be addressed in subsequent reports.
So far, it’s known that most (63%) patients were discharged home, 6% experienced new-onset atrial fibrillation, and 6.6% needed a new permanent pacemaker or implantable cardioverter-defibrillator.
The study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. Dr. Mack reported no other disclosures; a co-author reported travel support from the STS and a second reported consulting for Janssen, Boehringer Ingelheim, and Sanofi.
Postmarket outcomes with the first commercially available U.S. transcatheter aortic valve replacement device are comparable with randomized trial and international registry experience, national registry results suggest.
The Edwards LifeSciences Sapien XT valve was successfully implanted in 92% of 7,710 TAVR patients, two-thirds with a transfemoral approach.
The primary outcomes of in-hospital all-cause mortality and stroke were 5.5% and 2%, respectively, Dr. Michael J. Mack reported at the American Heart Association scientific sessions.
Conversion to open-heart surgery was needed in only 1% of patients, but associated with a 49% incidence of in-hospital mortality.
Major bleeding and vascular complications were relatively low, at 3.5% and 6.4%, respectively, despite the overall lack of experience and use of larger sheath delivery systems. Acute renal insufficiency occurred in 5.5% of patients.
The 30-day death and stroke rates were 7.6% and 2.8% among 3,113 patients with sufficient follow-up. Most deaths were due to noncardiovascular causes, he noted.
This is the first public report from the national Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry, and comes amid calls for increased postmarket surveillance of high-risk medical devices.
The results also help address whether outcomes after a controlled commercial rollout of the first-generation valve hold up to those from clinical trials and the global TAVR experience, now based on second- and third-generation devices, according to Dr. Mack, past STS president and director of cardiovascular research and medicine at the Heart Hospital Baylor Plano in Plano, Texas.
The Food and Drug Administration initially approved the Edwards valve for severe, symptomatic aortic stenosis in inoperable patients in 2011 and expanded its label in September 2012 to include operable, high-risk patients using either a transfemoral or transapical approach.
The TVT analysis comprised 1,559 inoperable and 6,151 high-risk, operable patients who underwent TAVR at 224 participating registry hospitals from November 2011 to May 2013. Their median STS predicted risk of operative mortality (PROM) was 7%, but varied widely from 1.2% to 17.4%. Their median age was 84 years.
The risk profile of patients was generally lower in the registry than in randomized trials and European reports, and may have contributed to the good outcomes, Dr. Mack acknowledged. The mean PROM was 11.2% among inoperable patients and 11.8% among high-risk, operable patients in the pivotal PARTNER trial, which was used for the device’s approval.
Although incomplete data may have been entered into the risk calculator, the other plausible explanation is "risk creep," or that patients with lower surgical risk are being treated with the less-invasive procedure, leading to better outcomes, he noted.
Other possible contributors to the registry outcomes include a shorter U.S. learning curve due to international collaboration, inclusion of at least 35 highly experienced PARTNER study centers in the registry, and mandated training by the manufacturer including a company employed clinical specialist during all procedures.
Still, the results stack up well. Germany, which has led the TAVR revolution, had an in-hospital mortality of 5.1% with a transfemoral approach and 7.7% with a transapical approach in 2011 in the German Aortic Valve Registry.
In the PARTNER trial, 30-day mortality was 5% among inoperable patients, 3.7% among high-risk, operable patients by a transfemoral approach, and 8.7% among high-risk, operable patients by a transapical approach.
This compares with 30-day mortality rates of 6.1%, 4.6%, and 9.8%, respectively, in the TVT registry, Dr. Mack reported.
The TVT registry captured an estimated 88% of TAVR procedures performed between May 2012, when the Centers for Medicare and Medicaid Services issued its national coverage determination, and the end of the study. Notably, 30-day outcomes were reported from only 114 hospitals or 51% of the 244 hospitals in the registry. The results were published simultaneously with Dr. Mack’s presentation (JAMA 2013;310:2069-77. doi:10.1001/jama/2013.282043).
More complete long-term outcomes at 30 days and 1 year are needed to have a more comprehensive assessment of TAVR outcomes in the United States, Dr. Mack cautioned. Patient health status and quality of life outcomes will also be addressed in subsequent reports.
So far, it’s known that most (63%) patients were discharged home, 6% experienced new-onset atrial fibrillation, and 6.6% needed a new permanent pacemaker or implantable cardioverter-defibrillator.
The study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. Dr. Mack reported no other disclosures; a co-author reported travel support from the STS and a second reported consulting for Janssen, Boehringer Ingelheim, and Sanofi.
Postmarket outcomes with the first commercially available U.S. transcatheter aortic valve replacement device are comparable with randomized trial and international registry experience, national registry results suggest.
The Edwards LifeSciences Sapien XT valve was successfully implanted in 92% of 7,710 TAVR patients, two-thirds with a transfemoral approach.
The primary outcomes of in-hospital all-cause mortality and stroke were 5.5% and 2%, respectively, Dr. Michael J. Mack reported at the American Heart Association scientific sessions.
Conversion to open-heart surgery was needed in only 1% of patients, but associated with a 49% incidence of in-hospital mortality.
Major bleeding and vascular complications were relatively low, at 3.5% and 6.4%, respectively, despite the overall lack of experience and use of larger sheath delivery systems. Acute renal insufficiency occurred in 5.5% of patients.
The 30-day death and stroke rates were 7.6% and 2.8% among 3,113 patients with sufficient follow-up. Most deaths were due to noncardiovascular causes, he noted.
This is the first public report from the national Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry, and comes amid calls for increased postmarket surveillance of high-risk medical devices.
The results also help address whether outcomes after a controlled commercial rollout of the first-generation valve hold up to those from clinical trials and the global TAVR experience, now based on second- and third-generation devices, according to Dr. Mack, past STS president and director of cardiovascular research and medicine at the Heart Hospital Baylor Plano in Plano, Texas.
The Food and Drug Administration initially approved the Edwards valve for severe, symptomatic aortic stenosis in inoperable patients in 2011 and expanded its label in September 2012 to include operable, high-risk patients using either a transfemoral or transapical approach.
The TVT analysis comprised 1,559 inoperable and 6,151 high-risk, operable patients who underwent TAVR at 224 participating registry hospitals from November 2011 to May 2013. Their median STS predicted risk of operative mortality (PROM) was 7%, but varied widely from 1.2% to 17.4%. Their median age was 84 years.
The risk profile of patients was generally lower in the registry than in randomized trials and European reports, and may have contributed to the good outcomes, Dr. Mack acknowledged. The mean PROM was 11.2% among inoperable patients and 11.8% among high-risk, operable patients in the pivotal PARTNER trial, which was used for the device’s approval.
Although incomplete data may have been entered into the risk calculator, the other plausible explanation is "risk creep," or that patients with lower surgical risk are being treated with the less-invasive procedure, leading to better outcomes, he noted.
Other possible contributors to the registry outcomes include a shorter U.S. learning curve due to international collaboration, inclusion of at least 35 highly experienced PARTNER study centers in the registry, and mandated training by the manufacturer including a company employed clinical specialist during all procedures.
Still, the results stack up well. Germany, which has led the TAVR revolution, had an in-hospital mortality of 5.1% with a transfemoral approach and 7.7% with a transapical approach in 2011 in the German Aortic Valve Registry.
In the PARTNER trial, 30-day mortality was 5% among inoperable patients, 3.7% among high-risk, operable patients by a transfemoral approach, and 8.7% among high-risk, operable patients by a transapical approach.
This compares with 30-day mortality rates of 6.1%, 4.6%, and 9.8%, respectively, in the TVT registry, Dr. Mack reported.
The TVT registry captured an estimated 88% of TAVR procedures performed between May 2012, when the Centers for Medicare and Medicaid Services issued its national coverage determination, and the end of the study. Notably, 30-day outcomes were reported from only 114 hospitals or 51% of the 244 hospitals in the registry. The results were published simultaneously with Dr. Mack’s presentation (JAMA 2013;310:2069-77. doi:10.1001/jama/2013.282043).
More complete long-term outcomes at 30 days and 1 year are needed to have a more comprehensive assessment of TAVR outcomes in the United States, Dr. Mack cautioned. Patient health status and quality of life outcomes will also be addressed in subsequent reports.
So far, it’s known that most (63%) patients were discharged home, 6% experienced new-onset atrial fibrillation, and 6.6% needed a new permanent pacemaker or implantable cardioverter-defibrillator.
The study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. Dr. Mack reported no other disclosures; a co-author reported travel support from the STS and a second reported consulting for Janssen, Boehringer Ingelheim, and Sanofi.
FROM THE AHA SCIENTIFIC SESSIONS
Major finding: The 30-day death rate was 7.6% and stroke rate 2.8%.
Data source: A retrospective analysis of 7,710 patients undergoing post-approval TAVR with the Edwards Sapien XT device from November 2011 to May 2013.
Disclosures: The study was funded by the American College of Cardiology Foundation and the Society of Thoracic Surgeons. Dr. Mack reported no other disclosures; a co-author reported travel support from the STS and a second reported consulting for Janssen, Boehringer Ingelheim, and Sanofi.
Women choose mastectomy to gain control
SAN FRANCISCO – Fear and a desire for control over breast cancer may drive women to choose mastectomy over less aggressive management, a qualitative study of 30 patients has shown.
She interviewed 15 women who were candidates for breast-conserving surgery but chose unilateral mastectomy and 15 average-risk women who were candidates for surgery in one breast but also chose prophylactic contralateral mastectomy.
Fear led patients to overestimate their risk of local recurrence and contralateral cancer and to misunderstand their odds of dying of breast cancer. The fear combined with wanting to eliminate and control the risk of cancer resulted in the patient choosing mastectomy or bilateral mastectomy, factors that probably are contributing to increasing rates of mastectomy for early-stage breast cancer, Dr. Andrea M. Covelli reported in a poster at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
When deciding on treatment, the women sought out multiple sources of information but gave greatest weight to the experiences of people they’d known with breast cancer and information from breast cancer survivors. It was the patients, not clinicians, who raised the topic of contralateral prophylactic mastectomy, which some patients chose in an attempt to eliminate any risk of contralateral breast cancer.
"More surgery is seen as more control," reported Dr. Covelli of the University of Toronto. A better understanding of patients’ decision process may help physicians be better able to discuss issues important to their patients in making treatment decisions.
Dr. Covelli conducted semistructured one-on-one interviews with patients with early-stage breast cancer chosen from five hospitals in the greater Toronto area to represent a variety of ages and ethnicities. Twelve were treated at academic cancer centers, 6 were treated at academic noncancer centers, and 12 were treated at community medical centers.
She identified several themes in the results. The diagnosis brought shock and fear. Patients discussed both breast-conserving surgery and unilateral mastectomy during their surgical consultation, during which the physician discouraged contralateral prophylactic mastectomy. Patients relied on multiple sources of information in their decision making, but the greatest impact came from the experiences of others with breast cancer, she reported.
Women who chose unilateral mastectomy did so most often out of fear of recurrence and the misguided notion that it would give them a survival advantage. Occasionally, they chose unilateral mastectomy to avoid radiation therapy.
Women who also chose contralateral prophylactic mastectomy initiated discussions about it, which their surgeons then discouraged. These patients chose it anyway because they overestimated the risk of contralateral cancer and mistakenly believed it would improve their chance of survival. Occasionally they added contralateral prophylactic mastectomy for body symmetry.
In essence, patients chose these more aggressive surgeries because they were actively trying to control their cancer outcomes and ensure that they "never have to go through this again," Dr. Covelli said.
The study cohort had a mean age of 55 years, with ages ranging from 36 to 84 years.
Dr. Covelli has received funding from Roche Canada and the Canadian Breast Cancer Foundation Physician Fellowship Award.
On Twitter @sherryboschert
This study asks the question, What motivates a woman with early-stage breast cancer to choose mastectomy, whether that be a unilateral mastectomy when she’s a candidate for breast conservation or the addition of a contralateral prophylactic mastectomy in the absence of an indication?
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The bottom line is that the diagnosis is met with fear and shock. When we present options in a very neutral, evidence-based way, we are talking to our patients about breast-conserving surgery and mastectomy. And we are, and we should be, talking about whether there’s a role for contralateral prophylactic surgery.
Bearing witness is something that needs to be understood here. A lot of the discussion that you have with your patients is going to be interpreted based on what those patients are hearing, seeing, and witnessing in their own lives. So, if Aunt Judy had breast-conserving surgery and died 5 years later, you’ve got to take that into account.
There is a desire for control. There is a need to reduce risks so it never happens to them again, and there is a desire to increase their odds of surviving. That comes down to patients’ decision-making experience, their reasons for choosing a surgery that is far more aggressive than it possibly should be, and their goal to control cancer. We’re seeing an increasing mastectomy rate – more surgery, more control.
There is a process of deliberation where we take many factors into consideration before determining what we want to do. The implication based on this abstract, I think, is whether clinicians need to identify the deliberations that are leading to a decision before acting surgically.
Dr. Covelli’s preliminary work suggests that decisions around surgery are incredibly complex, and ensuring decisions are informed is complicated. Learning how patients deliberate is important – what experiences and what social networks are informing that decision? (And I don’t mean Twitter and Facebook, I mean in patients’ own real, face-to-face lives.) What is the role of the preoperative work-up in influencing those deliberations? How is that preoperative MRI influencing these decisions, based on anything that potentially might be happening?
I think this is very provocative work that can go further. The take-home points for me: Engage cognitively, engage with evidence, engage with data, but you have to engage practically. You need to know: Where is that person hearing information that I’m not telling her? How is she processing that information with information that I have just given? Engage cognitively; engage affectively.
Dr. Don S. Dizon is a medical gynecologic oncologist and director of the oncology sexual health clinic at Massachusetts General Hospital, Boston. These are excerpts of his remarks as the discussant of Dr. Covelli’s study at the meeting. He disclosed that he has been employed by UpToDate.
This study asks the question, What motivates a woman with early-stage breast cancer to choose mastectomy, whether that be a unilateral mastectomy when she’s a candidate for breast conservation or the addition of a contralateral prophylactic mastectomy in the absence of an indication?
|
|
The bottom line is that the diagnosis is met with fear and shock. When we present options in a very neutral, evidence-based way, we are talking to our patients about breast-conserving surgery and mastectomy. And we are, and we should be, talking about whether there’s a role for contralateral prophylactic surgery.
Bearing witness is something that needs to be understood here. A lot of the discussion that you have with your patients is going to be interpreted based on what those patients are hearing, seeing, and witnessing in their own lives. So, if Aunt Judy had breast-conserving surgery and died 5 years later, you’ve got to take that into account.
There is a desire for control. There is a need to reduce risks so it never happens to them again, and there is a desire to increase their odds of surviving. That comes down to patients’ decision-making experience, their reasons for choosing a surgery that is far more aggressive than it possibly should be, and their goal to control cancer. We’re seeing an increasing mastectomy rate – more surgery, more control.
There is a process of deliberation where we take many factors into consideration before determining what we want to do. The implication based on this abstract, I think, is whether clinicians need to identify the deliberations that are leading to a decision before acting surgically.
Dr. Covelli’s preliminary work suggests that decisions around surgery are incredibly complex, and ensuring decisions are informed is complicated. Learning how patients deliberate is important – what experiences and what social networks are informing that decision? (And I don’t mean Twitter and Facebook, I mean in patients’ own real, face-to-face lives.) What is the role of the preoperative work-up in influencing those deliberations? How is that preoperative MRI influencing these decisions, based on anything that potentially might be happening?
I think this is very provocative work that can go further. The take-home points for me: Engage cognitively, engage with evidence, engage with data, but you have to engage practically. You need to know: Where is that person hearing information that I’m not telling her? How is she processing that information with information that I have just given? Engage cognitively; engage affectively.
Dr. Don S. Dizon is a medical gynecologic oncologist and director of the oncology sexual health clinic at Massachusetts General Hospital, Boston. These are excerpts of his remarks as the discussant of Dr. Covelli’s study at the meeting. He disclosed that he has been employed by UpToDate.
This study asks the question, What motivates a woman with early-stage breast cancer to choose mastectomy, whether that be a unilateral mastectomy when she’s a candidate for breast conservation or the addition of a contralateral prophylactic mastectomy in the absence of an indication?
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The bottom line is that the diagnosis is met with fear and shock. When we present options in a very neutral, evidence-based way, we are talking to our patients about breast-conserving surgery and mastectomy. And we are, and we should be, talking about whether there’s a role for contralateral prophylactic surgery.
Bearing witness is something that needs to be understood here. A lot of the discussion that you have with your patients is going to be interpreted based on what those patients are hearing, seeing, and witnessing in their own lives. So, if Aunt Judy had breast-conserving surgery and died 5 years later, you’ve got to take that into account.
There is a desire for control. There is a need to reduce risks so it never happens to them again, and there is a desire to increase their odds of surviving. That comes down to patients’ decision-making experience, their reasons for choosing a surgery that is far more aggressive than it possibly should be, and their goal to control cancer. We’re seeing an increasing mastectomy rate – more surgery, more control.
There is a process of deliberation where we take many factors into consideration before determining what we want to do. The implication based on this abstract, I think, is whether clinicians need to identify the deliberations that are leading to a decision before acting surgically.
Dr. Covelli’s preliminary work suggests that decisions around surgery are incredibly complex, and ensuring decisions are informed is complicated. Learning how patients deliberate is important – what experiences and what social networks are informing that decision? (And I don’t mean Twitter and Facebook, I mean in patients’ own real, face-to-face lives.) What is the role of the preoperative work-up in influencing those deliberations? How is that preoperative MRI influencing these decisions, based on anything that potentially might be happening?
I think this is very provocative work that can go further. The take-home points for me: Engage cognitively, engage with evidence, engage with data, but you have to engage practically. You need to know: Where is that person hearing information that I’m not telling her? How is she processing that information with information that I have just given? Engage cognitively; engage affectively.
Dr. Don S. Dizon is a medical gynecologic oncologist and director of the oncology sexual health clinic at Massachusetts General Hospital, Boston. These are excerpts of his remarks as the discussant of Dr. Covelli’s study at the meeting. He disclosed that he has been employed by UpToDate.
SAN FRANCISCO – Fear and a desire for control over breast cancer may drive women to choose mastectomy over less aggressive management, a qualitative study of 30 patients has shown.
She interviewed 15 women who were candidates for breast-conserving surgery but chose unilateral mastectomy and 15 average-risk women who were candidates for surgery in one breast but also chose prophylactic contralateral mastectomy.
Fear led patients to overestimate their risk of local recurrence and contralateral cancer and to misunderstand their odds of dying of breast cancer. The fear combined with wanting to eliminate and control the risk of cancer resulted in the patient choosing mastectomy or bilateral mastectomy, factors that probably are contributing to increasing rates of mastectomy for early-stage breast cancer, Dr. Andrea M. Covelli reported in a poster at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
When deciding on treatment, the women sought out multiple sources of information but gave greatest weight to the experiences of people they’d known with breast cancer and information from breast cancer survivors. It was the patients, not clinicians, who raised the topic of contralateral prophylactic mastectomy, which some patients chose in an attempt to eliminate any risk of contralateral breast cancer.
"More surgery is seen as more control," reported Dr. Covelli of the University of Toronto. A better understanding of patients’ decision process may help physicians be better able to discuss issues important to their patients in making treatment decisions.
Dr. Covelli conducted semistructured one-on-one interviews with patients with early-stage breast cancer chosen from five hospitals in the greater Toronto area to represent a variety of ages and ethnicities. Twelve were treated at academic cancer centers, 6 were treated at academic noncancer centers, and 12 were treated at community medical centers.
She identified several themes in the results. The diagnosis brought shock and fear. Patients discussed both breast-conserving surgery and unilateral mastectomy during their surgical consultation, during which the physician discouraged contralateral prophylactic mastectomy. Patients relied on multiple sources of information in their decision making, but the greatest impact came from the experiences of others with breast cancer, she reported.
Women who chose unilateral mastectomy did so most often out of fear of recurrence and the misguided notion that it would give them a survival advantage. Occasionally, they chose unilateral mastectomy to avoid radiation therapy.
Women who also chose contralateral prophylactic mastectomy initiated discussions about it, which their surgeons then discouraged. These patients chose it anyway because they overestimated the risk of contralateral cancer and mistakenly believed it would improve their chance of survival. Occasionally they added contralateral prophylactic mastectomy for body symmetry.
In essence, patients chose these more aggressive surgeries because they were actively trying to control their cancer outcomes and ensure that they "never have to go through this again," Dr. Covelli said.
The study cohort had a mean age of 55 years, with ages ranging from 36 to 84 years.
Dr. Covelli has received funding from Roche Canada and the Canadian Breast Cancer Foundation Physician Fellowship Award.
On Twitter @sherryboschert
SAN FRANCISCO – Fear and a desire for control over breast cancer may drive women to choose mastectomy over less aggressive management, a qualitative study of 30 patients has shown.
She interviewed 15 women who were candidates for breast-conserving surgery but chose unilateral mastectomy and 15 average-risk women who were candidates for surgery in one breast but also chose prophylactic contralateral mastectomy.
Fear led patients to overestimate their risk of local recurrence and contralateral cancer and to misunderstand their odds of dying of breast cancer. The fear combined with wanting to eliminate and control the risk of cancer resulted in the patient choosing mastectomy or bilateral mastectomy, factors that probably are contributing to increasing rates of mastectomy for early-stage breast cancer, Dr. Andrea M. Covelli reported in a poster at a breast cancer symposium sponsored by the American Society of Clinical Oncology.
When deciding on treatment, the women sought out multiple sources of information but gave greatest weight to the experiences of people they’d known with breast cancer and information from breast cancer survivors. It was the patients, not clinicians, who raised the topic of contralateral prophylactic mastectomy, which some patients chose in an attempt to eliminate any risk of contralateral breast cancer.
"More surgery is seen as more control," reported Dr. Covelli of the University of Toronto. A better understanding of patients’ decision process may help physicians be better able to discuss issues important to their patients in making treatment decisions.
Dr. Covelli conducted semistructured one-on-one interviews with patients with early-stage breast cancer chosen from five hospitals in the greater Toronto area to represent a variety of ages and ethnicities. Twelve were treated at academic cancer centers, 6 were treated at academic noncancer centers, and 12 were treated at community medical centers.
She identified several themes in the results. The diagnosis brought shock and fear. Patients discussed both breast-conserving surgery and unilateral mastectomy during their surgical consultation, during which the physician discouraged contralateral prophylactic mastectomy. Patients relied on multiple sources of information in their decision making, but the greatest impact came from the experiences of others with breast cancer, she reported.
Women who chose unilateral mastectomy did so most often out of fear of recurrence and the misguided notion that it would give them a survival advantage. Occasionally, they chose unilateral mastectomy to avoid radiation therapy.
Women who also chose contralateral prophylactic mastectomy initiated discussions about it, which their surgeons then discouraged. These patients chose it anyway because they overestimated the risk of contralateral cancer and mistakenly believed it would improve their chance of survival. Occasionally they added contralateral prophylactic mastectomy for body symmetry.
In essence, patients chose these more aggressive surgeries because they were actively trying to control their cancer outcomes and ensure that they "never have to go through this again," Dr. Covelli said.
The study cohort had a mean age of 55 years, with ages ranging from 36 to 84 years.
Dr. Covelli has received funding from Roche Canada and the Canadian Breast Cancer Foundation Physician Fellowship Award.
On Twitter @sherryboschert
AT THE ASCO BREAST CANCER SYMPOSIUM
Major finding: Fear and a desire for control over cancer drove women to choose mastectomy.
Data source: A qualitative study of 30 women with early-stage breast cancer who were candidates for breast-conserving surgery but chose unilateral mastectomy with or without contralateral prophylactic mastectomy.
Disclosures: Dr. Covelli has received funding from Roche Canada and the Canadian Breast Cancer Foundation Physician Fellowship Award.
Murthy nominated to be Surgeon General
President Obama has nominated Dr. Vivek Murthy, a hospitalist at Brigham and Women’s Hospital in Boston and a staunch defender of the Affordable Care Act, to be the nation’s top doctor.
Dr. Murthy has been a strong supporter of President Obama and his health reform efforts since 2008. He is co-founder and president of Doctors for America, a group that was originally launched in 2008 as Doctors for Obama to directly support Mr. Obama’s election.
Over the last few years, Doctors for America has deployed its physician members around the country to argue for the benefits of the Affordable Care Act. The group filed an amicus brief with the Supreme Court in support of upholding the ACA’s individual insurance mandate.
During the 2012 campaign, Dr. Murthy was a volunteer adviser to President Obama’s campaign.
In an interview with this news organization in 2012, Dr. Murthy said he wasn’t politically active for most of his life. But in the last few years, he entered politics as a way to push his views on how to reform health care. He said that it is important for physicians to be involved in politics because of their unique view of the health care system.
"As individual physicians and also as leaders in our community, we can play a role in helping to give more voice to the perspective of physicians and patients," he said in the interview. "If these perspectives are missing as our health care system is being redesigned then we’re not going to have a system that ultimately works."
Dr. Murthy also has focused on public health. In 1995, he co-founded VISIONS Worldwide, a nonprofit organization involved in HIV/AIDS education in India and the United States. And in 2011, President Obama appointed him to serve on the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health.
If confirmed by the Senate, Dr. Murthy would replace acting Surgeon General Boris D. Lushniak and serve a 4-year term.
On Twitter @MaryEllenNY
President Obama has nominated Dr. Vivek Murthy, a hospitalist at Brigham and Women’s Hospital in Boston and a staunch defender of the Affordable Care Act, to be the nation’s top doctor.
Dr. Murthy has been a strong supporter of President Obama and his health reform efforts since 2008. He is co-founder and president of Doctors for America, a group that was originally launched in 2008 as Doctors for Obama to directly support Mr. Obama’s election.
Over the last few years, Doctors for America has deployed its physician members around the country to argue for the benefits of the Affordable Care Act. The group filed an amicus brief with the Supreme Court in support of upholding the ACA’s individual insurance mandate.
During the 2012 campaign, Dr. Murthy was a volunteer adviser to President Obama’s campaign.
In an interview with this news organization in 2012, Dr. Murthy said he wasn’t politically active for most of his life. But in the last few years, he entered politics as a way to push his views on how to reform health care. He said that it is important for physicians to be involved in politics because of their unique view of the health care system.
"As individual physicians and also as leaders in our community, we can play a role in helping to give more voice to the perspective of physicians and patients," he said in the interview. "If these perspectives are missing as our health care system is being redesigned then we’re not going to have a system that ultimately works."
Dr. Murthy also has focused on public health. In 1995, he co-founded VISIONS Worldwide, a nonprofit organization involved in HIV/AIDS education in India and the United States. And in 2011, President Obama appointed him to serve on the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health.
If confirmed by the Senate, Dr. Murthy would replace acting Surgeon General Boris D. Lushniak and serve a 4-year term.
On Twitter @MaryEllenNY
President Obama has nominated Dr. Vivek Murthy, a hospitalist at Brigham and Women’s Hospital in Boston and a staunch defender of the Affordable Care Act, to be the nation’s top doctor.
Dr. Murthy has been a strong supporter of President Obama and his health reform efforts since 2008. He is co-founder and president of Doctors for America, a group that was originally launched in 2008 as Doctors for Obama to directly support Mr. Obama’s election.
Over the last few years, Doctors for America has deployed its physician members around the country to argue for the benefits of the Affordable Care Act. The group filed an amicus brief with the Supreme Court in support of upholding the ACA’s individual insurance mandate.
During the 2012 campaign, Dr. Murthy was a volunteer adviser to President Obama’s campaign.
In an interview with this news organization in 2012, Dr. Murthy said he wasn’t politically active for most of his life. But in the last few years, he entered politics as a way to push his views on how to reform health care. He said that it is important for physicians to be involved in politics because of their unique view of the health care system.
"As individual physicians and also as leaders in our community, we can play a role in helping to give more voice to the perspective of physicians and patients," he said in the interview. "If these perspectives are missing as our health care system is being redesigned then we’re not going to have a system that ultimately works."
Dr. Murthy also has focused on public health. In 1995, he co-founded VISIONS Worldwide, a nonprofit organization involved in HIV/AIDS education in India and the United States. And in 2011, President Obama appointed him to serve on the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health.
If confirmed by the Senate, Dr. Murthy would replace acting Surgeon General Boris D. Lushniak and serve a 4-year term.
On Twitter @MaryEllenNY
Obama offers another year to some canceled plans
Individuals who have had their health insurance policies canceled over the last few weeks may be able to keep them because of an administrative fix.
At a Nov. 14 press conference, President Barack Obama said he was making an administrative change that would allow health plans to continue to offer existing plans to their current enrollees throughout 2014, even if those plans don’t meet the coverage standards under the Affordable Care Act.
Whether to offer the plans now is up to insurance companies and state insurance commissioners, but the ACA is no longer a barrier, President Obama said.
If insurers continue to offer these plans in 2014, they must spell out to their customers which insurance protections the plans are lacking and what may be available on the health insurance exchanges.
Under the ACA, health plans that were in place before the law was signed in March 2010 are "grandfathered" in place and consumers can keep them. However, if insurers make changes to those plans, the plans must come into compliance with ACA requirements. The ACA also requires plans created after March 2010 to meet the law’s requirements starting on Jan. 1, 2014.
Under the action announced by President Obama, plans that have been created or altered since 2010 can continue to be offered to existing enrollees in 2014.
The announcement came after several congressional Democrats began to join their Republican colleagues in calling for a change that would allow Americans to keep their current health plans. The House is set to vote on Nov. 15 on a bill introduced by Rep. Fred Upton (R-Mich.) that would essentially grandfather all existing health plans during 2014. Unlike the President’s fix, the Upton proposal would allow current plans to continue to enroll new members.
President Obama said he now regrets the pledge he made that if Americans like their health plans they could keep them. While it was true for about 95% of Americans, he said, the grandfathering clause crafted by the administration did not go far enough in allowing more people to keep their plans. "That’s on me," he said during the press conference.
The President’s announcement was greeted with skepticism by House Speaker John Boehner (R-Ohio), who urged Democrats to join him in supporting Rep. Upton’s bill (H.R. 3350) instead.
Speaker Boehner said the Obama administration misled the public with the "if you like your health plan, you can keep it" pledge. "It’s clear that the American people simply can’t trust this White House," he said.
Health care insurers also expressed displeasure with the President’s announcement on grandfathered plans, saying that it has the potential to "destabilize" the insurance market.
"Premiums have already been set for next year based on an assumption of when consumers will be transitioning to the new marketplace. If, due to these changes, fewer younger and healthier people choose to purchase coverage in the exchange, premiums will increase in the marketplace and there will be fewer choices for consumers," Karen Ignagni, president and CEO of America’s Health Insurance Plans, said in a statement. "Additional steps must be taken to stabilize the marketplace and mitigate the adverse impact on consumers."
On Twitter @MaryEllenNY
Individuals who have had their health insurance policies canceled over the last few weeks may be able to keep them because of an administrative fix.
At a Nov. 14 press conference, President Barack Obama said he was making an administrative change that would allow health plans to continue to offer existing plans to their current enrollees throughout 2014, even if those plans don’t meet the coverage standards under the Affordable Care Act.
Whether to offer the plans now is up to insurance companies and state insurance commissioners, but the ACA is no longer a barrier, President Obama said.
If insurers continue to offer these plans in 2014, they must spell out to their customers which insurance protections the plans are lacking and what may be available on the health insurance exchanges.
Under the ACA, health plans that were in place before the law was signed in March 2010 are "grandfathered" in place and consumers can keep them. However, if insurers make changes to those plans, the plans must come into compliance with ACA requirements. The ACA also requires plans created after March 2010 to meet the law’s requirements starting on Jan. 1, 2014.
Under the action announced by President Obama, plans that have been created or altered since 2010 can continue to be offered to existing enrollees in 2014.
The announcement came after several congressional Democrats began to join their Republican colleagues in calling for a change that would allow Americans to keep their current health plans. The House is set to vote on Nov. 15 on a bill introduced by Rep. Fred Upton (R-Mich.) that would essentially grandfather all existing health plans during 2014. Unlike the President’s fix, the Upton proposal would allow current plans to continue to enroll new members.
President Obama said he now regrets the pledge he made that if Americans like their health plans they could keep them. While it was true for about 95% of Americans, he said, the grandfathering clause crafted by the administration did not go far enough in allowing more people to keep their plans. "That’s on me," he said during the press conference.
The President’s announcement was greeted with skepticism by House Speaker John Boehner (R-Ohio), who urged Democrats to join him in supporting Rep. Upton’s bill (H.R. 3350) instead.
Speaker Boehner said the Obama administration misled the public with the "if you like your health plan, you can keep it" pledge. "It’s clear that the American people simply can’t trust this White House," he said.
Health care insurers also expressed displeasure with the President’s announcement on grandfathered plans, saying that it has the potential to "destabilize" the insurance market.
"Premiums have already been set for next year based on an assumption of when consumers will be transitioning to the new marketplace. If, due to these changes, fewer younger and healthier people choose to purchase coverage in the exchange, premiums will increase in the marketplace and there will be fewer choices for consumers," Karen Ignagni, president and CEO of America’s Health Insurance Plans, said in a statement. "Additional steps must be taken to stabilize the marketplace and mitigate the adverse impact on consumers."
On Twitter @MaryEllenNY
Individuals who have had their health insurance policies canceled over the last few weeks may be able to keep them because of an administrative fix.
At a Nov. 14 press conference, President Barack Obama said he was making an administrative change that would allow health plans to continue to offer existing plans to their current enrollees throughout 2014, even if those plans don’t meet the coverage standards under the Affordable Care Act.
Whether to offer the plans now is up to insurance companies and state insurance commissioners, but the ACA is no longer a barrier, President Obama said.
If insurers continue to offer these plans in 2014, they must spell out to their customers which insurance protections the plans are lacking and what may be available on the health insurance exchanges.
Under the ACA, health plans that were in place before the law was signed in March 2010 are "grandfathered" in place and consumers can keep them. However, if insurers make changes to those plans, the plans must come into compliance with ACA requirements. The ACA also requires plans created after March 2010 to meet the law’s requirements starting on Jan. 1, 2014.
Under the action announced by President Obama, plans that have been created or altered since 2010 can continue to be offered to existing enrollees in 2014.
The announcement came after several congressional Democrats began to join their Republican colleagues in calling for a change that would allow Americans to keep their current health plans. The House is set to vote on Nov. 15 on a bill introduced by Rep. Fred Upton (R-Mich.) that would essentially grandfather all existing health plans during 2014. Unlike the President’s fix, the Upton proposal would allow current plans to continue to enroll new members.
President Obama said he now regrets the pledge he made that if Americans like their health plans they could keep them. While it was true for about 95% of Americans, he said, the grandfathering clause crafted by the administration did not go far enough in allowing more people to keep their plans. "That’s on me," he said during the press conference.
The President’s announcement was greeted with skepticism by House Speaker John Boehner (R-Ohio), who urged Democrats to join him in supporting Rep. Upton’s bill (H.R. 3350) instead.
Speaker Boehner said the Obama administration misled the public with the "if you like your health plan, you can keep it" pledge. "It’s clear that the American people simply can’t trust this White House," he said.
Health care insurers also expressed displeasure with the President’s announcement on grandfathered plans, saying that it has the potential to "destabilize" the insurance market.
"Premiums have already been set for next year based on an assumption of when consumers will be transitioning to the new marketplace. If, due to these changes, fewer younger and healthier people choose to purchase coverage in the exchange, premiums will increase in the marketplace and there will be fewer choices for consumers," Karen Ignagni, president and CEO of America’s Health Insurance Plans, said in a statement. "Additional steps must be taken to stabilize the marketplace and mitigate the adverse impact on consumers."
On Twitter @MaryEllenNY
Fewer than 27,000 have selected a plan through healthcare.gov
Just under 27,000 Americans chose – but did not necessarily pay for – health insurance through the federal healthcare.gov website during its first month of operation.
The Department of Health and Human Services reports that from Oct. 1 to Nov. 2, a total of 106,185 people – 26,794 via healthcare.gov and 79,391 via state-based health insurance exchanges – had selected a plan for enrollment. Hundreds of thousands more (396,261) had been determined to be eligible for Medicaid or the Children’s Health Insurance Plan (CHIP). The majority of those (212,865) went through one of the 15 state-based exchanges, while 183,396 got the determination through healthcare.gov, which serves as the health insurance exchange for 36 states.
HHS Secretary Kathleen Sebelius said in a briefing with reporters that the Administration at present could not release the number of people who have paid for insurance. Those data will be available by Dec. 15, which is the deadline for getting coverage that starts Jan. 1.
But the numbers indicate that the "marketplace is working" and that people are enrolling in person, over the phone, and online, Ms. Sebelius said. She added that the data show that people have not bought plans yet are still shopping.
"People want to make sure their doctors are in their network, they want to see what kind of benefits they have, they want to check out options, they want to talk to people," she said. The expectation is that "these numbers will grow substantially over next 5 months."
Physicians may not be aware of whether they are participating in an exchange plan or they may not be participating. A recent survey by the Medical Society of the State of New York found that a third of members weren’t sure if they were in an exchange plan network and another third said they would not participate in an exchange plan.
In an interview, Dr. Stephen L. Brotherton, president of the Texas Medical Association, said that "the street information is different" from what the Centers for Medicare & Medicaid Services is reporting on what consumers can learn about physician networks.
Meanwhile, Ms. Sebelius said that interest in purchasing health insurance is "reflected in the numbers of people who are seeking information and shopping for plans."
According to the HHS report, there have been about 27 million unique visitors to healthcare.gov and 3.1 million calls to state and federal call centers.
In the first month, 846,184 applications, representing just over 1.5 million Americans, were completed through the state and federal online sites. HHS says that this figure represents about 22% of the estimated 7 million people the Congressional Budget Office said were likely to enroll in a plan in 2014. About a half million people who submitted applications were not eligible for a health insurance exchange plan. Out of the 1 million who have been determined to be eligible, about 106,000 have selected a plan through the federal or state exchanges.
HHS says there were an additional 259,107 paper and phone applications for plans through the federal exchange.
The HHS report found that shopping online was the primary mode for most exchange users. On average, 93% of state exchange applications that were submitted and completed were done electronically. That dropped to 67% for applications submitted and completed through healthcare.gov.
On Nov. 12, CMS officials said that the agency would be sending "waves" of e-mails to some 275,000 people who had tried to get on healthcare.gov in the early weeks and had not succeeded. They also said that the site was currently configured to handle any added demand from people responding to those e-mails.
Ms. Sebelius said that she remains optimistic that enrollment figures will grow. "Will we convert 100%? Probably not, but I don’t think that was ever the expectation," she said.
"But I think a number of the people who are currently in the shopping mode will at the end of the day enroll in coverage."
On Twitter @aliciaault
Just under 27,000 Americans chose – but did not necessarily pay for – health insurance through the federal healthcare.gov website during its first month of operation.
The Department of Health and Human Services reports that from Oct. 1 to Nov. 2, a total of 106,185 people – 26,794 via healthcare.gov and 79,391 via state-based health insurance exchanges – had selected a plan for enrollment. Hundreds of thousands more (396,261) had been determined to be eligible for Medicaid or the Children’s Health Insurance Plan (CHIP). The majority of those (212,865) went through one of the 15 state-based exchanges, while 183,396 got the determination through healthcare.gov, which serves as the health insurance exchange for 36 states.
HHS Secretary Kathleen Sebelius said in a briefing with reporters that the Administration at present could not release the number of people who have paid for insurance. Those data will be available by Dec. 15, which is the deadline for getting coverage that starts Jan. 1.
But the numbers indicate that the "marketplace is working" and that people are enrolling in person, over the phone, and online, Ms. Sebelius said. She added that the data show that people have not bought plans yet are still shopping.
"People want to make sure their doctors are in their network, they want to see what kind of benefits they have, they want to check out options, they want to talk to people," she said. The expectation is that "these numbers will grow substantially over next 5 months."
Physicians may not be aware of whether they are participating in an exchange plan or they may not be participating. A recent survey by the Medical Society of the State of New York found that a third of members weren’t sure if they were in an exchange plan network and another third said they would not participate in an exchange plan.
In an interview, Dr. Stephen L. Brotherton, president of the Texas Medical Association, said that "the street information is different" from what the Centers for Medicare & Medicaid Services is reporting on what consumers can learn about physician networks.
Meanwhile, Ms. Sebelius said that interest in purchasing health insurance is "reflected in the numbers of people who are seeking information and shopping for plans."
According to the HHS report, there have been about 27 million unique visitors to healthcare.gov and 3.1 million calls to state and federal call centers.
In the first month, 846,184 applications, representing just over 1.5 million Americans, were completed through the state and federal online sites. HHS says that this figure represents about 22% of the estimated 7 million people the Congressional Budget Office said were likely to enroll in a plan in 2014. About a half million people who submitted applications were not eligible for a health insurance exchange plan. Out of the 1 million who have been determined to be eligible, about 106,000 have selected a plan through the federal or state exchanges.
HHS says there were an additional 259,107 paper and phone applications for plans through the federal exchange.
The HHS report found that shopping online was the primary mode for most exchange users. On average, 93% of state exchange applications that were submitted and completed were done electronically. That dropped to 67% for applications submitted and completed through healthcare.gov.
On Nov. 12, CMS officials said that the agency would be sending "waves" of e-mails to some 275,000 people who had tried to get on healthcare.gov in the early weeks and had not succeeded. They also said that the site was currently configured to handle any added demand from people responding to those e-mails.
Ms. Sebelius said that she remains optimistic that enrollment figures will grow. "Will we convert 100%? Probably not, but I don’t think that was ever the expectation," she said.
"But I think a number of the people who are currently in the shopping mode will at the end of the day enroll in coverage."
On Twitter @aliciaault
Just under 27,000 Americans chose – but did not necessarily pay for – health insurance through the federal healthcare.gov website during its first month of operation.
The Department of Health and Human Services reports that from Oct. 1 to Nov. 2, a total of 106,185 people – 26,794 via healthcare.gov and 79,391 via state-based health insurance exchanges – had selected a plan for enrollment. Hundreds of thousands more (396,261) had been determined to be eligible for Medicaid or the Children’s Health Insurance Plan (CHIP). The majority of those (212,865) went through one of the 15 state-based exchanges, while 183,396 got the determination through healthcare.gov, which serves as the health insurance exchange for 36 states.
HHS Secretary Kathleen Sebelius said in a briefing with reporters that the Administration at present could not release the number of people who have paid for insurance. Those data will be available by Dec. 15, which is the deadline for getting coverage that starts Jan. 1.
But the numbers indicate that the "marketplace is working" and that people are enrolling in person, over the phone, and online, Ms. Sebelius said. She added that the data show that people have not bought plans yet are still shopping.
"People want to make sure their doctors are in their network, they want to see what kind of benefits they have, they want to check out options, they want to talk to people," she said. The expectation is that "these numbers will grow substantially over next 5 months."
Physicians may not be aware of whether they are participating in an exchange plan or they may not be participating. A recent survey by the Medical Society of the State of New York found that a third of members weren’t sure if they were in an exchange plan network and another third said they would not participate in an exchange plan.
In an interview, Dr. Stephen L. Brotherton, president of the Texas Medical Association, said that "the street information is different" from what the Centers for Medicare & Medicaid Services is reporting on what consumers can learn about physician networks.
Meanwhile, Ms. Sebelius said that interest in purchasing health insurance is "reflected in the numbers of people who are seeking information and shopping for plans."
According to the HHS report, there have been about 27 million unique visitors to healthcare.gov and 3.1 million calls to state and federal call centers.
In the first month, 846,184 applications, representing just over 1.5 million Americans, were completed through the state and federal online sites. HHS says that this figure represents about 22% of the estimated 7 million people the Congressional Budget Office said were likely to enroll in a plan in 2014. About a half million people who submitted applications were not eligible for a health insurance exchange plan. Out of the 1 million who have been determined to be eligible, about 106,000 have selected a plan through the federal or state exchanges.
HHS says there were an additional 259,107 paper and phone applications for plans through the federal exchange.
The HHS report found that shopping online was the primary mode for most exchange users. On average, 93% of state exchange applications that were submitted and completed were done electronically. That dropped to 67% for applications submitted and completed through healthcare.gov.
On Nov. 12, CMS officials said that the agency would be sending "waves" of e-mails to some 275,000 people who had tried to get on healthcare.gov in the early weeks and had not succeeded. They also said that the site was currently configured to handle any added demand from people responding to those e-mails.
Ms. Sebelius said that she remains optimistic that enrollment figures will grow. "Will we convert 100%? Probably not, but I don’t think that was ever the expectation," she said.
"But I think a number of the people who are currently in the shopping mode will at the end of the day enroll in coverage."
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In phase III trial, bevacizumab prolongs progression-free survival for ovarian cancer
AMSTERDAM – Despite finding no overall survival benefit by adding bevacizumab to standard chemotherapy for newly diagnosed or platinum-resistant advanced ovarian cancer, the results of two phase III clinical trials remain "practice changing," according to a commentator Dr. Rebecca Kristeleit at the the multidisciplinary European cancer congresses.
Final overall survival results from the ICON7 trial showed that, in more than 1,500 women with newly diagnosed advanced ovarian cancer, there was a nonstatistical (P =.85) difference in overall survival of about 0.9 months using the restricted mean when all patients were considered.
In the AURELIA trial, conducted in 361 women with platinum-resistant disease, the hazard ratio for overall survival was 0.85, in favor of the addition of bevacizumab to chemotherapy, although this was not statistically significant (P = .174). The median overall survival was 16.6 months vs. 13.3 months in the control arm.
"The message I take from ICON7 is that there is a significant overall survival benefit in the high-risk group," said Dr. Kristeleit. "It’s an important clinical improvement, and it’s most important in the poor-prognosis patients, the ones who are inoperable, and the ones who are stage IV."
Regarding AURELIA, Dr. Kristeleit, a senior lecturer and consultant medical oncologist at University College London, said, "The study has shown a significant progression-free survival benefit, and we need to remember that it has doubled this in this really hard to treat group of ovarian cancer patients where there is significant clinical need."
ICON7: Bevacizumab in front-line treatment
The ICON7 (International Collaboration on Ovarian Neoplasms) study investigated the safety and efficacy of adding bevacizumab (7.5 mg/kg every 3 weeks) to standard chemotherapy in women with newly diagnosed ovarian cancer who were recruited and treated at 253 centers. The mean age of patients in the trial was 57 years.
The primary efficacy findings from the study were reported 3 years ago at the annual Congress of the European Society for Medical Oncology and published in the New England Journal of Medicine (2011;365:2484-96). These findings showed a clear benefit of adding the targeted agent to carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m2) given every 3 weeks for six cycles vs. chemotherapy alone, with median progression-free survival times of 19.0 vs. 17.3 months (HR, 0.81; P = .0041), respectively.
Now, with a median follow-up of 49 months, "it’s reassuring to see the progression-free survival is essentially the same [19.9 vs. 17.5 months]," observed study investigator Dr. Amit Oza of the Princess Margaret Cancer Centre at the University of Toronto.
Dr. Oza noted that 502 (33%) women met prespecified criteria for having a "poor prognosis," including women with suboptimally debulked stage III disease, those with stage IV disease, and those who could not have surgery, potentially putting them at high risk of progression. In those women, bevacizumab improved progression-free survival by a median of 5.5 months (HR, 0.73, P =.001), or 4.1 months using the restricted mean as the data were found to be non-proportional.
Final overall survival in these high-risk women was improved by a median of 9.4 months by the additional use of bevacizumab (HR, 0.78, P = .03), or 4.8 months using the restricted mean, from 34.5 months with chemotherapy alone to 39.3 months by the addition of the targeted agent.
"The overall survival difference in the high-risk subgroup is clinically meaningful," Dr. Oza said.
AURELIA: Bevacizumab in platinum-resistant disease
AURELIA was an open-label, randomized trial involving women who had progressive ovarian cancer within 6 months of receiving platinum-based chemotherapy. Women were randomized to receive chemotherapy alone (n = 182) or to chemotherapy plus bevacizumab (n = 179). The choice of chemotherapy was at the investigators’ discretion from a choice of weekly paclitaxel (80 mg/m2 on days 1, 8, 15, and 22), topotecan (4 mg/m2 on days 1, 8, and 15), or pegylated liposomal doxorubicin (PLD, 40 mg/m2 on day 1). Bevacizumab was given at a dose of 15 mg/kg every 3 weeks.
The primary endpoint was progression-free survival, with secondary endpoints of overall survival, quality of life, and, of course, safety and tolerability. The primary endpoint findings were presented last year at the annual meeting American Society of Clinical Oncology (J. Clin. Oncol. 2012;30 Suppl:LBA5002) and showed that the addition of bevacizumab almost doubled progression-free survival from 3.4 months with chemotherapy alone to 6.7 months when bevacizumab was added (HR, 0.48, P less than .001).
"The study was not powered to detect a significant difference in overall survival," said Dr. Petronella O. Witteveen, who was one of the AURELIA study investigators. Dr. Witteveen of the University Medical Center Utrecht in the Netherlands commented that overall survival was a key secondary endpoint for the trial and that interpretation of these data were complicated by the high percentage (40%) of patients in the chemotherapy arm that were allowed to crossover to additional treatment with bevacizumab.
Although no difference between the treatment arms could be seen in the final overall survival analysis, exploratory findings hinted that patients who received bevacizumab in combination with weekly paclitaxel might have had a survival advantage. The median overall survival in the cohort of patients who received bevacizumab in addition to weekly paclitaxel (n = 60) was 22.4 months vs. 13.2 months in the patients who received the chemotherapy alone (n = 55; HR, 0.65). Overall survival in the topotecan and PLD cohorts did not show any benefit of the addition of bevacizumab, with median overall survival times of just over 13-14 months whether or not bevacizumab was added to chemotherapy.
Updated safety findings showed no undue concerns or new side effects, with a higher percentage of patients experiencing hypertension if treated with bevacizumab rather than chemotherapy alone (7.8% vs. 1.1%). "There were strict instructions to try to reduce the number of gastrointestinal perforations," Dr. Witteveen noted. This resulted in a low rate (1.1% vs. 0%) of this adverse event, she observed
"Practice-changing trials"
"I think these are practice-changing trials," Dr. Kristeleit commented, stating that bevacizumab is clearly an active drug in advanced bulky ovarian cancer.
Based on the ICON7 findings, "first-line bevacizumab and 3-weekly chemotherapy should be considered a standard of care in high risk ovarian cancer," she said.
Meanwhile AURELIA shows, "Bevacizumab with weekly paclitaxel should be considered a new paradigm in platinum-resistant ovarian cancer."
Bevacizumab (Avastin) was recently approved for use in combination with chemotherapy in the first- and second-line treatment of advanced ovarian cancer in Europe. In the second-line setting, it is indicated in platinum-sensitive disease and not platinum-resistant disease as tested in the AURELIA trial. Bevacizumab is not currently licensed for ovarian cancer treatment in the United States.
Roche sponsored the AURELIA study. Dr. Witteveen had no conflicts of interest; some of her coinvestigators disclosed ties with Roche, GlaxoSmithKline, and Novartis. ICON-7 was funded by Roche and the National Institute for Health Research through the National Cancer Research Network in the United Kingdom. Dr. Oza disclosed ties with Roche. Dr. Kristeleit disclosed ties with Roche, Clovis, Janssen, Lytix, and Novartis.
AMSTERDAM – Despite finding no overall survival benefit by adding bevacizumab to standard chemotherapy for newly diagnosed or platinum-resistant advanced ovarian cancer, the results of two phase III clinical trials remain "practice changing," according to a commentator Dr. Rebecca Kristeleit at the the multidisciplinary European cancer congresses.
Final overall survival results from the ICON7 trial showed that, in more than 1,500 women with newly diagnosed advanced ovarian cancer, there was a nonstatistical (P =.85) difference in overall survival of about 0.9 months using the restricted mean when all patients were considered.
In the AURELIA trial, conducted in 361 women with platinum-resistant disease, the hazard ratio for overall survival was 0.85, in favor of the addition of bevacizumab to chemotherapy, although this was not statistically significant (P = .174). The median overall survival was 16.6 months vs. 13.3 months in the control arm.
"The message I take from ICON7 is that there is a significant overall survival benefit in the high-risk group," said Dr. Kristeleit. "It’s an important clinical improvement, and it’s most important in the poor-prognosis patients, the ones who are inoperable, and the ones who are stage IV."
Regarding AURELIA, Dr. Kristeleit, a senior lecturer and consultant medical oncologist at University College London, said, "The study has shown a significant progression-free survival benefit, and we need to remember that it has doubled this in this really hard to treat group of ovarian cancer patients where there is significant clinical need."
ICON7: Bevacizumab in front-line treatment
The ICON7 (International Collaboration on Ovarian Neoplasms) study investigated the safety and efficacy of adding bevacizumab (7.5 mg/kg every 3 weeks) to standard chemotherapy in women with newly diagnosed ovarian cancer who were recruited and treated at 253 centers. The mean age of patients in the trial was 57 years.
The primary efficacy findings from the study were reported 3 years ago at the annual Congress of the European Society for Medical Oncology and published in the New England Journal of Medicine (2011;365:2484-96). These findings showed a clear benefit of adding the targeted agent to carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m2) given every 3 weeks for six cycles vs. chemotherapy alone, with median progression-free survival times of 19.0 vs. 17.3 months (HR, 0.81; P = .0041), respectively.
Now, with a median follow-up of 49 months, "it’s reassuring to see the progression-free survival is essentially the same [19.9 vs. 17.5 months]," observed study investigator Dr. Amit Oza of the Princess Margaret Cancer Centre at the University of Toronto.
Dr. Oza noted that 502 (33%) women met prespecified criteria for having a "poor prognosis," including women with suboptimally debulked stage III disease, those with stage IV disease, and those who could not have surgery, potentially putting them at high risk of progression. In those women, bevacizumab improved progression-free survival by a median of 5.5 months (HR, 0.73, P =.001), or 4.1 months using the restricted mean as the data were found to be non-proportional.
Final overall survival in these high-risk women was improved by a median of 9.4 months by the additional use of bevacizumab (HR, 0.78, P = .03), or 4.8 months using the restricted mean, from 34.5 months with chemotherapy alone to 39.3 months by the addition of the targeted agent.
"The overall survival difference in the high-risk subgroup is clinically meaningful," Dr. Oza said.
AURELIA: Bevacizumab in platinum-resistant disease
AURELIA was an open-label, randomized trial involving women who had progressive ovarian cancer within 6 months of receiving platinum-based chemotherapy. Women were randomized to receive chemotherapy alone (n = 182) or to chemotherapy plus bevacizumab (n = 179). The choice of chemotherapy was at the investigators’ discretion from a choice of weekly paclitaxel (80 mg/m2 on days 1, 8, 15, and 22), topotecan (4 mg/m2 on days 1, 8, and 15), or pegylated liposomal doxorubicin (PLD, 40 mg/m2 on day 1). Bevacizumab was given at a dose of 15 mg/kg every 3 weeks.
The primary endpoint was progression-free survival, with secondary endpoints of overall survival, quality of life, and, of course, safety and tolerability. The primary endpoint findings were presented last year at the annual meeting American Society of Clinical Oncology (J. Clin. Oncol. 2012;30 Suppl:LBA5002) and showed that the addition of bevacizumab almost doubled progression-free survival from 3.4 months with chemotherapy alone to 6.7 months when bevacizumab was added (HR, 0.48, P less than .001).
"The study was not powered to detect a significant difference in overall survival," said Dr. Petronella O. Witteveen, who was one of the AURELIA study investigators. Dr. Witteveen of the University Medical Center Utrecht in the Netherlands commented that overall survival was a key secondary endpoint for the trial and that interpretation of these data were complicated by the high percentage (40%) of patients in the chemotherapy arm that were allowed to crossover to additional treatment with bevacizumab.
Although no difference between the treatment arms could be seen in the final overall survival analysis, exploratory findings hinted that patients who received bevacizumab in combination with weekly paclitaxel might have had a survival advantage. The median overall survival in the cohort of patients who received bevacizumab in addition to weekly paclitaxel (n = 60) was 22.4 months vs. 13.2 months in the patients who received the chemotherapy alone (n = 55; HR, 0.65). Overall survival in the topotecan and PLD cohorts did not show any benefit of the addition of bevacizumab, with median overall survival times of just over 13-14 months whether or not bevacizumab was added to chemotherapy.
Updated safety findings showed no undue concerns or new side effects, with a higher percentage of patients experiencing hypertension if treated with bevacizumab rather than chemotherapy alone (7.8% vs. 1.1%). "There were strict instructions to try to reduce the number of gastrointestinal perforations," Dr. Witteveen noted. This resulted in a low rate (1.1% vs. 0%) of this adverse event, she observed
"Practice-changing trials"
"I think these are practice-changing trials," Dr. Kristeleit commented, stating that bevacizumab is clearly an active drug in advanced bulky ovarian cancer.
Based on the ICON7 findings, "first-line bevacizumab and 3-weekly chemotherapy should be considered a standard of care in high risk ovarian cancer," she said.
Meanwhile AURELIA shows, "Bevacizumab with weekly paclitaxel should be considered a new paradigm in platinum-resistant ovarian cancer."
Bevacizumab (Avastin) was recently approved for use in combination with chemotherapy in the first- and second-line treatment of advanced ovarian cancer in Europe. In the second-line setting, it is indicated in platinum-sensitive disease and not platinum-resistant disease as tested in the AURELIA trial. Bevacizumab is not currently licensed for ovarian cancer treatment in the United States.
Roche sponsored the AURELIA study. Dr. Witteveen had no conflicts of interest; some of her coinvestigators disclosed ties with Roche, GlaxoSmithKline, and Novartis. ICON-7 was funded by Roche and the National Institute for Health Research through the National Cancer Research Network in the United Kingdom. Dr. Oza disclosed ties with Roche. Dr. Kristeleit disclosed ties with Roche, Clovis, Janssen, Lytix, and Novartis.
AMSTERDAM – Despite finding no overall survival benefit by adding bevacizumab to standard chemotherapy for newly diagnosed or platinum-resistant advanced ovarian cancer, the results of two phase III clinical trials remain "practice changing," according to a commentator Dr. Rebecca Kristeleit at the the multidisciplinary European cancer congresses.
Final overall survival results from the ICON7 trial showed that, in more than 1,500 women with newly diagnosed advanced ovarian cancer, there was a nonstatistical (P =.85) difference in overall survival of about 0.9 months using the restricted mean when all patients were considered.
In the AURELIA trial, conducted in 361 women with platinum-resistant disease, the hazard ratio for overall survival was 0.85, in favor of the addition of bevacizumab to chemotherapy, although this was not statistically significant (P = .174). The median overall survival was 16.6 months vs. 13.3 months in the control arm.
"The message I take from ICON7 is that there is a significant overall survival benefit in the high-risk group," said Dr. Kristeleit. "It’s an important clinical improvement, and it’s most important in the poor-prognosis patients, the ones who are inoperable, and the ones who are stage IV."
Regarding AURELIA, Dr. Kristeleit, a senior lecturer and consultant medical oncologist at University College London, said, "The study has shown a significant progression-free survival benefit, and we need to remember that it has doubled this in this really hard to treat group of ovarian cancer patients where there is significant clinical need."
ICON7: Bevacizumab in front-line treatment
The ICON7 (International Collaboration on Ovarian Neoplasms) study investigated the safety and efficacy of adding bevacizumab (7.5 mg/kg every 3 weeks) to standard chemotherapy in women with newly diagnosed ovarian cancer who were recruited and treated at 253 centers. The mean age of patients in the trial was 57 years.
The primary efficacy findings from the study were reported 3 years ago at the annual Congress of the European Society for Medical Oncology and published in the New England Journal of Medicine (2011;365:2484-96). These findings showed a clear benefit of adding the targeted agent to carboplatin (AUC 5 or 6) and paclitaxel (175 mg/m2) given every 3 weeks for six cycles vs. chemotherapy alone, with median progression-free survival times of 19.0 vs. 17.3 months (HR, 0.81; P = .0041), respectively.
Now, with a median follow-up of 49 months, "it’s reassuring to see the progression-free survival is essentially the same [19.9 vs. 17.5 months]," observed study investigator Dr. Amit Oza of the Princess Margaret Cancer Centre at the University of Toronto.
Dr. Oza noted that 502 (33%) women met prespecified criteria for having a "poor prognosis," including women with suboptimally debulked stage III disease, those with stage IV disease, and those who could not have surgery, potentially putting them at high risk of progression. In those women, bevacizumab improved progression-free survival by a median of 5.5 months (HR, 0.73, P =.001), or 4.1 months using the restricted mean as the data were found to be non-proportional.
Final overall survival in these high-risk women was improved by a median of 9.4 months by the additional use of bevacizumab (HR, 0.78, P = .03), or 4.8 months using the restricted mean, from 34.5 months with chemotherapy alone to 39.3 months by the addition of the targeted agent.
"The overall survival difference in the high-risk subgroup is clinically meaningful," Dr. Oza said.
AURELIA: Bevacizumab in platinum-resistant disease
AURELIA was an open-label, randomized trial involving women who had progressive ovarian cancer within 6 months of receiving platinum-based chemotherapy. Women were randomized to receive chemotherapy alone (n = 182) or to chemotherapy plus bevacizumab (n = 179). The choice of chemotherapy was at the investigators’ discretion from a choice of weekly paclitaxel (80 mg/m2 on days 1, 8, 15, and 22), topotecan (4 mg/m2 on days 1, 8, and 15), or pegylated liposomal doxorubicin (PLD, 40 mg/m2 on day 1). Bevacizumab was given at a dose of 15 mg/kg every 3 weeks.
The primary endpoint was progression-free survival, with secondary endpoints of overall survival, quality of life, and, of course, safety and tolerability. The primary endpoint findings were presented last year at the annual meeting American Society of Clinical Oncology (J. Clin. Oncol. 2012;30 Suppl:LBA5002) and showed that the addition of bevacizumab almost doubled progression-free survival from 3.4 months with chemotherapy alone to 6.7 months when bevacizumab was added (HR, 0.48, P less than .001).
"The study was not powered to detect a significant difference in overall survival," said Dr. Petronella O. Witteveen, who was one of the AURELIA study investigators. Dr. Witteveen of the University Medical Center Utrecht in the Netherlands commented that overall survival was a key secondary endpoint for the trial and that interpretation of these data were complicated by the high percentage (40%) of patients in the chemotherapy arm that were allowed to crossover to additional treatment with bevacizumab.
Although no difference between the treatment arms could be seen in the final overall survival analysis, exploratory findings hinted that patients who received bevacizumab in combination with weekly paclitaxel might have had a survival advantage. The median overall survival in the cohort of patients who received bevacizumab in addition to weekly paclitaxel (n = 60) was 22.4 months vs. 13.2 months in the patients who received the chemotherapy alone (n = 55; HR, 0.65). Overall survival in the topotecan and PLD cohorts did not show any benefit of the addition of bevacizumab, with median overall survival times of just over 13-14 months whether or not bevacizumab was added to chemotherapy.
Updated safety findings showed no undue concerns or new side effects, with a higher percentage of patients experiencing hypertension if treated with bevacizumab rather than chemotherapy alone (7.8% vs. 1.1%). "There were strict instructions to try to reduce the number of gastrointestinal perforations," Dr. Witteveen noted. This resulted in a low rate (1.1% vs. 0%) of this adverse event, she observed
"Practice-changing trials"
"I think these are practice-changing trials," Dr. Kristeleit commented, stating that bevacizumab is clearly an active drug in advanced bulky ovarian cancer.
Based on the ICON7 findings, "first-line bevacizumab and 3-weekly chemotherapy should be considered a standard of care in high risk ovarian cancer," she said.
Meanwhile AURELIA shows, "Bevacizumab with weekly paclitaxel should be considered a new paradigm in platinum-resistant ovarian cancer."
Bevacizumab (Avastin) was recently approved for use in combination with chemotherapy in the first- and second-line treatment of advanced ovarian cancer in Europe. In the second-line setting, it is indicated in platinum-sensitive disease and not platinum-resistant disease as tested in the AURELIA trial. Bevacizumab is not currently licensed for ovarian cancer treatment in the United States.
Roche sponsored the AURELIA study. Dr. Witteveen had no conflicts of interest; some of her coinvestigators disclosed ties with Roche, GlaxoSmithKline, and Novartis. ICON-7 was funded by Roche and the National Institute for Health Research through the National Cancer Research Network in the United Kingdom. Dr. Oza disclosed ties with Roche. Dr. Kristeleit disclosed ties with Roche, Clovis, Janssen, Lytix, and Novartis.
AT THE EUROPEAN CANCER CONGRESS 2013
Major findings: The hazard ratios for overall survival were 0.78 (P = .007) in "high-risk" newly diagnosed patients and 0.85 (P = .174) in platinum-resistant patients.
Data source: Two multicenter, randomized, phase III, controlled trials of bevacizumab added to chemotherapy for the first-line (ICON7; n = 1,528) or platinum-resistant (AURELIA; n = 361) treatment of advanced ovarian cancer.
Disclosures: Roche sponsored the AURELIA study. Dr. Witteveen had no conflicts of interest; some of her coinvestigators disclosed ties with Roche, GSK, and Novartis. ICON7 was funded by Roche and the National Institute for Health Research through the National Cancer Research Network in the United Kingdom. Dr. Oza disclosed ties with Roche. Dr. Kristeleit disclosed ties with Roche, Clovis, Janssen, Lytix, and Novartis.
