Patients at risk of RA may already have abnormal aortic stiffness

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Tue, 03/19/2019 - 15:56

 

Patients at risk of rheumatoid arthritis may have already developed abnormal aortic stiffness, according to a study of potential RA patients who underwent cardiac MRI.

“To our knowledge, this is the first study showing subclinical increase in aortic stiffness in at-risk individuals for RA, with values numerically close to those seen in early, treatment-naive RA,” wrote Graham Fent, MBChB, of the University of Leeds (England) and his associates. The study was published in Annals of the Rheumatic Diseases.

Hypothesizing that patients with no systemic inflammation but circulating anti–cyclic citrullinated peptide (CCP) antibodies may already have cardiovascular concerns, Dr. Fent and his colleagues recruited 18 individuals at risk of developing RA and 30 healthy controls. The groups were matched for age and gender and then underwent multiparametric 3.0 Tesla cardiac MRI with late gadolinium enhancement. The at-risk individuals were classified as being at either low (n = 10) or high (n = 8) risk of RA. Over 12 months, five of the at-risk patients progressed to RA.



According to the cardiac MRI findings, aortic distensibility was lower – and thus arterial stiffness was greater – in the at-risk group (3.6 x 10–3 per mm Hg) versus the healthy controls (4.9 x 10–3 per mm Hg). The difference was even more distinct in the high-risk group (3.1 x 10–3 per mm Hg), compared with the low-risk group (4.2 x 10–3 per mm Hg). The group who eventually progressed to RA also showed lower levels of distensibility (3.2 x 10–3 per mm Hg).

The coauthors acknowledged that the major limitation of their study was a lack of control groups. However, they noted that such a pronounced level of aortic stiffness in the high-risk and RA groups should be seen as “implying a particular role of CCP antibodies.”

The study was supported by the U.K. National Institute for Health Research. One author reported being funded by a National Institute for Health Research grant; another reported being funded by a British Heart Foundation Personal Chair.

SOURCE: Fent G et al. Ann Rheum Dis. 2019 Mar 9. doi: 10.1136/annrheumdis-2018-214975.

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Patients at risk of rheumatoid arthritis may have already developed abnormal aortic stiffness, according to a study of potential RA patients who underwent cardiac MRI.

“To our knowledge, this is the first study showing subclinical increase in aortic stiffness in at-risk individuals for RA, with values numerically close to those seen in early, treatment-naive RA,” wrote Graham Fent, MBChB, of the University of Leeds (England) and his associates. The study was published in Annals of the Rheumatic Diseases.

Hypothesizing that patients with no systemic inflammation but circulating anti–cyclic citrullinated peptide (CCP) antibodies may already have cardiovascular concerns, Dr. Fent and his colleagues recruited 18 individuals at risk of developing RA and 30 healthy controls. The groups were matched for age and gender and then underwent multiparametric 3.0 Tesla cardiac MRI with late gadolinium enhancement. The at-risk individuals were classified as being at either low (n = 10) or high (n = 8) risk of RA. Over 12 months, five of the at-risk patients progressed to RA.



According to the cardiac MRI findings, aortic distensibility was lower – and thus arterial stiffness was greater – in the at-risk group (3.6 x 10–3 per mm Hg) versus the healthy controls (4.9 x 10–3 per mm Hg). The difference was even more distinct in the high-risk group (3.1 x 10–3 per mm Hg), compared with the low-risk group (4.2 x 10–3 per mm Hg). The group who eventually progressed to RA also showed lower levels of distensibility (3.2 x 10–3 per mm Hg).

The coauthors acknowledged that the major limitation of their study was a lack of control groups. However, they noted that such a pronounced level of aortic stiffness in the high-risk and RA groups should be seen as “implying a particular role of CCP antibodies.”

The study was supported by the U.K. National Institute for Health Research. One author reported being funded by a National Institute for Health Research grant; another reported being funded by a British Heart Foundation Personal Chair.

SOURCE: Fent G et al. Ann Rheum Dis. 2019 Mar 9. doi: 10.1136/annrheumdis-2018-214975.

 

Patients at risk of rheumatoid arthritis may have already developed abnormal aortic stiffness, according to a study of potential RA patients who underwent cardiac MRI.

“To our knowledge, this is the first study showing subclinical increase in aortic stiffness in at-risk individuals for RA, with values numerically close to those seen in early, treatment-naive RA,” wrote Graham Fent, MBChB, of the University of Leeds (England) and his associates. The study was published in Annals of the Rheumatic Diseases.

Hypothesizing that patients with no systemic inflammation but circulating anti–cyclic citrullinated peptide (CCP) antibodies may already have cardiovascular concerns, Dr. Fent and his colleagues recruited 18 individuals at risk of developing RA and 30 healthy controls. The groups were matched for age and gender and then underwent multiparametric 3.0 Tesla cardiac MRI with late gadolinium enhancement. The at-risk individuals were classified as being at either low (n = 10) or high (n = 8) risk of RA. Over 12 months, five of the at-risk patients progressed to RA.



According to the cardiac MRI findings, aortic distensibility was lower – and thus arterial stiffness was greater – in the at-risk group (3.6 x 10–3 per mm Hg) versus the healthy controls (4.9 x 10–3 per mm Hg). The difference was even more distinct in the high-risk group (3.1 x 10–3 per mm Hg), compared with the low-risk group (4.2 x 10–3 per mm Hg). The group who eventually progressed to RA also showed lower levels of distensibility (3.2 x 10–3 per mm Hg).

The coauthors acknowledged that the major limitation of their study was a lack of control groups. However, they noted that such a pronounced level of aortic stiffness in the high-risk and RA groups should be seen as “implying a particular role of CCP antibodies.”

The study was supported by the U.K. National Institute for Health Research. One author reported being funded by a National Institute for Health Research grant; another reported being funded by a British Heart Foundation Personal Chair.

SOURCE: Fent G et al. Ann Rheum Dis. 2019 Mar 9. doi: 10.1136/annrheumdis-2018-214975.

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FDA approves atezolizumab for first-line ES-SCLC treatment

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Tue, 03/19/2019 - 13:43

 

The Food and Drug Administration has approved atezolizumab (Tecentriq), in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).

Approval was based on results from the phase 3 IMpower133 study, in which 403 treatment-naive patients with ES-SCLC received atezolizumab at 1,200 mg with carboplatin at 5 mg/mL per minute on day 1 and etoposide 100 mg/m2 on days 1, 2, and 3 of a 21-day cycle for four cycles, followed by atezolizumab at 1,200 mg once every 3 weeks until disease progression or unacceptable toxicity; or received placebo with the same dosage of carboplatin and etoposide for a similar duration.

Overall survival was significantly better in patients who received atezolizumab, compared with placebo (12.3 vs. 10.3 months; hazard ratio, 0.70; 95% confidence interval, 0.54-0.91; P = .0069), as was progression-free survival (5.2 vs. 4.3 months; HR, 0.77; 95% CI, 0.62-0.96; P = .017).



The most common adverse events associated with atezolizumab in the study were fatigue/asthenia, nausea, alopecia, constipation, and decreased appetite.

According to the FDA, the recommended dose is 1,200 mg IV over 60 minutes every 3 weeks. When administered on the same day as chemotherapy, atezolizumab should be given first. If the first infusion is tolerated, all subsequent infusions can be delivered over 30 minutes.

Find the full press release on the FDA website.

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The Food and Drug Administration has approved atezolizumab (Tecentriq), in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).

Approval was based on results from the phase 3 IMpower133 study, in which 403 treatment-naive patients with ES-SCLC received atezolizumab at 1,200 mg with carboplatin at 5 mg/mL per minute on day 1 and etoposide 100 mg/m2 on days 1, 2, and 3 of a 21-day cycle for four cycles, followed by atezolizumab at 1,200 mg once every 3 weeks until disease progression or unacceptable toxicity; or received placebo with the same dosage of carboplatin and etoposide for a similar duration.

Overall survival was significantly better in patients who received atezolizumab, compared with placebo (12.3 vs. 10.3 months; hazard ratio, 0.70; 95% confidence interval, 0.54-0.91; P = .0069), as was progression-free survival (5.2 vs. 4.3 months; HR, 0.77; 95% CI, 0.62-0.96; P = .017).



The most common adverse events associated with atezolizumab in the study were fatigue/asthenia, nausea, alopecia, constipation, and decreased appetite.

According to the FDA, the recommended dose is 1,200 mg IV over 60 minutes every 3 weeks. When administered on the same day as chemotherapy, atezolizumab should be given first. If the first infusion is tolerated, all subsequent infusions can be delivered over 30 minutes.

Find the full press release on the FDA website.

 

The Food and Drug Administration has approved atezolizumab (Tecentriq), in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).

Approval was based on results from the phase 3 IMpower133 study, in which 403 treatment-naive patients with ES-SCLC received atezolizumab at 1,200 mg with carboplatin at 5 mg/mL per minute on day 1 and etoposide 100 mg/m2 on days 1, 2, and 3 of a 21-day cycle for four cycles, followed by atezolizumab at 1,200 mg once every 3 weeks until disease progression or unacceptable toxicity; or received placebo with the same dosage of carboplatin and etoposide for a similar duration.

Overall survival was significantly better in patients who received atezolizumab, compared with placebo (12.3 vs. 10.3 months; hazard ratio, 0.70; 95% confidence interval, 0.54-0.91; P = .0069), as was progression-free survival (5.2 vs. 4.3 months; HR, 0.77; 95% CI, 0.62-0.96; P = .017).



The most common adverse events associated with atezolizumab in the study were fatigue/asthenia, nausea, alopecia, constipation, and decreased appetite.

According to the FDA, the recommended dose is 1,200 mg IV over 60 minutes every 3 weeks. When administered on the same day as chemotherapy, atezolizumab should be given first. If the first infusion is tolerated, all subsequent infusions can be delivered over 30 minutes.

Find the full press release on the FDA website.

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Socioeconomic status affects scleroderma severity in African Americans

Don’t overlook socioeconomics, but don’t discount genetics
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Thu, 03/28/2019 - 07:34

 

Socioeconomic status appears to play a key role in affecting mortality and the frequency of severe pulmonary disease among African American scleroderma patients when compared with other groups, according to findings from an analysis of single-center cohort data over a 10-year period.

Dr. Virginia Steen

Indeed, among patients in the cohort of 402 scleroderma patients at MedStar Georgetown University Hospital in Washington, lower household income was predictive of higher mortality during follow-up, independent of race, according to first author Duncan F. Moore, MD, and his colleagues at the hospital.

Previous studies have demonstrated increased risk for scleroderma in African American patients, who also are more likely than non–African Americans to be diagnosed at a younger age and to have conditions including more diffuse cutaneous disease, more severe restrictive lung disease, more cardiac and renal involvement, and increased mortality, the authors wrote in Arthritis Care & Research.

“We did clearly show that African Americans have worse outcomes and severe pulmonary involvement, but I was surprised that there still was a major contribution of socioeconomic status affecting outcomes for all patients, even though only 10% of our patients were indigent and on medical assistance,” Virginia Steen, MD, senior author of the study and professor of rheumatology at Georgetown University, said in an interview. “I still feel strongly that there are likely genetic issues as to why African Americans have such severe disease. We are eager to learn more from the GRASP [Genome Research in African American Scleroderma Patients] study, which is specifically looking at the genetic issues in African American scleroderma patients,” she said.

Of the 402 scleroderma patients at MedStar Georgetown who were seen during 2006-2016, 202 were African American. A total of 186 African American and 184 non–African American patients in the study met the 2013 American College of Rheumatology/European League Against Rheumatism criteria for systemic sclerosis (SSc). Demographics including gender (87% female) and age (mean of 48 years) were similar between the groups.

Overall, the African American patients showed more severe lung disease, more pulmonary hypertension, and more severe cardiac involvement than did non–African American patients, and autoantibodies were significantly different between the groups.

During follow-up, mortality proved much higher among African Americans at 21%, compared with 11% in non–African Americans (P = .005). However, the unadjusted hazard ratio for death declined from 2.061 (P = .006) to a nonsignificant 1.256 after adjustment for socioeconomic variables.



All socioeconomic measures showed significant differences between the groups. African Americans were more likely to be single and disabled at the initial study visit and to have Medicaid, but they were less likely to be a homemaker, have private insurance, or have a college degree. African Americans’ $74,000 median household income (based on ZIP code) was also a statistically significant $23,000 less than non–African American patients. But the researchers noted that “for every additional $10,000 of household income, independent of race, the hazard of death during follow-up declined by 15.5%.”

Notable differences in antibodies appeared between the groups, with more African American patients having isolated nucleolar ANA, anti-U1RNP antibody, or other positive antinuclear antibodies without SSc-specific antibodies. African American patients also were less likely to have anticentromere or anti-RNA polymerase III antibodies.

The study findings were limited by several factors, including possible bias in the matching process and the use of only index values for socioeconomic variables, the researchers noted.

Regardless of relative socioeconomic and genetic influences, “it is clear that African Americans with scleroderma merit more intensive efforts to facilitate timely diagnosis and access to continued evaluation and suppressive treatment, particularly with respect to cardiopulmonary involvement,” they wrote.

Next steps for research, according to Dr. Steen, include studying clinical subsets of African American patients to try to identify factors to predict outcomes, including the nucleolar pattern ANA, overlap with lupus, history of hypertension, and the relationship with renal crisis.

“We are also looking at whether the African American patients are less responsive to mycophenolate than the non–African American patients. We definitely need to find ways to be more aggressive at identifying and treating African American patients early in their disease,” she added.

The researchers had no financial conflicts to disclose. Dr. Steen serves on the MDedge Rheumatology Editorial Advisory Board.

SOURCE: Moore DF et al. Arthritis Care Res. 2019 March 1. doi: 10.1002/acr.23861.

Body

 

“Not only do patients who manifest the diffuse cutaneous subset of disease experience a more severe course, but so do affected persons of African American race,” Nadia D. Morgan, MBBS, and Allan C. Gelber, MD, wrote in an accompanying editorial. The effects of socioeconomic status should not be overlooked based on the current study, in which the inclusion of socioeconomic factors eliminated the significance of association between race and mortality among scleroderma patients, they wrote.

Dr. Nadia D. Morgan
However, larger studies are needed, and Dr. Morgan and Dr. Gelber referenced several studies, including the Genome Research in African American Scleroderma Patients (GRASP) cohort study, which retrospectively and prospectively enrolled African Americans with scleroderma seen during 1987-2016. The researchers in the GRASP study identified genetic variants related to fibrosis as significantly associated with a diffuse cutaneous subset of scleroderma that was common in the African-American study population.

“Overall, and in the context of these published reports which underscore the disproportionate and adverse impact of scleroderma among African Americans, and in light of the ongoing efforts of the GRASP study, the current paper by Moore et al. emphasizes the importance of socioeconomic status, and of socioeconomic determinants of health, to account for differences in clinically relevant outcomes,” they wrote.

Dr. Allan C. Gelber
However, an optimal study would involve multiple centers and examine the independent contributions of not only socioeconomic status but also clinical, serologic, and genetic determinants on health outcomes in scleroderma, they noted (Arthritis Care Res. 2019. doi: 10.1002/acr.23860).

Dr. Gelber is affiliated with the division of rheumatology at Johns Hopkins University, Baltimore. Dr. Morgan, who was also with Johns Hopkins, died before publication of the editorial. They made no conflict of interest disclosures.

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“Not only do patients who manifest the diffuse cutaneous subset of disease experience a more severe course, but so do affected persons of African American race,” Nadia D. Morgan, MBBS, and Allan C. Gelber, MD, wrote in an accompanying editorial. The effects of socioeconomic status should not be overlooked based on the current study, in which the inclusion of socioeconomic factors eliminated the significance of association between race and mortality among scleroderma patients, they wrote.

Dr. Nadia D. Morgan
However, larger studies are needed, and Dr. Morgan and Dr. Gelber referenced several studies, including the Genome Research in African American Scleroderma Patients (GRASP) cohort study, which retrospectively and prospectively enrolled African Americans with scleroderma seen during 1987-2016. The researchers in the GRASP study identified genetic variants related to fibrosis as significantly associated with a diffuse cutaneous subset of scleroderma that was common in the African-American study population.

“Overall, and in the context of these published reports which underscore the disproportionate and adverse impact of scleroderma among African Americans, and in light of the ongoing efforts of the GRASP study, the current paper by Moore et al. emphasizes the importance of socioeconomic status, and of socioeconomic determinants of health, to account for differences in clinically relevant outcomes,” they wrote.

Dr. Allan C. Gelber
However, an optimal study would involve multiple centers and examine the independent contributions of not only socioeconomic status but also clinical, serologic, and genetic determinants on health outcomes in scleroderma, they noted (Arthritis Care Res. 2019. doi: 10.1002/acr.23860).

Dr. Gelber is affiliated with the division of rheumatology at Johns Hopkins University, Baltimore. Dr. Morgan, who was also with Johns Hopkins, died before publication of the editorial. They made no conflict of interest disclosures.

Body

 

“Not only do patients who manifest the diffuse cutaneous subset of disease experience a more severe course, but so do affected persons of African American race,” Nadia D. Morgan, MBBS, and Allan C. Gelber, MD, wrote in an accompanying editorial. The effects of socioeconomic status should not be overlooked based on the current study, in which the inclusion of socioeconomic factors eliminated the significance of association between race and mortality among scleroderma patients, they wrote.

Dr. Nadia D. Morgan
However, larger studies are needed, and Dr. Morgan and Dr. Gelber referenced several studies, including the Genome Research in African American Scleroderma Patients (GRASP) cohort study, which retrospectively and prospectively enrolled African Americans with scleroderma seen during 1987-2016. The researchers in the GRASP study identified genetic variants related to fibrosis as significantly associated with a diffuse cutaneous subset of scleroderma that was common in the African-American study population.

“Overall, and in the context of these published reports which underscore the disproportionate and adverse impact of scleroderma among African Americans, and in light of the ongoing efforts of the GRASP study, the current paper by Moore et al. emphasizes the importance of socioeconomic status, and of socioeconomic determinants of health, to account for differences in clinically relevant outcomes,” they wrote.

Dr. Allan C. Gelber
However, an optimal study would involve multiple centers and examine the independent contributions of not only socioeconomic status but also clinical, serologic, and genetic determinants on health outcomes in scleroderma, they noted (Arthritis Care Res. 2019. doi: 10.1002/acr.23860).

Dr. Gelber is affiliated with the division of rheumatology at Johns Hopkins University, Baltimore. Dr. Morgan, who was also with Johns Hopkins, died before publication of the editorial. They made no conflict of interest disclosures.

Title
Don’t overlook socioeconomics, but don’t discount genetics
Don’t overlook socioeconomics, but don’t discount genetics

 

Socioeconomic status appears to play a key role in affecting mortality and the frequency of severe pulmonary disease among African American scleroderma patients when compared with other groups, according to findings from an analysis of single-center cohort data over a 10-year period.

Dr. Virginia Steen

Indeed, among patients in the cohort of 402 scleroderma patients at MedStar Georgetown University Hospital in Washington, lower household income was predictive of higher mortality during follow-up, independent of race, according to first author Duncan F. Moore, MD, and his colleagues at the hospital.

Previous studies have demonstrated increased risk for scleroderma in African American patients, who also are more likely than non–African Americans to be diagnosed at a younger age and to have conditions including more diffuse cutaneous disease, more severe restrictive lung disease, more cardiac and renal involvement, and increased mortality, the authors wrote in Arthritis Care & Research.

“We did clearly show that African Americans have worse outcomes and severe pulmonary involvement, but I was surprised that there still was a major contribution of socioeconomic status affecting outcomes for all patients, even though only 10% of our patients were indigent and on medical assistance,” Virginia Steen, MD, senior author of the study and professor of rheumatology at Georgetown University, said in an interview. “I still feel strongly that there are likely genetic issues as to why African Americans have such severe disease. We are eager to learn more from the GRASP [Genome Research in African American Scleroderma Patients] study, which is specifically looking at the genetic issues in African American scleroderma patients,” she said.

Of the 402 scleroderma patients at MedStar Georgetown who were seen during 2006-2016, 202 were African American. A total of 186 African American and 184 non–African American patients in the study met the 2013 American College of Rheumatology/European League Against Rheumatism criteria for systemic sclerosis (SSc). Demographics including gender (87% female) and age (mean of 48 years) were similar between the groups.

Overall, the African American patients showed more severe lung disease, more pulmonary hypertension, and more severe cardiac involvement than did non–African American patients, and autoantibodies were significantly different between the groups.

During follow-up, mortality proved much higher among African Americans at 21%, compared with 11% in non–African Americans (P = .005). However, the unadjusted hazard ratio for death declined from 2.061 (P = .006) to a nonsignificant 1.256 after adjustment for socioeconomic variables.



All socioeconomic measures showed significant differences between the groups. African Americans were more likely to be single and disabled at the initial study visit and to have Medicaid, but they were less likely to be a homemaker, have private insurance, or have a college degree. African Americans’ $74,000 median household income (based on ZIP code) was also a statistically significant $23,000 less than non–African American patients. But the researchers noted that “for every additional $10,000 of household income, independent of race, the hazard of death during follow-up declined by 15.5%.”

Notable differences in antibodies appeared between the groups, with more African American patients having isolated nucleolar ANA, anti-U1RNP antibody, or other positive antinuclear antibodies without SSc-specific antibodies. African American patients also were less likely to have anticentromere or anti-RNA polymerase III antibodies.

The study findings were limited by several factors, including possible bias in the matching process and the use of only index values for socioeconomic variables, the researchers noted.

Regardless of relative socioeconomic and genetic influences, “it is clear that African Americans with scleroderma merit more intensive efforts to facilitate timely diagnosis and access to continued evaluation and suppressive treatment, particularly with respect to cardiopulmonary involvement,” they wrote.

Next steps for research, according to Dr. Steen, include studying clinical subsets of African American patients to try to identify factors to predict outcomes, including the nucleolar pattern ANA, overlap with lupus, history of hypertension, and the relationship with renal crisis.

“We are also looking at whether the African American patients are less responsive to mycophenolate than the non–African American patients. We definitely need to find ways to be more aggressive at identifying and treating African American patients early in their disease,” she added.

The researchers had no financial conflicts to disclose. Dr. Steen serves on the MDedge Rheumatology Editorial Advisory Board.

SOURCE: Moore DF et al. Arthritis Care Res. 2019 March 1. doi: 10.1002/acr.23861.

 

Socioeconomic status appears to play a key role in affecting mortality and the frequency of severe pulmonary disease among African American scleroderma patients when compared with other groups, according to findings from an analysis of single-center cohort data over a 10-year period.

Dr. Virginia Steen

Indeed, among patients in the cohort of 402 scleroderma patients at MedStar Georgetown University Hospital in Washington, lower household income was predictive of higher mortality during follow-up, independent of race, according to first author Duncan F. Moore, MD, and his colleagues at the hospital.

Previous studies have demonstrated increased risk for scleroderma in African American patients, who also are more likely than non–African Americans to be diagnosed at a younger age and to have conditions including more diffuse cutaneous disease, more severe restrictive lung disease, more cardiac and renal involvement, and increased mortality, the authors wrote in Arthritis Care & Research.

“We did clearly show that African Americans have worse outcomes and severe pulmonary involvement, but I was surprised that there still was a major contribution of socioeconomic status affecting outcomes for all patients, even though only 10% of our patients were indigent and on medical assistance,” Virginia Steen, MD, senior author of the study and professor of rheumatology at Georgetown University, said in an interview. “I still feel strongly that there are likely genetic issues as to why African Americans have such severe disease. We are eager to learn more from the GRASP [Genome Research in African American Scleroderma Patients] study, which is specifically looking at the genetic issues in African American scleroderma patients,” she said.

Of the 402 scleroderma patients at MedStar Georgetown who were seen during 2006-2016, 202 were African American. A total of 186 African American and 184 non–African American patients in the study met the 2013 American College of Rheumatology/European League Against Rheumatism criteria for systemic sclerosis (SSc). Demographics including gender (87% female) and age (mean of 48 years) were similar between the groups.

Overall, the African American patients showed more severe lung disease, more pulmonary hypertension, and more severe cardiac involvement than did non–African American patients, and autoantibodies were significantly different between the groups.

During follow-up, mortality proved much higher among African Americans at 21%, compared with 11% in non–African Americans (P = .005). However, the unadjusted hazard ratio for death declined from 2.061 (P = .006) to a nonsignificant 1.256 after adjustment for socioeconomic variables.



All socioeconomic measures showed significant differences between the groups. African Americans were more likely to be single and disabled at the initial study visit and to have Medicaid, but they were less likely to be a homemaker, have private insurance, or have a college degree. African Americans’ $74,000 median household income (based on ZIP code) was also a statistically significant $23,000 less than non–African American patients. But the researchers noted that “for every additional $10,000 of household income, independent of race, the hazard of death during follow-up declined by 15.5%.”

Notable differences in antibodies appeared between the groups, with more African American patients having isolated nucleolar ANA, anti-U1RNP antibody, or other positive antinuclear antibodies without SSc-specific antibodies. African American patients also were less likely to have anticentromere or anti-RNA polymerase III antibodies.

The study findings were limited by several factors, including possible bias in the matching process and the use of only index values for socioeconomic variables, the researchers noted.

Regardless of relative socioeconomic and genetic influences, “it is clear that African Americans with scleroderma merit more intensive efforts to facilitate timely diagnosis and access to continued evaluation and suppressive treatment, particularly with respect to cardiopulmonary involvement,” they wrote.

Next steps for research, according to Dr. Steen, include studying clinical subsets of African American patients to try to identify factors to predict outcomes, including the nucleolar pattern ANA, overlap with lupus, history of hypertension, and the relationship with renal crisis.

“We are also looking at whether the African American patients are less responsive to mycophenolate than the non–African American patients. We definitely need to find ways to be more aggressive at identifying and treating African American patients early in their disease,” she added.

The researchers had no financial conflicts to disclose. Dr. Steen serves on the MDedge Rheumatology Editorial Advisory Board.

SOURCE: Moore DF et al. Arthritis Care Res. 2019 March 1. doi: 10.1002/acr.23861.

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Will inpatient albumin help in decompensated cirrhosis?

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Wed, 03/20/2019 - 11:19

 

In light of apparently conflicting results from two recent major studies, it may be too early to consider outpatient albumin administration in patients with decompensated cirrhosis, according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

Andrew D. Bowser/MDedge News
Dr. Vijay Shah

“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.

In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.

Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.

By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).

While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).

Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.

“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”

There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.

Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.

Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.

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In light of apparently conflicting results from two recent major studies, it may be too early to consider outpatient albumin administration in patients with decompensated cirrhosis, according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

Andrew D. Bowser/MDedge News
Dr. Vijay Shah

“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.

In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.

Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.

By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).

While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).

Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.

“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”

There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.

Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.

Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.

 

In light of apparently conflicting results from two recent major studies, it may be too early to consider outpatient albumin administration in patients with decompensated cirrhosis, according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

Andrew D. Bowser/MDedge News
Dr. Vijay Shah

“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.

In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.

Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.

By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).

While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).

Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.

“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”

There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.

Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.

Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.

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Resistant hypertension hits SLE patients hard

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Tue, 03/19/2019 - 15:46

Patients with systemic lupus erythematosus (SLE) were 72% more likely to have resistant hypertension than were control patients at a tertiary care center.

wildpixel/Thinkstock

A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.


The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.

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Patients with systemic lupus erythematosus (SLE) were 72% more likely to have resistant hypertension than were control patients at a tertiary care center.

wildpixel/Thinkstock

A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.


The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.

Patients with systemic lupus erythematosus (SLE) were 72% more likely to have resistant hypertension than were control patients at a tertiary care center.

wildpixel/Thinkstock

A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.


The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.

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Neratinib shows promise in HER2-mutant cervical cancer

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– Treatment with the pan-HER tyrosine kinase inhibitor neratinib leads to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, preliminary efficacy results from the phase 2 SUMMIT basket trial suggest.

Of 11 trial subjects evaluable for efficacy, 3 (27%) had objective confirmed responses and 6 others had stable disease for at least 16 weeks (clinical benefit rate, 55%). Median progression-free survival was 7 months, Anishka D’Souza, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Study subjects included HER2-mutant metastatic cervical cancer patients. Most (89%) had adenocarcinoma and 11% had squamous cell carcinoma, said Dr. D’Souza of the University of Southern California, Los Angeles.

The median number of total prior regimens was two, with a range of one to four, she said. Patients received oral neratinib at a dose of 240 mg once daily.

The treatment was generally well tolerated; the most common adverse event was diarrhea, with only one grade 3/4 case occurring, she said, noting that high-dose loperamide prophylaxis was mandatory during cycle 1 because of the high incidence of diarrhea.

Though preliminary, the findings are notable as somatic HER2 (ERBB2) mutations, observed in about 5% of metastatic cervical cancer cases, are associated with poor prognosis, she explained, noting that there are limited treatment options and few long-term durable responses.

“There is a great need for additional treatment options,” she said.

Neratinib has been shown to have single-agent clinical activity in multiple HER2‑mutant cancers, so Dr. D’Souza and her colleagues are assessing its safety and efficacy as either monotherapy or in combination with other treatments across multiple tumor types. The current analysis focuses on the cohort of patients who received neratinib monotherapy.

Neratinib use in this cohort led to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, she said, adding that “this is an ongoing study and we are continuing to enroll patients to expand our dataset.”

Dr. D’Souza reported having no financial disclosures.

SOURCE: D’Souza A et al. SGO 2019, Abstract 18.

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– Treatment with the pan-HER tyrosine kinase inhibitor neratinib leads to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, preliminary efficacy results from the phase 2 SUMMIT basket trial suggest.

Of 11 trial subjects evaluable for efficacy, 3 (27%) had objective confirmed responses and 6 others had stable disease for at least 16 weeks (clinical benefit rate, 55%). Median progression-free survival was 7 months, Anishka D’Souza, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Study subjects included HER2-mutant metastatic cervical cancer patients. Most (89%) had adenocarcinoma and 11% had squamous cell carcinoma, said Dr. D’Souza of the University of Southern California, Los Angeles.

The median number of total prior regimens was two, with a range of one to four, she said. Patients received oral neratinib at a dose of 240 mg once daily.

The treatment was generally well tolerated; the most common adverse event was diarrhea, with only one grade 3/4 case occurring, she said, noting that high-dose loperamide prophylaxis was mandatory during cycle 1 because of the high incidence of diarrhea.

Though preliminary, the findings are notable as somatic HER2 (ERBB2) mutations, observed in about 5% of metastatic cervical cancer cases, are associated with poor prognosis, she explained, noting that there are limited treatment options and few long-term durable responses.

“There is a great need for additional treatment options,” she said.

Neratinib has been shown to have single-agent clinical activity in multiple HER2‑mutant cancers, so Dr. D’Souza and her colleagues are assessing its safety and efficacy as either monotherapy or in combination with other treatments across multiple tumor types. The current analysis focuses on the cohort of patients who received neratinib monotherapy.

Neratinib use in this cohort led to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, she said, adding that “this is an ongoing study and we are continuing to enroll patients to expand our dataset.”

Dr. D’Souza reported having no financial disclosures.

SOURCE: D’Souza A et al. SGO 2019, Abstract 18.

 

– Treatment with the pan-HER tyrosine kinase inhibitor neratinib leads to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, preliminary efficacy results from the phase 2 SUMMIT basket trial suggest.

Of 11 trial subjects evaluable for efficacy, 3 (27%) had objective confirmed responses and 6 others had stable disease for at least 16 weeks (clinical benefit rate, 55%). Median progression-free survival was 7 months, Anishka D’Souza, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Study subjects included HER2-mutant metastatic cervical cancer patients. Most (89%) had adenocarcinoma and 11% had squamous cell carcinoma, said Dr. D’Souza of the University of Southern California, Los Angeles.

The median number of total prior regimens was two, with a range of one to four, she said. Patients received oral neratinib at a dose of 240 mg once daily.

The treatment was generally well tolerated; the most common adverse event was diarrhea, with only one grade 3/4 case occurring, she said, noting that high-dose loperamide prophylaxis was mandatory during cycle 1 because of the high incidence of diarrhea.

Though preliminary, the findings are notable as somatic HER2 (ERBB2) mutations, observed in about 5% of metastatic cervical cancer cases, are associated with poor prognosis, she explained, noting that there are limited treatment options and few long-term durable responses.

“There is a great need for additional treatment options,” she said.

Neratinib has been shown to have single-agent clinical activity in multiple HER2‑mutant cancers, so Dr. D’Souza and her colleagues are assessing its safety and efficacy as either monotherapy or in combination with other treatments across multiple tumor types. The current analysis focuses on the cohort of patients who received neratinib monotherapy.

Neratinib use in this cohort led to durable responses and disease control in heavily pretreated metastatic patients with HER2-mutant cervical cancer, she said, adding that “this is an ongoing study and we are continuing to enroll patients to expand our dataset.”

Dr. D’Souza reported having no financial disclosures.

SOURCE: D’Souza A et al. SGO 2019, Abstract 18.

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Perceived cancer risk may improve access to HPV vaccine

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Mon, 09/23/2019 - 14:53

 

– The perceived risk of HPV-related cancer appears to overcome variables that typically impede access to HPV vaccination, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Dr. Jennifer Y. Pierce

An analysis showed that adolescents in Alabama are more likely to receive the HPV vaccine if they live below the poverty line and reside in rural areas. The study also revealed a positive association between vaccine uptake and the incidence of HPV-related cancer by county.

These results suggest the perceived risk of HPV-related cancer may outweigh rurality and poverty—factors that might otherwise hinder access to health care, according to Jennifer Y. Pierce, MD, of Mitchell Cancer Institute in Mobile, Ala.

She discussed this idea when presenting the study results at the meeting.

“There are 39,000 preventable cases of HPV-related cancer in the United States,” Dr. Pierce said. “In Alabama, we are [ranked] third for cervical cancer incidence and first for cervical cancer mortality. When we look at vaccination rates in Alabama, unfortunately, we have the opposite problem. We are 45th for HPV vaccination.”

Dr. Pierce also noted that, nationally, adolescents in rural areas are 11% less likely to be vaccinated than their peers in urban areas.

“When we looked in Alabama, that did not exist,” Dr. Pierce said. “So we wanted to know, ‘What are the factors associated with HPV vaccination rate, by county, in the state of Alabama?’ because we had widely disparate rates by county.”

Dr. Pierce and her colleagues looked at data from the U.S. census, county health rankings for Alabama, the Alabama state cancer registry, and other sources. The researchers wanted to determine rates of HPV vaccination in 13- to 17-year-olds as well as rates of HPV-related cancers and variables associated with HPV vaccination by county.

Dr. Pierce said that, of the 67 counties in Alabama, 50%-70% of them are rural. Forty of them have a higher percent poverty level than the state mean. Twenty-three counties have no pediatrician, and four counties have no vaccine provider other than the health department.

By county, cancer rates were positively associated with HPV vaccination in both sexes. Higher cervical cancer rates correlated with higher HPV vaccination rates in females (r = .49; P = .011) and males (r = .46; P = .017). Higher HPV-related cancer rates in males correlated with higher HPV vaccination rates in females (r = .49; P = .001) and males (r = .46; P = .001).

The researchers found no significant association between vaccine uptake and the primary care provider ratio or the number of pediatricians per county. However, private insurance (r = –.40; P = .001) and higher median household income (r = –.40; P = .0007) were associated with lower HPV vaccine uptake. Rurality (r = .27; P = .025) and having a higher percentage of people below the poverty line (r = .39; P = .0011) were associated with higher vaccine uptake.

“How do we explain this paradox?” Dr. Pierce asked. “I think, really, it speaks to the strong commitment of our county public health departments who have, for a long time, been pushing the HPV vaccine and are doing a fairly good job of vaccinating. But I think, even more so, we need to focus on this question of perceived risk.”

“Our poor, rural adolescents in Alabama are being vaccinated at a higher rate than their more affluent peers, and those HPV vaccination rates appear to be directly linked to the cancer incidence rates in those counties.”

Dr. Pierce had no disclosures.

SOURCE: Pierce JY et al. SGO 2019, Abstract 13.

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– The perceived risk of HPV-related cancer appears to overcome variables that typically impede access to HPV vaccination, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Dr. Jennifer Y. Pierce

An analysis showed that adolescents in Alabama are more likely to receive the HPV vaccine if they live below the poverty line and reside in rural areas. The study also revealed a positive association between vaccine uptake and the incidence of HPV-related cancer by county.

These results suggest the perceived risk of HPV-related cancer may outweigh rurality and poverty—factors that might otherwise hinder access to health care, according to Jennifer Y. Pierce, MD, of Mitchell Cancer Institute in Mobile, Ala.

She discussed this idea when presenting the study results at the meeting.

“There are 39,000 preventable cases of HPV-related cancer in the United States,” Dr. Pierce said. “In Alabama, we are [ranked] third for cervical cancer incidence and first for cervical cancer mortality. When we look at vaccination rates in Alabama, unfortunately, we have the opposite problem. We are 45th for HPV vaccination.”

Dr. Pierce also noted that, nationally, adolescents in rural areas are 11% less likely to be vaccinated than their peers in urban areas.

“When we looked in Alabama, that did not exist,” Dr. Pierce said. “So we wanted to know, ‘What are the factors associated with HPV vaccination rate, by county, in the state of Alabama?’ because we had widely disparate rates by county.”

Dr. Pierce and her colleagues looked at data from the U.S. census, county health rankings for Alabama, the Alabama state cancer registry, and other sources. The researchers wanted to determine rates of HPV vaccination in 13- to 17-year-olds as well as rates of HPV-related cancers and variables associated with HPV vaccination by county.

Dr. Pierce said that, of the 67 counties in Alabama, 50%-70% of them are rural. Forty of them have a higher percent poverty level than the state mean. Twenty-three counties have no pediatrician, and four counties have no vaccine provider other than the health department.

By county, cancer rates were positively associated with HPV vaccination in both sexes. Higher cervical cancer rates correlated with higher HPV vaccination rates in females (r = .49; P = .011) and males (r = .46; P = .017). Higher HPV-related cancer rates in males correlated with higher HPV vaccination rates in females (r = .49; P = .001) and males (r = .46; P = .001).

The researchers found no significant association between vaccine uptake and the primary care provider ratio or the number of pediatricians per county. However, private insurance (r = –.40; P = .001) and higher median household income (r = –.40; P = .0007) were associated with lower HPV vaccine uptake. Rurality (r = .27; P = .025) and having a higher percentage of people below the poverty line (r = .39; P = .0011) were associated with higher vaccine uptake.

“How do we explain this paradox?” Dr. Pierce asked. “I think, really, it speaks to the strong commitment of our county public health departments who have, for a long time, been pushing the HPV vaccine and are doing a fairly good job of vaccinating. But I think, even more so, we need to focus on this question of perceived risk.”

“Our poor, rural adolescents in Alabama are being vaccinated at a higher rate than their more affluent peers, and those HPV vaccination rates appear to be directly linked to the cancer incidence rates in those counties.”

Dr. Pierce had no disclosures.

SOURCE: Pierce JY et al. SGO 2019, Abstract 13.

 

– The perceived risk of HPV-related cancer appears to overcome variables that typically impede access to HPV vaccination, according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Dr. Jennifer Y. Pierce

An analysis showed that adolescents in Alabama are more likely to receive the HPV vaccine if they live below the poverty line and reside in rural areas. The study also revealed a positive association between vaccine uptake and the incidence of HPV-related cancer by county.

These results suggest the perceived risk of HPV-related cancer may outweigh rurality and poverty—factors that might otherwise hinder access to health care, according to Jennifer Y. Pierce, MD, of Mitchell Cancer Institute in Mobile, Ala.

She discussed this idea when presenting the study results at the meeting.

“There are 39,000 preventable cases of HPV-related cancer in the United States,” Dr. Pierce said. “In Alabama, we are [ranked] third for cervical cancer incidence and first for cervical cancer mortality. When we look at vaccination rates in Alabama, unfortunately, we have the opposite problem. We are 45th for HPV vaccination.”

Dr. Pierce also noted that, nationally, adolescents in rural areas are 11% less likely to be vaccinated than their peers in urban areas.

“When we looked in Alabama, that did not exist,” Dr. Pierce said. “So we wanted to know, ‘What are the factors associated with HPV vaccination rate, by county, in the state of Alabama?’ because we had widely disparate rates by county.”

Dr. Pierce and her colleagues looked at data from the U.S. census, county health rankings for Alabama, the Alabama state cancer registry, and other sources. The researchers wanted to determine rates of HPV vaccination in 13- to 17-year-olds as well as rates of HPV-related cancers and variables associated with HPV vaccination by county.

Dr. Pierce said that, of the 67 counties in Alabama, 50%-70% of them are rural. Forty of them have a higher percent poverty level than the state mean. Twenty-three counties have no pediatrician, and four counties have no vaccine provider other than the health department.

By county, cancer rates were positively associated with HPV vaccination in both sexes. Higher cervical cancer rates correlated with higher HPV vaccination rates in females (r = .49; P = .011) and males (r = .46; P = .017). Higher HPV-related cancer rates in males correlated with higher HPV vaccination rates in females (r = .49; P = .001) and males (r = .46; P = .001).

The researchers found no significant association between vaccine uptake and the primary care provider ratio or the number of pediatricians per county. However, private insurance (r = –.40; P = .001) and higher median household income (r = –.40; P = .0007) were associated with lower HPV vaccine uptake. Rurality (r = .27; P = .025) and having a higher percentage of people below the poverty line (r = .39; P = .0011) were associated with higher vaccine uptake.

“How do we explain this paradox?” Dr. Pierce asked. “I think, really, it speaks to the strong commitment of our county public health departments who have, for a long time, been pushing the HPV vaccine and are doing a fairly good job of vaccinating. But I think, even more so, we need to focus on this question of perceived risk.”

“Our poor, rural adolescents in Alabama are being vaccinated at a higher rate than their more affluent peers, and those HPV vaccination rates appear to be directly linked to the cancer incidence rates in those counties.”

Dr. Pierce had no disclosures.

SOURCE: Pierce JY et al. SGO 2019, Abstract 13.

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WISP: Early data provide further support for ISDO in women at high OC risk

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Tue, 03/19/2019 - 11:41

 

– Women at high risk for ovarian cancer who undergo risk-reducing salpingo-oophorectomy (RRSO) or interval salpingectomy with delayed oophorectomy (ISDO) experience significant reductions in cancer distress, according to preliminary findings from the WISP (Women Choosing Surgical Prevention) study.

Sharon Worcester/MDedge News
Dr. Karen H. Lu

However, those who choose RRSO experience worse menopausal symptoms and higher rates of regret, Karen H. Lu, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. Of 183 women enrolled to date in the prospective, nonrandomized, multicenter study, 91 underwent RRSO and 92 underwent ISDO at a median age of 40.9 and 37.5 years, respectively. Significant decreases in cancer-related distress as measured using the Impact of Event scale were seen in both groups at 6-month follow-up after surgery: The mean scores in the RRSO arm were 19.6 at baseline and 10.9 at 6 months, and in the ISDO arm they were 20.8 and 14.0, respectively.

The decrease in scores at 6 months did not differ significantly between study arms, but women in the RRSO arm had a significantly increased incidence of hot flashes, night sweats, vaginal dryness, and weight gain after surgery, said Dr. Lu, professor and chair in the department of gynecologic oncology and reproductive medicine and the J. Taylor Wharton Distinguished Chair in Gynecologic Oncology at the University of Texas MD Anderson Cancer Center, Houston.


“There was a significant difference in quality of life physical scores in RRSO versus the salpingectomy arm,” she said, adding that no difference was seen between the groups in quality of life mental scores.

The level of decision regret was significantly higher in the women who underwent RRSO (scores,14.1 vs. 8.7 on the 100-point scale), she noted.

“We hypothesized that use of HRT [hormone replacement therapy] after RRSO may have accounted for this difference, and looked at the two subsets,” she said. “Within the RRSO group, 25% did not go on HRT, and while higher than ISDO scores, these scores did not account for the large difference in decision regret.”

About half of the women had a history of breast cancer.

“Clinically, this agrees with what we see in that women with a prior history of breast cancer have less angst about undergoing RRSO,” she said, adding that 75% of women in the RRSO arm did go on HRT, and “these women represent the majority of our ‘previvors’ – healthy women with no history of cancer who struggle with the RRSO decision and who are able to take HRT.”

“Interestingly, compared to ISDO, RRSO women on HRT had the highest decisional regret,” she said.



An analysis of numerous possible predictors of decisional regret showed that only baseline depression score was a significant independent predictor, she noted.

Study participants are premenopausal women aged 30-50 years who have a high risk of ovarian cancer because of a pathogenic germline mutation in an ovarian cancer predisposition gene, and a normal CA125 and transvaginal ultrasound within 6 months before enrollment. All receive scripted counseling about the recommended age for oophorectomy and can choose their study arm. Planned enrollment at nine participating U.S. centers is 270 women.

The RRSO and ISDO arms at current enrollment are statistically similar with respect to mutation type, education level, breast cancer history, and first/second-degree ovarian cancer, but significantly more women in the ISDO arm had undergone risk-reducing mastectomy (51% vs. 35%), Dr. Lu noted, adding that to date no ovarian cancers have been identified at initial surgery, between surgeries, or at the time of completion oophorectomy in the ISDO patients – although only two women in that arm have undergone completion oophorectomy.

In the RRSO arm, one high-grade serous tubal intraepithelial neoplasia (STIC) was found at the time of surgery in a PALB2 mutation carrier.

“We believe this is the first report of a STIC in a PALB2 carrier. This woman was 39 years old with a strong family history of breast and ovarian cancer,” she said.

The findings suggest that “for these high-risk women who underwent ISDO ... the option encouraged them to undergo limited but potentially lifesaving surgical prophylaxis at an earlier age rather than wait to undergo full surgical prophylaxis at the upper-accepted age limit due to fear of early menopause,” Dr. Lu said.

Safety continues to be closely monitored in this study and the use of ISDO outside of the clinical trial setting is not recommended, she added, noting that an expansion of both WISP and the TUBA trial, for which preliminary results showing similar outcomes were also presented at the SGO meeting, is planned.

Dr. Lu reported having no disclosures.

SOURCE: Lu KH et al. SGO 2019, Late-Breaking Abstract 3.

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– Women at high risk for ovarian cancer who undergo risk-reducing salpingo-oophorectomy (RRSO) or interval salpingectomy with delayed oophorectomy (ISDO) experience significant reductions in cancer distress, according to preliminary findings from the WISP (Women Choosing Surgical Prevention) study.

Sharon Worcester/MDedge News
Dr. Karen H. Lu

However, those who choose RRSO experience worse menopausal symptoms and higher rates of regret, Karen H. Lu, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. Of 183 women enrolled to date in the prospective, nonrandomized, multicenter study, 91 underwent RRSO and 92 underwent ISDO at a median age of 40.9 and 37.5 years, respectively. Significant decreases in cancer-related distress as measured using the Impact of Event scale were seen in both groups at 6-month follow-up after surgery: The mean scores in the RRSO arm were 19.6 at baseline and 10.9 at 6 months, and in the ISDO arm they were 20.8 and 14.0, respectively.

The decrease in scores at 6 months did not differ significantly between study arms, but women in the RRSO arm had a significantly increased incidence of hot flashes, night sweats, vaginal dryness, and weight gain after surgery, said Dr. Lu, professor and chair in the department of gynecologic oncology and reproductive medicine and the J. Taylor Wharton Distinguished Chair in Gynecologic Oncology at the University of Texas MD Anderson Cancer Center, Houston.


“There was a significant difference in quality of life physical scores in RRSO versus the salpingectomy arm,” she said, adding that no difference was seen between the groups in quality of life mental scores.

The level of decision regret was significantly higher in the women who underwent RRSO (scores,14.1 vs. 8.7 on the 100-point scale), she noted.

“We hypothesized that use of HRT [hormone replacement therapy] after RRSO may have accounted for this difference, and looked at the two subsets,” she said. “Within the RRSO group, 25% did not go on HRT, and while higher than ISDO scores, these scores did not account for the large difference in decision regret.”

About half of the women had a history of breast cancer.

“Clinically, this agrees with what we see in that women with a prior history of breast cancer have less angst about undergoing RRSO,” she said, adding that 75% of women in the RRSO arm did go on HRT, and “these women represent the majority of our ‘previvors’ – healthy women with no history of cancer who struggle with the RRSO decision and who are able to take HRT.”

“Interestingly, compared to ISDO, RRSO women on HRT had the highest decisional regret,” she said.



An analysis of numerous possible predictors of decisional regret showed that only baseline depression score was a significant independent predictor, she noted.

Study participants are premenopausal women aged 30-50 years who have a high risk of ovarian cancer because of a pathogenic germline mutation in an ovarian cancer predisposition gene, and a normal CA125 and transvaginal ultrasound within 6 months before enrollment. All receive scripted counseling about the recommended age for oophorectomy and can choose their study arm. Planned enrollment at nine participating U.S. centers is 270 women.

The RRSO and ISDO arms at current enrollment are statistically similar with respect to mutation type, education level, breast cancer history, and first/second-degree ovarian cancer, but significantly more women in the ISDO arm had undergone risk-reducing mastectomy (51% vs. 35%), Dr. Lu noted, adding that to date no ovarian cancers have been identified at initial surgery, between surgeries, or at the time of completion oophorectomy in the ISDO patients – although only two women in that arm have undergone completion oophorectomy.

In the RRSO arm, one high-grade serous tubal intraepithelial neoplasia (STIC) was found at the time of surgery in a PALB2 mutation carrier.

“We believe this is the first report of a STIC in a PALB2 carrier. This woman was 39 years old with a strong family history of breast and ovarian cancer,” she said.

The findings suggest that “for these high-risk women who underwent ISDO ... the option encouraged them to undergo limited but potentially lifesaving surgical prophylaxis at an earlier age rather than wait to undergo full surgical prophylaxis at the upper-accepted age limit due to fear of early menopause,” Dr. Lu said.

Safety continues to be closely monitored in this study and the use of ISDO outside of the clinical trial setting is not recommended, she added, noting that an expansion of both WISP and the TUBA trial, for which preliminary results showing similar outcomes were also presented at the SGO meeting, is planned.

Dr. Lu reported having no disclosures.

SOURCE: Lu KH et al. SGO 2019, Late-Breaking Abstract 3.

 

– Women at high risk for ovarian cancer who undergo risk-reducing salpingo-oophorectomy (RRSO) or interval salpingectomy with delayed oophorectomy (ISDO) experience significant reductions in cancer distress, according to preliminary findings from the WISP (Women Choosing Surgical Prevention) study.

Sharon Worcester/MDedge News
Dr. Karen H. Lu

However, those who choose RRSO experience worse menopausal symptoms and higher rates of regret, Karen H. Lu, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. Of 183 women enrolled to date in the prospective, nonrandomized, multicenter study, 91 underwent RRSO and 92 underwent ISDO at a median age of 40.9 and 37.5 years, respectively. Significant decreases in cancer-related distress as measured using the Impact of Event scale were seen in both groups at 6-month follow-up after surgery: The mean scores in the RRSO arm were 19.6 at baseline and 10.9 at 6 months, and in the ISDO arm they were 20.8 and 14.0, respectively.

The decrease in scores at 6 months did not differ significantly between study arms, but women in the RRSO arm had a significantly increased incidence of hot flashes, night sweats, vaginal dryness, and weight gain after surgery, said Dr. Lu, professor and chair in the department of gynecologic oncology and reproductive medicine and the J. Taylor Wharton Distinguished Chair in Gynecologic Oncology at the University of Texas MD Anderson Cancer Center, Houston.


“There was a significant difference in quality of life physical scores in RRSO versus the salpingectomy arm,” she said, adding that no difference was seen between the groups in quality of life mental scores.

The level of decision regret was significantly higher in the women who underwent RRSO (scores,14.1 vs. 8.7 on the 100-point scale), she noted.

“We hypothesized that use of HRT [hormone replacement therapy] after RRSO may have accounted for this difference, and looked at the two subsets,” she said. “Within the RRSO group, 25% did not go on HRT, and while higher than ISDO scores, these scores did not account for the large difference in decision regret.”

About half of the women had a history of breast cancer.

“Clinically, this agrees with what we see in that women with a prior history of breast cancer have less angst about undergoing RRSO,” she said, adding that 75% of women in the RRSO arm did go on HRT, and “these women represent the majority of our ‘previvors’ – healthy women with no history of cancer who struggle with the RRSO decision and who are able to take HRT.”

“Interestingly, compared to ISDO, RRSO women on HRT had the highest decisional regret,” she said.



An analysis of numerous possible predictors of decisional regret showed that only baseline depression score was a significant independent predictor, she noted.

Study participants are premenopausal women aged 30-50 years who have a high risk of ovarian cancer because of a pathogenic germline mutation in an ovarian cancer predisposition gene, and a normal CA125 and transvaginal ultrasound within 6 months before enrollment. All receive scripted counseling about the recommended age for oophorectomy and can choose their study arm. Planned enrollment at nine participating U.S. centers is 270 women.

The RRSO and ISDO arms at current enrollment are statistically similar with respect to mutation type, education level, breast cancer history, and first/second-degree ovarian cancer, but significantly more women in the ISDO arm had undergone risk-reducing mastectomy (51% vs. 35%), Dr. Lu noted, adding that to date no ovarian cancers have been identified at initial surgery, between surgeries, or at the time of completion oophorectomy in the ISDO patients – although only two women in that arm have undergone completion oophorectomy.

In the RRSO arm, one high-grade serous tubal intraepithelial neoplasia (STIC) was found at the time of surgery in a PALB2 mutation carrier.

“We believe this is the first report of a STIC in a PALB2 carrier. This woman was 39 years old with a strong family history of breast and ovarian cancer,” she said.

The findings suggest that “for these high-risk women who underwent ISDO ... the option encouraged them to undergo limited but potentially lifesaving surgical prophylaxis at an earlier age rather than wait to undergo full surgical prophylaxis at the upper-accepted age limit due to fear of early menopause,” Dr. Lu said.

Safety continues to be closely monitored in this study and the use of ISDO outside of the clinical trial setting is not recommended, she added, noting that an expansion of both WISP and the TUBA trial, for which preliminary results showing similar outcomes were also presented at the SGO meeting, is planned.

Dr. Lu reported having no disclosures.

SOURCE: Lu KH et al. SGO 2019, Late-Breaking Abstract 3.

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AUGUSTUS: Dual surpasses triple therapy when AFib patients have PCI or ACS

Findings hammer a nail in the coffin for warfarin plus aspirin
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– For patients with atrial fibrillation and either a recent acute coronary syndrome or percutaneous coronary intervention, combined treatment for 6 months with the anticoagulant apixaban and a P2Y12 inhibitor antiplatelet drug, but without aspirin, was safer than and as effective as a regimen that either also included aspirin or that substituted a vitamin K antagonist, such as warfarin, for the direct-acting oral anticoagulant, based on results from a multicenter, randomized trial with more than 4,600 patients.

The apixaban plus P2Y12 inhibitor (typically, clopidogrel) combination “resulted in less bleeding and fewer hospitalizations without significant differences in ischemic events than regimens that included a vitamin K antagonist, aspirin, or both,” Renato D. Lopes, MD, said at the annual meeting of the American College of Cardiology. Concurrently, his report of the results also appeared in an online article.


This finding in the AUGUSTUS trial gives clinicians more guidance for the long-standing dilemma of how to best prevent arterial thrombus formation in patients with atrial fibrillation (AFib). To prevent a stroke, these patients routinely receive treatment with an anticoagulant when they have an acute coronary syndrome (ACS) event or undergo percutaneous coronary intervention (PCI). Typically, they receive several months of dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor to prevent a clot from forming in the stented or unstable region of a coronary artery.

These patients are not uncommon; this circumstance occurs for about 20% of all AFib patients, and poses the question of what is the safest and most effective way to treat them. Should they get triple therapy with an anticoagulant, aspirin, and a P2Y12 inhibitor, an option that could cause excess bleeding; or should one of the three drugs drop out with the potential for an increased rate of ischemic events? The AUGUSTUS findings suggest that one solution is treatment with a combination of the direct-acting oral anticoagulant apixaban (Eliquis) and the P2Y12 inhibitor clopidogrel (Plavix) but without aspirin.

For the majority of patients like the ones enrolled, “less is more.” By dropping aspirin from the treatment mix, patients did better, said Dr. Lopes, a professor of medicine at Duke University in Durham, N.C.

Dr. Lopes and his associates designed AUGUSTUS (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart) as a two-by-two factorial study to address two different questions: During 6 months of treatment, how did apixaban compare with a vitamin K antagonist (usually warfarin) in these patients for safety and efficacy, and how did aspirin compare with placebo in this setting for the same endpoints?

The trial enrolled 4,614 patients at 492 sites in 33 countries. All patients in the study received a P2Y12 inhibitor, with 93% treated with clopidogrel. The study had roughly as many patients as the combined total of patients enrolled in two smaller, prior studies that had looked at roughly the same questions in similar patients.

“The aspirin part is the more interesting, and probably more unique and important finding,” John H. Alexander, MD, a coinvestigator on the study, said in a video interview. Regardless of the anticoagulant used, patients who received aspirin had a 16% rate of major bleeds or clinically relevant non-major bleeds, compared with a 9% rate among those on placebo, a statistically significant result that underscored the bleeding risk posed by adding aspirin to an anticoagulant and a P2Y12 inhibitor.

The results also showed no statistically significant difference in any efficacy measure with or without aspirin, including the rate of death or hospitalization, or of any individual ischemic endpoint. However the results showed a signal of a small increase in the rates of each of three types of ischemic events – stent thrombosis, MI, and need for urgent revascularization, each of which showed a numerical increase when aspirin was dropped. But the increase was small.

Dr. Lopes calculated that, for example, to prevent one episode of stent thrombosis by treating with aspirin also would cause 15 major or clinically relevant non-major bleeds, which makes inclusion of aspirin something of a judgment call for each patient, said Dr. Alexander, a professor of medicine at Duke. An AFib patient with a high risk for thrombosis but a low risk for bleeding following PCI or an ACS event might be a reasonable patient to treat with aspirin along with apixaban and a P2Y12 inhibitor, he explained.

The rate of major or clinically relevant bleeds was 11% with apixaban and 15% with a vitamin K antagonist, a statistically significant difference. Patients treated with apixaban also had a significantly reduced rate of death or hospitalization, 24%, compared with 27% among those on the vitamin K antagonist, as well as a significantly lower rate of stroke.

Overall the lowest bleeding rate was in patients on apixaban but no aspirin, a 7% rate, while the highest rate was in patients on a vitamin K antagonist plus aspirin, a 19% rate.

Dr. Alexander said that it would be an overreach to extrapolate these findings to other direct-acting oral anticoagulants, compared with a vitamin K antagonist, but he believed that the findings the study generated about aspirin were probably relevant regardless of the anticoagulant used.
 

Body

 

It’s very reassuring to see that you can use a direct-acting oral anticoagulant like apixaban along with a P2Y12 inhibitor, but with no aspirin, and have no statistically significant increase in ischemic events. This is a fantastic finding. The finding shows once again that warfarin is a problematic drug. As the cost for direct-acting oral anticoagulants has decreased, their use has increased.

These results were not unexpected and also are probably the final nail in the coffin for using a combination of warfarin and aspirin. Prior findings from the PIONEER AF-PCI study that used rivaroxaban (N Engl J Med. 2016 Dec 22;375[25]:2423-34) and from the RE-DUAL PCI study that used dabigatran (N Engl J Med. 2017 Oct 19;377[16]:1513-24) also showed the advantages of using a direct-acting oral anticoagulant when compared with a vitamin K antagonist in this setting, The AUGUSTUS trial, with just over 4,600 patients, had nearly as many patients as the roughly 4,850 enrolled in these two prior studies put together.

Dhanunjaya Lakkireddy, MD , is medical director of the Kansas City Heart Rhythm Institute in Overland Park. He had no disclosures. He made these comments as the designated discussant during a press briefing.

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Body

 

It’s very reassuring to see that you can use a direct-acting oral anticoagulant like apixaban along with a P2Y12 inhibitor, but with no aspirin, and have no statistically significant increase in ischemic events. This is a fantastic finding. The finding shows once again that warfarin is a problematic drug. As the cost for direct-acting oral anticoagulants has decreased, their use has increased.

These results were not unexpected and also are probably the final nail in the coffin for using a combination of warfarin and aspirin. Prior findings from the PIONEER AF-PCI study that used rivaroxaban (N Engl J Med. 2016 Dec 22;375[25]:2423-34) and from the RE-DUAL PCI study that used dabigatran (N Engl J Med. 2017 Oct 19;377[16]:1513-24) also showed the advantages of using a direct-acting oral anticoagulant when compared with a vitamin K antagonist in this setting, The AUGUSTUS trial, with just over 4,600 patients, had nearly as many patients as the roughly 4,850 enrolled in these two prior studies put together.

Dhanunjaya Lakkireddy, MD , is medical director of the Kansas City Heart Rhythm Institute in Overland Park. He had no disclosures. He made these comments as the designated discussant during a press briefing.

Body

 

It’s very reassuring to see that you can use a direct-acting oral anticoagulant like apixaban along with a P2Y12 inhibitor, but with no aspirin, and have no statistically significant increase in ischemic events. This is a fantastic finding. The finding shows once again that warfarin is a problematic drug. As the cost for direct-acting oral anticoagulants has decreased, their use has increased.

These results were not unexpected and also are probably the final nail in the coffin for using a combination of warfarin and aspirin. Prior findings from the PIONEER AF-PCI study that used rivaroxaban (N Engl J Med. 2016 Dec 22;375[25]:2423-34) and from the RE-DUAL PCI study that used dabigatran (N Engl J Med. 2017 Oct 19;377[16]:1513-24) also showed the advantages of using a direct-acting oral anticoagulant when compared with a vitamin K antagonist in this setting, The AUGUSTUS trial, with just over 4,600 patients, had nearly as many patients as the roughly 4,850 enrolled in these two prior studies put together.

Dhanunjaya Lakkireddy, MD , is medical director of the Kansas City Heart Rhythm Institute in Overland Park. He had no disclosures. He made these comments as the designated discussant during a press briefing.

Title
Findings hammer a nail in the coffin for warfarin plus aspirin
Findings hammer a nail in the coffin for warfarin plus aspirin

– For patients with atrial fibrillation and either a recent acute coronary syndrome or percutaneous coronary intervention, combined treatment for 6 months with the anticoagulant apixaban and a P2Y12 inhibitor antiplatelet drug, but without aspirin, was safer than and as effective as a regimen that either also included aspirin or that substituted a vitamin K antagonist, such as warfarin, for the direct-acting oral anticoagulant, based on results from a multicenter, randomized trial with more than 4,600 patients.

The apixaban plus P2Y12 inhibitor (typically, clopidogrel) combination “resulted in less bleeding and fewer hospitalizations without significant differences in ischemic events than regimens that included a vitamin K antagonist, aspirin, or both,” Renato D. Lopes, MD, said at the annual meeting of the American College of Cardiology. Concurrently, his report of the results also appeared in an online article.


This finding in the AUGUSTUS trial gives clinicians more guidance for the long-standing dilemma of how to best prevent arterial thrombus formation in patients with atrial fibrillation (AFib). To prevent a stroke, these patients routinely receive treatment with an anticoagulant when they have an acute coronary syndrome (ACS) event or undergo percutaneous coronary intervention (PCI). Typically, they receive several months of dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor to prevent a clot from forming in the stented or unstable region of a coronary artery.

These patients are not uncommon; this circumstance occurs for about 20% of all AFib patients, and poses the question of what is the safest and most effective way to treat them. Should they get triple therapy with an anticoagulant, aspirin, and a P2Y12 inhibitor, an option that could cause excess bleeding; or should one of the three drugs drop out with the potential for an increased rate of ischemic events? The AUGUSTUS findings suggest that one solution is treatment with a combination of the direct-acting oral anticoagulant apixaban (Eliquis) and the P2Y12 inhibitor clopidogrel (Plavix) but without aspirin.

For the majority of patients like the ones enrolled, “less is more.” By dropping aspirin from the treatment mix, patients did better, said Dr. Lopes, a professor of medicine at Duke University in Durham, N.C.

Dr. Lopes and his associates designed AUGUSTUS (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart) as a two-by-two factorial study to address two different questions: During 6 months of treatment, how did apixaban compare with a vitamin K antagonist (usually warfarin) in these patients for safety and efficacy, and how did aspirin compare with placebo in this setting for the same endpoints?

The trial enrolled 4,614 patients at 492 sites in 33 countries. All patients in the study received a P2Y12 inhibitor, with 93% treated with clopidogrel. The study had roughly as many patients as the combined total of patients enrolled in two smaller, prior studies that had looked at roughly the same questions in similar patients.

“The aspirin part is the more interesting, and probably more unique and important finding,” John H. Alexander, MD, a coinvestigator on the study, said in a video interview. Regardless of the anticoagulant used, patients who received aspirin had a 16% rate of major bleeds or clinically relevant non-major bleeds, compared with a 9% rate among those on placebo, a statistically significant result that underscored the bleeding risk posed by adding aspirin to an anticoagulant and a P2Y12 inhibitor.

The results also showed no statistically significant difference in any efficacy measure with or without aspirin, including the rate of death or hospitalization, or of any individual ischemic endpoint. However the results showed a signal of a small increase in the rates of each of three types of ischemic events – stent thrombosis, MI, and need for urgent revascularization, each of which showed a numerical increase when aspirin was dropped. But the increase was small.

Dr. Lopes calculated that, for example, to prevent one episode of stent thrombosis by treating with aspirin also would cause 15 major or clinically relevant non-major bleeds, which makes inclusion of aspirin something of a judgment call for each patient, said Dr. Alexander, a professor of medicine at Duke. An AFib patient with a high risk for thrombosis but a low risk for bleeding following PCI or an ACS event might be a reasonable patient to treat with aspirin along with apixaban and a P2Y12 inhibitor, he explained.

The rate of major or clinically relevant bleeds was 11% with apixaban and 15% with a vitamin K antagonist, a statistically significant difference. Patients treated with apixaban also had a significantly reduced rate of death or hospitalization, 24%, compared with 27% among those on the vitamin K antagonist, as well as a significantly lower rate of stroke.

Overall the lowest bleeding rate was in patients on apixaban but no aspirin, a 7% rate, while the highest rate was in patients on a vitamin K antagonist plus aspirin, a 19% rate.

Dr. Alexander said that it would be an overreach to extrapolate these findings to other direct-acting oral anticoagulants, compared with a vitamin K antagonist, but he believed that the findings the study generated about aspirin were probably relevant regardless of the anticoagulant used.
 

– For patients with atrial fibrillation and either a recent acute coronary syndrome or percutaneous coronary intervention, combined treatment for 6 months with the anticoagulant apixaban and a P2Y12 inhibitor antiplatelet drug, but without aspirin, was safer than and as effective as a regimen that either also included aspirin or that substituted a vitamin K antagonist, such as warfarin, for the direct-acting oral anticoagulant, based on results from a multicenter, randomized trial with more than 4,600 patients.

The apixaban plus P2Y12 inhibitor (typically, clopidogrel) combination “resulted in less bleeding and fewer hospitalizations without significant differences in ischemic events than regimens that included a vitamin K antagonist, aspirin, or both,” Renato D. Lopes, MD, said at the annual meeting of the American College of Cardiology. Concurrently, his report of the results also appeared in an online article.


This finding in the AUGUSTUS trial gives clinicians more guidance for the long-standing dilemma of how to best prevent arterial thrombus formation in patients with atrial fibrillation (AFib). To prevent a stroke, these patients routinely receive treatment with an anticoagulant when they have an acute coronary syndrome (ACS) event or undergo percutaneous coronary intervention (PCI). Typically, they receive several months of dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor to prevent a clot from forming in the stented or unstable region of a coronary artery.

These patients are not uncommon; this circumstance occurs for about 20% of all AFib patients, and poses the question of what is the safest and most effective way to treat them. Should they get triple therapy with an anticoagulant, aspirin, and a P2Y12 inhibitor, an option that could cause excess bleeding; or should one of the three drugs drop out with the potential for an increased rate of ischemic events? The AUGUSTUS findings suggest that one solution is treatment with a combination of the direct-acting oral anticoagulant apixaban (Eliquis) and the P2Y12 inhibitor clopidogrel (Plavix) but without aspirin.

For the majority of patients like the ones enrolled, “less is more.” By dropping aspirin from the treatment mix, patients did better, said Dr. Lopes, a professor of medicine at Duke University in Durham, N.C.

Dr. Lopes and his associates designed AUGUSTUS (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart) as a two-by-two factorial study to address two different questions: During 6 months of treatment, how did apixaban compare with a vitamin K antagonist (usually warfarin) in these patients for safety and efficacy, and how did aspirin compare with placebo in this setting for the same endpoints?

The trial enrolled 4,614 patients at 492 sites in 33 countries. All patients in the study received a P2Y12 inhibitor, with 93% treated with clopidogrel. The study had roughly as many patients as the combined total of patients enrolled in two smaller, prior studies that had looked at roughly the same questions in similar patients.

“The aspirin part is the more interesting, and probably more unique and important finding,” John H. Alexander, MD, a coinvestigator on the study, said in a video interview. Regardless of the anticoagulant used, patients who received aspirin had a 16% rate of major bleeds or clinically relevant non-major bleeds, compared with a 9% rate among those on placebo, a statistically significant result that underscored the bleeding risk posed by adding aspirin to an anticoagulant and a P2Y12 inhibitor.

The results also showed no statistically significant difference in any efficacy measure with or without aspirin, including the rate of death or hospitalization, or of any individual ischemic endpoint. However the results showed a signal of a small increase in the rates of each of three types of ischemic events – stent thrombosis, MI, and need for urgent revascularization, each of which showed a numerical increase when aspirin was dropped. But the increase was small.

Dr. Lopes calculated that, for example, to prevent one episode of stent thrombosis by treating with aspirin also would cause 15 major or clinically relevant non-major bleeds, which makes inclusion of aspirin something of a judgment call for each patient, said Dr. Alexander, a professor of medicine at Duke. An AFib patient with a high risk for thrombosis but a low risk for bleeding following PCI or an ACS event might be a reasonable patient to treat with aspirin along with apixaban and a P2Y12 inhibitor, he explained.

The rate of major or clinically relevant bleeds was 11% with apixaban and 15% with a vitamin K antagonist, a statistically significant difference. Patients treated with apixaban also had a significantly reduced rate of death or hospitalization, 24%, compared with 27% among those on the vitamin K antagonist, as well as a significantly lower rate of stroke.

Overall the lowest bleeding rate was in patients on apixaban but no aspirin, a 7% rate, while the highest rate was in patients on a vitamin K antagonist plus aspirin, a 19% rate.

Dr. Alexander said that it would be an overreach to extrapolate these findings to other direct-acting oral anticoagulants, compared with a vitamin K antagonist, but he believed that the findings the study generated about aspirin were probably relevant regardless of the anticoagulant used.
 

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Medscape Article

Improving research dissemination among hospitalists

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Social media a great platform

 

Medical journals and societies are trying to figure out ways to use social media to connect with hospitalists and others interested in their subject matter, says Charlie Wray, DO, MS, lead author of a paper proposing a way they can do that: implementing a journal-sponsored club on Twitter.

“At the Journal of Hospital Medicine (JHM), we noticed that there was a large community of hospitalists on Twitter who were looking for a community to engage in hospital medicine topics,” Dr. Wray said. “We created #JHMChat to bring the hospital medicine community together on a regular basis to talk about pertinent research, medical education philosophies, and value-based care interventions. Our ultimate goal was to increase engagement, networking, and communication among this community, while highlighting the work that is being published in JHM.”

A study of #JHMChat showed that social media is a great platform for large organizations to reach out, connect, and create a community around, he added. “We were very surprised by both the Twitter metrics (i.e., number of participants and overall impressions), which showed very large dissemination numbers, in addition to the external dissemination metrics (i.e., page views and altmetrics scores), which showed that each chat basically corresponded to a release of a new issue. This could be informative to other journals as they look for ways to increase their web traffic or disseminate their work to their respective audiences.”

Dr. Wray hopes the study alerts hospitalists to the fact that there is a large and ever-growing community available within social media.

“Second, we know that careers in hospital medicine can be tough, regardless of whether you’re at a community hospital or a large academic center. Knowing that there is a community with which you can connect to is both comforting and reassuring.”
 

Reference

Wray C et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018 Nov;13(11):764-9.

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Social media a great platform

Social media a great platform

 

Medical journals and societies are trying to figure out ways to use social media to connect with hospitalists and others interested in their subject matter, says Charlie Wray, DO, MS, lead author of a paper proposing a way they can do that: implementing a journal-sponsored club on Twitter.

“At the Journal of Hospital Medicine (JHM), we noticed that there was a large community of hospitalists on Twitter who were looking for a community to engage in hospital medicine topics,” Dr. Wray said. “We created #JHMChat to bring the hospital medicine community together on a regular basis to talk about pertinent research, medical education philosophies, and value-based care interventions. Our ultimate goal was to increase engagement, networking, and communication among this community, while highlighting the work that is being published in JHM.”

A study of #JHMChat showed that social media is a great platform for large organizations to reach out, connect, and create a community around, he added. “We were very surprised by both the Twitter metrics (i.e., number of participants and overall impressions), which showed very large dissemination numbers, in addition to the external dissemination metrics (i.e., page views and altmetrics scores), which showed that each chat basically corresponded to a release of a new issue. This could be informative to other journals as they look for ways to increase their web traffic or disseminate their work to their respective audiences.”

Dr. Wray hopes the study alerts hospitalists to the fact that there is a large and ever-growing community available within social media.

“Second, we know that careers in hospital medicine can be tough, regardless of whether you’re at a community hospital or a large academic center. Knowing that there is a community with which you can connect to is both comforting and reassuring.”
 

Reference

Wray C et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018 Nov;13(11):764-9.

 

Medical journals and societies are trying to figure out ways to use social media to connect with hospitalists and others interested in their subject matter, says Charlie Wray, DO, MS, lead author of a paper proposing a way they can do that: implementing a journal-sponsored club on Twitter.

“At the Journal of Hospital Medicine (JHM), we noticed that there was a large community of hospitalists on Twitter who were looking for a community to engage in hospital medicine topics,” Dr. Wray said. “We created #JHMChat to bring the hospital medicine community together on a regular basis to talk about pertinent research, medical education philosophies, and value-based care interventions. Our ultimate goal was to increase engagement, networking, and communication among this community, while highlighting the work that is being published in JHM.”

A study of #JHMChat showed that social media is a great platform for large organizations to reach out, connect, and create a community around, he added. “We were very surprised by both the Twitter metrics (i.e., number of participants and overall impressions), which showed very large dissemination numbers, in addition to the external dissemination metrics (i.e., page views and altmetrics scores), which showed that each chat basically corresponded to a release of a new issue. This could be informative to other journals as they look for ways to increase their web traffic or disseminate their work to their respective audiences.”

Dr. Wray hopes the study alerts hospitalists to the fact that there is a large and ever-growing community available within social media.

“Second, we know that careers in hospital medicine can be tough, regardless of whether you’re at a community hospital or a large academic center. Knowing that there is a community with which you can connect to is both comforting and reassuring.”
 

Reference

Wray C et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018 Nov;13(11):764-9.

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Hide sidebar & use full width
render the right sidebar.