Adjuvant denosumab did not improve bone metastasis–free survival and related outcomes in women with early-stage breast cancer, according to a phase 3 trial.

“We hypothesised that denosumab would modify the clinical course of early breast cancer, delaying the development of clinical bone metastases with or without disease recurrence at other sites,” reported Robert Coleman, MBBS, MD, of the University of Sheffield, England, and colleagues. Their report is in The Lancet Oncology.

The randomized, placebo-controlled, phase 3 D-CARE study included 4,509 women with early-stage, high-risk disease. The effects of adding denosumab to standard-of-care adjuvant or neoadjuvant chemotherapy was studied in 389 institutions around the globe. In the initial treatment phase, study patients received denosumab or placebo every 3-4 weeks in combination with adjuvant or neoadjuvant chemotherapy for approximately 6 months.

After completion of chemotherapy, the dosing interval was extended to every 12 weeks (range, 14 days) for a total of 5 years. The median age of women who received denosumab was 50 years (range, 44-59 years), 65% of whom were hormone receptor positive, HER2-negative. In the study, patients were stratified by various factors, including type of therapy, age, lymph node status, geographical region, and others. The primary outcome was a composite endpoint of bone metastasis–free survival.

At 5-year follow-up, the researchers found no significant difference in bone metastasis–free survival between the denosumab and placebo treatment arms (median survival not reached in either arm; P = .70). With respect to safety, the most frequently seen grade 3 or higher treatment-emergent adverse events were neutropenia (15% vs. 15%), febrile neutropenia (5% vs. 6%), and leukopenia (3% vs. 3%). Positively adjudicated osteonecrosis of the jaw occurred in 122 (5%) of 2,241 patients treated with denosumab versus 4 (less than 1%) of 2,218 patients treated with placebo, Dr. Coleman and colleagues wrote.

The researchers acknowledged that a key limitation of the study was the smaller than anticipated number of events for efficacy outcomes. As a result, the study protocol was modified, which could have limited the statistical power of the study. “The results of this study do not support a role for denosumab as an antitumour agent in this setting,” they concluded.

Amgen funded the study. The authors reported financial affiliations with AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Celgene, Covance, Lilly, Medivation, Merck Serono, Merck Sharp and Dohme, Novartis, Pfizer, and several others.

SOURCE: Coleman R et al. Lancet Oncol. 2019 Dec 2. doi: 10.1016/S1470-2045(19)30687-4.

Adjuvant denosumab did not improve bone metastasis–free survival and related outcomes in women with early-stage breast cancer, according to a phase 3 trial.

“We hypothesised that denosumab would modify the clinical course of early breast cancer, delaying the development of clinical bone metastases with or without disease recurrence at other sites,” reported Robert Coleman, MBBS, MD, of the University of Sheffield, England, and colleagues. Their report is in The Lancet Oncology.

The randomized, placebo-controlled, phase 3 D-CARE study included 4,509 women with early-stage, high-risk disease. The effects of adding denosumab to standard-of-care adjuvant or neoadjuvant chemotherapy was studied in 389 institutions around the globe. In the initial treatment phase, study patients received denosumab or placebo every 3-4 weeks in combination with adjuvant or neoadjuvant chemotherapy for approximately 6 months.

After completion of chemotherapy, the dosing interval was extended to every 12 weeks (range, 14 days) for a total of 5 years. The median age of women who received denosumab was 50 years (range, 44-59 years), 65% of whom were hormone receptor positive, HER2-negative. In the study, patients were stratified by various factors, including type of therapy, age, lymph node status, geographical region, and others. The primary outcome was a composite endpoint of bone metastasis–free survival.

At 5-year follow-up, the researchers found no significant difference in bone metastasis–free survival between the denosumab and placebo treatment arms (median survival not reached in either arm; P = .70). With respect to safety, the most frequently seen grade 3 or higher treatment-emergent adverse events were neutropenia (15% vs. 15%), febrile neutropenia (5% vs. 6%), and leukopenia (3% vs. 3%). Positively adjudicated osteonecrosis of the jaw occurred in 122 (5%) of 2,241 patients treated with denosumab versus 4 (less than 1%) of 2,218 patients treated with placebo, Dr. Coleman and colleagues wrote.

The researchers acknowledged that a key limitation of the study was the smaller than anticipated number of events for efficacy outcomes. As a result, the study protocol was modified, which could have limited the statistical power of the study. “The results of this study do not support a role for denosumab as an antitumour agent in this setting,” they concluded.

Amgen funded the study. The authors reported financial affiliations with AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Celgene, Covance, Lilly, Medivation, Merck Serono, Merck Sharp and Dohme, Novartis, Pfizer, and several others.

SOURCE: Coleman R et al. Lancet Oncol. 2019 Dec 2. doi: 10.1016/S1470-2045(19)30687-4.

Adjuvant denosumab did not improve bone metastasis–free survival and related outcomes in women with early-stage breast cancer, according to a phase 3 trial.

“We hypothesised that denosumab would modify the clinical course of early breast cancer, delaying the development of clinical bone metastases with or without disease recurrence at other sites,” reported Robert Coleman, MBBS, MD, of the University of Sheffield, England, and colleagues. Their report is in The Lancet Oncology.

The randomized, placebo-controlled, phase 3 D-CARE study included 4,509 women with early-stage, high-risk disease. The effects of adding denosumab to standard-of-care adjuvant or neoadjuvant chemotherapy was studied in 389 institutions around the globe. In the initial treatment phase, study patients received denosumab or placebo every 3-4 weeks in combination with adjuvant or neoadjuvant chemotherapy for approximately 6 months.

After completion of chemotherapy, the dosing interval was extended to every 12 weeks (range, 14 days) for a total of 5 years. The median age of women who received denosumab was 50 years (range, 44-59 years), 65% of whom were hormone receptor positive, HER2-negative. In the study, patients were stratified by various factors, including type of therapy, age, lymph node status, geographical region, and others. The primary outcome was a composite endpoint of bone metastasis–free survival.

At 5-year follow-up, the researchers found no significant difference in bone metastasis–free survival between the denosumab and placebo treatment arms (median survival not reached in either arm; P = .70). With respect to safety, the most frequently seen grade 3 or higher treatment-emergent adverse events were neutropenia (15% vs. 15%), febrile neutropenia (5% vs. 6%), and leukopenia (3% vs. 3%). Positively adjudicated osteonecrosis of the jaw occurred in 122 (5%) of 2,241 patients treated with denosumab versus 4 (less than 1%) of 2,218 patients treated with placebo, Dr. Coleman and colleagues wrote.

The researchers acknowledged that a key limitation of the study was the smaller than anticipated number of events for efficacy outcomes. As a result, the study protocol was modified, which could have limited the statistical power of the study. “The results of this study do not support a role for denosumab as an antitumour agent in this setting,” they concluded.

Amgen funded the study. The authors reported financial affiliations with AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Celgene, Covance, Lilly, Medivation, Merck Serono, Merck Sharp and Dohme, Novartis, Pfizer, and several others.

SOURCE: Coleman R et al. Lancet Oncol. 2019 Dec 2. doi: 10.1016/S1470-2045(19)30687-4.

Lipoprotein(a) molar concentration, rather than apolipoprotein(a) size, appears to be the factor that drives lipoprotein(a)-based cardiovascular disease, according to research published in the Journal of the American College of Cardiology.

The causal association between lipoprotein(a), or Lp(a), and cardiovascular disease has been previously established, but exactly what attribute of Lp(a) is related to cardiovascular risk is not known, Daniel F. Gudbjartsson, PhD, of deCODE genetics and the University of Iceland in Reykjavik, and colleagues wrote in their study. The researchers set out to determine whether Lp(a) molar concentration or apolipoprotein(a), or apo(a), size affects cardiovascular risk. In addition, Dr. Gudbjartsson and colleagues examined the relationship between Lp(a) and type 2 diabetes. While low levels of Lp(a) have been linked to type 2 diabetes, the researchers sought to examine whether low Lp(a) molar concentration levels were also associated with type 2 diabetes risk.

“With Lp(a)-lowering drugs being developed, it is important to understand which attributes of Lp(a) best capture the cardiovascular risk and the consequences of Lp(a) lowering,” noted Dr. Gudbjartsson and colleagues.

Using Mendelian randomization, the researchers assessed Lp(a) molar concentration and kringle IV type 2 (KIV-2) repeat sequence variants to determine a causal relationship between both variants and disease risk. Lp(a) molar concentration serum samples were measured using particle-enhanced turbidimetric immunoassay, while KIV-2 repeats were genotyped with real-time polymerase chain reaction.

Overall, 143,087 participants from Iceland had their genetic information analyzed; of these, 17,715 participants had coronary artery disease, and 8,734 had type 2 diabetes. Lp(a) molecular concentration was analyzed in 12,137 participants and genetically imputed into 130,950 Icelanders, and KIV-2 repeats were estimated in 22,771 Icelanders and genetically imputed into 120,316 Icelanders.

Dr. Gudbjartsson and colleagues found there was a dose-dependent association between Lp(a) molar concentration and risk of coronary artery disease (CAD), peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. In participants in whom Lp(a) molar concentration was at the 79th percentile (50 units of molarity [nM]), the odds ratio was 1.11, and for those in the 99th percentile (250 nM), there was an odds ratio of 2.01 when compared with participants with a median Lp(a) molar concentration of 14 nM. “Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size,” the researchers said.

Participants who were not at increased risk for CAD included those with few KIV-2 repeats and participants with the splice variant G4925A. “This suggested that risk prediction based on Lp(a) should only depend on molar concentration and that treatment of Lp(a) should focus on lowering the molar concentration in subjects with high Lp(a) levels, regardless of the apo(a) size distribution,” Dr. Gudbjartsson and colleagues wrote.

Among participants with type 2 diabetes examined, the 10% of participants with Lp(a) molar concentrations of less than 3.5 nM were at the highest risk of developing type 2 diabetes.

In an accompanying editorial, Benoit J. Arsenault, PhD, of the Quebec Heart and Lung Institute, said that the findings of an association between Lp(a) concentration and atherosclerotic cardiovascular diseases (ASCVD) from Gudbjartsson et al. are important, particularly if they can be replicated in more diverse populations (doi: 10.1016/j.jacc.2019.06.083). “Investigating the association between Lp(a) levels, apo(a) isoform size, and ASCVD risk in different populations is important because the distribution of Lp(a) levels appears to be different across ethnic groups,” he said.

Despite the link between absolute Lp(a) concentrations and cardiovascular disease, cardiovascular outcome trials will need be conducted, Dr. Arsenault noted.

“In the post-statin and post-genomic era, finding much needed therapeutic targets for residual cardiovascular risk can be compared to a gold-digging expedition. Like a map to the location of the gold, GWAS [genome-wide association studies] and Mendelian randomization studies are consistently pointing us in the direction of Lp(a),” he said. “It is time to coordinate our efforts to dig where the map told us, to see once and for all if we will find the golden target of residual cardiovascular risk that we are hoping for and to give hope to high-risk patients with elevated Lp(a) levels.”

Dr. Gudbjartsson and 19 other authors reported being employees of deCODE genetics, owned by Amgen, which is developing Lp(a)-lowering drugs related to the study findings. The other authors reported no relevant conflict of interest. Dr. Arsenault reported being supported by the Fonds de recherche du Québec: Santé and the Canadian Institutes of Health Research; has received research funding from Pfizer, Merck, and Ionis; and was a former consultant for Pfizer and Novartis.

SOURCE: Gudbjartsson DF et al. J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.10.019.

Lipoprotein(a) molar concentration, rather than apolipoprotein(a) size, appears to be the factor that drives lipoprotein(a)-based cardiovascular disease, according to research published in the Journal of the American College of Cardiology.

The causal association between lipoprotein(a), or Lp(a), and cardiovascular disease has been previously established, but exactly what attribute of Lp(a) is related to cardiovascular risk is not known, Daniel F. Gudbjartsson, PhD, of deCODE genetics and the University of Iceland in Reykjavik, and colleagues wrote in their study. The researchers set out to determine whether Lp(a) molar concentration or apolipoprotein(a), or apo(a), size affects cardiovascular risk. In addition, Dr. Gudbjartsson and colleagues examined the relationship between Lp(a) and type 2 diabetes. While low levels of Lp(a) have been linked to type 2 diabetes, the researchers sought to examine whether low Lp(a) molar concentration levels were also associated with type 2 diabetes risk.

“With Lp(a)-lowering drugs being developed, it is important to understand which attributes of Lp(a) best capture the cardiovascular risk and the consequences of Lp(a) lowering,” noted Dr. Gudbjartsson and colleagues.

Using Mendelian randomization, the researchers assessed Lp(a) molar concentration and kringle IV type 2 (KIV-2) repeat sequence variants to determine a causal relationship between both variants and disease risk. Lp(a) molar concentration serum samples were measured using particle-enhanced turbidimetric immunoassay, while KIV-2 repeats were genotyped with real-time polymerase chain reaction.

Overall, 143,087 participants from Iceland had their genetic information analyzed; of these, 17,715 participants had coronary artery disease, and 8,734 had type 2 diabetes. Lp(a) molecular concentration was analyzed in 12,137 participants and genetically imputed into 130,950 Icelanders, and KIV-2 repeats were estimated in 22,771 Icelanders and genetically imputed into 120,316 Icelanders.

Dr. Gudbjartsson and colleagues found there was a dose-dependent association between Lp(a) molar concentration and risk of coronary artery disease (CAD), peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. In participants in whom Lp(a) molar concentration was at the 79th percentile (50 units of molarity [nM]), the odds ratio was 1.11, and for those in the 99th percentile (250 nM), there was an odds ratio of 2.01 when compared with participants with a median Lp(a) molar concentration of 14 nM. “Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size,” the researchers said.

Participants who were not at increased risk for CAD included those with few KIV-2 repeats and participants with the splice variant G4925A. “This suggested that risk prediction based on Lp(a) should only depend on molar concentration and that treatment of Lp(a) should focus on lowering the molar concentration in subjects with high Lp(a) levels, regardless of the apo(a) size distribution,” Dr. Gudbjartsson and colleagues wrote.

Among participants with type 2 diabetes examined, the 10% of participants with Lp(a) molar concentrations of less than 3.5 nM were at the highest risk of developing type 2 diabetes.

In an accompanying editorial, Benoit J. Arsenault, PhD, of the Quebec Heart and Lung Institute, said that the findings of an association between Lp(a) concentration and atherosclerotic cardiovascular diseases (ASCVD) from Gudbjartsson et al. are important, particularly if they can be replicated in more diverse populations (doi: 10.1016/j.jacc.2019.06.083). “Investigating the association between Lp(a) levels, apo(a) isoform size, and ASCVD risk in different populations is important because the distribution of Lp(a) levels appears to be different across ethnic groups,” he said.

Despite the link between absolute Lp(a) concentrations and cardiovascular disease, cardiovascular outcome trials will need be conducted, Dr. Arsenault noted.

“In the post-statin and post-genomic era, finding much needed therapeutic targets for residual cardiovascular risk can be compared to a gold-digging expedition. Like a map to the location of the gold, GWAS [genome-wide association studies] and Mendelian randomization studies are consistently pointing us in the direction of Lp(a),” he said. “It is time to coordinate our efforts to dig where the map told us, to see once and for all if we will find the golden target of residual cardiovascular risk that we are hoping for and to give hope to high-risk patients with elevated Lp(a) levels.”

Dr. Gudbjartsson and 19 other authors reported being employees of deCODE genetics, owned by Amgen, which is developing Lp(a)-lowering drugs related to the study findings. The other authors reported no relevant conflict of interest. Dr. Arsenault reported being supported by the Fonds de recherche du Québec: Santé and the Canadian Institutes of Health Research; has received research funding from Pfizer, Merck, and Ionis; and was a former consultant for Pfizer and Novartis.

SOURCE: Gudbjartsson DF et al. J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.10.019.

Lipoprotein(a) molar concentration, rather than apolipoprotein(a) size, appears to be the factor that drives lipoprotein(a)-based cardiovascular disease, according to research published in the Journal of the American College of Cardiology.

The causal association between lipoprotein(a), or Lp(a), and cardiovascular disease has been previously established, but exactly what attribute of Lp(a) is related to cardiovascular risk is not known, Daniel F. Gudbjartsson, PhD, of deCODE genetics and the University of Iceland in Reykjavik, and colleagues wrote in their study. The researchers set out to determine whether Lp(a) molar concentration or apolipoprotein(a), or apo(a), size affects cardiovascular risk. In addition, Dr. Gudbjartsson and colleagues examined the relationship between Lp(a) and type 2 diabetes. While low levels of Lp(a) have been linked to type 2 diabetes, the researchers sought to examine whether low Lp(a) molar concentration levels were also associated with type 2 diabetes risk.

“With Lp(a)-lowering drugs being developed, it is important to understand which attributes of Lp(a) best capture the cardiovascular risk and the consequences of Lp(a) lowering,” noted Dr. Gudbjartsson and colleagues.

Using Mendelian randomization, the researchers assessed Lp(a) molar concentration and kringle IV type 2 (KIV-2) repeat sequence variants to determine a causal relationship between both variants and disease risk. Lp(a) molar concentration serum samples were measured using particle-enhanced turbidimetric immunoassay, while KIV-2 repeats were genotyped with real-time polymerase chain reaction.

Overall, 143,087 participants from Iceland had their genetic information analyzed; of these, 17,715 participants had coronary artery disease, and 8,734 had type 2 diabetes. Lp(a) molecular concentration was analyzed in 12,137 participants and genetically imputed into 130,950 Icelanders, and KIV-2 repeats were estimated in 22,771 Icelanders and genetically imputed into 120,316 Icelanders.

Dr. Gudbjartsson and colleagues found there was a dose-dependent association between Lp(a) molar concentration and risk of coronary artery disease (CAD), peripheral artery disease, aortic valve stenosis, heart failure, and lifespan. In participants in whom Lp(a) molar concentration was at the 79th percentile (50 units of molarity [nM]), the odds ratio was 1.11, and for those in the 99th percentile (250 nM), there was an odds ratio of 2.01 when compared with participants with a median Lp(a) molar concentration of 14 nM. “Lp(a) molar concentration fully explained the Lp(a) association with CAD, and there was no residual association with apo(a) size,” the researchers said.

Participants who were not at increased risk for CAD included those with few KIV-2 repeats and participants with the splice variant G4925A. “This suggested that risk prediction based on Lp(a) should only depend on molar concentration and that treatment of Lp(a) should focus on lowering the molar concentration in subjects with high Lp(a) levels, regardless of the apo(a) size distribution,” Dr. Gudbjartsson and colleagues wrote.

Among participants with type 2 diabetes examined, the 10% of participants with Lp(a) molar concentrations of less than 3.5 nM were at the highest risk of developing type 2 diabetes.

In an accompanying editorial, Benoit J. Arsenault, PhD, of the Quebec Heart and Lung Institute, said that the findings of an association between Lp(a) concentration and atherosclerotic cardiovascular diseases (ASCVD) from Gudbjartsson et al. are important, particularly if they can be replicated in more diverse populations (doi: 10.1016/j.jacc.2019.06.083). “Investigating the association between Lp(a) levels, apo(a) isoform size, and ASCVD risk in different populations is important because the distribution of Lp(a) levels appears to be different across ethnic groups,” he said.

Despite the link between absolute Lp(a) concentrations and cardiovascular disease, cardiovascular outcome trials will need be conducted, Dr. Arsenault noted.

“In the post-statin and post-genomic era, finding much needed therapeutic targets for residual cardiovascular risk can be compared to a gold-digging expedition. Like a map to the location of the gold, GWAS [genome-wide association studies] and Mendelian randomization studies are consistently pointing us in the direction of Lp(a),” he said. “It is time to coordinate our efforts to dig where the map told us, to see once and for all if we will find the golden target of residual cardiovascular risk that we are hoping for and to give hope to high-risk patients with elevated Lp(a) levels.”

Dr. Gudbjartsson and 19 other authors reported being employees of deCODE genetics, owned by Amgen, which is developing Lp(a)-lowering drugs related to the study findings. The other authors reported no relevant conflict of interest. Dr. Arsenault reported being supported by the Fonds de recherche du Québec: Santé and the Canadian Institutes of Health Research; has received research funding from Pfizer, Merck, and Ionis; and was a former consultant for Pfizer and Novartis.

SOURCE: Gudbjartsson DF et al. J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.10.019.

While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.

©Thinkstock

“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.

To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).

Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.

Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).

After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.

In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).

Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.

“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.

Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.

The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.

SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.

While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.

©Thinkstock

“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.

To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).

Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.

Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).

After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.

In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).

Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.

“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.

Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.

The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.

SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.

While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.

©Thinkstock

“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.

To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).

Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.

Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).

After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.

In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).

Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.

“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.

Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.

The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.

SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.

PHILADELPHIA – A 32-gene screening test for stroke risk identified a subgroup of atrial fibrillation (AFib) patients with an elevated rate of ischemic strokes despite having a low stroke risk by conventional criteria by their CHA2DS2-VASc score in a post-hoc analysis of more than 11,000 patients enrolled in a recent drug trial.

Mitchel L. Zoler/MDedge News

Overall, AFib patients in the highest tertile for genetic risk based on a 32 gene-loci test had a 31% increase rate of ischemic stroke during a median 2.8 years of follow-up compared with patients in the tertile with the lowest risk based on the 32-loci screen, Nicholas A. Marston, MD, said at the American Heart Association scientific sessions. This suggested that the genetic test had roughly the same association with an increased stroke risk as several components of the CHA2DS2-VASc score, such as female sex, an age of 65-74 years old, or having heart failure as a comorbidity, each of which links with an increased risk for ischemic stroke of about 31%-38%, Dr. Marston noted.

The genetic test produced even sharper discrimination among the patients with the lowest stroke risk as measured by their CHA2DS2-VASc score (Circulation. 2012 Aug 14;126[7]: 860-5). Among the slightly more than 3,000 patients in the study with a CHA2DS2-VASc score of three or less, those in the subgroup with the highest risk by the 32-loci screen had a stroke rate during follow-up that was 76% higher than those in the low or intermediate tertile for their genetic score. Among the 796 patients with a CHA2DS2-VASc score of just 1 or 2, those who also fell into the highest level of risk on the 32-loci screen had a stroke rate 3.5-fold higher than those with a similar CHA2DS2-VASc score but in the low and intermediate tertiles by the 32-loci screen.

The additional risk prediction provided by the 32-loci test was statistically significant in the analysis of the 3,071 patients with a CHA2DS2-VASc score of 3 or less after adjustment for age, sex, ancestry, and the individual components of the CHA2DS2-VASc score, which includes factors such as hypertension, diabetes, and heart failure, said Dr. Marston, a cardiologist at Brigham and Women’s Hospital in Boston. The 3.5-fold elevation among patients with a high genetic-risk score in the cohort of 796 patients with a CHA2DS2-VASc score of 1 or 2 just missed statistical significance (P = .06), possibly because the number of patients in the analysis was relatively low. Future research should explore the predictive value of the genetic risk score in patients with a CHA2DS2-VASc score of 0 or 1, the “group where therapeutic decisions could be altered” depending on the genetic risk score, he explained.

Dr. Marston and his associates used data collected in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which was designed to assess the safety and efficacy of the direct-acting oral anticoagulant edoxaban in patients with AFib (New Engl J Med. 2013 Nov 28; 369[21]: 2091-2104). The 32-loci panel to measure a person’s genetic risk for stroke came from a 2018 report by a multinational team of researchers (Nature Genetics. 2018 Apr;50[4]: 524-37). The new analysis applied this 32-loci genetic test panel to 11.164 unrelated AFib patients with European ancestry from the ENGAGE AF-TIMIT 48 database. They divided this cohort into tertiles based on having a low, intermediate, or high stroke risk as assessed by the 32-loci genetic test. The analysis focused on patients enrolled in the trial who had European ancestry because the 32-loci screening test relied predominantly on data collected from people with this genetic background, Dr. Marston said.

mzoler@mdedge.com

SOURCE: Marston NA et al. AHA 2019, Abstract 336.

PHILADELPHIA – A 32-gene screening test for stroke risk identified a subgroup of atrial fibrillation (AFib) patients with an elevated rate of ischemic strokes despite having a low stroke risk by conventional criteria by their CHA2DS2-VASc score in a post-hoc analysis of more than 11,000 patients enrolled in a recent drug trial.

Mitchel L. Zoler/MDedge News

Overall, AFib patients in the highest tertile for genetic risk based on a 32 gene-loci test had a 31% increase rate of ischemic stroke during a median 2.8 years of follow-up compared with patients in the tertile with the lowest risk based on the 32-loci screen, Nicholas A. Marston, MD, said at the American Heart Association scientific sessions. This suggested that the genetic test had roughly the same association with an increased stroke risk as several components of the CHA2DS2-VASc score, such as female sex, an age of 65-74 years old, or having heart failure as a comorbidity, each of which links with an increased risk for ischemic stroke of about 31%-38%, Dr. Marston noted.

The genetic test produced even sharper discrimination among the patients with the lowest stroke risk as measured by their CHA2DS2-VASc score (Circulation. 2012 Aug 14;126[7]: 860-5). Among the slightly more than 3,000 patients in the study with a CHA2DS2-VASc score of three or less, those in the subgroup with the highest risk by the 32-loci screen had a stroke rate during follow-up that was 76% higher than those in the low or intermediate tertile for their genetic score. Among the 796 patients with a CHA2DS2-VASc score of just 1 or 2, those who also fell into the highest level of risk on the 32-loci screen had a stroke rate 3.5-fold higher than those with a similar CHA2DS2-VASc score but in the low and intermediate tertiles by the 32-loci screen.

The additional risk prediction provided by the 32-loci test was statistically significant in the analysis of the 3,071 patients with a CHA2DS2-VASc score of 3 or less after adjustment for age, sex, ancestry, and the individual components of the CHA2DS2-VASc score, which includes factors such as hypertension, diabetes, and heart failure, said Dr. Marston, a cardiologist at Brigham and Women’s Hospital in Boston. The 3.5-fold elevation among patients with a high genetic-risk score in the cohort of 796 patients with a CHA2DS2-VASc score of 1 or 2 just missed statistical significance (P = .06), possibly because the number of patients in the analysis was relatively low. Future research should explore the predictive value of the genetic risk score in patients with a CHA2DS2-VASc score of 0 or 1, the “group where therapeutic decisions could be altered” depending on the genetic risk score, he explained.

Dr. Marston and his associates used data collected in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which was designed to assess the safety and efficacy of the direct-acting oral anticoagulant edoxaban in patients with AFib (New Engl J Med. 2013 Nov 28; 369[21]: 2091-2104). The 32-loci panel to measure a person’s genetic risk for stroke came from a 2018 report by a multinational team of researchers (Nature Genetics. 2018 Apr;50[4]: 524-37). The new analysis applied this 32-loci genetic test panel to 11.164 unrelated AFib patients with European ancestry from the ENGAGE AF-TIMIT 48 database. They divided this cohort into tertiles based on having a low, intermediate, or high stroke risk as assessed by the 32-loci genetic test. The analysis focused on patients enrolled in the trial who had European ancestry because the 32-loci screening test relied predominantly on data collected from people with this genetic background, Dr. Marston said.

mzoler@mdedge.com

SOURCE: Marston NA et al. AHA 2019, Abstract 336.

PHILADELPHIA – A 32-gene screening test for stroke risk identified a subgroup of atrial fibrillation (AFib) patients with an elevated rate of ischemic strokes despite having a low stroke risk by conventional criteria by their CHA2DS2-VASc score in a post-hoc analysis of more than 11,000 patients enrolled in a recent drug trial.

Mitchel L. Zoler/MDedge News

Overall, AFib patients in the highest tertile for genetic risk based on a 32 gene-loci test had a 31% increase rate of ischemic stroke during a median 2.8 years of follow-up compared with patients in the tertile with the lowest risk based on the 32-loci screen, Nicholas A. Marston, MD, said at the American Heart Association scientific sessions. This suggested that the genetic test had roughly the same association with an increased stroke risk as several components of the CHA2DS2-VASc score, such as female sex, an age of 65-74 years old, or having heart failure as a comorbidity, each of which links with an increased risk for ischemic stroke of about 31%-38%, Dr. Marston noted.

The genetic test produced even sharper discrimination among the patients with the lowest stroke risk as measured by their CHA2DS2-VASc score (Circulation. 2012 Aug 14;126[7]: 860-5). Among the slightly more than 3,000 patients in the study with a CHA2DS2-VASc score of three or less, those in the subgroup with the highest risk by the 32-loci screen had a stroke rate during follow-up that was 76% higher than those in the low or intermediate tertile for their genetic score. Among the 796 patients with a CHA2DS2-VASc score of just 1 or 2, those who also fell into the highest level of risk on the 32-loci screen had a stroke rate 3.5-fold higher than those with a similar CHA2DS2-VASc score but in the low and intermediate tertiles by the 32-loci screen.

The additional risk prediction provided by the 32-loci test was statistically significant in the analysis of the 3,071 patients with a CHA2DS2-VASc score of 3 or less after adjustment for age, sex, ancestry, and the individual components of the CHA2DS2-VASc score, which includes factors such as hypertension, diabetes, and heart failure, said Dr. Marston, a cardiologist at Brigham and Women’s Hospital in Boston. The 3.5-fold elevation among patients with a high genetic-risk score in the cohort of 796 patients with a CHA2DS2-VASc score of 1 or 2 just missed statistical significance (P = .06), possibly because the number of patients in the analysis was relatively low. Future research should explore the predictive value of the genetic risk score in patients with a CHA2DS2-VASc score of 0 or 1, the “group where therapeutic decisions could be altered” depending on the genetic risk score, he explained.

Dr. Marston and his associates used data collected in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which was designed to assess the safety and efficacy of the direct-acting oral anticoagulant edoxaban in patients with AFib (New Engl J Med. 2013 Nov 28; 369[21]: 2091-2104). The 32-loci panel to measure a person’s genetic risk for stroke came from a 2018 report by a multinational team of researchers (Nature Genetics. 2018 Apr;50[4]: 524-37). The new analysis applied this 32-loci genetic test panel to 11.164 unrelated AFib patients with European ancestry from the ENGAGE AF-TIMIT 48 database. They divided this cohort into tertiles based on having a low, intermediate, or high stroke risk as assessed by the 32-loci genetic test. The analysis focused on patients enrolled in the trial who had European ancestry because the 32-loci screening test relied predominantly on data collected from people with this genetic background, Dr. Marston said.

mzoler@mdedge.com

SOURCE: Marston NA et al. AHA 2019, Abstract 336.

One in four high school students and one in 10 middle school students have recently used e-cigarettes, the most frequently used tobacco product among youth, according to new findings from the Centers for Disease Control and Prevention.

diego_cervo/Thinkstock

Just over half of high school students and about a quarter of middle school students have ever tried a tobacco product, and more than a third of students have ever tried an e-cigarette, according to results from the 2019 National Youth Tobacco Survey. These results were published in the Morbidity and Mortality Weekly Report on Dec. 6.

Adolescent cigarette smoking rates have continued their decline, hitting their lowest rate ever in 2019, but e-cigarette use, or “vaping,” has continued to increase. E-cigarette use surpassed that of all other tobacco products in 2014 and has remained the most common—as well as the least likely to be perceived as harmful, researchers reported.

“Although most current youth tobacco product users are not daily users, estimates of frequent e-cigarette use among high school students were comparable to those observed for cigarette and smokeless tobacco product users in 2019,” wrote Teresa W. Wang, PhD, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, and associates at the CDC and Food and Drug Administration. “Youth use of tobacco products in any form is unsafe, regardless of whether the products are smoked, smokeless, or electronic.”

The high prevalence of e-cigarette use was no surprise to Karen Wilson, MD, chief of the division of general pediatrics at the Icahn School of Medicine at Mount Sinai and Mount Sinai Kravis Children’s Hospital, New York, and chair of the American Academy of Pediatrics’ Tobacco Consortium.

“It also fits with what we’re seeing anecdotally,” Dr. Wilson said in an interview. “We hear the statistic that 30% of high school students are using them, but high school students will say it’s much more than that.”

It’s therefore important for physicians to be proactive in talking to youth about these products. “They should absolutely be screening for vaping and know all about the different products,” including JUUL, Suorin, nicotine toothpicks, and candies and other products, Dr. Wilson said. “Pediatricians need to be asking their teenagers open-ended questions about what are kids using now.”

The American Academy of Pediatrics has resources available to help pediatricians and families of youth using e-cigarettes and vaping devices, she added.
 

Main findings

The researchers reported data from the annual, cross-sectional National Youth Tobacco Survey, administered to U.S. students in public and private schools in all 50 states and the District of Columbia. The results were divided into middle school (grades 6-8) and high school (grades 9-12) from 251 participating schools between February 2019 and May 2019.

The survey has been done using pencil and paper questionnaires since it began in 1999, but this year’s surveys were digital for the first time. Among the 19,018 questionnaires completed (student response rate 85.3%), 8,837 were middle school and 10,097 were high school. The weighted analysis of results represents 27 million students: 11.9 million in middle school and 15 million in high school.

More than half (53.3%) of high school students reported ever having tried a tobacco product, and 31.2% reported having used one in the past 30 days. In middle school, 24.3% of students reported ever using a tobacco product, and 12.5% have used one in the past month.

Tobacco products include cigarettes (traditional/combusted), electronic cigarettes, cigars, smokeless tobacco, hookahs, pipe tobacco, and bidis, which are small brown cigarettes wrapped in leaves. Among the electronic tobacco products mentioned in the survey were NJOY, Blu, Vuse, MarkTen, Logic, Vapin Plus, eGo and Halo.

The most common product for youth to try was e-cigarettes, which 35% of middle and high school students had ever tried. Just under a quarter of students (23%) had used a tobacco product in the past month, and e-cigarettes were again the most commonly used overall by that group, cited by 20% of recent users. Cigars (5.3%), cigarettes (4.3%), smokeless tobacco (3.5%), hookahs (2.6%) and pipes (under 1%) were used much less frequently.

Frequent use, defined as at least 20 of the previous 30 days, was most common among youth using smokeless tobacco (34.1% of current users) and e-cigarettes (30.4%) and least common among cigar smokers (16.8%). Among those currently using any tobacco product, 24.7% said they had cravings for a product within the past month, and 13.7% wanted to use it within a half hour of waking up.

More than half of those who currently used any tobacco products (57.8%) were seriously considering quitting, and a similar proportion (57.5%) had stopped using all tobacco products for at least 1 day in an attempt to quit.

“Many [adolescents] will tell you they will use it until they don’t have the availability of getting it,” Dr. Wilson said. “The problem is that they’re becoming so addicted to the high-nicotine products that they’re going farther and farther out of their way to try to get these products so that they can satisfy their addictions.”

Policies restricting access, such as increasing the age for sales to 21 and increasing taxes on products, can reduce tobacco use among youth, Dr. Wilson said.

“It will encourage teenagers to get help for their addiction by using FDA-approved devices or nicotine replacement therapy and behavioral interventions rather than relying on an unproven and potentially dangerous product,” she said.
 

Reasons for use, flavor, and harm perception

The most common flavored tobacco product used among youth was e-cigarettes, reported by 68.8% of current e-cigarette users, followed by smokeless tobacco (48%), cigarettes (46.7%, only menthol), cigars, pipe tobacco, and hookahs.

The top reasons youth cited for trying e-cigarettes were curiosity (55.3%), a friend or family member’s use (30.8%), and their availability in a wide range of flavors (22.4%). Almost as popular as flavor availability was e-cigarette users’ interest in doing “tricks” with the product (21.2%).

The cross-sectional questionnaire method of the study precluded the ability to draw conclusions about why students might perceive a particular tobacco product as more or less harmful. However, public health officials have expressed concern that flavors reduce the perceived harm that can come from the products. Dr. Wilson said the attraction to e-cigarette flavors is “huge.”

“If electronic cigarettes were only available in tobacco flavor, I do not believe that many teenagers at all would try them,” Dr. Wilson said. “They think because they’re sweet and flavored that they actually aren’t harmful. It makes the kids think these are safe products.”

More than one in four students (28.2%) perceived intermittent e-cigarette use as causing little to no harm, and only 16.4% similarly saw little or no harm from intermittent hookah use, compared with 11.5% for smokeless tobacco and 9.5% for cigarettes. Less than a third of respondents (32.3%) saw intermittent e-cigarette use as causing a lot of harm, compared with much higher percentages for cigarettes (54.9%) and smokeless tobacco (52.5%).

Part of the problem with harm perception is the narrative promoted by e-cigarette companies, Dr. Wilson said.

“From the very beginning, they started with a campaign that called this harmless water vapor, which it is absolutely not,” she said. “It’s an aerosol of toxic chemicals and nicotine, which is addictive. We know that nicotine that can impact scores of cognitive tests and impulsivity. We have no idea what these really high levels [of nicotine] will do.”

Further, potential long-term harm is still an open question, she pointed out.

“We also know that these are particulates and toxins that are being inhaled into the lungs,” Dr. Wilson said. “We know they have some impact on asthma, and we don’t know what the impact is for using for 10 or 20 years.”

Curiosity about e-cigarettes and about traditional cigarettes were prevalent in similar proportions among youth who had never tried a tobacco product: 39.1% of never-users were curious about e-cigarettes, and 37% about traditional cigarettes. In addition to curiosity, researchers assess susceptibility among those who have never tried a tobacco product and found nearly identical susceptibility to e-cigarettes (45%) and traditional cigarettes (45.9%).

The survey also asked students about their exposure to tobacco advertising or promotions from a wide range of sources: convenience stores, supermarkets, gas stations, the Internet, television, video streaming, cinemas, and newspapers or magazines. Among the students who reported going to these sources, 69.3% had seen e-cigarette marketing, and 81.7% had seen marketing for other tobacco products, including cigarettes.

SOURCE: Wang TW et al. MMWR Surveill Summ. 2019 Nov 6;68(12):1-22. doi: 10.15585/mmwr.ss6812a1.

One in four high school students and one in 10 middle school students have recently used e-cigarettes, the most frequently used tobacco product among youth, according to new findings from the Centers for Disease Control and Prevention.

diego_cervo/Thinkstock

Just over half of high school students and about a quarter of middle school students have ever tried a tobacco product, and more than a third of students have ever tried an e-cigarette, according to results from the 2019 National Youth Tobacco Survey. These results were published in the Morbidity and Mortality Weekly Report on Dec. 6.

Adolescent cigarette smoking rates have continued their decline, hitting their lowest rate ever in 2019, but e-cigarette use, or “vaping,” has continued to increase. E-cigarette use surpassed that of all other tobacco products in 2014 and has remained the most common—as well as the least likely to be perceived as harmful, researchers reported.

“Although most current youth tobacco product users are not daily users, estimates of frequent e-cigarette use among high school students were comparable to those observed for cigarette and smokeless tobacco product users in 2019,” wrote Teresa W. Wang, PhD, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, and associates at the CDC and Food and Drug Administration. “Youth use of tobacco products in any form is unsafe, regardless of whether the products are smoked, smokeless, or electronic.”

The high prevalence of e-cigarette use was no surprise to Karen Wilson, MD, chief of the division of general pediatrics at the Icahn School of Medicine at Mount Sinai and Mount Sinai Kravis Children’s Hospital, New York, and chair of the American Academy of Pediatrics’ Tobacco Consortium.

“It also fits with what we’re seeing anecdotally,” Dr. Wilson said in an interview. “We hear the statistic that 30% of high school students are using them, but high school students will say it’s much more than that.”

It’s therefore important for physicians to be proactive in talking to youth about these products. “They should absolutely be screening for vaping and know all about the different products,” including JUUL, Suorin, nicotine toothpicks, and candies and other products, Dr. Wilson said. “Pediatricians need to be asking their teenagers open-ended questions about what are kids using now.”

The American Academy of Pediatrics has resources available to help pediatricians and families of youth using e-cigarettes and vaping devices, she added.
 

Main findings

The researchers reported data from the annual, cross-sectional National Youth Tobacco Survey, administered to U.S. students in public and private schools in all 50 states and the District of Columbia. The results were divided into middle school (grades 6-8) and high school (grades 9-12) from 251 participating schools between February 2019 and May 2019.

The survey has been done using pencil and paper questionnaires since it began in 1999, but this year’s surveys were digital for the first time. Among the 19,018 questionnaires completed (student response rate 85.3%), 8,837 were middle school and 10,097 were high school. The weighted analysis of results represents 27 million students: 11.9 million in middle school and 15 million in high school.

More than half (53.3%) of high school students reported ever having tried a tobacco product, and 31.2% reported having used one in the past 30 days. In middle school, 24.3% of students reported ever using a tobacco product, and 12.5% have used one in the past month.

Tobacco products include cigarettes (traditional/combusted), electronic cigarettes, cigars, smokeless tobacco, hookahs, pipe tobacco, and bidis, which are small brown cigarettes wrapped in leaves. Among the electronic tobacco products mentioned in the survey were NJOY, Blu, Vuse, MarkTen, Logic, Vapin Plus, eGo and Halo.

The most common product for youth to try was e-cigarettes, which 35% of middle and high school students had ever tried. Just under a quarter of students (23%) had used a tobacco product in the past month, and e-cigarettes were again the most commonly used overall by that group, cited by 20% of recent users. Cigars (5.3%), cigarettes (4.3%), smokeless tobacco (3.5%), hookahs (2.6%) and pipes (under 1%) were used much less frequently.

Frequent use, defined as at least 20 of the previous 30 days, was most common among youth using smokeless tobacco (34.1% of current users) and e-cigarettes (30.4%) and least common among cigar smokers (16.8%). Among those currently using any tobacco product, 24.7% said they had cravings for a product within the past month, and 13.7% wanted to use it within a half hour of waking up.

More than half of those who currently used any tobacco products (57.8%) were seriously considering quitting, and a similar proportion (57.5%) had stopped using all tobacco products for at least 1 day in an attempt to quit.

“Many [adolescents] will tell you they will use it until they don’t have the availability of getting it,” Dr. Wilson said. “The problem is that they’re becoming so addicted to the high-nicotine products that they’re going farther and farther out of their way to try to get these products so that they can satisfy their addictions.”

Policies restricting access, such as increasing the age for sales to 21 and increasing taxes on products, can reduce tobacco use among youth, Dr. Wilson said.

“It will encourage teenagers to get help for their addiction by using FDA-approved devices or nicotine replacement therapy and behavioral interventions rather than relying on an unproven and potentially dangerous product,” she said.
 

Reasons for use, flavor, and harm perception

The most common flavored tobacco product used among youth was e-cigarettes, reported by 68.8% of current e-cigarette users, followed by smokeless tobacco (48%), cigarettes (46.7%, only menthol), cigars, pipe tobacco, and hookahs.

The top reasons youth cited for trying e-cigarettes were curiosity (55.3%), a friend or family member’s use (30.8%), and their availability in a wide range of flavors (22.4%). Almost as popular as flavor availability was e-cigarette users’ interest in doing “tricks” with the product (21.2%).

The cross-sectional questionnaire method of the study precluded the ability to draw conclusions about why students might perceive a particular tobacco product as more or less harmful. However, public health officials have expressed concern that flavors reduce the perceived harm that can come from the products. Dr. Wilson said the attraction to e-cigarette flavors is “huge.”

“If electronic cigarettes were only available in tobacco flavor, I do not believe that many teenagers at all would try them,” Dr. Wilson said. “They think because they’re sweet and flavored that they actually aren’t harmful. It makes the kids think these are safe products.”

More than one in four students (28.2%) perceived intermittent e-cigarette use as causing little to no harm, and only 16.4% similarly saw little or no harm from intermittent hookah use, compared with 11.5% for smokeless tobacco and 9.5% for cigarettes. Less than a third of respondents (32.3%) saw intermittent e-cigarette use as causing a lot of harm, compared with much higher percentages for cigarettes (54.9%) and smokeless tobacco (52.5%).

Part of the problem with harm perception is the narrative promoted by e-cigarette companies, Dr. Wilson said.

“From the very beginning, they started with a campaign that called this harmless water vapor, which it is absolutely not,” she said. “It’s an aerosol of toxic chemicals and nicotine, which is addictive. We know that nicotine that can impact scores of cognitive tests and impulsivity. We have no idea what these really high levels [of nicotine] will do.”

Further, potential long-term harm is still an open question, she pointed out.

“We also know that these are particulates and toxins that are being inhaled into the lungs,” Dr. Wilson said. “We know they have some impact on asthma, and we don’t know what the impact is for using for 10 or 20 years.”

Curiosity about e-cigarettes and about traditional cigarettes were prevalent in similar proportions among youth who had never tried a tobacco product: 39.1% of never-users were curious about e-cigarettes, and 37% about traditional cigarettes. In addition to curiosity, researchers assess susceptibility among those who have never tried a tobacco product and found nearly identical susceptibility to e-cigarettes (45%) and traditional cigarettes (45.9%).

The survey also asked students about their exposure to tobacco advertising or promotions from a wide range of sources: convenience stores, supermarkets, gas stations, the Internet, television, video streaming, cinemas, and newspapers or magazines. Among the students who reported going to these sources, 69.3% had seen e-cigarette marketing, and 81.7% had seen marketing for other tobacco products, including cigarettes.

SOURCE: Wang TW et al. MMWR Surveill Summ. 2019 Nov 6;68(12):1-22. doi: 10.15585/mmwr.ss6812a1.

One in four high school students and one in 10 middle school students have recently used e-cigarettes, the most frequently used tobacco product among youth, according to new findings from the Centers for Disease Control and Prevention.

diego_cervo/Thinkstock

Just over half of high school students and about a quarter of middle school students have ever tried a tobacco product, and more than a third of students have ever tried an e-cigarette, according to results from the 2019 National Youth Tobacco Survey. These results were published in the Morbidity and Mortality Weekly Report on Dec. 6.

Adolescent cigarette smoking rates have continued their decline, hitting their lowest rate ever in 2019, but e-cigarette use, or “vaping,” has continued to increase. E-cigarette use surpassed that of all other tobacco products in 2014 and has remained the most common—as well as the least likely to be perceived as harmful, researchers reported.

“Although most current youth tobacco product users are not daily users, estimates of frequent e-cigarette use among high school students were comparable to those observed for cigarette and smokeless tobacco product users in 2019,” wrote Teresa W. Wang, PhD, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, and associates at the CDC and Food and Drug Administration. “Youth use of tobacco products in any form is unsafe, regardless of whether the products are smoked, smokeless, or electronic.”

The high prevalence of e-cigarette use was no surprise to Karen Wilson, MD, chief of the division of general pediatrics at the Icahn School of Medicine at Mount Sinai and Mount Sinai Kravis Children’s Hospital, New York, and chair of the American Academy of Pediatrics’ Tobacco Consortium.

“It also fits with what we’re seeing anecdotally,” Dr. Wilson said in an interview. “We hear the statistic that 30% of high school students are using them, but high school students will say it’s much more than that.”

It’s therefore important for physicians to be proactive in talking to youth about these products. “They should absolutely be screening for vaping and know all about the different products,” including JUUL, Suorin, nicotine toothpicks, and candies and other products, Dr. Wilson said. “Pediatricians need to be asking their teenagers open-ended questions about what are kids using now.”

The American Academy of Pediatrics has resources available to help pediatricians and families of youth using e-cigarettes and vaping devices, she added.
 

Main findings

The researchers reported data from the annual, cross-sectional National Youth Tobacco Survey, administered to U.S. students in public and private schools in all 50 states and the District of Columbia. The results were divided into middle school (grades 6-8) and high school (grades 9-12) from 251 participating schools between February 2019 and May 2019.

The survey has been done using pencil and paper questionnaires since it began in 1999, but this year’s surveys were digital for the first time. Among the 19,018 questionnaires completed (student response rate 85.3%), 8,837 were middle school and 10,097 were high school. The weighted analysis of results represents 27 million students: 11.9 million in middle school and 15 million in high school.

More than half (53.3%) of high school students reported ever having tried a tobacco product, and 31.2% reported having used one in the past 30 days. In middle school, 24.3% of students reported ever using a tobacco product, and 12.5% have used one in the past month.

Tobacco products include cigarettes (traditional/combusted), electronic cigarettes, cigars, smokeless tobacco, hookahs, pipe tobacco, and bidis, which are small brown cigarettes wrapped in leaves. Among the electronic tobacco products mentioned in the survey were NJOY, Blu, Vuse, MarkTen, Logic, Vapin Plus, eGo and Halo.

The most common product for youth to try was e-cigarettes, which 35% of middle and high school students had ever tried. Just under a quarter of students (23%) had used a tobacco product in the past month, and e-cigarettes were again the most commonly used overall by that group, cited by 20% of recent users. Cigars (5.3%), cigarettes (4.3%), smokeless tobacco (3.5%), hookahs (2.6%) and pipes (under 1%) were used much less frequently.

Frequent use, defined as at least 20 of the previous 30 days, was most common among youth using smokeless tobacco (34.1% of current users) and e-cigarettes (30.4%) and least common among cigar smokers (16.8%). Among those currently using any tobacco product, 24.7% said they had cravings for a product within the past month, and 13.7% wanted to use it within a half hour of waking up.

More than half of those who currently used any tobacco products (57.8%) were seriously considering quitting, and a similar proportion (57.5%) had stopped using all tobacco products for at least 1 day in an attempt to quit.

“Many [adolescents] will tell you they will use it until they don’t have the availability of getting it,” Dr. Wilson said. “The problem is that they’re becoming so addicted to the high-nicotine products that they’re going farther and farther out of their way to try to get these products so that they can satisfy their addictions.”

Policies restricting access, such as increasing the age for sales to 21 and increasing taxes on products, can reduce tobacco use among youth, Dr. Wilson said.

“It will encourage teenagers to get help for their addiction by using FDA-approved devices or nicotine replacement therapy and behavioral interventions rather than relying on an unproven and potentially dangerous product,” she said.
 

Reasons for use, flavor, and harm perception

The most common flavored tobacco product used among youth was e-cigarettes, reported by 68.8% of current e-cigarette users, followed by smokeless tobacco (48%), cigarettes (46.7%, only menthol), cigars, pipe tobacco, and hookahs.

The top reasons youth cited for trying e-cigarettes were curiosity (55.3%), a friend or family member’s use (30.8%), and their availability in a wide range of flavors (22.4%). Almost as popular as flavor availability was e-cigarette users’ interest in doing “tricks” with the product (21.2%).

The cross-sectional questionnaire method of the study precluded the ability to draw conclusions about why students might perceive a particular tobacco product as more or less harmful. However, public health officials have expressed concern that flavors reduce the perceived harm that can come from the products. Dr. Wilson said the attraction to e-cigarette flavors is “huge.”

“If electronic cigarettes were only available in tobacco flavor, I do not believe that many teenagers at all would try them,” Dr. Wilson said. “They think because they’re sweet and flavored that they actually aren’t harmful. It makes the kids think these are safe products.”

More than one in four students (28.2%) perceived intermittent e-cigarette use as causing little to no harm, and only 16.4% similarly saw little or no harm from intermittent hookah use, compared with 11.5% for smokeless tobacco and 9.5% for cigarettes. Less than a third of respondents (32.3%) saw intermittent e-cigarette use as causing a lot of harm, compared with much higher percentages for cigarettes (54.9%) and smokeless tobacco (52.5%).

Part of the problem with harm perception is the narrative promoted by e-cigarette companies, Dr. Wilson said.

“From the very beginning, they started with a campaign that called this harmless water vapor, which it is absolutely not,” she said. “It’s an aerosol of toxic chemicals and nicotine, which is addictive. We know that nicotine that can impact scores of cognitive tests and impulsivity. We have no idea what these really high levels [of nicotine] will do.”

Further, potential long-term harm is still an open question, she pointed out.

“We also know that these are particulates and toxins that are being inhaled into the lungs,” Dr. Wilson said. “We know they have some impact on asthma, and we don’t know what the impact is for using for 10 or 20 years.”

Curiosity about e-cigarettes and about traditional cigarettes were prevalent in similar proportions among youth who had never tried a tobacco product: 39.1% of never-users were curious about e-cigarettes, and 37% about traditional cigarettes. In addition to curiosity, researchers assess susceptibility among those who have never tried a tobacco product and found nearly identical susceptibility to e-cigarettes (45%) and traditional cigarettes (45.9%).

The survey also asked students about their exposure to tobacco advertising or promotions from a wide range of sources: convenience stores, supermarkets, gas stations, the Internet, television, video streaming, cinemas, and newspapers or magazines. Among the students who reported going to these sources, 69.3% had seen e-cigarette marketing, and 81.7% had seen marketing for other tobacco products, including cigarettes.

SOURCE: Wang TW et al. MMWR Surveill Summ. 2019 Nov 6;68(12):1-22. doi: 10.15585/mmwr.ss6812a1.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

ATLANTA – Patients with rheumatoid arthritis were more at risk of postoperative infection because of a high Charlson Comorbidity Index or longer surgery time than because of perioperative use of antirheumatic medications, according to a presentation at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Anna Shmagel, MD, of the University of Minnesota in Minneapolis and colleagues performed a retrospective cohort study of 154 patients with seropositive RA who were in the Fairview Health System between Jan. 2010 and Dec. 2017 and underwent either orthopedic or major organ surgery. The patients were classified based on their use of disease-modifying antirheumatic drugs (DMARDs) and biologics alone or in combination, with patients divided into “no DMARD or biologic,” “DMARD but no biologic” and “biologic with or without DMARD” groups.

The question of whether to discontinue antirheumatic medications before surgery is still controversial, with conflicting evidence across studies, Dr. Shmagel said in her presentation. A study by Giles and colleagues found 10 of 91 patients (11%) RA who underwent an orthopedic surgical procedure developed a postoperative infection, with patients receiving tumor necrosis factor (TNF) inhibitors more likely to develop an infection, compared with patients who were not receiving TNF inhibitors (Arthritis Care Res. 2006. doi: 10.1002/art.21841).

However, other studies have challenged that idea, and a 2018 study from Goodman and colleagues raised the issue of whether patients stopping biologics prior to surgery are at increased risk of flares. Of 120 RA patients in their study who underwent total hip or total knee arthroplasty, 75% of patients flared at 6 weeks after surgery. While patients who halted biologics before surgery were more likely to flare, stopping biologics did not predict flaring after surgery (J Rheumatol. 2018. doi: 10.3899/jrheum.170366).

“It’s not entirely clear whether these theories are related to what we do with antirheumatic medications, but we felt that it was pertinent to further study this question.” Dr. Shmagel said.

Dr. Shmagel and colleagues examined the 30-day infection rate of RA patients postoperatively, with 30-day readmission and 30-day mortality rates as secondary outcomes. Patient-associated factors such as age, gender, race, body mass index, smoking status, Charlson Comorbidity Index, income, and use of corticosteroids were analyzed as covariates in addition to factors involving surgery such as expected surgery time, perioperative antibiotic use, and whether the procedure was elective or emergency surgery.

A majority of the patients in the study across all groups were white women about 63 years old with a body mass index above 30 kg/m² and almost all undergoing electing surgery compared with emergency surgery. While patients in each group were similar with regard to Charlson Comorbidity Index, expected length of surgery, and percentage of patients undergoing elective surgery, patients in the biologic with or without DMARD group had a significantly lower median income level compared with those in the other two groups (P = .01).

Overall, there were 244 surgeries in 154 patients, with 117 surgeries in the group not receiving biologics or DMARDs, 95 surgeries in the group receiving DMARDs but no biologics, and 32 surgeries in the biologics with or without DMARD group. In the DMARD but no biologics group, most patients were receiving methotrexate (45%) or hydroxychloroquine (44%), while the most common biologics in the biologics with or without DMARD group were infliximab (25%), tocilizumab (19%), abatacept (16%), etanercept (13%), rituximab (9%), and tofacitinib (9%).

There was an 11% overall rate of infection, with a similar rate of infection across all groups (P = .09). While there was a higher rate of surgical site infections among patients in the biologics with or without DMARD group (9%) and a higher percentage of urinary tract infections in the no DMARD and no biologics group (4%), the results were not statistically significant. When the rate of infections was examined by type of surgery, there were no significant differences between infections from musculoskeletal surgery (P = .7) and major organ surgery (P = .8).

The overall 30-day readmission rate was 12%, but there were no statistically significant differences between groups. Although there were five deaths in the study, four deaths were in the group not receiving DMARDs or biologics, and one death was in the biologic with or without DMARD group.

Higher Charlson Comorbidity Index did predict infection risk, with an odds ratio of 1.37 per 1-point increase in the index (95% confidence interval, 1.10-1.70). Length of surgery also increased the risk of infection, with an OR of 1.16 per 15-minute increase in surgery time (95% CI, 1.09-1.23).

Dr. Shmagel noted that the retrospective nature of the study and the midwestern cohort may mean the results are not generalizable to other populations and that larger randomized trials should be considered. “Certainly, a larger study with more events would be needed,” she said.

This study was funded by the University of Minnesota. Dr. Shmagel reported no relevant conflicts of interest.

SOURCE: Kerski M et al. Arthritis Rheumatol. 2019;71 (suppl 10), Abstract 1805.

SAN DIEGO – Many factors drive addiction. But clinicians often fail to address the important role played by abusive intimate partners, a psychiatrist told colleagues at the annual meeting of the American Academy of Addiction Psychiatry.

Photodisc/Thinkstock

Violence is not the only source of harm, said Carole Warshaw, MD, as abusers also turn to sabotage, gaslighting, and manipulation – especially when substance users seek help.

“Abusive partners deliberately engage in behaviors designed to undermine their partner’s sanity or sobriety,” said Dr. Warshaw, director of the National Center on Domestic Violence, Trauma & Mental Health in Chicago, in a presentation at the meeting. “We’ve talked a lot about drivers of the opioid epidemic, including pharmaceutical industry greed and disorders of despair. But nobody’s been really talking about gender-based violence as a potential driver of the opioid epidemic, including intimate-partner violence, trafficking, and commercial sex exploitation.”

Dr. Warshaw highlighted the findings of a 2014 study that examined the survey responses of 2,546 adult women (54% white, 19% black, 19% Hispanic) who called the National Domestic Violence Hotline. The study, led by Dr. Warshaw, only included women who had experienced domestic violence and were not in immediate crisis.

The women answered questions about abusive partners, and their responses were often emotional, Dr. Warshaw said. “People would say: ‘No one asked me this before,’ and they’d be in tears. It was just very moving for people to start thinking about this.”

Gaslighting, sabotage, and accusations of mental illness were common. More than 85% of respondents said their current or ex-partner had called them “crazy,” and 74% agreed that “your partner or ex-partner has ... deliberately done things to make you feel like you are going crazy or losing your mind.”

Strategies of abusive partners include sabotaging and discrediting their partners’ attempts at recovery, Dr. Warshaw said. Half of callers agreed that a partner or ex-partner “tried to prevent or discourage you from getting ... help or taking medication you were prescribed for your feelings.”

About 92% of callers who said they’d tried to get help in recent years “reported that their partner or ex-partner had threatened to report their alcohol or other drug use to authorities to keep them from getting something they wanted or needed,” the study found.

All of the abuse can create a kind of addiction feedback loop, she said. “Research has consistently documented that abuse by an intimate partner increases a person’s risk for developing a range of health and mental health conditions – including depression, PTSD, anxiety – that are risk factors for opioid and substance use.”

One resource that clinicians can use to protect patients from abusive and manipulative partners is her center’s toolkit on “Coercion Related to Mental Health and Substance Use in the Context of Intimate Partner Violence.”

The toolkit, she said, provides insight into how to integrate questions about abusive partners into your practice and how to partner with domestic violence programs.

Dr. Warshaw reported no relevant disclosures.

SAN DIEGO – Many factors drive addiction. But clinicians often fail to address the important role played by abusive intimate partners, a psychiatrist told colleagues at the annual meeting of the American Academy of Addiction Psychiatry.

Photodisc/Thinkstock

Violence is not the only source of harm, said Carole Warshaw, MD, as abusers also turn to sabotage, gaslighting, and manipulation – especially when substance users seek help.

“Abusive partners deliberately engage in behaviors designed to undermine their partner’s sanity or sobriety,” said Dr. Warshaw, director of the National Center on Domestic Violence, Trauma & Mental Health in Chicago, in a presentation at the meeting. “We’ve talked a lot about drivers of the opioid epidemic, including pharmaceutical industry greed and disorders of despair. But nobody’s been really talking about gender-based violence as a potential driver of the opioid epidemic, including intimate-partner violence, trafficking, and commercial sex exploitation.”

Dr. Warshaw highlighted the findings of a 2014 study that examined the survey responses of 2,546 adult women (54% white, 19% black, 19% Hispanic) who called the National Domestic Violence Hotline. The study, led by Dr. Warshaw, only included women who had experienced domestic violence and were not in immediate crisis.

The women answered questions about abusive partners, and their responses were often emotional, Dr. Warshaw said. “People would say: ‘No one asked me this before,’ and they’d be in tears. It was just very moving for people to start thinking about this.”

Gaslighting, sabotage, and accusations of mental illness were common. More than 85% of respondents said their current or ex-partner had called them “crazy,” and 74% agreed that “your partner or ex-partner has ... deliberately done things to make you feel like you are going crazy or losing your mind.”

Strategies of abusive partners include sabotaging and discrediting their partners’ attempts at recovery, Dr. Warshaw said. Half of callers agreed that a partner or ex-partner “tried to prevent or discourage you from getting ... help or taking medication you were prescribed for your feelings.”

About 92% of callers who said they’d tried to get help in recent years “reported that their partner or ex-partner had threatened to report their alcohol or other drug use to authorities to keep them from getting something they wanted or needed,” the study found.

All of the abuse can create a kind of addiction feedback loop, she said. “Research has consistently documented that abuse by an intimate partner increases a person’s risk for developing a range of health and mental health conditions – including depression, PTSD, anxiety – that are risk factors for opioid and substance use.”

One resource that clinicians can use to protect patients from abusive and manipulative partners is her center’s toolkit on “Coercion Related to Mental Health and Substance Use in the Context of Intimate Partner Violence.”

The toolkit, she said, provides insight into how to integrate questions about abusive partners into your practice and how to partner with domestic violence programs.

Dr. Warshaw reported no relevant disclosures.

SAN DIEGO – Many factors drive addiction. But clinicians often fail to address the important role played by abusive intimate partners, a psychiatrist told colleagues at the annual meeting of the American Academy of Addiction Psychiatry.

Photodisc/Thinkstock

Violence is not the only source of harm, said Carole Warshaw, MD, as abusers also turn to sabotage, gaslighting, and manipulation – especially when substance users seek help.

“Abusive partners deliberately engage in behaviors designed to undermine their partner’s sanity or sobriety,” said Dr. Warshaw, director of the National Center on Domestic Violence, Trauma & Mental Health in Chicago, in a presentation at the meeting. “We’ve talked a lot about drivers of the opioid epidemic, including pharmaceutical industry greed and disorders of despair. But nobody’s been really talking about gender-based violence as a potential driver of the opioid epidemic, including intimate-partner violence, trafficking, and commercial sex exploitation.”

Dr. Warshaw highlighted the findings of a 2014 study that examined the survey responses of 2,546 adult women (54% white, 19% black, 19% Hispanic) who called the National Domestic Violence Hotline. The study, led by Dr. Warshaw, only included women who had experienced domestic violence and were not in immediate crisis.

The women answered questions about abusive partners, and their responses were often emotional, Dr. Warshaw said. “People would say: ‘No one asked me this before,’ and they’d be in tears. It was just very moving for people to start thinking about this.”

Gaslighting, sabotage, and accusations of mental illness were common. More than 85% of respondents said their current or ex-partner had called them “crazy,” and 74% agreed that “your partner or ex-partner has ... deliberately done things to make you feel like you are going crazy or losing your mind.”

Strategies of abusive partners include sabotaging and discrediting their partners’ attempts at recovery, Dr. Warshaw said. Half of callers agreed that a partner or ex-partner “tried to prevent or discourage you from getting ... help or taking medication you were prescribed for your feelings.”

About 92% of callers who said they’d tried to get help in recent years “reported that their partner or ex-partner had threatened to report their alcohol or other drug use to authorities to keep them from getting something they wanted or needed,” the study found.

All of the abuse can create a kind of addiction feedback loop, she said. “Research has consistently documented that abuse by an intimate partner increases a person’s risk for developing a range of health and mental health conditions – including depression, PTSD, anxiety – that are risk factors for opioid and substance use.”

One resource that clinicians can use to protect patients from abusive and manipulative partners is her center’s toolkit on “Coercion Related to Mental Health and Substance Use in the Context of Intimate Partner Violence.”

The toolkit, she said, provides insight into how to integrate questions about abusive partners into your practice and how to partner with domestic violence programs.

Dr. Warshaw reported no relevant disclosures.

SAN DIEGO – Addiction specialists have a message for American policymakers who are rushing to create laws to allow the use of medical and recreational marijuana: You’re doing it wrong, but we know how you can do it right.

Smithore

“We can have spirited debates on these policies, recreational, medical decriminalization, etc. But we can’t argue how we’ve done a poor job implementing these policies in the United States,” psychiatrist Kevin P. Hill, MD, of Harvard Medical School, Boston, said in a symposium about cannabis policy at the annual meeting of the American Academy of Addiction Psychiatry.

The AAAP is proposing a “model state law” regarding cannabis. Among other things, the proposal urges states to:

• Ban recreational use of cannabis until the age of 21, and perhaps even until 25.
• Not denote psychiatric indications such as posttraumatic stress disorder, anxiety, and depression as qualifying conditions for the use of medical marijuana.
• Educate the public about potential harms of cannabis.
• Provide state-level regulation that includes funding of high-grade analytic equipment to test cannabis.
• Maintain a public registry that reports annually on adverse outcomes.

Research suggests that marijuana use has spiked in recent years, Dr. Hill said. Meanwhile, states have dramatically broadened the legality of marijuana. According to the National Conference of State Legislatures, 33 states and the District of Columbia allow the medical use of marijuana. Of those, 11 states and the District of Columbia also allow the adult use of recreational marijuana. Several other states allow access to cannabidiol (CBD)/low-THC products in some cases (www.ncsl.org/research/health/state-medical-marijuana-laws.aspx).

The problem, Dr. Hill said, is that there’s “a big gap between what the science says and what the laws are saying, unfortunately. So we’re in this precarious spot.”

He pointed to his own 2015 review of cannabinoid studies that found high-quality evidence for an effect for just three conditions – chronic pain, neuropathic pain, and spasticity associated with multiple sclerosis. The study notes that Food and Drug Administration–approved cannabinoids are also available to treat nausea and vomiting linked to chemotherapy and to boost appetite in patients with wasting disease. (JAMA. 2015 Jun 23-30;313(24):2474-83).

However, states have listed dozens of conditions – 53 overall – as qualifying conditions for the use of medical marijuana, Dr. Hill said. And, he said, “the reality is that a lot of people who are using medical cannabis don’t have any of these conditions,” he said.

Researchers at the symposium focused on the use of cannabis as a treatment for addiction and other psychiatric illnesses.

Four states have legalized the use of cannabis in patients with opioid use disorder, said cannabis researcher Ziva D. Cooper, PhD, of the University of California, Los Angeles, who spoke at the symposium. But can cannabis actually reduce opioid use? Preliminary clinical data suggest THC could reduce opioid use, Dr. Cooper said, while population and state-level research is mixed.

What about other mental health disorders? Posttraumatic stress disorder is commonly listed as a qualifying condition for medical marijuana use in state laws. And some states, like California, give physicians wide leeway in recommending marijuana use for patients with conditions that aren’t listed in the law.

However, symposium speaker and psychiatrist Frances R. Levin, MD, of New York State Psychiatric Institute, pointed to a 2019 review that suggests “there is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, posttraumatic stress disorder, or psychosis” (Lancet Psychiatry. 2019 Dec;6[12]:995-1010). 

What now? The AAAP hopes lawmakers will pay attention to its proposed model state law, which will be published soon in the association’s journal, the American Journal on Addictions.

SAN DIEGO – Addiction specialists have a message for American policymakers who are rushing to create laws to allow the use of medical and recreational marijuana: You’re doing it wrong, but we know how you can do it right.

Smithore

“We can have spirited debates on these policies, recreational, medical decriminalization, etc. But we can’t argue how we’ve done a poor job implementing these policies in the United States,” psychiatrist Kevin P. Hill, MD, of Harvard Medical School, Boston, said in a symposium about cannabis policy at the annual meeting of the American Academy of Addiction Psychiatry.

The AAAP is proposing a “model state law” regarding cannabis. Among other things, the proposal urges states to:

• Ban recreational use of cannabis until the age of 21, and perhaps even until 25.
• Not denote psychiatric indications such as posttraumatic stress disorder, anxiety, and depression as qualifying conditions for the use of medical marijuana.
• Educate the public about potential harms of cannabis.
• Provide state-level regulation that includes funding of high-grade analytic equipment to test cannabis.
• Maintain a public registry that reports annually on adverse outcomes.

Research suggests that marijuana use has spiked in recent years, Dr. Hill said. Meanwhile, states have dramatically broadened the legality of marijuana. According to the National Conference of State Legislatures, 33 states and the District of Columbia allow the medical use of marijuana. Of those, 11 states and the District of Columbia also allow the adult use of recreational marijuana. Several other states allow access to cannabidiol (CBD)/low-THC products in some cases (www.ncsl.org/research/health/state-medical-marijuana-laws.aspx).

The problem, Dr. Hill said, is that there’s “a big gap between what the science says and what the laws are saying, unfortunately. So we’re in this precarious spot.”

He pointed to his own 2015 review of cannabinoid studies that found high-quality evidence for an effect for just three conditions – chronic pain, neuropathic pain, and spasticity associated with multiple sclerosis. The study notes that Food and Drug Administration–approved cannabinoids are also available to treat nausea and vomiting linked to chemotherapy and to boost appetite in patients with wasting disease. (JAMA. 2015 Jun 23-30;313(24):2474-83).

However, states have listed dozens of conditions – 53 overall – as qualifying conditions for the use of medical marijuana, Dr. Hill said. And, he said, “the reality is that a lot of people who are using medical cannabis don’t have any of these conditions,” he said.

Researchers at the symposium focused on the use of cannabis as a treatment for addiction and other psychiatric illnesses.

Four states have legalized the use of cannabis in patients with opioid use disorder, said cannabis researcher Ziva D. Cooper, PhD, of the University of California, Los Angeles, who spoke at the symposium. But can cannabis actually reduce opioid use? Preliminary clinical data suggest THC could reduce opioid use, Dr. Cooper said, while population and state-level research is mixed.

What about other mental health disorders? Posttraumatic stress disorder is commonly listed as a qualifying condition for medical marijuana use in state laws. And some states, like California, give physicians wide leeway in recommending marijuana use for patients with conditions that aren’t listed in the law.

However, symposium speaker and psychiatrist Frances R. Levin, MD, of New York State Psychiatric Institute, pointed to a 2019 review that suggests “there is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, posttraumatic stress disorder, or psychosis” (Lancet Psychiatry. 2019 Dec;6[12]:995-1010). 

What now? The AAAP hopes lawmakers will pay attention to its proposed model state law, which will be published soon in the association’s journal, the American Journal on Addictions.

SAN DIEGO – Addiction specialists have a message for American policymakers who are rushing to create laws to allow the use of medical and recreational marijuana: You’re doing it wrong, but we know how you can do it right.

Smithore

“We can have spirited debates on these policies, recreational, medical decriminalization, etc. But we can’t argue how we’ve done a poor job implementing these policies in the United States,” psychiatrist Kevin P. Hill, MD, of Harvard Medical School, Boston, said in a symposium about cannabis policy at the annual meeting of the American Academy of Addiction Psychiatry.

The AAAP is proposing a “model state law” regarding cannabis. Among other things, the proposal urges states to:

• Ban recreational use of cannabis until the age of 21, and perhaps even until 25.
• Not denote psychiatric indications such as posttraumatic stress disorder, anxiety, and depression as qualifying conditions for the use of medical marijuana.
• Educate the public about potential harms of cannabis.
• Provide state-level regulation that includes funding of high-grade analytic equipment to test cannabis.
• Maintain a public registry that reports annually on adverse outcomes.

Research suggests that marijuana use has spiked in recent years, Dr. Hill said. Meanwhile, states have dramatically broadened the legality of marijuana. According to the National Conference of State Legislatures, 33 states and the District of Columbia allow the medical use of marijuana. Of those, 11 states and the District of Columbia also allow the adult use of recreational marijuana. Several other states allow access to cannabidiol (CBD)/low-THC products in some cases (www.ncsl.org/research/health/state-medical-marijuana-laws.aspx).

The problem, Dr. Hill said, is that there’s “a big gap between what the science says and what the laws are saying, unfortunately. So we’re in this precarious spot.”

He pointed to his own 2015 review of cannabinoid studies that found high-quality evidence for an effect for just three conditions – chronic pain, neuropathic pain, and spasticity associated with multiple sclerosis. The study notes that Food and Drug Administration–approved cannabinoids are also available to treat nausea and vomiting linked to chemotherapy and to boost appetite in patients with wasting disease. (JAMA. 2015 Jun 23-30;313(24):2474-83).

However, states have listed dozens of conditions – 53 overall – as qualifying conditions for the use of medical marijuana, Dr. Hill said. And, he said, “the reality is that a lot of people who are using medical cannabis don’t have any of these conditions,” he said.

Researchers at the symposium focused on the use of cannabis as a treatment for addiction and other psychiatric illnesses.

Four states have legalized the use of cannabis in patients with opioid use disorder, said cannabis researcher Ziva D. Cooper, PhD, of the University of California, Los Angeles, who spoke at the symposium. But can cannabis actually reduce opioid use? Preliminary clinical data suggest THC could reduce opioid use, Dr. Cooper said, while population and state-level research is mixed.

What about other mental health disorders? Posttraumatic stress disorder is commonly listed as a qualifying condition for medical marijuana use in state laws. And some states, like California, give physicians wide leeway in recommending marijuana use for patients with conditions that aren’t listed in the law.

However, symposium speaker and psychiatrist Frances R. Levin, MD, of New York State Psychiatric Institute, pointed to a 2019 review that suggests “there is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, posttraumatic stress disorder, or psychosis” (Lancet Psychiatry. 2019 Dec;6[12]:995-1010). 

What now? The AAAP hopes lawmakers will pay attention to its proposed model state law, which will be published soon in the association’s journal, the American Journal on Addictions.

Despite several reports of dramatic efficacy and reasonable safety using catheter ablation of atrial fibrillation (AFib) in patients with heart failure, many clinicians, including many heart failure specialists, remain skeptical about whether existing evidence supports using ablation routinely in selected heart failure patients.

Mitchel L. Zoler/MDedge News

Though concerns vary, one core stumbling block is inadequate confidence that the ablation outcomes reported from studies represent the benefit that the average American heart failure patient might expect to receive from ablation done outside of a study. A related issue is whether atrial fibrillation ablation in patients with heart failure is cost effective, especially at sites that did not participate in the published studies.

The first part of this article discussed the building evidence that radiofrequency catheter ablation of atrial fibrillation (AFib) can produce striking reductions in all-cause mortality of nearly 50%, and a greater than one-third cut in cardiovascular hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF), according to one recent meta-analysis (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]:e007414). A key question about the implications of these findings is their generalizability.

“Experience is an issue, and I agree that not every operator should do it. A common perception is that ablation doesn’t work, but that mindset is changing,” said Luigi Di Biase, MD, director of arrhythmia services at Montefiore Medical Center and professor of medicine at Albert Einstein College of Medicine in New York. He noted that some apparent ablations failures happen because the treatment is used too late. “Ablation will fail if it is done too late. Think about using ablation earlier,” he advised. “The earlier you ablate, the earlier you reduce the AFib burden and the sooner the patient benefits. Ablation is a cost-effective, first-line strategy for younger patients with paroxysmal AFib. The unanswered question is whether it is cost effective for patients who have both AFib and heart failure. It may be, because in addition to the mortality benefit, there are likely savings from a lower rate of hospitalizations. A clearer picture should emerge from the cost-effectiveness analysis of CASTLE-AF.”

CASTLE-AF (Catheter Ablation Versus Standard Conventional Therapy in Patients With Left Ventricular Dysfunction and Atrial Fibrillation), which randomized patients with heart failure and AFib to ablation or medical management (N Engl J Med. 2018 Feb 1;378[5]:417-27), is one of the highest-profile studies reported so far showing AFib ablation’s efficacy in patients with heart failure. However, it has drawn skepticism over its generalizability because of its long enrollment period of 8 years despite running at 33 worldwide sites, and by its winnowing of 3,013 patients assessed down to the 398 actually enrolled and 363 randomized and included in the efficacy analysis.

“CASTLE-HF showed a remarkable benefit. The problem was that it took years and years to enroll the patients,” commented Mariell Jessup, MD, a heart failure specialist and chief science and medical officer of the American Heart Association in Dallas.

At the annual congress of the European Society of Cardiology in September 2019, French researchers reported data that supported the generalizability of the CASTLE-AF findings. The study used data collected from 252,395 patients in the French national hospital-discharge database during 2010-2018 who had diagnoses of both heart failure and AFib. Among these patients, 1,384 underwent catheter ablation and the remaining 251,011 were managed without ablation.

During a median follow-up of 537 days (about 1.5 years), the incidence of both all-cause death and heart failure hospitalization were both significantly lower in the ablated patients. The ablated patients were also much younger and were more often men, but both groups had several prevalent comorbidities at roughly similar rates. To better match the groups, the French researchers ran both a multivariate analysis, and then an even more intensively adjusting propensity-score analysis that compared the ablated patients with 1,384 closely matched patients from the nonablated group. Both analyses showed substantial incremental benefit from ablation. In the propensity score–matched analysis, ablation was linked with a relative 66% cut in all-cause death, and a relative 71% reduction in heart failure hospitalizations, compared with the patients who did not undergo ablation, reported Arnaud Bisson, MD, a cardiologist at the University of Tours (France).

Another recent assessment of the generalizability of the AFib ablation trial findings used data from nearly 184,000 U.S. patients treated for AFib during 2009-2016 in an administrative database, including more than 12,000 treated with ablation. This analysis did not take into account the coexistence of heart failure. After propensity-score matching of the ablated patients with a similar subgroup of those managed medically, the results showed a 25% relative cut in the combined primary endpoint used in the CABANA (Catheter Ablation vs. Anti-Arrhythmic Drug Therapy for Atrial Fibrillation Trial) study (JAMA. 2019 Mar 15;321[134]:1261-74). Among the 74% of ablated patients who met the enrollment criteria for CABANA, the primary endpoint reduction was even greater, a 30% drop relative to matched patients who did not undergo ablation (Eur Heart J. 2019 Apr 21;40[16]:1257-64).

Mitchel L. Zoler/MDedge News

“Professional societies are working to clarify best practices for procedural volume, outcomes, etc.,” said Jonathan P. Piccini, MD, a cardiac electrophysiologist at Duke University, Durham, N.C., and a CABANA coinvestigator. “There are some data on ablation cost effectiveness, and they generally favor” positive cost efficacy, with more analyses now in progress,” he noted in an interview.

Many unanswered questions remain about AFib in heart failure patients and how aggressively to use ablation to treat it. Most of the data so far have come from patients with HFrEF, and so most experts consider AFib ablation in patients with heart failure with preserved ejection fraction (HFpEF) a big unknown, although nearly 80% of the heart failure patients enrolled in CABANA (the largest randomized trial of AFib ablation with more than 2,200 patients) had left ventricular ejection fraction of 50% or greater, which translates into HFpEF. Another gray area is how to think about asymptomatic (also called subclinical) AFib and whether that warrants ablation in heart failure patients. The presence or absence of symptoms is a major consideration because the traditional indication for ablation has been to reduce or eliminate symptoms like palpitations, a step that can substantially improve patients’ quality of life as well as their left ventricular function. The indication to ablate asymptomatic AFib for the purpose of improving survival and reducing hospitalizations is the new and controversial concept. Yet it has been embraced by some heart failure physicians.

“Whether or not AFib is symptomatic doesn’t matter” in a heart failure patient, said Maria Rosa Costanzo, MD, a heart failure physician at Edward Heart Hospital in Naperville, Ill. “A patient with AFib doesn’t get the atrial contribution to cardiac output. When we look deeper, a patient with ‘asymptomatic’ AFib often has symptoms, such as new fatigue or obstructive sleep apnea, so when you see a patient with asymptomatic AFib look for sleep apnea, a trigger for AFib,” Dr. Costanzo advised. “Sleep apnea, AFib, and heart failure form a triad” that often clusters in patients, and the three conditions interact in a vicious circle of reinforcing comorbidities, she said in an interview.

The cardiac electrophysiology and arrhythmia community clearly realizes that catheter ablation of AFib, in patients with or without heart failure, has many unaddressed questions about who should administer it and who should undergo it. In March 2019, the National Heart, Lung, and Blood Institute held a workshop on AFib ablation. “Numerous knowledge gaps remain” about the best way to use ablation, said a summary of the workshop (Circulation. 2019 Nov 20;doi: 10.1161/CIRCULATIONAHA.119.042706). Among the research needs highlighted by the workshop was “more definitive studies ... to delineate the impact of AFib ablation on outcomes in patients with heart failure with preserved ejection fraction.” The workshop recommended establishing a national U.S. registry for AFib ablations with a reliable source of funding, as well as “establishing the cause-effect relationship between ventricular dysfunction and AFib, and the potential moderating role of atrial structure and function.” The workshop also raised the possibility of sham-controlled assessments of AFib ablation, while conceding that enrollment into such trials would probably be very challenging.

The upshot is that, even while ablation advocates agree on the need for more study, clinicians are using AFib ablation on a growing number of heart failure patients (as well as on growing numbers of patients with AFib but without heart failure), with a focus on treating those who “have refractory symptoms or evidence of tachycardia-induced cardiomyopathy,” said Dr. Piccini. Extending that to a first-line, class I indication for heart failure patients seems to need more data, and also needs clinicians to collectively raise their comfort level with the ablation concept. If results from additional studies now underway support the dramatic efficacy and reasonable safety that’s already been seen with ablation, then increased comfort should follow.

CABANA received funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. CASTLE-AF was funded by Biotronik. Dr. Di Biase, Dr. Jessup, and Dr. Bisson had no disclosures. Dr. Piccini has been a consultant to Allergan, Biotronik, Medtronic, Phillips, and Sanofi Aventis; he has received research funding from Abbott, ARCA, Boston Scientific, Gilead, and Johnson & Johnson; and he had a financial relationship with GlaxoSmithKline. Dr. Costanzo has been a consultant to Abbott.

This is part 2 of a 2-part story. See part 1 here.

mzoler@mdedge.com

Despite several reports of dramatic efficacy and reasonable safety using catheter ablation of atrial fibrillation (AFib) in patients with heart failure, many clinicians, including many heart failure specialists, remain skeptical about whether existing evidence supports using ablation routinely in selected heart failure patients.

Mitchel L. Zoler/MDedge News

Though concerns vary, one core stumbling block is inadequate confidence that the ablation outcomes reported from studies represent the benefit that the average American heart failure patient might expect to receive from ablation done outside of a study. A related issue is whether atrial fibrillation ablation in patients with heart failure is cost effective, especially at sites that did not participate in the published studies.

The first part of this article discussed the building evidence that radiofrequency catheter ablation of atrial fibrillation (AFib) can produce striking reductions in all-cause mortality of nearly 50%, and a greater than one-third cut in cardiovascular hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF), according to one recent meta-analysis (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]:e007414). A key question about the implications of these findings is their generalizability.

“Experience is an issue, and I agree that not every operator should do it. A common perception is that ablation doesn’t work, but that mindset is changing,” said Luigi Di Biase, MD, director of arrhythmia services at Montefiore Medical Center and professor of medicine at Albert Einstein College of Medicine in New York. He noted that some apparent ablations failures happen because the treatment is used too late. “Ablation will fail if it is done too late. Think about using ablation earlier,” he advised. “The earlier you ablate, the earlier you reduce the AFib burden and the sooner the patient benefits. Ablation is a cost-effective, first-line strategy for younger patients with paroxysmal AFib. The unanswered question is whether it is cost effective for patients who have both AFib and heart failure. It may be, because in addition to the mortality benefit, there are likely savings from a lower rate of hospitalizations. A clearer picture should emerge from the cost-effectiveness analysis of CASTLE-AF.”

CASTLE-AF (Catheter Ablation Versus Standard Conventional Therapy in Patients With Left Ventricular Dysfunction and Atrial Fibrillation), which randomized patients with heart failure and AFib to ablation or medical management (N Engl J Med. 2018 Feb 1;378[5]:417-27), is one of the highest-profile studies reported so far showing AFib ablation’s efficacy in patients with heart failure. However, it has drawn skepticism over its generalizability because of its long enrollment period of 8 years despite running at 33 worldwide sites, and by its winnowing of 3,013 patients assessed down to the 398 actually enrolled and 363 randomized and included in the efficacy analysis.

“CASTLE-HF showed a remarkable benefit. The problem was that it took years and years to enroll the patients,” commented Mariell Jessup, MD, a heart failure specialist and chief science and medical officer of the American Heart Association in Dallas.

At the annual congress of the European Society of Cardiology in September 2019, French researchers reported data that supported the generalizability of the CASTLE-AF findings. The study used data collected from 252,395 patients in the French national hospital-discharge database during 2010-2018 who had diagnoses of both heart failure and AFib. Among these patients, 1,384 underwent catheter ablation and the remaining 251,011 were managed without ablation.

During a median follow-up of 537 days (about 1.5 years), the incidence of both all-cause death and heart failure hospitalization were both significantly lower in the ablated patients. The ablated patients were also much younger and were more often men, but both groups had several prevalent comorbidities at roughly similar rates. To better match the groups, the French researchers ran both a multivariate analysis, and then an even more intensively adjusting propensity-score analysis that compared the ablated patients with 1,384 closely matched patients from the nonablated group. Both analyses showed substantial incremental benefit from ablation. In the propensity score–matched analysis, ablation was linked with a relative 66% cut in all-cause death, and a relative 71% reduction in heart failure hospitalizations, compared with the patients who did not undergo ablation, reported Arnaud Bisson, MD, a cardiologist at the University of Tours (France).

Another recent assessment of the generalizability of the AFib ablation trial findings used data from nearly 184,000 U.S. patients treated for AFib during 2009-2016 in an administrative database, including more than 12,000 treated with ablation. This analysis did not take into account the coexistence of heart failure. After propensity-score matching of the ablated patients with a similar subgroup of those managed medically, the results showed a 25% relative cut in the combined primary endpoint used in the CABANA (Catheter Ablation vs. Anti-Arrhythmic Drug Therapy for Atrial Fibrillation Trial) study (JAMA. 2019 Mar 15;321[134]:1261-74). Among the 74% of ablated patients who met the enrollment criteria for CABANA, the primary endpoint reduction was even greater, a 30% drop relative to matched patients who did not undergo ablation (Eur Heart J. 2019 Apr 21;40[16]:1257-64).

Mitchel L. Zoler/MDedge News

“Professional societies are working to clarify best practices for procedural volume, outcomes, etc.,” said Jonathan P. Piccini, MD, a cardiac electrophysiologist at Duke University, Durham, N.C., and a CABANA coinvestigator. “There are some data on ablation cost effectiveness, and they generally favor” positive cost efficacy, with more analyses now in progress,” he noted in an interview.

Many unanswered questions remain about AFib in heart failure patients and how aggressively to use ablation to treat it. Most of the data so far have come from patients with HFrEF, and so most experts consider AFib ablation in patients with heart failure with preserved ejection fraction (HFpEF) a big unknown, although nearly 80% of the heart failure patients enrolled in CABANA (the largest randomized trial of AFib ablation with more than 2,200 patients) had left ventricular ejection fraction of 50% or greater, which translates into HFpEF. Another gray area is how to think about asymptomatic (also called subclinical) AFib and whether that warrants ablation in heart failure patients. The presence or absence of symptoms is a major consideration because the traditional indication for ablation has been to reduce or eliminate symptoms like palpitations, a step that can substantially improve patients’ quality of life as well as their left ventricular function. The indication to ablate asymptomatic AFib for the purpose of improving survival and reducing hospitalizations is the new and controversial concept. Yet it has been embraced by some heart failure physicians.

“Whether or not AFib is symptomatic doesn’t matter” in a heart failure patient, said Maria Rosa Costanzo, MD, a heart failure physician at Edward Heart Hospital in Naperville, Ill. “A patient with AFib doesn’t get the atrial contribution to cardiac output. When we look deeper, a patient with ‘asymptomatic’ AFib often has symptoms, such as new fatigue or obstructive sleep apnea, so when you see a patient with asymptomatic AFib look for sleep apnea, a trigger for AFib,” Dr. Costanzo advised. “Sleep apnea, AFib, and heart failure form a triad” that often clusters in patients, and the three conditions interact in a vicious circle of reinforcing comorbidities, she said in an interview.

The cardiac electrophysiology and arrhythmia community clearly realizes that catheter ablation of AFib, in patients with or without heart failure, has many unaddressed questions about who should administer it and who should undergo it. In March 2019, the National Heart, Lung, and Blood Institute held a workshop on AFib ablation. “Numerous knowledge gaps remain” about the best way to use ablation, said a summary of the workshop (Circulation. 2019 Nov 20;doi: 10.1161/CIRCULATIONAHA.119.042706). Among the research needs highlighted by the workshop was “more definitive studies ... to delineate the impact of AFib ablation on outcomes in patients with heart failure with preserved ejection fraction.” The workshop recommended establishing a national U.S. registry for AFib ablations with a reliable source of funding, as well as “establishing the cause-effect relationship between ventricular dysfunction and AFib, and the potential moderating role of atrial structure and function.” The workshop also raised the possibility of sham-controlled assessments of AFib ablation, while conceding that enrollment into such trials would probably be very challenging.

The upshot is that, even while ablation advocates agree on the need for more study, clinicians are using AFib ablation on a growing number of heart failure patients (as well as on growing numbers of patients with AFib but without heart failure), with a focus on treating those who “have refractory symptoms or evidence of tachycardia-induced cardiomyopathy,” said Dr. Piccini. Extending that to a first-line, class I indication for heart failure patients seems to need more data, and also needs clinicians to collectively raise their comfort level with the ablation concept. If results from additional studies now underway support the dramatic efficacy and reasonable safety that’s already been seen with ablation, then increased comfort should follow.

CABANA received funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. CASTLE-AF was funded by Biotronik. Dr. Di Biase, Dr. Jessup, and Dr. Bisson had no disclosures. Dr. Piccini has been a consultant to Allergan, Biotronik, Medtronic, Phillips, and Sanofi Aventis; he has received research funding from Abbott, ARCA, Boston Scientific, Gilead, and Johnson & Johnson; and he had a financial relationship with GlaxoSmithKline. Dr. Costanzo has been a consultant to Abbott.

This is part 2 of a 2-part story. See part 1 here.

mzoler@mdedge.com

Despite several reports of dramatic efficacy and reasonable safety using catheter ablation of atrial fibrillation (AFib) in patients with heart failure, many clinicians, including many heart failure specialists, remain skeptical about whether existing evidence supports using ablation routinely in selected heart failure patients.

Mitchel L. Zoler/MDedge News

Though concerns vary, one core stumbling block is inadequate confidence that the ablation outcomes reported from studies represent the benefit that the average American heart failure patient might expect to receive from ablation done outside of a study. A related issue is whether atrial fibrillation ablation in patients with heart failure is cost effective, especially at sites that did not participate in the published studies.

The first part of this article discussed the building evidence that radiofrequency catheter ablation of atrial fibrillation (AFib) can produce striking reductions in all-cause mortality of nearly 50%, and a greater than one-third cut in cardiovascular hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF), according to one recent meta-analysis (Circ Arrhythm Electrophysiol. 2019 Sep;12[9]:e007414). A key question about the implications of these findings is their generalizability.

“Experience is an issue, and I agree that not every operator should do it. A common perception is that ablation doesn’t work, but that mindset is changing,” said Luigi Di Biase, MD, director of arrhythmia services at Montefiore Medical Center and professor of medicine at Albert Einstein College of Medicine in New York. He noted that some apparent ablations failures happen because the treatment is used too late. “Ablation will fail if it is done too late. Think about using ablation earlier,” he advised. “The earlier you ablate, the earlier you reduce the AFib burden and the sooner the patient benefits. Ablation is a cost-effective, first-line strategy for younger patients with paroxysmal AFib. The unanswered question is whether it is cost effective for patients who have both AFib and heart failure. It may be, because in addition to the mortality benefit, there are likely savings from a lower rate of hospitalizations. A clearer picture should emerge from the cost-effectiveness analysis of CASTLE-AF.”

CASTLE-AF (Catheter Ablation Versus Standard Conventional Therapy in Patients With Left Ventricular Dysfunction and Atrial Fibrillation), which randomized patients with heart failure and AFib to ablation or medical management (N Engl J Med. 2018 Feb 1;378[5]:417-27), is one of the highest-profile studies reported so far showing AFib ablation’s efficacy in patients with heart failure. However, it has drawn skepticism over its generalizability because of its long enrollment period of 8 years despite running at 33 worldwide sites, and by its winnowing of 3,013 patients assessed down to the 398 actually enrolled and 363 randomized and included in the efficacy analysis.

“CASTLE-HF showed a remarkable benefit. The problem was that it took years and years to enroll the patients,” commented Mariell Jessup, MD, a heart failure specialist and chief science and medical officer of the American Heart Association in Dallas.

At the annual congress of the European Society of Cardiology in September 2019, French researchers reported data that supported the generalizability of the CASTLE-AF findings. The study used data collected from 252,395 patients in the French national hospital-discharge database during 2010-2018 who had diagnoses of both heart failure and AFib. Among these patients, 1,384 underwent catheter ablation and the remaining 251,011 were managed without ablation.

During a median follow-up of 537 days (about 1.5 years), the incidence of both all-cause death and heart failure hospitalization were both significantly lower in the ablated patients. The ablated patients were also much younger and were more often men, but both groups had several prevalent comorbidities at roughly similar rates. To better match the groups, the French researchers ran both a multivariate analysis, and then an even more intensively adjusting propensity-score analysis that compared the ablated patients with 1,384 closely matched patients from the nonablated group. Both analyses showed substantial incremental benefit from ablation. In the propensity score–matched analysis, ablation was linked with a relative 66% cut in all-cause death, and a relative 71% reduction in heart failure hospitalizations, compared with the patients who did not undergo ablation, reported Arnaud Bisson, MD, a cardiologist at the University of Tours (France).

Another recent assessment of the generalizability of the AFib ablation trial findings used data from nearly 184,000 U.S. patients treated for AFib during 2009-2016 in an administrative database, including more than 12,000 treated with ablation. This analysis did not take into account the coexistence of heart failure. After propensity-score matching of the ablated patients with a similar subgroup of those managed medically, the results showed a 25% relative cut in the combined primary endpoint used in the CABANA (Catheter Ablation vs. Anti-Arrhythmic Drug Therapy for Atrial Fibrillation Trial) study (JAMA. 2019 Mar 15;321[134]:1261-74). Among the 74% of ablated patients who met the enrollment criteria for CABANA, the primary endpoint reduction was even greater, a 30% drop relative to matched patients who did not undergo ablation (Eur Heart J. 2019 Apr 21;40[16]:1257-64).

Mitchel L. Zoler/MDedge News

“Professional societies are working to clarify best practices for procedural volume, outcomes, etc.,” said Jonathan P. Piccini, MD, a cardiac electrophysiologist at Duke University, Durham, N.C., and a CABANA coinvestigator. “There are some data on ablation cost effectiveness, and they generally favor” positive cost efficacy, with more analyses now in progress,” he noted in an interview.

Many unanswered questions remain about AFib in heart failure patients and how aggressively to use ablation to treat it. Most of the data so far have come from patients with HFrEF, and so most experts consider AFib ablation in patients with heart failure with preserved ejection fraction (HFpEF) a big unknown, although nearly 80% of the heart failure patients enrolled in CABANA (the largest randomized trial of AFib ablation with more than 2,200 patients) had left ventricular ejection fraction of 50% or greater, which translates into HFpEF. Another gray area is how to think about asymptomatic (also called subclinical) AFib and whether that warrants ablation in heart failure patients. The presence or absence of symptoms is a major consideration because the traditional indication for ablation has been to reduce or eliminate symptoms like palpitations, a step that can substantially improve patients’ quality of life as well as their left ventricular function. The indication to ablate asymptomatic AFib for the purpose of improving survival and reducing hospitalizations is the new and controversial concept. Yet it has been embraced by some heart failure physicians.

“Whether or not AFib is symptomatic doesn’t matter” in a heart failure patient, said Maria Rosa Costanzo, MD, a heart failure physician at Edward Heart Hospital in Naperville, Ill. “A patient with AFib doesn’t get the atrial contribution to cardiac output. When we look deeper, a patient with ‘asymptomatic’ AFib often has symptoms, such as new fatigue or obstructive sleep apnea, so when you see a patient with asymptomatic AFib look for sleep apnea, a trigger for AFib,” Dr. Costanzo advised. “Sleep apnea, AFib, and heart failure form a triad” that often clusters in patients, and the three conditions interact in a vicious circle of reinforcing comorbidities, she said in an interview.

The cardiac electrophysiology and arrhythmia community clearly realizes that catheter ablation of AFib, in patients with or without heart failure, has many unaddressed questions about who should administer it and who should undergo it. In March 2019, the National Heart, Lung, and Blood Institute held a workshop on AFib ablation. “Numerous knowledge gaps remain” about the best way to use ablation, said a summary of the workshop (Circulation. 2019 Nov 20;doi: 10.1161/CIRCULATIONAHA.119.042706). Among the research needs highlighted by the workshop was “more definitive studies ... to delineate the impact of AFib ablation on outcomes in patients with heart failure with preserved ejection fraction.” The workshop recommended establishing a national U.S. registry for AFib ablations with a reliable source of funding, as well as “establishing the cause-effect relationship between ventricular dysfunction and AFib, and the potential moderating role of atrial structure and function.” The workshop also raised the possibility of sham-controlled assessments of AFib ablation, while conceding that enrollment into such trials would probably be very challenging.

The upshot is that, even while ablation advocates agree on the need for more study, clinicians are using AFib ablation on a growing number of heart failure patients (as well as on growing numbers of patients with AFib but without heart failure), with a focus on treating those who “have refractory symptoms or evidence of tachycardia-induced cardiomyopathy,” said Dr. Piccini. Extending that to a first-line, class I indication for heart failure patients seems to need more data, and also needs clinicians to collectively raise their comfort level with the ablation concept. If results from additional studies now underway support the dramatic efficacy and reasonable safety that’s already been seen with ablation, then increased comfort should follow.

CABANA received funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. CASTLE-AF was funded by Biotronik. Dr. Di Biase, Dr. Jessup, and Dr. Bisson had no disclosures. Dr. Piccini has been a consultant to Allergan, Biotronik, Medtronic, Phillips, and Sanofi Aventis; he has received research funding from Abbott, ARCA, Boston Scientific, Gilead, and Johnson & Johnson; and he had a financial relationship with GlaxoSmithKline. Dr. Costanzo has been a consultant to Abbott.

This is part 2 of a 2-part story. See part 1 here.

mzoler@mdedge.com

PHILADELPHIA – The definition and treatment of heart failure with reduced ejection fraction should change based on recent findings and analyses from major trials, said a key heart failure leader at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The people charged with writing U.S. guidelines for heart failure management already have enough evidence to change the recommended way of using sacubitril/valsartan (Entresto) in patients with heart failure with reduced ejection fraction (HFrEF), said Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern University, Chicago. Accumulated evidence from studies and more than 5 years of experience in routine practice with the angiotensin receptor neprilysin inhibitor (ARNI) combination sacubitril/valsartan for treating HFrEF patients justifies striking the existing recommendation to first start patients on an ACE inhibitor or angiotensin receptor blocker and only after that switching to sacubitril/valsartan, a sequence that has rankled some clinicians as an unnecessary delay and barrier to starting patients on the ARNI regimen.

U.S. guidelines should now suggest that ARNI treatment start immediately, suggested Dr. Yancy, who chaired the AHA/American College of Cardiology panel that updated U.S. guidelines for heart failure management in 2013 (Circulation. 2013 Oct 15;128[16]:e240-327), 2016 (J Am Coll Cardiol. 2016 Sep;68[13]:1476-88), and 2017 (Circulation. 2017 Aug 8; 136[6]:e137-61).

Expanding the heart failure group for sacubitril/valsartan

Dr. Yancy also proposed a second major and immediate change to the existing heart failure guideline based on a new appreciation of a heart failure population that could benefit from ARNI treatment: patients with “mid-range” heart failure, defined by a left ventricular ejection fraction (LVEF) of 41%-49% that places them between patients with HFrEF with an ejection fraction of 40% or less, and those with heart failure with preserved ejection fraction (HFpEF) of 50% or more. As yet unchanged in the 2013 AHA/ACC heart failure guideline is the proposition that patients with heart failure and an ejection fraction of 41%-49% have “borderline” heart failure with characteristics, treatment patterns, and outcomes “similar to patients with HFpEF.”

That premise should now go out the window, urged Dr. Yancy, based on a new analysis of data collected from both the recent PARAGON-HF trial of sacubitril/valsartan in patients with HFpEF and ejection fractions of 45% or higher (N Engl J Med. 2019 Oct 24;381[17]:1609-20) and the landmark PARADIGM-HF trial that established sacubitril/valsartan as a treatment for patients with HFrEF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). A combined analysis of the more than 13,000 total patients in both studies suggested that “patients with ejection fraction lower than normal, which includes those with so-called heart failure with mid-range ejection fraction or borderline ejection fraction, would likely benefit from sacubitril/valsartan, compared with RAS inhibition,” concluded the authors of the new analysis (Circulation. 2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044586).

Dr. Yancy argued that, based on this new analysis, a further revision to the 2013 guideline should say that patients with heart failure with a LVEF of 41%-49% have characteristics, treatment responses, and outcomes that “appear similar to those of patient with HFrEF,” a sharp departure from the existing text that lumps these patients with the HFpEF subgroup. “There appears to be a signal that extends the benefit of ARNI to patients with ejection fractions above the current threshold for HFrEF but below what is typically HFpEF,” he said.

Bringing SGLT2 inhibitors into heart failure management

Dr. Yancy also cited recently reported data from another landmark trial, DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), as an impetus for both another immediate change to the guideline and for a potential second change pending a report of confirmatory evidence that may arrive in 2020.

The DAPA-HF results showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) was just as effective for preventing all-cause death and heart failure hospitalizations and urgent visits in patients without type 2 diabetes as it is in patients with type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008), a remarkable finding for an agent that came onto the U.S. market as a diabetes drug specifically aimed at reducing levels of glycosylated hemoglobin.

Dr. Yancy proposed an immediate guideline change to acknowledge the proven protection against incident heart failure that treatment with a SGLT2 inhibitor gives patients with type 2 diabetes. There is now “a strong opportunity to use an SGLT2 inhibitor in patients with type 2 diabetes to reduce the incidence of heart failure,” he said.

And he added that, if results from EMPEROR REDUCED (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), studying the SGLT2 inhibitor empagliflozin (Jardiance) in HFrEF patients with and without type 2 diabetes, can confirm the efficacy of a second drug from this class in preventing heart failure events in patients with HFrEF but without diabetes, then the time will have arrived for another guideline change to establish the SGLT2 inhibitors as a new “foundational” drug for the management of all HFrEF patients, regardless of their level of glycemic control. The SGLT2 inhibitors are a particularly attractive additional drug because they are taken once daily orally with no need for dosage adjustment, so far they have shown excellent safety in patients without diabetes with no episodes of hypoglycemia or ketoacidosis, and they have even shown evidence for heart failure benefit in patients older than 75 years, Dr. Yancy noted.

Dr. Yancy had no relevant disclosures.

mzoler@mdedge.com

PHILADELPHIA – The definition and treatment of heart failure with reduced ejection fraction should change based on recent findings and analyses from major trials, said a key heart failure leader at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The people charged with writing U.S. guidelines for heart failure management already have enough evidence to change the recommended way of using sacubitril/valsartan (Entresto) in patients with heart failure with reduced ejection fraction (HFrEF), said Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern University, Chicago. Accumulated evidence from studies and more than 5 years of experience in routine practice with the angiotensin receptor neprilysin inhibitor (ARNI) combination sacubitril/valsartan for treating HFrEF patients justifies striking the existing recommendation to first start patients on an ACE inhibitor or angiotensin receptor blocker and only after that switching to sacubitril/valsartan, a sequence that has rankled some clinicians as an unnecessary delay and barrier to starting patients on the ARNI regimen.

U.S. guidelines should now suggest that ARNI treatment start immediately, suggested Dr. Yancy, who chaired the AHA/American College of Cardiology panel that updated U.S. guidelines for heart failure management in 2013 (Circulation. 2013 Oct 15;128[16]:e240-327), 2016 (J Am Coll Cardiol. 2016 Sep;68[13]:1476-88), and 2017 (Circulation. 2017 Aug 8; 136[6]:e137-61).

Expanding the heart failure group for sacubitril/valsartan

Dr. Yancy also proposed a second major and immediate change to the existing heart failure guideline based on a new appreciation of a heart failure population that could benefit from ARNI treatment: patients with “mid-range” heart failure, defined by a left ventricular ejection fraction (LVEF) of 41%-49% that places them between patients with HFrEF with an ejection fraction of 40% or less, and those with heart failure with preserved ejection fraction (HFpEF) of 50% or more. As yet unchanged in the 2013 AHA/ACC heart failure guideline is the proposition that patients with heart failure and an ejection fraction of 41%-49% have “borderline” heart failure with characteristics, treatment patterns, and outcomes “similar to patients with HFpEF.”

That premise should now go out the window, urged Dr. Yancy, based on a new analysis of data collected from both the recent PARAGON-HF trial of sacubitril/valsartan in patients with HFpEF and ejection fractions of 45% or higher (N Engl J Med. 2019 Oct 24;381[17]:1609-20) and the landmark PARADIGM-HF trial that established sacubitril/valsartan as a treatment for patients with HFrEF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). A combined analysis of the more than 13,000 total patients in both studies suggested that “patients with ejection fraction lower than normal, which includes those with so-called heart failure with mid-range ejection fraction or borderline ejection fraction, would likely benefit from sacubitril/valsartan, compared with RAS inhibition,” concluded the authors of the new analysis (Circulation. 2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044586).

Dr. Yancy argued that, based on this new analysis, a further revision to the 2013 guideline should say that patients with heart failure with a LVEF of 41%-49% have characteristics, treatment responses, and outcomes that “appear similar to those of patient with HFrEF,” a sharp departure from the existing text that lumps these patients with the HFpEF subgroup. “There appears to be a signal that extends the benefit of ARNI to patients with ejection fractions above the current threshold for HFrEF but below what is typically HFpEF,” he said.

Bringing SGLT2 inhibitors into heart failure management

Dr. Yancy also cited recently reported data from another landmark trial, DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), as an impetus for both another immediate change to the guideline and for a potential second change pending a report of confirmatory evidence that may arrive in 2020.

The DAPA-HF results showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) was just as effective for preventing all-cause death and heart failure hospitalizations and urgent visits in patients without type 2 diabetes as it is in patients with type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008), a remarkable finding for an agent that came onto the U.S. market as a diabetes drug specifically aimed at reducing levels of glycosylated hemoglobin.

Dr. Yancy proposed an immediate guideline change to acknowledge the proven protection against incident heart failure that treatment with a SGLT2 inhibitor gives patients with type 2 diabetes. There is now “a strong opportunity to use an SGLT2 inhibitor in patients with type 2 diabetes to reduce the incidence of heart failure,” he said.

And he added that, if results from EMPEROR REDUCED (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), studying the SGLT2 inhibitor empagliflozin (Jardiance) in HFrEF patients with and without type 2 diabetes, can confirm the efficacy of a second drug from this class in preventing heart failure events in patients with HFrEF but without diabetes, then the time will have arrived for another guideline change to establish the SGLT2 inhibitors as a new “foundational” drug for the management of all HFrEF patients, regardless of their level of glycemic control. The SGLT2 inhibitors are a particularly attractive additional drug because they are taken once daily orally with no need for dosage adjustment, so far they have shown excellent safety in patients without diabetes with no episodes of hypoglycemia or ketoacidosis, and they have even shown evidence for heart failure benefit in patients older than 75 years, Dr. Yancy noted.

Dr. Yancy had no relevant disclosures.

mzoler@mdedge.com

PHILADELPHIA – The definition and treatment of heart failure with reduced ejection fraction should change based on recent findings and analyses from major trials, said a key heart failure leader at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The people charged with writing U.S. guidelines for heart failure management already have enough evidence to change the recommended way of using sacubitril/valsartan (Entresto) in patients with heart failure with reduced ejection fraction (HFrEF), said Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern University, Chicago. Accumulated evidence from studies and more than 5 years of experience in routine practice with the angiotensin receptor neprilysin inhibitor (ARNI) combination sacubitril/valsartan for treating HFrEF patients justifies striking the existing recommendation to first start patients on an ACE inhibitor or angiotensin receptor blocker and only after that switching to sacubitril/valsartan, a sequence that has rankled some clinicians as an unnecessary delay and barrier to starting patients on the ARNI regimen.

U.S. guidelines should now suggest that ARNI treatment start immediately, suggested Dr. Yancy, who chaired the AHA/American College of Cardiology panel that updated U.S. guidelines for heart failure management in 2013 (Circulation. 2013 Oct 15;128[16]:e240-327), 2016 (J Am Coll Cardiol. 2016 Sep;68[13]:1476-88), and 2017 (Circulation. 2017 Aug 8; 136[6]:e137-61).

Expanding the heart failure group for sacubitril/valsartan

Dr. Yancy also proposed a second major and immediate change to the existing heart failure guideline based on a new appreciation of a heart failure population that could benefit from ARNI treatment: patients with “mid-range” heart failure, defined by a left ventricular ejection fraction (LVEF) of 41%-49% that places them between patients with HFrEF with an ejection fraction of 40% or less, and those with heart failure with preserved ejection fraction (HFpEF) of 50% or more. As yet unchanged in the 2013 AHA/ACC heart failure guideline is the proposition that patients with heart failure and an ejection fraction of 41%-49% have “borderline” heart failure with characteristics, treatment patterns, and outcomes “similar to patients with HFpEF.”

That premise should now go out the window, urged Dr. Yancy, based on a new analysis of data collected from both the recent PARAGON-HF trial of sacubitril/valsartan in patients with HFpEF and ejection fractions of 45% or higher (N Engl J Med. 2019 Oct 24;381[17]:1609-20) and the landmark PARADIGM-HF trial that established sacubitril/valsartan as a treatment for patients with HFrEF (N Engl J Med. 2014 Sep 11;371[11]:993-1004). A combined analysis of the more than 13,000 total patients in both studies suggested that “patients with ejection fraction lower than normal, which includes those with so-called heart failure with mid-range ejection fraction or borderline ejection fraction, would likely benefit from sacubitril/valsartan, compared with RAS inhibition,” concluded the authors of the new analysis (Circulation. 2019 Nov 17. doi: 10.1161/CIRCULATIONAHA.119.044586).

Dr. Yancy argued that, based on this new analysis, a further revision to the 2013 guideline should say that patients with heart failure with a LVEF of 41%-49% have characteristics, treatment responses, and outcomes that “appear similar to those of patient with HFrEF,” a sharp departure from the existing text that lumps these patients with the HFpEF subgroup. “There appears to be a signal that extends the benefit of ARNI to patients with ejection fractions above the current threshold for HFrEF but below what is typically HFpEF,” he said.

Bringing SGLT2 inhibitors into heart failure management

Dr. Yancy also cited recently reported data from another landmark trial, DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), as an impetus for both another immediate change to the guideline and for a potential second change pending a report of confirmatory evidence that may arrive in 2020.

The DAPA-HF results showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) was just as effective for preventing all-cause death and heart failure hospitalizations and urgent visits in patients without type 2 diabetes as it is in patients with type 2 diabetes (N Engl J Med. 2019 Nov 21;381[21]:1995-2008), a remarkable finding for an agent that came onto the U.S. market as a diabetes drug specifically aimed at reducing levels of glycosylated hemoglobin.

Dr. Yancy proposed an immediate guideline change to acknowledge the proven protection against incident heart failure that treatment with a SGLT2 inhibitor gives patients with type 2 diabetes. There is now “a strong opportunity to use an SGLT2 inhibitor in patients with type 2 diabetes to reduce the incidence of heart failure,” he said.

And he added that, if results from EMPEROR REDUCED (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), studying the SGLT2 inhibitor empagliflozin (Jardiance) in HFrEF patients with and without type 2 diabetes, can confirm the efficacy of a second drug from this class in preventing heart failure events in patients with HFrEF but without diabetes, then the time will have arrived for another guideline change to establish the SGLT2 inhibitors as a new “foundational” drug for the management of all HFrEF patients, regardless of their level of glycemic control. The SGLT2 inhibitors are a particularly attractive additional drug because they are taken once daily orally with no need for dosage adjustment, so far they have shown excellent safety in patients without diabetes with no episodes of hypoglycemia or ketoacidosis, and they have even shown evidence for heart failure benefit in patients older than 75 years, Dr. Yancy noted.

Dr. Yancy had no relevant disclosures.

mzoler@mdedge.com