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Atopic eczema linked to cardiovascular disease risk
according to a case-control study published online May 23 in BMJ.
In a population-based cohort study, researchers compared the electronic health records of 387,439 adults with eczema and 1,528,477 patients without eczema in the United Kingddom, matched according to age, sex, general practice, and calendar time, during 1998-2015. Patients were followed up for a median of 5.1 years
With the exception of cardiovascular death, atopic eczema was associated with all cardiovascular outcomes (MI, unstable angina, heart failure, atrial fibrillation, and stroke). The associations were stronger for severe atopic eczema, with significantly higher risks of MI, unstable angina, atrial fibrillation, stroke, cardiovascular death, and coronary revascularization among individuals with severe atopic eczema, compared with controls.
After adjustment for potential mediators such as body mass index, smoking, hyperlipidemia, diabetes, and severe alcohol use, individuals with severe eczema had a significant 37% increased risk of MI, 67% greater risk of heart failure, 35% greater risk of atrial fibrillation, 30% greater risk of cardiovascular death, and 36% greater risk of coronary revascularization, compared with controls with no eczema.
Increased cardiovascular risks also were seen in individuals whose atopic eczema was active more than half the time at follow-up. This group had a 37% greater risk of heart failure, 36% greater risk of unstable angina, and 19% greater risk of stroke, as well as significantly elevated risks of MI, atrial fibrillation, cardiovascular death, and coronary revascularization, compared with those without eczema.
Overall, atopic eczema contributed around 2.4% of the population-attributable risk for unstable angina, and 1.9% for heart failure (the highest population attributable risks). Ethnicity or high-dose corticosteroid use did not significantly impact outcomes.
Richard J. Silverwood, PhD, from the London School of Hygiene and Tropical Medicine, and his coauthors wrote that previous work examining the relationship between atopic eczema and cardiovascular disease had shown inconsistent outcomes, with some studies even pointing to a possible protective effect of mild atopic eczema.
“Mechanistic work suggests that atopic eczema may be associated with increased platelet activation and decreased fibrinolysis, which may increase the risk of clotting, though a recent study found no association with metabolite levels,” the authors wrote.
They noted that the strengths of their study were that it was largest to examine the association between atopic eczema and cardiovascular risk, and that they had access to data on body mass index, smoking, and severe alcohol use for most of the study population, which enabled them to adjust for these potential mediators.
“Consideration should be given to developing prevention strategies to reduce the risk of cardiovascular disease among patients with severe or predominantly active atopic eczema, including awareness of and screening for conventional cardiovascular risk factors by those providing clinical care,” they wrote.
The study was supported by the Wellcome Trust, and no relevant conflicts of interest were declared.
SOURCE: Silverwood R et al. BMJ 2018 May 23;361:k1786. doi: 10.1136/bmj.k1786.
The evidence in favor of a link between chronic inflammatory conditions, such as rheumatoid arthritis, and cardiovascular disease is growing. However, there are conflicting data and some of the uncertainty may be a result of a dose-response effect, where the increased cardiovascular risk is seen only in people with more severe disease.
This study and its finding of increased cardiovascular risk in patients with severe or more active eczema supports the case for targeted screening of this group for standard cardiovascular disease risk factors. It also could prompt incorporation of severe eczema as an independent cardiovascular disease risk factor in calculation of thresholds for primary prevention interventions.
The findings also may have implications for health care resources allocated to treatment of eczema, as prevention of cardiovascular disease could contribute to the argument in favor of the more expensive next-generation biologic treatments for eczema that are becoming available.
John R. Ingram, MD, is senior lecturer and consultant dermatologist, dermatology and academic wound healing in the division of infection and immunity at Cardiff (U.K.) University. These comments are taken from an accompanying editorial No conflicts of interest were declared. (BMJ. 2018 May 23. doi: 10.1136/bmj.k2064).
The evidence in favor of a link between chronic inflammatory conditions, such as rheumatoid arthritis, and cardiovascular disease is growing. However, there are conflicting data and some of the uncertainty may be a result of a dose-response effect, where the increased cardiovascular risk is seen only in people with more severe disease.
This study and its finding of increased cardiovascular risk in patients with severe or more active eczema supports the case for targeted screening of this group for standard cardiovascular disease risk factors. It also could prompt incorporation of severe eczema as an independent cardiovascular disease risk factor in calculation of thresholds for primary prevention interventions.
The findings also may have implications for health care resources allocated to treatment of eczema, as prevention of cardiovascular disease could contribute to the argument in favor of the more expensive next-generation biologic treatments for eczema that are becoming available.
John R. Ingram, MD, is senior lecturer and consultant dermatologist, dermatology and academic wound healing in the division of infection and immunity at Cardiff (U.K.) University. These comments are taken from an accompanying editorial No conflicts of interest were declared. (BMJ. 2018 May 23. doi: 10.1136/bmj.k2064).
The evidence in favor of a link between chronic inflammatory conditions, such as rheumatoid arthritis, and cardiovascular disease is growing. However, there are conflicting data and some of the uncertainty may be a result of a dose-response effect, where the increased cardiovascular risk is seen only in people with more severe disease.
This study and its finding of increased cardiovascular risk in patients with severe or more active eczema supports the case for targeted screening of this group for standard cardiovascular disease risk factors. It also could prompt incorporation of severe eczema as an independent cardiovascular disease risk factor in calculation of thresholds for primary prevention interventions.
The findings also may have implications for health care resources allocated to treatment of eczema, as prevention of cardiovascular disease could contribute to the argument in favor of the more expensive next-generation biologic treatments for eczema that are becoming available.
John R. Ingram, MD, is senior lecturer and consultant dermatologist, dermatology and academic wound healing in the division of infection and immunity at Cardiff (U.K.) University. These comments are taken from an accompanying editorial No conflicts of interest were declared. (BMJ. 2018 May 23. doi: 10.1136/bmj.k2064).
according to a case-control study published online May 23 in BMJ.
In a population-based cohort study, researchers compared the electronic health records of 387,439 adults with eczema and 1,528,477 patients without eczema in the United Kingddom, matched according to age, sex, general practice, and calendar time, during 1998-2015. Patients were followed up for a median of 5.1 years
With the exception of cardiovascular death, atopic eczema was associated with all cardiovascular outcomes (MI, unstable angina, heart failure, atrial fibrillation, and stroke). The associations were stronger for severe atopic eczema, with significantly higher risks of MI, unstable angina, atrial fibrillation, stroke, cardiovascular death, and coronary revascularization among individuals with severe atopic eczema, compared with controls.
After adjustment for potential mediators such as body mass index, smoking, hyperlipidemia, diabetes, and severe alcohol use, individuals with severe eczema had a significant 37% increased risk of MI, 67% greater risk of heart failure, 35% greater risk of atrial fibrillation, 30% greater risk of cardiovascular death, and 36% greater risk of coronary revascularization, compared with controls with no eczema.
Increased cardiovascular risks also were seen in individuals whose atopic eczema was active more than half the time at follow-up. This group had a 37% greater risk of heart failure, 36% greater risk of unstable angina, and 19% greater risk of stroke, as well as significantly elevated risks of MI, atrial fibrillation, cardiovascular death, and coronary revascularization, compared with those without eczema.
Overall, atopic eczema contributed around 2.4% of the population-attributable risk for unstable angina, and 1.9% for heart failure (the highest population attributable risks). Ethnicity or high-dose corticosteroid use did not significantly impact outcomes.
Richard J. Silverwood, PhD, from the London School of Hygiene and Tropical Medicine, and his coauthors wrote that previous work examining the relationship between atopic eczema and cardiovascular disease had shown inconsistent outcomes, with some studies even pointing to a possible protective effect of mild atopic eczema.
“Mechanistic work suggests that atopic eczema may be associated with increased platelet activation and decreased fibrinolysis, which may increase the risk of clotting, though a recent study found no association with metabolite levels,” the authors wrote.
They noted that the strengths of their study were that it was largest to examine the association between atopic eczema and cardiovascular risk, and that they had access to data on body mass index, smoking, and severe alcohol use for most of the study population, which enabled them to adjust for these potential mediators.
“Consideration should be given to developing prevention strategies to reduce the risk of cardiovascular disease among patients with severe or predominantly active atopic eczema, including awareness of and screening for conventional cardiovascular risk factors by those providing clinical care,” they wrote.
The study was supported by the Wellcome Trust, and no relevant conflicts of interest were declared.
SOURCE: Silverwood R et al. BMJ 2018 May 23;361:k1786. doi: 10.1136/bmj.k1786.
according to a case-control study published online May 23 in BMJ.
In a population-based cohort study, researchers compared the electronic health records of 387,439 adults with eczema and 1,528,477 patients without eczema in the United Kingddom, matched according to age, sex, general practice, and calendar time, during 1998-2015. Patients were followed up for a median of 5.1 years
With the exception of cardiovascular death, atopic eczema was associated with all cardiovascular outcomes (MI, unstable angina, heart failure, atrial fibrillation, and stroke). The associations were stronger for severe atopic eczema, with significantly higher risks of MI, unstable angina, atrial fibrillation, stroke, cardiovascular death, and coronary revascularization among individuals with severe atopic eczema, compared with controls.
After adjustment for potential mediators such as body mass index, smoking, hyperlipidemia, diabetes, and severe alcohol use, individuals with severe eczema had a significant 37% increased risk of MI, 67% greater risk of heart failure, 35% greater risk of atrial fibrillation, 30% greater risk of cardiovascular death, and 36% greater risk of coronary revascularization, compared with controls with no eczema.
Increased cardiovascular risks also were seen in individuals whose atopic eczema was active more than half the time at follow-up. This group had a 37% greater risk of heart failure, 36% greater risk of unstable angina, and 19% greater risk of stroke, as well as significantly elevated risks of MI, atrial fibrillation, cardiovascular death, and coronary revascularization, compared with those without eczema.
Overall, atopic eczema contributed around 2.4% of the population-attributable risk for unstable angina, and 1.9% for heart failure (the highest population attributable risks). Ethnicity or high-dose corticosteroid use did not significantly impact outcomes.
Richard J. Silverwood, PhD, from the London School of Hygiene and Tropical Medicine, and his coauthors wrote that previous work examining the relationship between atopic eczema and cardiovascular disease had shown inconsistent outcomes, with some studies even pointing to a possible protective effect of mild atopic eczema.
“Mechanistic work suggests that atopic eczema may be associated with increased platelet activation and decreased fibrinolysis, which may increase the risk of clotting, though a recent study found no association with metabolite levels,” the authors wrote.
They noted that the strengths of their study were that it was largest to examine the association between atopic eczema and cardiovascular risk, and that they had access to data on body mass index, smoking, and severe alcohol use for most of the study population, which enabled them to adjust for these potential mediators.
“Consideration should be given to developing prevention strategies to reduce the risk of cardiovascular disease among patients with severe or predominantly active atopic eczema, including awareness of and screening for conventional cardiovascular risk factors by those providing clinical care,” they wrote.
The study was supported by the Wellcome Trust, and no relevant conflicts of interest were declared.
SOURCE: Silverwood R et al. BMJ 2018 May 23;361:k1786. doi: 10.1136/bmj.k1786.
FROM THE BMJ
Key clinical point: Severe atopic eczema may be associated with a significantly increased risk of cardiovascular disease.
Major finding: Individuals with severe atopic eczema were at increased for cardiovascular disease, including a 67% greater risk of heart failure.
Study details: A population-based case-control cohort study in 387,439 patients with atopic eczema, compared with more than 1 million controls.
Disclosures: The study was supported by the Wellcome Trust, and no relevant conflicts of interest were declared.
Source: Silverwood R et al. BMJ. 2018 May 23;361:k1786.
Antidepressant use linked to increased weight gain
Taking antidepressants appears associated with weight gain in a recent study, though the researchers caution that the link might not be causal. Antidepressant use already was lowest in those with an initially normal BMI, and it increased with each category of greater BMI.
“Participants of normal weight showed an increased risk of transitioning to overweight or obesity, and overweight participants were more likely to become obese if they were treated with an antidepressant,” Rafael Gafoor, PhD, of King’s College London, and his associates wrote in BMJ.
“The risk of weight gain was substantially increased during the second and third years of treatment,” they reported. “The risk of weight gain remained increased during at least 6 years of follow-up.”
The researchers retrospectively analyzed EHRs from the U.K. Clinical Practice Research Datalink, representing about 7% of general practices in the United Kingdom, to compare the risk of weight gain among those who were and were not prescribed antidepressants. Of more than 2 million registered participants, a random sample of those with at least three measurements for body mass index (BMI), representing different weight classes, were included.
Out of 136,762 men and 157,957 women, 13% of the men and 22.4% of the women received prescriptions for antidepressants. The 10-year follow-up period included more than 1.8 million person-years. The proportion of people gaining at least 5% in BMI was 11.1% in those with antidepressants prescriptions, compared with 8.1% in those not prescribed antidepressants.
“Antidepressant use was greater in patients with comorbidity and coprescriptions, particularly with diagnoses of stroke and diabetes or coprescribing of antiepileptics or antipsychotics, than in those without,” the researchers wrote. “Antidepressant use was also associated with current smoking and higher deprivation category.”
The researchers adjusted the analysis to account for age, sex, initial BMI classification, smoking, prescriptions for antiepileptics or antipsychotics, year, region of residence, socioeconomic status, or having received advice on weight management or diet. They also accounted for diabetes, coronary heart disease, stroke, cancer, and depression diagnoses, and they eliminated the 280 days before a newborn delivery to account for pregnancy-related weight increases.
After adjustment for those potential confounders, people prescribed antidepressants were 21% more likely to experience substantial weight gain than those not prescribed them (adjusted rate ratio = 1.21; P less than .001). The researchers, cautioned, however, that residual confounding might have inflated the risk.
Those who had a normal weight when they began taking antidepressants had 29% greater risk of gaining enough weight to meet the criteria for overweight or obesity. Likewise, those already overweight when first prescribed antidepressants were 29% more likely to develop obesity.
For every 27 patients who took antidepressants for at least 1 year, 1 of them gained at least 5% in BMI during the subsequent year. Again, however, the researchers emphasized the absence of evidence for causality and the risk of bias from confounding.
Mirtazapine was the antidepressant associated with the highest incidence ratio of weight gain, but that drug was prescribed infrequently.
“From a clinical perspective, these observations reinforce the need for active body weight management to accompany widespread antidepressant treatment, although this might often be met with limited success,” the authors wrote.
The research was funded by the National Health Service Foundation Trust and by King’s College London. Aside from one author’s employment with the U.K. Clinical Practice Research Datalink data source, the authors had no disclosures.
SOURCE: Gafoor R et al. BMJ. 2018;361:k1951. doi: 10.1136/bmj.k1951.
Taking antidepressants appears associated with weight gain in a recent study, though the researchers caution that the link might not be causal. Antidepressant use already was lowest in those with an initially normal BMI, and it increased with each category of greater BMI.
“Participants of normal weight showed an increased risk of transitioning to overweight or obesity, and overweight participants were more likely to become obese if they were treated with an antidepressant,” Rafael Gafoor, PhD, of King’s College London, and his associates wrote in BMJ.
“The risk of weight gain was substantially increased during the second and third years of treatment,” they reported. “The risk of weight gain remained increased during at least 6 years of follow-up.”
The researchers retrospectively analyzed EHRs from the U.K. Clinical Practice Research Datalink, representing about 7% of general practices in the United Kingdom, to compare the risk of weight gain among those who were and were not prescribed antidepressants. Of more than 2 million registered participants, a random sample of those with at least three measurements for body mass index (BMI), representing different weight classes, were included.
Out of 136,762 men and 157,957 women, 13% of the men and 22.4% of the women received prescriptions for antidepressants. The 10-year follow-up period included more than 1.8 million person-years. The proportion of people gaining at least 5% in BMI was 11.1% in those with antidepressants prescriptions, compared with 8.1% in those not prescribed antidepressants.
“Antidepressant use was greater in patients with comorbidity and coprescriptions, particularly with diagnoses of stroke and diabetes or coprescribing of antiepileptics or antipsychotics, than in those without,” the researchers wrote. “Antidepressant use was also associated with current smoking and higher deprivation category.”
The researchers adjusted the analysis to account for age, sex, initial BMI classification, smoking, prescriptions for antiepileptics or antipsychotics, year, region of residence, socioeconomic status, or having received advice on weight management or diet. They also accounted for diabetes, coronary heart disease, stroke, cancer, and depression diagnoses, and they eliminated the 280 days before a newborn delivery to account for pregnancy-related weight increases.
After adjustment for those potential confounders, people prescribed antidepressants were 21% more likely to experience substantial weight gain than those not prescribed them (adjusted rate ratio = 1.21; P less than .001). The researchers, cautioned, however, that residual confounding might have inflated the risk.
Those who had a normal weight when they began taking antidepressants had 29% greater risk of gaining enough weight to meet the criteria for overweight or obesity. Likewise, those already overweight when first prescribed antidepressants were 29% more likely to develop obesity.
For every 27 patients who took antidepressants for at least 1 year, 1 of them gained at least 5% in BMI during the subsequent year. Again, however, the researchers emphasized the absence of evidence for causality and the risk of bias from confounding.
Mirtazapine was the antidepressant associated with the highest incidence ratio of weight gain, but that drug was prescribed infrequently.
“From a clinical perspective, these observations reinforce the need for active body weight management to accompany widespread antidepressant treatment, although this might often be met with limited success,” the authors wrote.
The research was funded by the National Health Service Foundation Trust and by King’s College London. Aside from one author’s employment with the U.K. Clinical Practice Research Datalink data source, the authors had no disclosures.
SOURCE: Gafoor R et al. BMJ. 2018;361:k1951. doi: 10.1136/bmj.k1951.
Taking antidepressants appears associated with weight gain in a recent study, though the researchers caution that the link might not be causal. Antidepressant use already was lowest in those with an initially normal BMI, and it increased with each category of greater BMI.
“Participants of normal weight showed an increased risk of transitioning to overweight or obesity, and overweight participants were more likely to become obese if they were treated with an antidepressant,” Rafael Gafoor, PhD, of King’s College London, and his associates wrote in BMJ.
“The risk of weight gain was substantially increased during the second and third years of treatment,” they reported. “The risk of weight gain remained increased during at least 6 years of follow-up.”
The researchers retrospectively analyzed EHRs from the U.K. Clinical Practice Research Datalink, representing about 7% of general practices in the United Kingdom, to compare the risk of weight gain among those who were and were not prescribed antidepressants. Of more than 2 million registered participants, a random sample of those with at least three measurements for body mass index (BMI), representing different weight classes, were included.
Out of 136,762 men and 157,957 women, 13% of the men and 22.4% of the women received prescriptions for antidepressants. The 10-year follow-up period included more than 1.8 million person-years. The proportion of people gaining at least 5% in BMI was 11.1% in those with antidepressants prescriptions, compared with 8.1% in those not prescribed antidepressants.
“Antidepressant use was greater in patients with comorbidity and coprescriptions, particularly with diagnoses of stroke and diabetes or coprescribing of antiepileptics or antipsychotics, than in those without,” the researchers wrote. “Antidepressant use was also associated with current smoking and higher deprivation category.”
The researchers adjusted the analysis to account for age, sex, initial BMI classification, smoking, prescriptions for antiepileptics or antipsychotics, year, region of residence, socioeconomic status, or having received advice on weight management or diet. They also accounted for diabetes, coronary heart disease, stroke, cancer, and depression diagnoses, and they eliminated the 280 days before a newborn delivery to account for pregnancy-related weight increases.
After adjustment for those potential confounders, people prescribed antidepressants were 21% more likely to experience substantial weight gain than those not prescribed them (adjusted rate ratio = 1.21; P less than .001). The researchers, cautioned, however, that residual confounding might have inflated the risk.
Those who had a normal weight when they began taking antidepressants had 29% greater risk of gaining enough weight to meet the criteria for overweight or obesity. Likewise, those already overweight when first prescribed antidepressants were 29% more likely to develop obesity.
For every 27 patients who took antidepressants for at least 1 year, 1 of them gained at least 5% in BMI during the subsequent year. Again, however, the researchers emphasized the absence of evidence for causality and the risk of bias from confounding.
Mirtazapine was the antidepressant associated with the highest incidence ratio of weight gain, but that drug was prescribed infrequently.
“From a clinical perspective, these observations reinforce the need for active body weight management to accompany widespread antidepressant treatment, although this might often be met with limited success,” the authors wrote.
The research was funded by the National Health Service Foundation Trust and by King’s College London. Aside from one author’s employment with the U.K. Clinical Practice Research Datalink data source, the authors had no disclosures.
SOURCE: Gafoor R et al. BMJ. 2018;361:k1951. doi: 10.1136/bmj.k1951.
FROM THE BMJ
Key clinical point: “These observations reinforce the need for active body weight management to accompany widespread antidepressant treatment.”
Major finding: People taking antidepressants had 21% higher risk of gaining at least 5% in body mass index and 29% greater risk of moving into a higher BMI category.
Study details: The findings are based on analysis of 10-year follow-up date from a British population-based cohort of 294,719 men and women, 18% of whom had been prescribed antidepressants.
Disclosures: The research was funded by the National Health Service Foundation Trust and by King’s College London. Aside from one author’s employment with the U.K. Clinical Practice Research Datalink data source, the authors had no disclosures.
Source: Gafoor R et al. BMJ. 2018;361:k1951. doi: 10.1136/bmj.k1951.
Hefty rewards pay off in smoking-cessation study
A new study finds it pays to pay people to stop lighting up: Smokers were more likely to quit if they had an opportunity to gain rewards worth $600 than if they simply received free cessation aids or free e-cigarettes.
The wide majority of the more than 6,000 smokers in the randomized study didn’t quit despite offers of various incentives. All the same, “programs that offered financial incentives tripled the rates of smoking cessation, reduced employers’ costs per successful quit, as compared with programs that offered cessation aids alone, and yielded total costs that compared favorably with the costs of employing smokers,” the study authors wrote.
The researchers reached out to employees and spouses at 54 companies that use wellness programs provided by the Vitality Institute, which supports research into health promotion. The institute provided grant support for the study.
Just over 6,000 employees and spouses who smoked were assigned to five groups. One group received usual care. The others received interventions: free smoking-cessation aids (nicotine replacement therapy, bupropion, or varenicline); free e-cigarettes; up to $600 worth of an unidentified “reward incentive” plus free cessation aids; and up to $600 via a redeemable deposit, plus free cessation aids.
Participants could only get the entire reward incentive or the full $600 redeemable deposit if they showed signs of sustained smoking cessation via blood or urine test at 1, 3, and 6 months.
The median age in the groups ranged from 43 to 45 years, and most were not college graduates. Just over half were women, and roughly 90% said they wanted to quit smoking.
Overall, 20% of the 6,006 participants logged onto the trial website, a sign that they were “engaged.” The number was highest in the free e-cigarette and reward groups (21%-23%) and lowest in the usual care group (16%).
The researchers focused on how many participants abstained from smoking – as confirmed by blood or urine test – for 6 months past the target quit date. The test data confirmed that just 1.3% of the total participants, 80 people, sustained cessation over 6 months.
Only 0.1% of the usual-care group sustained smoking cessation, and the number wasn’t much higher (0.5%) in the free cessation aids group.
One percent of those in the free e-cigarette group sustained cessation. However, the researchers noted there wasn’t a significant difference in the quit rates between the usual care, free cessation aid, and free e-cigarette groups.
“The observation of greater e-cigarette use in the free e-cigarette group than in the free cessation aids group, coupled with the absence of benefit of free e-cigarettes versus no intervention, supports the conclusion that offering free e-cigarettes does not promote smoking cessation,” they cautioned.
In the reward incentive and $600 redeemable-deposit groups, 2% and 2.9% of participants quit over a sustained period, respectively. Cessation rates in the $600 deposit group were superior to the free cessation aid group (P less than .001) and the free e-cigarette group (P = .008). Cessation rates in the incentive group were superior to those in the free cessation aid group (P = .006).
“Average costs per participant assigned to each intervention were lowest in the usual-care group ($0.82) and highest in the redeemable-deposit group ($100.96),” the researchers reported. “The overall cost of each program per participant who was abstinent for 6 months was lower in the rewards and redeemable-deposit groups than in the free e-cigarettes or free cessation aids groups.”
The study received grant support from the Vitality Institute. Most of the study authors reported no relevant disclosures. One author reported serving on the scientific advisory board of VAL Health, and another reported various grants and personal fees.
SOURCE: Halpern SD et al. N Engl J Med. 2018 May 23. doi: 10.1056/NEJMsa1715757.
A new study finds it pays to pay people to stop lighting up: Smokers were more likely to quit if they had an opportunity to gain rewards worth $600 than if they simply received free cessation aids or free e-cigarettes.
The wide majority of the more than 6,000 smokers in the randomized study didn’t quit despite offers of various incentives. All the same, “programs that offered financial incentives tripled the rates of smoking cessation, reduced employers’ costs per successful quit, as compared with programs that offered cessation aids alone, and yielded total costs that compared favorably with the costs of employing smokers,” the study authors wrote.
The researchers reached out to employees and spouses at 54 companies that use wellness programs provided by the Vitality Institute, which supports research into health promotion. The institute provided grant support for the study.
Just over 6,000 employees and spouses who smoked were assigned to five groups. One group received usual care. The others received interventions: free smoking-cessation aids (nicotine replacement therapy, bupropion, or varenicline); free e-cigarettes; up to $600 worth of an unidentified “reward incentive” plus free cessation aids; and up to $600 via a redeemable deposit, plus free cessation aids.
Participants could only get the entire reward incentive or the full $600 redeemable deposit if they showed signs of sustained smoking cessation via blood or urine test at 1, 3, and 6 months.
The median age in the groups ranged from 43 to 45 years, and most were not college graduates. Just over half were women, and roughly 90% said they wanted to quit smoking.
Overall, 20% of the 6,006 participants logged onto the trial website, a sign that they were “engaged.” The number was highest in the free e-cigarette and reward groups (21%-23%) and lowest in the usual care group (16%).
The researchers focused on how many participants abstained from smoking – as confirmed by blood or urine test – for 6 months past the target quit date. The test data confirmed that just 1.3% of the total participants, 80 people, sustained cessation over 6 months.
Only 0.1% of the usual-care group sustained smoking cessation, and the number wasn’t much higher (0.5%) in the free cessation aids group.
One percent of those in the free e-cigarette group sustained cessation. However, the researchers noted there wasn’t a significant difference in the quit rates between the usual care, free cessation aid, and free e-cigarette groups.
“The observation of greater e-cigarette use in the free e-cigarette group than in the free cessation aids group, coupled with the absence of benefit of free e-cigarettes versus no intervention, supports the conclusion that offering free e-cigarettes does not promote smoking cessation,” they cautioned.
In the reward incentive and $600 redeemable-deposit groups, 2% and 2.9% of participants quit over a sustained period, respectively. Cessation rates in the $600 deposit group were superior to the free cessation aid group (P less than .001) and the free e-cigarette group (P = .008). Cessation rates in the incentive group were superior to those in the free cessation aid group (P = .006).
“Average costs per participant assigned to each intervention were lowest in the usual-care group ($0.82) and highest in the redeemable-deposit group ($100.96),” the researchers reported. “The overall cost of each program per participant who was abstinent for 6 months was lower in the rewards and redeemable-deposit groups than in the free e-cigarettes or free cessation aids groups.”
The study received grant support from the Vitality Institute. Most of the study authors reported no relevant disclosures. One author reported serving on the scientific advisory board of VAL Health, and another reported various grants and personal fees.
SOURCE: Halpern SD et al. N Engl J Med. 2018 May 23. doi: 10.1056/NEJMsa1715757.
A new study finds it pays to pay people to stop lighting up: Smokers were more likely to quit if they had an opportunity to gain rewards worth $600 than if they simply received free cessation aids or free e-cigarettes.
The wide majority of the more than 6,000 smokers in the randomized study didn’t quit despite offers of various incentives. All the same, “programs that offered financial incentives tripled the rates of smoking cessation, reduced employers’ costs per successful quit, as compared with programs that offered cessation aids alone, and yielded total costs that compared favorably with the costs of employing smokers,” the study authors wrote.
The researchers reached out to employees and spouses at 54 companies that use wellness programs provided by the Vitality Institute, which supports research into health promotion. The institute provided grant support for the study.
Just over 6,000 employees and spouses who smoked were assigned to five groups. One group received usual care. The others received interventions: free smoking-cessation aids (nicotine replacement therapy, bupropion, or varenicline); free e-cigarettes; up to $600 worth of an unidentified “reward incentive” plus free cessation aids; and up to $600 via a redeemable deposit, plus free cessation aids.
Participants could only get the entire reward incentive or the full $600 redeemable deposit if they showed signs of sustained smoking cessation via blood or urine test at 1, 3, and 6 months.
The median age in the groups ranged from 43 to 45 years, and most were not college graduates. Just over half were women, and roughly 90% said they wanted to quit smoking.
Overall, 20% of the 6,006 participants logged onto the trial website, a sign that they were “engaged.” The number was highest in the free e-cigarette and reward groups (21%-23%) and lowest in the usual care group (16%).
The researchers focused on how many participants abstained from smoking – as confirmed by blood or urine test – for 6 months past the target quit date. The test data confirmed that just 1.3% of the total participants, 80 people, sustained cessation over 6 months.
Only 0.1% of the usual-care group sustained smoking cessation, and the number wasn’t much higher (0.5%) in the free cessation aids group.
One percent of those in the free e-cigarette group sustained cessation. However, the researchers noted there wasn’t a significant difference in the quit rates between the usual care, free cessation aid, and free e-cigarette groups.
“The observation of greater e-cigarette use in the free e-cigarette group than in the free cessation aids group, coupled with the absence of benefit of free e-cigarettes versus no intervention, supports the conclusion that offering free e-cigarettes does not promote smoking cessation,” they cautioned.
In the reward incentive and $600 redeemable-deposit groups, 2% and 2.9% of participants quit over a sustained period, respectively. Cessation rates in the $600 deposit group were superior to the free cessation aid group (P less than .001) and the free e-cigarette group (P = .008). Cessation rates in the incentive group were superior to those in the free cessation aid group (P = .006).
“Average costs per participant assigned to each intervention were lowest in the usual-care group ($0.82) and highest in the redeemable-deposit group ($100.96),” the researchers reported. “The overall cost of each program per participant who was abstinent for 6 months was lower in the rewards and redeemable-deposit groups than in the free e-cigarettes or free cessation aids groups.”
The study received grant support from the Vitality Institute. Most of the study authors reported no relevant disclosures. One author reported serving on the scientific advisory board of VAL Health, and another reported various grants and personal fees.
SOURCE: Halpern SD et al. N Engl J Med. 2018 May 23. doi: 10.1056/NEJMsa1715757.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Smokers are more likely to sustain cessation if they receive incentives worth $600.
Major finding: Cessation rates for 6 months past target quit date reached as high as 2.9% in smokers who had the opportunity to gain rewards, while they didn’t top 1% in those who received free cessation aids or free e-cigarettes.
Study details: A randomized, prospective study of 6,006 smokers (employees of 54 companies and spouses) who were assigned to usual care or one of four intervention groups.
Disclosures: The study received grant support from the Vitality Institute. Most of the study authors reported no relevant disclosures. One reported serving on the scientific advisory board of VAL Health, and another reported various grants and personal fees.
Source: Halpern SD et al. N Engl J Med. 2018 May 23. doi: 10.1056/NEJMsa1715757.
Doctors’ pay involves a lot of unseen work
“Doctors make a lot of money.” We hear that a lot, always from people who aren’t part of the profession.
Last month, I had to do my tax forms. Not my annual forms, but the quarterly withholding ones for the IRS, and for the state, along with the Arizona Department of Economic Security forms.
The whole thing takes me about 2 hours every 3 months. I suppose I could hire an accountant or office manager to deal with that stuff, but in solo practice, you do everything you can to keep the overhead low. So I do it myself.
Eight hours a year doesn’t sound too bad, but it got me thinking about all the other ways that work creeps into my home time.
I’m usually at the office around 5:00 a.m., when I start with reviewing charts, doing paperwork, and catching up on dictations until patients start at 8:00 a.m. From then on, they’re a steady stream until 4:00 p.m., when we close up and head home.
I get home and then have 1-2 hours of time paying bills, sorting mail, and catching up on phone calls and other unresolved issues.
On weekends, there’s always other stuff. Payroll for the coming weeks, office bills, and credit card statements I didn’t get to during the week, CME, forms, licensing paperwork, etc.
I’d guess about 15 hours/week goes into nonpatient-related stuff. Each year that’s more than 700 hours (or a little over a month) of extra time. Tack that on to the roughly 60 hours that I spend seeing patients between the office and hospital.
People say we make “a lot” (whatever that is), but they don’t see everything behind it. The 7-12 years of post-college training. The student loans of $200,000 and dating back to when I was 26 years old. The rising costs of overhead and dropping rates of reimbursement. The denied payments in disputes over claims. And, as mentioned above, the huge amount of time this job takes for stuff beyond just seeing patients.
We don’t get paid by the hour, but if we did, the rate would probably be a lot lower than what most would expect.
I suppose I could become employed, and let someone else worry about those things. But the financial impact doesn’t go away. Someone else still has to be doing those things, and since doctors are the ones who generate income in the majority of medical practices, the salaries for everyone else come out of ours. Plus, as I’ve previously written about, I’ve been employed before and got sick of the meetings and memos about cost-sharing, productivity numbers, and dollars earned per square foot.
But whenever I hear the refrain about our field being overpaid, I think about the actual hours the public doesn’t see (or care about). This isn’t a job for slackers, and
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“Doctors make a lot of money.” We hear that a lot, always from people who aren’t part of the profession.
Last month, I had to do my tax forms. Not my annual forms, but the quarterly withholding ones for the IRS, and for the state, along with the Arizona Department of Economic Security forms.
The whole thing takes me about 2 hours every 3 months. I suppose I could hire an accountant or office manager to deal with that stuff, but in solo practice, you do everything you can to keep the overhead low. So I do it myself.
Eight hours a year doesn’t sound too bad, but it got me thinking about all the other ways that work creeps into my home time.
I’m usually at the office around 5:00 a.m., when I start with reviewing charts, doing paperwork, and catching up on dictations until patients start at 8:00 a.m. From then on, they’re a steady stream until 4:00 p.m., when we close up and head home.
I get home and then have 1-2 hours of time paying bills, sorting mail, and catching up on phone calls and other unresolved issues.
On weekends, there’s always other stuff. Payroll for the coming weeks, office bills, and credit card statements I didn’t get to during the week, CME, forms, licensing paperwork, etc.
I’d guess about 15 hours/week goes into nonpatient-related stuff. Each year that’s more than 700 hours (or a little over a month) of extra time. Tack that on to the roughly 60 hours that I spend seeing patients between the office and hospital.
People say we make “a lot” (whatever that is), but they don’t see everything behind it. The 7-12 years of post-college training. The student loans of $200,000 and dating back to when I was 26 years old. The rising costs of overhead and dropping rates of reimbursement. The denied payments in disputes over claims. And, as mentioned above, the huge amount of time this job takes for stuff beyond just seeing patients.
We don’t get paid by the hour, but if we did, the rate would probably be a lot lower than what most would expect.
I suppose I could become employed, and let someone else worry about those things. But the financial impact doesn’t go away. Someone else still has to be doing those things, and since doctors are the ones who generate income in the majority of medical practices, the salaries for everyone else come out of ours. Plus, as I’ve previously written about, I’ve been employed before and got sick of the meetings and memos about cost-sharing, productivity numbers, and dollars earned per square foot.
But whenever I hear the refrain about our field being overpaid, I think about the actual hours the public doesn’t see (or care about). This isn’t a job for slackers, and
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“Doctors make a lot of money.” We hear that a lot, always from people who aren’t part of the profession.
Last month, I had to do my tax forms. Not my annual forms, but the quarterly withholding ones for the IRS, and for the state, along with the Arizona Department of Economic Security forms.
The whole thing takes me about 2 hours every 3 months. I suppose I could hire an accountant or office manager to deal with that stuff, but in solo practice, you do everything you can to keep the overhead low. So I do it myself.
Eight hours a year doesn’t sound too bad, but it got me thinking about all the other ways that work creeps into my home time.
I’m usually at the office around 5:00 a.m., when I start with reviewing charts, doing paperwork, and catching up on dictations until patients start at 8:00 a.m. From then on, they’re a steady stream until 4:00 p.m., when we close up and head home.
I get home and then have 1-2 hours of time paying bills, sorting mail, and catching up on phone calls and other unresolved issues.
On weekends, there’s always other stuff. Payroll for the coming weeks, office bills, and credit card statements I didn’t get to during the week, CME, forms, licensing paperwork, etc.
I’d guess about 15 hours/week goes into nonpatient-related stuff. Each year that’s more than 700 hours (or a little over a month) of extra time. Tack that on to the roughly 60 hours that I spend seeing patients between the office and hospital.
People say we make “a lot” (whatever that is), but they don’t see everything behind it. The 7-12 years of post-college training. The student loans of $200,000 and dating back to when I was 26 years old. The rising costs of overhead and dropping rates of reimbursement. The denied payments in disputes over claims. And, as mentioned above, the huge amount of time this job takes for stuff beyond just seeing patients.
We don’t get paid by the hour, but if we did, the rate would probably be a lot lower than what most would expect.
I suppose I could become employed, and let someone else worry about those things. But the financial impact doesn’t go away. Someone else still has to be doing those things, and since doctors are the ones who generate income in the majority of medical practices, the salaries for everyone else come out of ours. Plus, as I’ve previously written about, I’ve been employed before and got sick of the meetings and memos about cost-sharing, productivity numbers, and dollars earned per square foot.
But whenever I hear the refrain about our field being overpaid, I think about the actual hours the public doesn’t see (or care about). This isn’t a job for slackers, and
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Older CLL and NHL patients are more vulnerable to toxicities
Older patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) have an increased odds of experiencing treatment-related toxicities, even when treated with novel agents, according to findings reported in the Journal of Geriatric Oncology.
An analysis of 1,199 patients showed that CLL patients aged 65 years and older had significantly higher odds than younger patients of developing a grade three or four hematologic toxicity (adjusted odds ratio, 1.70; P = .009; 95% confidence interval, 1.57-1.84) or nonhematologic toxicity (OR, 1.47; P = .022; 95% CI, 1.39-1.55).
Investigators analyzed data obtained from the Alliance for Clinical Trials in Oncology to compare the incidence of toxicities between age groups. Of the 1,199 patients included in the analysis, 409 were 65 years of age or older, and 790 were younger than 65 years. Among these patients, 438 received only therapy with novel agents including biologic combinations, monoclonal antibodies, cell cycle inhibitors, chemoimmunotherapy, and immunomodulators, and 761 received novel agents in addition to chemotherapy.
Overall, 68% of CLL patients and 35% of NHL patients had at least one grade three or four hematologic toxicity, compared with 48% and 54% for nonhematologic toxicities, respectively.
Older CLL patients with at least one grade three or four toxicity in the first 3 months had similar overall survival (OS) and progression-free survival (PFS) as those without a toxicity. In contrast, older NHL patients with at least one grade three or four hematologic toxicity in the first 3 months had worse OS (HR, 3.14; P = .006; 95% CI, 2.25-4.39) and PFS (HR, 3.06; P = .011; 95% CI, 2.10-4.45) than patients without these toxicities. Nonhematologic toxicities were not significantly associated with survival outcomes for patients with NHL.
“The observed associations between hematologic toxicity and OS/PFS among older patients with NHL require further investigation,” the researchers wrote. “These findings could represent a direct effect of toxicity due to decreased physiologic reserve, decreased drug clearance, or an increased sensitivity of tissue to novel agents.”
The study was supported by a National Institutes of Health grant. Researchers reported relationships with Bartlett, KITE, Pfizer, Seattle Genetics, Roche-Genentech, Celgene, Pharmacyclics, and Gilead.
SOURCE: Tallarico M et al. J Geriatr Oncol. 2018 Apr 16. pii: S1879-4068(18)30131-0.
Older patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) have an increased odds of experiencing treatment-related toxicities, even when treated with novel agents, according to findings reported in the Journal of Geriatric Oncology.
An analysis of 1,199 patients showed that CLL patients aged 65 years and older had significantly higher odds than younger patients of developing a grade three or four hematologic toxicity (adjusted odds ratio, 1.70; P = .009; 95% confidence interval, 1.57-1.84) or nonhematologic toxicity (OR, 1.47; P = .022; 95% CI, 1.39-1.55).
Investigators analyzed data obtained from the Alliance for Clinical Trials in Oncology to compare the incidence of toxicities between age groups. Of the 1,199 patients included in the analysis, 409 were 65 years of age or older, and 790 were younger than 65 years. Among these patients, 438 received only therapy with novel agents including biologic combinations, monoclonal antibodies, cell cycle inhibitors, chemoimmunotherapy, and immunomodulators, and 761 received novel agents in addition to chemotherapy.
Overall, 68% of CLL patients and 35% of NHL patients had at least one grade three or four hematologic toxicity, compared with 48% and 54% for nonhematologic toxicities, respectively.
Older CLL patients with at least one grade three or four toxicity in the first 3 months had similar overall survival (OS) and progression-free survival (PFS) as those without a toxicity. In contrast, older NHL patients with at least one grade three or four hematologic toxicity in the first 3 months had worse OS (HR, 3.14; P = .006; 95% CI, 2.25-4.39) and PFS (HR, 3.06; P = .011; 95% CI, 2.10-4.45) than patients without these toxicities. Nonhematologic toxicities were not significantly associated with survival outcomes for patients with NHL.
“The observed associations between hematologic toxicity and OS/PFS among older patients with NHL require further investigation,” the researchers wrote. “These findings could represent a direct effect of toxicity due to decreased physiologic reserve, decreased drug clearance, or an increased sensitivity of tissue to novel agents.”
The study was supported by a National Institutes of Health grant. Researchers reported relationships with Bartlett, KITE, Pfizer, Seattle Genetics, Roche-Genentech, Celgene, Pharmacyclics, and Gilead.
SOURCE: Tallarico M et al. J Geriatr Oncol. 2018 Apr 16. pii: S1879-4068(18)30131-0.
Older patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) have an increased odds of experiencing treatment-related toxicities, even when treated with novel agents, according to findings reported in the Journal of Geriatric Oncology.
An analysis of 1,199 patients showed that CLL patients aged 65 years and older had significantly higher odds than younger patients of developing a grade three or four hematologic toxicity (adjusted odds ratio, 1.70; P = .009; 95% confidence interval, 1.57-1.84) or nonhematologic toxicity (OR, 1.47; P = .022; 95% CI, 1.39-1.55).
Investigators analyzed data obtained from the Alliance for Clinical Trials in Oncology to compare the incidence of toxicities between age groups. Of the 1,199 patients included in the analysis, 409 were 65 years of age or older, and 790 were younger than 65 years. Among these patients, 438 received only therapy with novel agents including biologic combinations, monoclonal antibodies, cell cycle inhibitors, chemoimmunotherapy, and immunomodulators, and 761 received novel agents in addition to chemotherapy.
Overall, 68% of CLL patients and 35% of NHL patients had at least one grade three or four hematologic toxicity, compared with 48% and 54% for nonhematologic toxicities, respectively.
Older CLL patients with at least one grade three or four toxicity in the first 3 months had similar overall survival (OS) and progression-free survival (PFS) as those without a toxicity. In contrast, older NHL patients with at least one grade three or four hematologic toxicity in the first 3 months had worse OS (HR, 3.14; P = .006; 95% CI, 2.25-4.39) and PFS (HR, 3.06; P = .011; 95% CI, 2.10-4.45) than patients without these toxicities. Nonhematologic toxicities were not significantly associated with survival outcomes for patients with NHL.
“The observed associations between hematologic toxicity and OS/PFS among older patients with NHL require further investigation,” the researchers wrote. “These findings could represent a direct effect of toxicity due to decreased physiologic reserve, decreased drug clearance, or an increased sensitivity of tissue to novel agents.”
The study was supported by a National Institutes of Health grant. Researchers reported relationships with Bartlett, KITE, Pfizer, Seattle Genetics, Roche-Genentech, Celgene, Pharmacyclics, and Gilead.
SOURCE: Tallarico M et al. J Geriatr Oncol. 2018 Apr 16. pii: S1879-4068(18)30131-0.
FROM THE JOURNAL OF GERIATRIC ONCOLOGY
Key clinical point:
Major finding: Older CLL patients had significantly higher odds of developing a grade three or four hematologic toxicity (adjusted odds ratio, 1.70; P = .009; 95% confidence interval, 1.57-1.84) or nonhematologic toxicity (OR, 1.47; P = .022; 95% CI 1.39-1.55).
Study details: An analysis of data from 1,199 CLL and NHL patients in the Alliance for Clinical Trials in Oncology.
Disclosures: The study was supported by a National Institutes of Health grant. Researchers reported relationships with Bartlett, KITE, Pfizer, Seattle Genetics, Roche-Genentech, Celgene, Pharmacyclics, and Gilead.
Source: Tallarico M et al. J Geriatr Oncol. 2018 Apr 16. pii: S1879-4068(18)30131-0.
Comorbid spondyloarthritis and fibromyalgia lower response to TNF inhibitors
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
LIVERPOOL, ENGLAND – Individuals with axial spondyloarthritis (axSpA) who have comorbid fibromyalgia do respond to biologic therapy but at a seemingly lower rate if they have a high symptom score during early assessments.
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) showed that participants with axSpA who were starting biologic therapy with a tumor necrosis factor inhibitor (TNFi) for the first time also had worse disease activity at baseline if they met fibromyalgia research criteria than if they did not.
“The issue of fibromyalgia as a comorbidity in axial SpA has been the subject of current considerable interest,” said Dr. Macfarlane, who is Clinical Chair in Epidemiology at the University of Aberdeen (Scotland), where the BSRBR-AS is run. This is for several reasons: “One is the challenge of identifying patients with axial SpA who have comorbid fibromyalgia.
“The second is the concern that comorbid fibromyalgia may have an effect on disease indices such as BASDAI [Bath Ankylosing Spondylitis Disease Activity Index],” Dr. Macfarlane observed.
This leads to the third issue: “Are patients with comorbid fibromyalgia inappropriately receiving biological therapy, and how do they respond if they do receive it?”
Previous data from the BSRBR-AS have shown that approximately one in five patients with axSpA meet research criteria for fibromyalgia (Arthritis Rheumatol. 2017;69:2144-50) and that the prevalence of the comorbidity was higher in those who met Assessment of SpondyloArthritis International Society imaging criteria and lower in those who only met clinical criteria (25% vs. 10%).
The current aims of the study presented by Dr. Macfarlane were to first quantify the extent to which meeting fibromyalgia criteria was associated with higher measures of disease activity and impact, and then to see if meeting these criteria was associated with a poorer response to first use of a TNFi.
In order to find out, Dr. Macfarlane and his associates examined data from the prospective BSRBR-AS, which has been running since 2012. The BSRBR-AS recruits patients with ASAS-confirmed axSpA who are newly starting biologics from 83 U.K. centers.
At recruitment and at 3 months, patients starting biologic treatment undergo several assessments, which since 2015 has included research criteria for fibromyalgia (J Rheumatol. 2011;38:1113–22). The latter incorporate a Widespread Pain Index rated 0-19 and a Symptom Severity Scale rated 0-12 and cover items such as fatigue and waking up unrefreshed, and the presence of lower abdominal pain or headaches.
To date, around 1,750 participants in the BSRBR-AS have completed the fibromyalgia criteria, Dr. Macfarlane said.
Across the board, baseline measures of disease activity were lower in patients who met the fibromyalgia criteria versus those who did not. This included the BASDAI and the Bath Ankylosing Spondylitis Functional Index, where scores were approximately 6.5 and 4.5 for each measure.
“Quality of life was significantly lower in those who were fibromyalgia positive,” Dr. Macfarlane said. Indeed, whatever the measure used, from the disease-specific Ankylosing Spondylitis Quality of Life (ASQoL) Scale to the general EuroQoL Quality of Life Scale, there were significant differences between those who did and did not meet fibromyalgia criteria. There were also higher scores for depression, anxiety, poorer-quality sleep, and higher levels of fatigue.
Patients treated with TNFi therapy showed improvement in both BASDAI and ASQoL scores regardless of whether they met fibromyalgia criteria, but crucially, the responses were still lower and significantly different from those without fibromyalgia.
An ASAS20 response to TNFi therapy was met by “slightly fewer” patients who met the fibromyalgia criteria than by those who did not at all follow-up points: at 3 months (about 35% vs. 45%), 6 months (about 58% vs. 61%), and 12 months (about 60% vs. 62%).
A high score on the Symptom Severity Scale but not the Widespread Pain Index of the fibromyalgia criteria was associated with a lower response to TNFi therapy at 3 months. “Such patients may benefit from the use of TNFi and nonpharmacological therapy,” Dr. Macfarlane said.
The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
SOURCE: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
REPORTING FROM RHEUMATOLOGY 2018
Key clinical point: Comorbid axial spondyloarthritis and fibromyalgia are associated with a lower response to biologic therapy.
Major finding: About 35% vs. 45% of patients who did and did not meet research criteria for fibromyalgia had an ASAS20 response at 3 months.
Study details: Data on 1,750 participants of the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS).
Disclosures: The BSRBR-AS is funded by the British Society for Rheumatology, which in turn receives funding from AbbVie, Pfizer, and UCB. Dr. Macfarlane did not provide any disclosures but has previously acknowledged receiving an honorarium from Pfizer and research funding from AbbVie and Pfizer for the Scotland Registry for Ankylosing Spondylitis study.
Source: Macfarlane GJ et al. Rheumatology. 2018;57(Suppl. 3):key075.183.
Tailored hemophilia prophylaxis could cut costs
Tailored frequency-escalated prophylaxis produced good outcomes with little arthropathy among boys with hemophilia A, according to findings from a prospective study.
The potential to use smaller amounts of clotting factor concentrates (CFCs) also offers a possible cost savings, Brian M. Feldman, MD, of the Hospital for Sick Children, Toronto, and his colleagues reported in the Lancet Haematology.
Prophylactic treatment to prevent bleeding episodes and avoid long term complications using regular CFCs is very effective but also very expensive. The Canadian Hemophilia Prophylaxis Study (CHPS) began 2 decades ago with the premise that, since CFC use accounts for most of the financial burden in severe hemophilia and because primary prophylaxis is started at a very young age, the burden on both the patient and the health care system could potentially be reduced by starting prophylaxis with CFC infusions at reduced frequency intervals. The individual’s subsequent bleeding episodes would then determine how the dose and frequency could be tailored.
In the study, 56 boys between the ages of 1 and 2.5 years with severe hemophilia A from 12 Canadian centers were enrolled in the CHPS, with a median time in the study of 10.2 years. Treatment was with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once weekly prophylaxis with 50 IU/kg and then escalating in frequency with appropriate dose adjustments as needed (step 1). The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores at completion of the study.
Participants were able to stay on once a week prophylaxis, without unacceptable bleeding, until a median age of 4.5 years. At this time, boys who developed unacceptable bleeding were escalated to twice-weekly prophylaxis at 30 IU/kg (step 2). The median age for beginning alternate day prophylaxis at 25 IU/kg (step 3) was 9.9 years of age.
The median annual SHL-rFVIII use was 3,582 IU/kg at age 2 years (n = 56), 4,041 IU/kg at age 6 years (n = 53), 3,638 IU/kg at age 10 years (n = 40), and 3,663 IU/kg at 14 years of age (n = 18). Overall adherence to the tailored regimen was a median of 86%, and no treatment-related safety events were observed during the study, including central venous catheter infections.
The median use of SHL-rFVIII on the tailored frequency-escalated prophylaxis is considerably less than the 6,000 IU/kg per year used in standard prophylaxis regimens, the researchers noted.
“We have previously shown, with a formal cost-benefit analysis using the value-of-information approach, that tailored frequency escalated prophylaxis provides substantial cost-benefit in a variety of scenarios. Our results from this study lend further support to these findings,” they wrote.
The median annualized index joint bleeding rate was 0.95 per year, but 30% of the boys in the study experienced “unacceptable breakthrough bleeding” during the study.
Overall joint health was “well preserved,” according to the researchers. The median Colorado Child Physical Examination Score at the end of the CHPS was 1 (range 0-12) for the left ankle and 1 for the right ankle, with all other joints having a median score of 0.
Activities of daily living and physical function, as well as health-related quality of life were generally good, the researchers reported.
The study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and by the Bayer/Canadian Blood Services/Héma-Québec Partnership Fund. Subsequent renewals were funded by Bayer. Dr. Feldman reported grants from Bayer during the conduct of the study and grants from Baxter/Baxalta/Shire outside the submitted work. Several coauthors also report multiple relationships with industry.
SOURCE: Feldman BM et al. Lancet Haematol. 2018 May 3. doi: 10.1016/S2352-3026(18)30048-6.
Tailored frequency-escalated prophylaxis produced good outcomes with little arthropathy among boys with hemophilia A, according to findings from a prospective study.
The potential to use smaller amounts of clotting factor concentrates (CFCs) also offers a possible cost savings, Brian M. Feldman, MD, of the Hospital for Sick Children, Toronto, and his colleagues reported in the Lancet Haematology.
Prophylactic treatment to prevent bleeding episodes and avoid long term complications using regular CFCs is very effective but also very expensive. The Canadian Hemophilia Prophylaxis Study (CHPS) began 2 decades ago with the premise that, since CFC use accounts for most of the financial burden in severe hemophilia and because primary prophylaxis is started at a very young age, the burden on both the patient and the health care system could potentially be reduced by starting prophylaxis with CFC infusions at reduced frequency intervals. The individual’s subsequent bleeding episodes would then determine how the dose and frequency could be tailored.
In the study, 56 boys between the ages of 1 and 2.5 years with severe hemophilia A from 12 Canadian centers were enrolled in the CHPS, with a median time in the study of 10.2 years. Treatment was with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once weekly prophylaxis with 50 IU/kg and then escalating in frequency with appropriate dose adjustments as needed (step 1). The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores at completion of the study.
Participants were able to stay on once a week prophylaxis, without unacceptable bleeding, until a median age of 4.5 years. At this time, boys who developed unacceptable bleeding were escalated to twice-weekly prophylaxis at 30 IU/kg (step 2). The median age for beginning alternate day prophylaxis at 25 IU/kg (step 3) was 9.9 years of age.
The median annual SHL-rFVIII use was 3,582 IU/kg at age 2 years (n = 56), 4,041 IU/kg at age 6 years (n = 53), 3,638 IU/kg at age 10 years (n = 40), and 3,663 IU/kg at 14 years of age (n = 18). Overall adherence to the tailored regimen was a median of 86%, and no treatment-related safety events were observed during the study, including central venous catheter infections.
The median use of SHL-rFVIII on the tailored frequency-escalated prophylaxis is considerably less than the 6,000 IU/kg per year used in standard prophylaxis regimens, the researchers noted.
“We have previously shown, with a formal cost-benefit analysis using the value-of-information approach, that tailored frequency escalated prophylaxis provides substantial cost-benefit in a variety of scenarios. Our results from this study lend further support to these findings,” they wrote.
The median annualized index joint bleeding rate was 0.95 per year, but 30% of the boys in the study experienced “unacceptable breakthrough bleeding” during the study.
Overall joint health was “well preserved,” according to the researchers. The median Colorado Child Physical Examination Score at the end of the CHPS was 1 (range 0-12) for the left ankle and 1 for the right ankle, with all other joints having a median score of 0.
Activities of daily living and physical function, as well as health-related quality of life were generally good, the researchers reported.
The study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and by the Bayer/Canadian Blood Services/Héma-Québec Partnership Fund. Subsequent renewals were funded by Bayer. Dr. Feldman reported grants from Bayer during the conduct of the study and grants from Baxter/Baxalta/Shire outside the submitted work. Several coauthors also report multiple relationships with industry.
SOURCE: Feldman BM et al. Lancet Haematol. 2018 May 3. doi: 10.1016/S2352-3026(18)30048-6.
Tailored frequency-escalated prophylaxis produced good outcomes with little arthropathy among boys with hemophilia A, according to findings from a prospective study.
The potential to use smaller amounts of clotting factor concentrates (CFCs) also offers a possible cost savings, Brian M. Feldman, MD, of the Hospital for Sick Children, Toronto, and his colleagues reported in the Lancet Haematology.
Prophylactic treatment to prevent bleeding episodes and avoid long term complications using regular CFCs is very effective but also very expensive. The Canadian Hemophilia Prophylaxis Study (CHPS) began 2 decades ago with the premise that, since CFC use accounts for most of the financial burden in severe hemophilia and because primary prophylaxis is started at a very young age, the burden on both the patient and the health care system could potentially be reduced by starting prophylaxis with CFC infusions at reduced frequency intervals. The individual’s subsequent bleeding episodes would then determine how the dose and frequency could be tailored.
In the study, 56 boys between the ages of 1 and 2.5 years with severe hemophilia A from 12 Canadian centers were enrolled in the CHPS, with a median time in the study of 10.2 years. Treatment was with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once weekly prophylaxis with 50 IU/kg and then escalating in frequency with appropriate dose adjustments as needed (step 1). The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores at completion of the study.
Participants were able to stay on once a week prophylaxis, without unacceptable bleeding, until a median age of 4.5 years. At this time, boys who developed unacceptable bleeding were escalated to twice-weekly prophylaxis at 30 IU/kg (step 2). The median age for beginning alternate day prophylaxis at 25 IU/kg (step 3) was 9.9 years of age.
The median annual SHL-rFVIII use was 3,582 IU/kg at age 2 years (n = 56), 4,041 IU/kg at age 6 years (n = 53), 3,638 IU/kg at age 10 years (n = 40), and 3,663 IU/kg at 14 years of age (n = 18). Overall adherence to the tailored regimen was a median of 86%, and no treatment-related safety events were observed during the study, including central venous catheter infections.
The median use of SHL-rFVIII on the tailored frequency-escalated prophylaxis is considerably less than the 6,000 IU/kg per year used in standard prophylaxis regimens, the researchers noted.
“We have previously shown, with a formal cost-benefit analysis using the value-of-information approach, that tailored frequency escalated prophylaxis provides substantial cost-benefit in a variety of scenarios. Our results from this study lend further support to these findings,” they wrote.
The median annualized index joint bleeding rate was 0.95 per year, but 30% of the boys in the study experienced “unacceptable breakthrough bleeding” during the study.
Overall joint health was “well preserved,” according to the researchers. The median Colorado Child Physical Examination Score at the end of the CHPS was 1 (range 0-12) for the left ankle and 1 for the right ankle, with all other joints having a median score of 0.
Activities of daily living and physical function, as well as health-related quality of life were generally good, the researchers reported.
The study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and by the Bayer/Canadian Blood Services/Héma-Québec Partnership Fund. Subsequent renewals were funded by Bayer. Dr. Feldman reported grants from Bayer during the conduct of the study and grants from Baxter/Baxalta/Shire outside the submitted work. Several coauthors also report multiple relationships with industry.
SOURCE: Feldman BM et al. Lancet Haematol. 2018 May 3. doi: 10.1016/S2352-3026(18)30048-6.
LANCET HAEMATOLOGY
Key clinical point:
Major finding: The median CPPES score at the end of the study was 1 (range 0-12) for the left ankle and 1 for the right ankle, with all other joints having a median score of 0.
Study details: Longitudinal design comprising 56 boys with severe hemophilia A who were followed for up to 16.1 years.
Disclosures: The study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and by the Bayer/Canadian Blood Services/Héma-Québec Partnership Fund. Subsequent renewals were funded by Bayer. Dr. Feldman reported grants from Bayer during the conduct of the study and grants from Baxter/Baxalta/Shire outside the submitted work. Several coauthors also report multiple relationships with industry.
Source: Feldman BM et al. Lancet Haematol. 2018 May 3. doi: 10.1016/S2352-3026(18)30048-6.
Congress passes ‘right to try’ legislation
Both houses of Congress have now approved a bill to provide terminally ill patients with access to experimental treatments, despite opposition from many Democrats and more than 100 patient and physician groups. President Trump is expected to sign the legislation.
By a vote of 250-169, the House passed S. 204, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 on May 22. All Republication House members voted for the bill, as did 22 Democrats. The Senate had passed the bill by unanimous consent in August 2017.
“This is dangerous legislation that threatens FDA’s [Food and Drug Administration’s] authority over insuring that medical treatments are effective,” Rep. Frank Pallone (D-N.J.), ranking member of the House Energy and Commerce Committee, said during the debate on the bill. “This bill needlessly exposes vulnerable patients to the risk of unproven medications.”
He noted the language will apply broadly to anyone who has been diagnosed with a disease but may not be terminal.
“The term ‘life-threatening disease or condition’ could include chronic and often manageable diseases, such as diabetes or chronic heart failure,” he said. “If all patients with diabetes and other chronic but manageable illnesses were eligible, you have greatly expanded the scope of the legislation well beyond the scope of most state laws and FDA’s expanded access program. This exposes an even greater number of patients to risk and undermines our clinical trial program by diverting patients from trials that could support full approval to the alternate pathway.”
The law notes that the experimental drug must have cleared phase 1 testing and experimentation, and development and testing must be ongoing. Treating physicians will not be compensated for certifying a patient as eligible to gain access to an investigational drug.
Patient and physician groups, including the American Society of Clinical Oncology, Friends of Cancer Research, American Lung Association, Cystic Fibrosis Foundation, and National Organization for Rare Disorders, voiced their opposition in a May 21 letter to House Republican and Democratic leaders.
“The Senate version of the legislation is less safe than the pathway proposed in the House version and is dangerous compared to the current [FDA] expanded access program,” according to the groups. “Both House and Senate versions would also remove FDA’s consultation on dosing, route of administration, dosing schedule, and other important safety measures available under FDA’s current expanded access program.”
The organizations noted that, while they did not support the House version, it “includes improved patient safeguards compared to the Senate version. The Senate version would negatively impact patient safety substantially, and our collective organizations are strongly opposed.”
President Trump has signaled he will sign the bill.
Both houses of Congress have now approved a bill to provide terminally ill patients with access to experimental treatments, despite opposition from many Democrats and more than 100 patient and physician groups. President Trump is expected to sign the legislation.
By a vote of 250-169, the House passed S. 204, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 on May 22. All Republication House members voted for the bill, as did 22 Democrats. The Senate had passed the bill by unanimous consent in August 2017.
“This is dangerous legislation that threatens FDA’s [Food and Drug Administration’s] authority over insuring that medical treatments are effective,” Rep. Frank Pallone (D-N.J.), ranking member of the House Energy and Commerce Committee, said during the debate on the bill. “This bill needlessly exposes vulnerable patients to the risk of unproven medications.”
He noted the language will apply broadly to anyone who has been diagnosed with a disease but may not be terminal.
“The term ‘life-threatening disease or condition’ could include chronic and often manageable diseases, such as diabetes or chronic heart failure,” he said. “If all patients with diabetes and other chronic but manageable illnesses were eligible, you have greatly expanded the scope of the legislation well beyond the scope of most state laws and FDA’s expanded access program. This exposes an even greater number of patients to risk and undermines our clinical trial program by diverting patients from trials that could support full approval to the alternate pathway.”
The law notes that the experimental drug must have cleared phase 1 testing and experimentation, and development and testing must be ongoing. Treating physicians will not be compensated for certifying a patient as eligible to gain access to an investigational drug.
Patient and physician groups, including the American Society of Clinical Oncology, Friends of Cancer Research, American Lung Association, Cystic Fibrosis Foundation, and National Organization for Rare Disorders, voiced their opposition in a May 21 letter to House Republican and Democratic leaders.
“The Senate version of the legislation is less safe than the pathway proposed in the House version and is dangerous compared to the current [FDA] expanded access program,” according to the groups. “Both House and Senate versions would also remove FDA’s consultation on dosing, route of administration, dosing schedule, and other important safety measures available under FDA’s current expanded access program.”
The organizations noted that, while they did not support the House version, it “includes improved patient safeguards compared to the Senate version. The Senate version would negatively impact patient safety substantially, and our collective organizations are strongly opposed.”
President Trump has signaled he will sign the bill.
Both houses of Congress have now approved a bill to provide terminally ill patients with access to experimental treatments, despite opposition from many Democrats and more than 100 patient and physician groups. President Trump is expected to sign the legislation.
By a vote of 250-169, the House passed S. 204, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 on May 22. All Republication House members voted for the bill, as did 22 Democrats. The Senate had passed the bill by unanimous consent in August 2017.
“This is dangerous legislation that threatens FDA’s [Food and Drug Administration’s] authority over insuring that medical treatments are effective,” Rep. Frank Pallone (D-N.J.), ranking member of the House Energy and Commerce Committee, said during the debate on the bill. “This bill needlessly exposes vulnerable patients to the risk of unproven medications.”
He noted the language will apply broadly to anyone who has been diagnosed with a disease but may not be terminal.
“The term ‘life-threatening disease or condition’ could include chronic and often manageable diseases, such as diabetes or chronic heart failure,” he said. “If all patients with diabetes and other chronic but manageable illnesses were eligible, you have greatly expanded the scope of the legislation well beyond the scope of most state laws and FDA’s expanded access program. This exposes an even greater number of patients to risk and undermines our clinical trial program by diverting patients from trials that could support full approval to the alternate pathway.”
The law notes that the experimental drug must have cleared phase 1 testing and experimentation, and development and testing must be ongoing. Treating physicians will not be compensated for certifying a patient as eligible to gain access to an investigational drug.
Patient and physician groups, including the American Society of Clinical Oncology, Friends of Cancer Research, American Lung Association, Cystic Fibrosis Foundation, and National Organization for Rare Disorders, voiced their opposition in a May 21 letter to House Republican and Democratic leaders.
“The Senate version of the legislation is less safe than the pathway proposed in the House version and is dangerous compared to the current [FDA] expanded access program,” according to the groups. “Both House and Senate versions would also remove FDA’s consultation on dosing, route of administration, dosing schedule, and other important safety measures available under FDA’s current expanded access program.”
The organizations noted that, while they did not support the House version, it “includes improved patient safeguards compared to the Senate version. The Senate version would negatively impact patient safety substantially, and our collective organizations are strongly opposed.”
President Trump has signaled he will sign the bill.
Breakthrough in noninvasive assessment of multivessel CAD
PARIS – A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire, in a prespecified secondary analysis of the SYNTAX II study.
That noninvasive method uses fractional flow reserve calculated from computed tomographic angiography, Carlos Collet, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
The results were hailed as a harbinger of a coming era in which interventional decision making will be based entirely upon noninvasively acquired anatomic and physiologic data. Conventional diagnostic angiography is predicted to fall by the wayside, with resultant savings in time and cost as well as avoidance of the risks of percutaneous diagnostic angiography, which entails considerably more radiation exposure than does noninvasive CT angiography (CTA).
“We are on the verge of a major change,” said Patrick W. Serruys, MD, PhD, professor of cardiology at Imperial College London, who was the senior coinvestigator in the study. “I think that the next disruptive moment in cardiology will be the introduction of the new generation of multislice CT scans replacing conventional cineangiography in the next 5-10 years. For the interventional cardiologist, to have the results of a multislice CT scan the day before a procedure is a wonderful bonus. You know in advance what you’re going to see, you can develop your treatment strategy, and you can spare contrast.”
Compared with conventional invasive angiographic assessment with the use of an intracoronary pressure wire to measure iFR, the noninvasively calculated SYNTAX II score had 95% sensitivity and 61% specificity for detection of functionally significant stenosis, with a positive predictive value of 81% and a negative predictive value of 87%. And this was achieved using older scanners and software considerably less accurate than today’s rapidly evolving state of the art, Dr. Collet noted.
Background
The original landmark SYNTAX trial led to development of an anatomically based SYNTAX score for use in stratifying risk and guiding treatment planning – coronary artery bypass grafting versus PCI – in patients with multivessel CAD. Both the U.S. and European guidelines recommend the use of this score, based on invasive angiography, giving it a Class IIa and I recommendation, respectively. Patients with a low-risk SYNTAX score of 22 or less were shown to have similar outcomes with PCI and coronary artery bypass grafting, while those with a score of 23 or more had better outcomes at 5-year follow-up with CABG.
Subsequently, incorporation of clinical characteristics formed the basis of the updated SYNTAX II score, with enhanced predictive accuracy allowing for projections of 4-year all-cause mortality with CABG versus PCI in a given patient (www.syntaxscore.com). The new SYNTAX II substudy takes things a giant step further by rendering the coronary imaging and physiology assessment noninvasive.
Simultaneous with Dr. Collet’s presentation at EuroPCR 2018, the study results were published in the Journal of the American College of Cardiology.
In an accompanying editorial, Bjarne L. Norgaard, MD, PhD, of Aarhus (Denmark) University and coauthors enthused, “These data suggest that we may be entering a new era in the management of CAD. The days of having patients entering the catheterization laboratory with nothing more than symptoms and a positive stress test result may be coming to an end. This study may be signaling a shifting paradigm in which CAD is diagnosed and thoroughly characterized noninvasively, and revascularization planning made in a collaborative fashion integrating the heart team, and a wealth of noninvasive data that will hopefully lead to more effective and cost-efficient revascularization strategies.”
What’s next
Elsewhere at EuroPCR 2018, Dr. Serruys presented the results of the SYNTAX III Revolution Trial, which randomized six pairs of heart teams – each comprising an interventional cardiologist, surgeon, and radiologist – to collectively assess and plan revascularization strategies for 223 patients with left main or triple-vessel CAD. One heart team in each pair was provided with a patient’s noninvasive CTA and FFR results, while the other team was given only the results of conventional angiography.
“There was almost perfect agreement between the heart teams on their decisions,” according to Dr. Serruys. “We were impressed that the surgeons were enthusiastic about the prospect of operating based on multislice CT alone.
On the basis of this evidence that heart teams found, the noninvasive assessment to be acceptable, he and his coinvestigators are organizing a multicenter trial to assess the feasibility and safety of the fully noninvasive stratification, compared with conventional angiography and invasive physiologic assessment of lesions. The primary safety endpoint will be the 1-month patency of bypass grafts.
The multislice scanner used in the SYNTAX III Revolution trial was the General Electric Revolution CT scanner, which enables imaging of the heart during a single heart beat. But Dr. Serruys said most of the big medical imaging companies with an eye to the near future are now developing multislice scanners specifically for the heart.
“They cost half the price and take only half the space of conventional scanners. I think these small units – which are not used for the brain, the abdomen, and all the rest – are going to play a big role in cardiology,” he predicted.
William Wijns, MD, codirector of EuroPCR, called the results of the SYNTAX II and SYNTAX III Revolution studies “transformative.” He and the other meeting organizers highlighted the studies in a special “deep-dive” session, which he urged younger interventionalists in particular to attend because he believes it’s likely they will be relying on these noninvasive assessments in the near future.
The SYNTAX III Revolution trial was sponsored by the European Cardiovascular Research Institute with support from GE Healthcare and HeartFlow. Dr. Serruys reported having no financial relationship with either company.
SOURCE: Collet C. EuroPCR 2018, Simultaneous publication (J Am Coll Cardiol 2018;71:40-53).
PARIS – A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire, in a prespecified secondary analysis of the SYNTAX II study.
That noninvasive method uses fractional flow reserve calculated from computed tomographic angiography, Carlos Collet, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
The results were hailed as a harbinger of a coming era in which interventional decision making will be based entirely upon noninvasively acquired anatomic and physiologic data. Conventional diagnostic angiography is predicted to fall by the wayside, with resultant savings in time and cost as well as avoidance of the risks of percutaneous diagnostic angiography, which entails considerably more radiation exposure than does noninvasive CT angiography (CTA).
“We are on the verge of a major change,” said Patrick W. Serruys, MD, PhD, professor of cardiology at Imperial College London, who was the senior coinvestigator in the study. “I think that the next disruptive moment in cardiology will be the introduction of the new generation of multislice CT scans replacing conventional cineangiography in the next 5-10 years. For the interventional cardiologist, to have the results of a multislice CT scan the day before a procedure is a wonderful bonus. You know in advance what you’re going to see, you can develop your treatment strategy, and you can spare contrast.”
Compared with conventional invasive angiographic assessment with the use of an intracoronary pressure wire to measure iFR, the noninvasively calculated SYNTAX II score had 95% sensitivity and 61% specificity for detection of functionally significant stenosis, with a positive predictive value of 81% and a negative predictive value of 87%. And this was achieved using older scanners and software considerably less accurate than today’s rapidly evolving state of the art, Dr. Collet noted.
Background
The original landmark SYNTAX trial led to development of an anatomically based SYNTAX score for use in stratifying risk and guiding treatment planning – coronary artery bypass grafting versus PCI – in patients with multivessel CAD. Both the U.S. and European guidelines recommend the use of this score, based on invasive angiography, giving it a Class IIa and I recommendation, respectively. Patients with a low-risk SYNTAX score of 22 or less were shown to have similar outcomes with PCI and coronary artery bypass grafting, while those with a score of 23 or more had better outcomes at 5-year follow-up with CABG.
Subsequently, incorporation of clinical characteristics formed the basis of the updated SYNTAX II score, with enhanced predictive accuracy allowing for projections of 4-year all-cause mortality with CABG versus PCI in a given patient (www.syntaxscore.com). The new SYNTAX II substudy takes things a giant step further by rendering the coronary imaging and physiology assessment noninvasive.
Simultaneous with Dr. Collet’s presentation at EuroPCR 2018, the study results were published in the Journal of the American College of Cardiology.
In an accompanying editorial, Bjarne L. Norgaard, MD, PhD, of Aarhus (Denmark) University and coauthors enthused, “These data suggest that we may be entering a new era in the management of CAD. The days of having patients entering the catheterization laboratory with nothing more than symptoms and a positive stress test result may be coming to an end. This study may be signaling a shifting paradigm in which CAD is diagnosed and thoroughly characterized noninvasively, and revascularization planning made in a collaborative fashion integrating the heart team, and a wealth of noninvasive data that will hopefully lead to more effective and cost-efficient revascularization strategies.”
What’s next
Elsewhere at EuroPCR 2018, Dr. Serruys presented the results of the SYNTAX III Revolution Trial, which randomized six pairs of heart teams – each comprising an interventional cardiologist, surgeon, and radiologist – to collectively assess and plan revascularization strategies for 223 patients with left main or triple-vessel CAD. One heart team in each pair was provided with a patient’s noninvasive CTA and FFR results, while the other team was given only the results of conventional angiography.
“There was almost perfect agreement between the heart teams on their decisions,” according to Dr. Serruys. “We were impressed that the surgeons were enthusiastic about the prospect of operating based on multislice CT alone.
On the basis of this evidence that heart teams found, the noninvasive assessment to be acceptable, he and his coinvestigators are organizing a multicenter trial to assess the feasibility and safety of the fully noninvasive stratification, compared with conventional angiography and invasive physiologic assessment of lesions. The primary safety endpoint will be the 1-month patency of bypass grafts.
The multislice scanner used in the SYNTAX III Revolution trial was the General Electric Revolution CT scanner, which enables imaging of the heart during a single heart beat. But Dr. Serruys said most of the big medical imaging companies with an eye to the near future are now developing multislice scanners specifically for the heart.
“They cost half the price and take only half the space of conventional scanners. I think these small units – which are not used for the brain, the abdomen, and all the rest – are going to play a big role in cardiology,” he predicted.
William Wijns, MD, codirector of EuroPCR, called the results of the SYNTAX II and SYNTAX III Revolution studies “transformative.” He and the other meeting organizers highlighted the studies in a special “deep-dive” session, which he urged younger interventionalists in particular to attend because he believes it’s likely they will be relying on these noninvasive assessments in the near future.
The SYNTAX III Revolution trial was sponsored by the European Cardiovascular Research Institute with support from GE Healthcare and HeartFlow. Dr. Serruys reported having no financial relationship with either company.
SOURCE: Collet C. EuroPCR 2018, Simultaneous publication (J Am Coll Cardiol 2018;71:40-53).
PARIS – A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire, in a prespecified secondary analysis of the SYNTAX II study.
That noninvasive method uses fractional flow reserve calculated from computed tomographic angiography, Carlos Collet, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
The results were hailed as a harbinger of a coming era in which interventional decision making will be based entirely upon noninvasively acquired anatomic and physiologic data. Conventional diagnostic angiography is predicted to fall by the wayside, with resultant savings in time and cost as well as avoidance of the risks of percutaneous diagnostic angiography, which entails considerably more radiation exposure than does noninvasive CT angiography (CTA).
“We are on the verge of a major change,” said Patrick W. Serruys, MD, PhD, professor of cardiology at Imperial College London, who was the senior coinvestigator in the study. “I think that the next disruptive moment in cardiology will be the introduction of the new generation of multislice CT scans replacing conventional cineangiography in the next 5-10 years. For the interventional cardiologist, to have the results of a multislice CT scan the day before a procedure is a wonderful bonus. You know in advance what you’re going to see, you can develop your treatment strategy, and you can spare contrast.”
Compared with conventional invasive angiographic assessment with the use of an intracoronary pressure wire to measure iFR, the noninvasively calculated SYNTAX II score had 95% sensitivity and 61% specificity for detection of functionally significant stenosis, with a positive predictive value of 81% and a negative predictive value of 87%. And this was achieved using older scanners and software considerably less accurate than today’s rapidly evolving state of the art, Dr. Collet noted.
Background
The original landmark SYNTAX trial led to development of an anatomically based SYNTAX score for use in stratifying risk and guiding treatment planning – coronary artery bypass grafting versus PCI – in patients with multivessel CAD. Both the U.S. and European guidelines recommend the use of this score, based on invasive angiography, giving it a Class IIa and I recommendation, respectively. Patients with a low-risk SYNTAX score of 22 or less were shown to have similar outcomes with PCI and coronary artery bypass grafting, while those with a score of 23 or more had better outcomes at 5-year follow-up with CABG.
Subsequently, incorporation of clinical characteristics formed the basis of the updated SYNTAX II score, with enhanced predictive accuracy allowing for projections of 4-year all-cause mortality with CABG versus PCI in a given patient (www.syntaxscore.com). The new SYNTAX II substudy takes things a giant step further by rendering the coronary imaging and physiology assessment noninvasive.
Simultaneous with Dr. Collet’s presentation at EuroPCR 2018, the study results were published in the Journal of the American College of Cardiology.
In an accompanying editorial, Bjarne L. Norgaard, MD, PhD, of Aarhus (Denmark) University and coauthors enthused, “These data suggest that we may be entering a new era in the management of CAD. The days of having patients entering the catheterization laboratory with nothing more than symptoms and a positive stress test result may be coming to an end. This study may be signaling a shifting paradigm in which CAD is diagnosed and thoroughly characterized noninvasively, and revascularization planning made in a collaborative fashion integrating the heart team, and a wealth of noninvasive data that will hopefully lead to more effective and cost-efficient revascularization strategies.”
What’s next
Elsewhere at EuroPCR 2018, Dr. Serruys presented the results of the SYNTAX III Revolution Trial, which randomized six pairs of heart teams – each comprising an interventional cardiologist, surgeon, and radiologist – to collectively assess and plan revascularization strategies for 223 patients with left main or triple-vessel CAD. One heart team in each pair was provided with a patient’s noninvasive CTA and FFR results, while the other team was given only the results of conventional angiography.
“There was almost perfect agreement between the heart teams on their decisions,” according to Dr. Serruys. “We were impressed that the surgeons were enthusiastic about the prospect of operating based on multislice CT alone.
On the basis of this evidence that heart teams found, the noninvasive assessment to be acceptable, he and his coinvestigators are organizing a multicenter trial to assess the feasibility and safety of the fully noninvasive stratification, compared with conventional angiography and invasive physiologic assessment of lesions. The primary safety endpoint will be the 1-month patency of bypass grafts.
The multislice scanner used in the SYNTAX III Revolution trial was the General Electric Revolution CT scanner, which enables imaging of the heart during a single heart beat. But Dr. Serruys said most of the big medical imaging companies with an eye to the near future are now developing multislice scanners specifically for the heart.
“They cost half the price and take only half the space of conventional scanners. I think these small units – which are not used for the brain, the abdomen, and all the rest – are going to play a big role in cardiology,” he predicted.
William Wijns, MD, codirector of EuroPCR, called the results of the SYNTAX II and SYNTAX III Revolution studies “transformative.” He and the other meeting organizers highlighted the studies in a special “deep-dive” session, which he urged younger interventionalists in particular to attend because he believes it’s likely they will be relying on these noninvasive assessments in the near future.
The SYNTAX III Revolution trial was sponsored by the European Cardiovascular Research Institute with support from GE Healthcare and HeartFlow. Dr. Serruys reported having no financial relationship with either company.
SOURCE: Collet C. EuroPCR 2018, Simultaneous publication (J Am Coll Cardiol 2018;71:40-53).
REPORTING FROM EUROPCR 2018
Key clinical point:
Major finding: A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel CAD by means of fractional flow reserve calculated from CT angiography yielded results comparable to conventional pressure-wire-based invasive angiographic assessment.
Study details: This prespecified secondary analysis of the SYNTAX II trial compared the results of noninvasive assessment of patients with triple-vessel CAD using FFR calculated from CT angiography with conventional angiography plus an invasive pressure wire.
Disclosures: The study was sponsored by the European Cardiovascular Research Institute with research grant support from Volcano and Boston Scientific. The presenter reported financial relationships with half a dozen medical device companies, but neither of those two.
Source: Collet C. EuroPCR 2018, simultaneous publication (J Am Coll Cardiol 2018;71:40-53).
A fib ablation in HFrEF patients gains momentum
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.
This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).
This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).
In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.
The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.
“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.
Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.
Despite these limitations, in trying to synthesize the CABANA and CASTLE-AF results, several electrophysiologists who heard the results agreed with Dr. Packer that the CABANA results confirmed the CASTLE-AF findings and helped strengthen the case for strongly considering AF ablation as first-line treatment in patients with heart failure.
“It’s clear that sinus rhythm is important in patients with heart failure. CASTLE-AF and now these results; that’s very strong to me,” said Eric N. Prystowsky, MD, a cardiac electrophysiologist with the St. Vincent Medical Group in Indianapolis and designated discussant for CABANA at the meeting.
“It’s confirmatory,” said Nassir F. Marrouche, MD, lead investigator for CASTLE-AF, and professor and director of the electrophysiology laboratory at the University of Utah in Salt Lake City.
The “signal” of benefit from AF ablation in heart failure patients in CABANA “replicates what was seen in CASTLE-AF. The results are highly consistent and very important regarding how to treat patients with AF and heart failure,” said Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “The data strongly suggest that catheter ablation is helpful for restoring and preserving [heart] muscle function,” Dr. Ruskin said in a video interview. He noted that AF occurs in at least about a quarter of heart failure patients.
Other cardiologists at the meeting noted that, on the basis of the CASTLE-AF results alone, they have already become more aggressive about treating AF with ablation in patients with heart failure in routine practice.
“It adds to the armamentarium for treatment of patients with heart failure,” said Johannes Brachmann, MD, professor and chief of cardiology at the Coburg (Germany) Clinic and a senior coinvestigator for CASTLE-AF.
William T. Abraham, MD, a heart failure specialist at The Ohio State University in Columbus, offered a broader perspective on where AF diagnosis, treatment, and ablation currently stand in U.S. heart failure practice.
“There is a very tight link between AF burden and worse outcomes in heart failure, so there is something intuitively appealing about restoring sinus rhythm in heart failure patients. I think most heart failure clinicians believe, like me, that heart failure patients with AF benefit from restoration of normal sinus rhythm. But I don’t believe that the CASTLE-AF results have so far had much impact on practice, in part because it was a relatively small study. The heart failure community is looking for some confirmation,” said Dr. Abraham, professor and director of cardiovascular medicine at Ohio State.
“I think the CABANA results are encouraging, but they came from only 15% of the enrolled patients who also had heart failure. CABANA adds to our knowledge, but I’m not sure it’s definitive for the heart failure population. I’m not sure it tells us if you treat patients with heart failure with anti-arrhythmia drugs and successfully maintain sinus rhythm do those patients do just as well as those who get ablated,” he said in an interview. “I’d love to see a study of heart failure patients maintained in sinus rhythm with drugs compared with those treated with ablation.”
For most patients with heart failure, the coexistence of AF is identified because of AF symptoms, or when asymptomatic AF is found in recordings made by an implanted cardiac device. “I’m more aggressive about addressing asymptomatic AF in my heart failure patients, and I believe the heart failure community is moving rapidly in that direction because of the association between higher AF burden and worse heart failure outcomes,” Dr. Abraham said.
A more cautious view came from another heart failure specialist, Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “It’s pretty evident that in certain patients with heart failure AF ablation might be the right treatment, but is it every HFrEF patient with AF?” he wondered. “It’s nice to have more evidence so we can be more comfortable sending heart failure patients for ablation, but I want to see more information about the risk” from ablation in heart failure patients, “the sustainability of the effect, and the consequences of ablation.”
But the reservations expressed by cardiologists like Dr. Yancy contrasted with the views of colleagues who consider the current evidence much more convincing.
“It seems logical to look harder for AF” in heart failure patients, based on the accumulated evidence from CASTLE-AF and CABANA, said Dr. Ruskin. “I don’t think we can offer advice to heart failure physicians to screen their heart failure patients for AF, but if it’s seen I think we have some useful information on how to address it.”
CASTLE-AF was funded by Biotronik. CABANA received partial funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude. Dr. Packer has been a consultant to and has received research funding from Biosense Webster, Boston Scientific, Medtronic, and St. Jude, and also from several other companies. Dr. Prystowsky as been a consultant to CardioNet and Medtronic, he has an equity interest in Stereotaxis, and he receives fellowship support from Medtronic and St. Jude. Dr. Marrouche has been a consultant to Biosense Webster, Biotronik, Boston Scientific, and St. Jude. He has received research support from Medtronic, and he has had financial relationships with several other companies. Dr. Ruskin has been a consultant to Biosense Webster and Medtronic and several other companies, has an ownership interest in Amgen, Cameron Health, InfoBionic, Newpace, Portola, and Regeneron, and has a fiduciary role in Pharmaco-Kinesis. Dr. Russo and Dr. Yancy had no disclosures. Dr. Brachmann has been a consultant to and has received research funding from Biotronik, Boston Scientific, St. Jude, and several other companies. Dr. Abraham has been a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude.
EXPERT ANALYSIS FROM HEART RHYTHM 2018