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EADV: Prophylactic photodynamic therapy benefits transplant recipients
COPENHAGEN – Twice-yearly prophylactic photodynamic therapy for primary prevention of actinic keratoses and squamous cell carcinomas is a novel and effective strategy that addresses the problem of accelerated photocarcinogenesis in organ transplant recipients, according to an interim analysis of a multinational, randomized, controlled trial.
“The overall aim is to prevent squamous cell carcinoma development. Photodynamic therapy is well established for secondary prevention of further AKs, and these very early data show that it can also be used for primary prevention in very high-risk patients,” Dr. Katrine Togsverd-Bo said at the annual congress of the European Academy of Dermatology and Venereology.
Accelerated carcinogenesis on sun-exposed skin is a major concern in organ transplant recipients (OTRs). They experience early onset of multiple AKs, with field cancerization and up to a 100-fold increased risk of squamous cell carcinomas (SCCs). Moreover, their SCCs are at substantially greater risk of metastasis than SCCs occurring in the general population, noted Dr. Togsverd-Bo of Bispebjerg Hospital and the University of Copenhagen.
She presented an interim analysis of an ongoing 5-year prospective randomized trial in 50 renal transplant recipients at academic dermatology centers in Copenhagen, Oslo, and Gothenburg, Sweden. All participants had clinically normal-appearing skin at baseline, with no history of AKs or SCCs. They are undergoing twice-yearly, split-side photodynamic therapy (PDT) on the face, forearm, and hand, with the opposite side serving as the untreated control.
To date, 25 patients have completed 3 years of the study. At 3 years of prospective follow-up by blinded evaluators, 50% of patients had AKs on their untreated side, compared with 26% on the prophylactic PDT side. The collective number of AKs on untreated skin was 43, compared with just 8 AKs on PDT-treated skin. Seven patients had AKs only on their untreated side, six had AKs on both sides, and none had any AKs only on their PDT-treated side.
The twice-yearly prophylactic PDT regimen consists of a 3-hour application of 20% methyl aminolevulinate as a photosensitizer followed by applications of a conventional LED light at 37 J/cm2.
Dr. Togsverd-Bo reported having no financial conflicts regarding her study.
COPENHAGEN – Twice-yearly prophylactic photodynamic therapy for primary prevention of actinic keratoses and squamous cell carcinomas is a novel and effective strategy that addresses the problem of accelerated photocarcinogenesis in organ transplant recipients, according to an interim analysis of a multinational, randomized, controlled trial.
“The overall aim is to prevent squamous cell carcinoma development. Photodynamic therapy is well established for secondary prevention of further AKs, and these very early data show that it can also be used for primary prevention in very high-risk patients,” Dr. Katrine Togsverd-Bo said at the annual congress of the European Academy of Dermatology and Venereology.
Accelerated carcinogenesis on sun-exposed skin is a major concern in organ transplant recipients (OTRs). They experience early onset of multiple AKs, with field cancerization and up to a 100-fold increased risk of squamous cell carcinomas (SCCs). Moreover, their SCCs are at substantially greater risk of metastasis than SCCs occurring in the general population, noted Dr. Togsverd-Bo of Bispebjerg Hospital and the University of Copenhagen.
She presented an interim analysis of an ongoing 5-year prospective randomized trial in 50 renal transplant recipients at academic dermatology centers in Copenhagen, Oslo, and Gothenburg, Sweden. All participants had clinically normal-appearing skin at baseline, with no history of AKs or SCCs. They are undergoing twice-yearly, split-side photodynamic therapy (PDT) on the face, forearm, and hand, with the opposite side serving as the untreated control.
To date, 25 patients have completed 3 years of the study. At 3 years of prospective follow-up by blinded evaluators, 50% of patients had AKs on their untreated side, compared with 26% on the prophylactic PDT side. The collective number of AKs on untreated skin was 43, compared with just 8 AKs on PDT-treated skin. Seven patients had AKs only on their untreated side, six had AKs on both sides, and none had any AKs only on their PDT-treated side.
The twice-yearly prophylactic PDT regimen consists of a 3-hour application of 20% methyl aminolevulinate as a photosensitizer followed by applications of a conventional LED light at 37 J/cm2.
Dr. Togsverd-Bo reported having no financial conflicts regarding her study.
COPENHAGEN – Twice-yearly prophylactic photodynamic therapy for primary prevention of actinic keratoses and squamous cell carcinomas is a novel and effective strategy that addresses the problem of accelerated photocarcinogenesis in organ transplant recipients, according to an interim analysis of a multinational, randomized, controlled trial.
“The overall aim is to prevent squamous cell carcinoma development. Photodynamic therapy is well established for secondary prevention of further AKs, and these very early data show that it can also be used for primary prevention in very high-risk patients,” Dr. Katrine Togsverd-Bo said at the annual congress of the European Academy of Dermatology and Venereology.
Accelerated carcinogenesis on sun-exposed skin is a major concern in organ transplant recipients (OTRs). They experience early onset of multiple AKs, with field cancerization and up to a 100-fold increased risk of squamous cell carcinomas (SCCs). Moreover, their SCCs are at substantially greater risk of metastasis than SCCs occurring in the general population, noted Dr. Togsverd-Bo of Bispebjerg Hospital and the University of Copenhagen.
She presented an interim analysis of an ongoing 5-year prospective randomized trial in 50 renal transplant recipients at academic dermatology centers in Copenhagen, Oslo, and Gothenburg, Sweden. All participants had clinically normal-appearing skin at baseline, with no history of AKs or SCCs. They are undergoing twice-yearly, split-side photodynamic therapy (PDT) on the face, forearm, and hand, with the opposite side serving as the untreated control.
To date, 25 patients have completed 3 years of the study. At 3 years of prospective follow-up by blinded evaluators, 50% of patients had AKs on their untreated side, compared with 26% on the prophylactic PDT side. The collective number of AKs on untreated skin was 43, compared with just 8 AKs on PDT-treated skin. Seven patients had AKs only on their untreated side, six had AKs on both sides, and none had any AKs only on their PDT-treated side.
The twice-yearly prophylactic PDT regimen consists of a 3-hour application of 20% methyl aminolevulinate as a photosensitizer followed by applications of a conventional LED light at 37 J/cm2.
Dr. Togsverd-Bo reported having no financial conflicts regarding her study.
AT THE EADV CONGRESS
Key clinical point: Prophylactic photodynamic therapy is a new and effective strategy for primary prevention of actinic keratoses and squamous cell carcinomas in organ transplant recipients.
Major finding: At 3 years of follow-up, 25 renal transplant recipients collectively had 8 actinic keratoses on the side of their face, forearms, and hands treated with twice-yearly prophylactic photodynamic therapy, compared with 43 AKs on the untreated control side.
Data source: This is an interim 3-year analysis from an ongoing 5-year prospective multinational, randomized, controlled trial involving 50 renal transplant recipients.
Disclosures: The presenter reported having no financial conflicts regarding this ongoing study.
EADV: Latest gruesome twosome: Psoriasis spawns renal disease
COPENHAGEN – Severe psoriasis is an independent risk factor for serious renal disease – and psoriatic arthritis multiplies that risk even further, according to a Taiwanese national study.
“We think this might be related to the higher inflammatory status associated with psoriatic arthritis. For those with mild psoriasis without psoriatic arthritis, the risk was not increased,” Dr. Ching-Chi Chi said at the annual congress of the European Academy of Dermatology and Venereology.
The past decade has brought a mountain of data documenting that psoriasis, a chronic inflammatory dermatosis, is associated with increased risks of cardiovascular disease, diabetes, and other metabolic abnormalities, noted Dr. Chi, professor of dermatology at Chang Gung University in Taoyuan.
He presented a nationwide retrospective cohort study utilizing Taiwan’s national health insurance system, which covers more than 99% of the population. The study included 4,633 patients with psoriasis diagnosed by a dermatologist or rheumatologist since 2005 and 922,534 controls. A total of 453 patients were classified as having severe psoriasis based upon ever having received systemic treatment or phototherapy; the other 4,180 were classified as having mild psoriasis.
Among the controls there were 36,615 incident cases of chronic kidney disease (CKD) and 9,493 new cases of end-stage renal disease (ESRD) during the study period, translating to rates of 676 per 1,000,000 person-years and 172 per 1,000,000 person-years, respectively. In contrast, patients with severe psoriasis had an incident CKD rate of 2,160 per 1,000,000 person-years and an ESRD rate of 876 per 1,000,000 person-years.
In a Cox regression analysis adjusted for potential confounders including age, gender, comorbid cardiovascular disease, gout, hypertension, dyslipidemia, and use of NSAIDs, severe psoriasis was independently associated with a 1.9-fold increased risk of new-onset CKD and a 3-fold increased risk of ESRD.
Although mild psoriasis alone wasn’t associated with increased risk of renal disease, the 254 patients with mild psoriasis and psoriatic arthritis were at 1.3-fold increased risk of CKD and 2.5-fold increased risk of incident ESRD, compared with controls. Moreover, among the 93 patients with severe psoriasis plus psoriatic arthritis, the risks of incident CKD and ESRD were increased by 2.6- and 6.7-fold over the control subjects.
The new Taiwanese national study confirms earlier work by Dr. Joel M. Gelfand and his coinvestigators at the University of Pennsylvania, Philadelphia. Their population-based cohort study and nested cross-sectional study utilizing a huge U.K. electronic medical records database analyzed 136,529 patients with mild psoriasis, 7,354 with severe psoriasis, and nearly 690,000 matched controls and concluded that moderate to severe psoriasis is associated with an increased risk of stage 3-5 chronic kidney disease (BMJ. 2013 Oct 15;347:f5961).
He reported having no financial conflicts regarding this study.
This article was updated October 29, 2015.
COPENHAGEN – Severe psoriasis is an independent risk factor for serious renal disease – and psoriatic arthritis multiplies that risk even further, according to a Taiwanese national study.
“We think this might be related to the higher inflammatory status associated with psoriatic arthritis. For those with mild psoriasis without psoriatic arthritis, the risk was not increased,” Dr. Ching-Chi Chi said at the annual congress of the European Academy of Dermatology and Venereology.
The past decade has brought a mountain of data documenting that psoriasis, a chronic inflammatory dermatosis, is associated with increased risks of cardiovascular disease, diabetes, and other metabolic abnormalities, noted Dr. Chi, professor of dermatology at Chang Gung University in Taoyuan.
He presented a nationwide retrospective cohort study utilizing Taiwan’s national health insurance system, which covers more than 99% of the population. The study included 4,633 patients with psoriasis diagnosed by a dermatologist or rheumatologist since 2005 and 922,534 controls. A total of 453 patients were classified as having severe psoriasis based upon ever having received systemic treatment or phototherapy; the other 4,180 were classified as having mild psoriasis.
Among the controls there were 36,615 incident cases of chronic kidney disease (CKD) and 9,493 new cases of end-stage renal disease (ESRD) during the study period, translating to rates of 676 per 1,000,000 person-years and 172 per 1,000,000 person-years, respectively. In contrast, patients with severe psoriasis had an incident CKD rate of 2,160 per 1,000,000 person-years and an ESRD rate of 876 per 1,000,000 person-years.
In a Cox regression analysis adjusted for potential confounders including age, gender, comorbid cardiovascular disease, gout, hypertension, dyslipidemia, and use of NSAIDs, severe psoriasis was independently associated with a 1.9-fold increased risk of new-onset CKD and a 3-fold increased risk of ESRD.
Although mild psoriasis alone wasn’t associated with increased risk of renal disease, the 254 patients with mild psoriasis and psoriatic arthritis were at 1.3-fold increased risk of CKD and 2.5-fold increased risk of incident ESRD, compared with controls. Moreover, among the 93 patients with severe psoriasis plus psoriatic arthritis, the risks of incident CKD and ESRD were increased by 2.6- and 6.7-fold over the control subjects.
The new Taiwanese national study confirms earlier work by Dr. Joel M. Gelfand and his coinvestigators at the University of Pennsylvania, Philadelphia. Their population-based cohort study and nested cross-sectional study utilizing a huge U.K. electronic medical records database analyzed 136,529 patients with mild psoriasis, 7,354 with severe psoriasis, and nearly 690,000 matched controls and concluded that moderate to severe psoriasis is associated with an increased risk of stage 3-5 chronic kidney disease (BMJ. 2013 Oct 15;347:f5961).
He reported having no financial conflicts regarding this study.
This article was updated October 29, 2015.
COPENHAGEN – Severe psoriasis is an independent risk factor for serious renal disease – and psoriatic arthritis multiplies that risk even further, according to a Taiwanese national study.
“We think this might be related to the higher inflammatory status associated with psoriatic arthritis. For those with mild psoriasis without psoriatic arthritis, the risk was not increased,” Dr. Ching-Chi Chi said at the annual congress of the European Academy of Dermatology and Venereology.
The past decade has brought a mountain of data documenting that psoriasis, a chronic inflammatory dermatosis, is associated with increased risks of cardiovascular disease, diabetes, and other metabolic abnormalities, noted Dr. Chi, professor of dermatology at Chang Gung University in Taoyuan.
He presented a nationwide retrospective cohort study utilizing Taiwan’s national health insurance system, which covers more than 99% of the population. The study included 4,633 patients with psoriasis diagnosed by a dermatologist or rheumatologist since 2005 and 922,534 controls. A total of 453 patients were classified as having severe psoriasis based upon ever having received systemic treatment or phototherapy; the other 4,180 were classified as having mild psoriasis.
Among the controls there were 36,615 incident cases of chronic kidney disease (CKD) and 9,493 new cases of end-stage renal disease (ESRD) during the study period, translating to rates of 676 per 1,000,000 person-years and 172 per 1,000,000 person-years, respectively. In contrast, patients with severe psoriasis had an incident CKD rate of 2,160 per 1,000,000 person-years and an ESRD rate of 876 per 1,000,000 person-years.
In a Cox regression analysis adjusted for potential confounders including age, gender, comorbid cardiovascular disease, gout, hypertension, dyslipidemia, and use of NSAIDs, severe psoriasis was independently associated with a 1.9-fold increased risk of new-onset CKD and a 3-fold increased risk of ESRD.
Although mild psoriasis alone wasn’t associated with increased risk of renal disease, the 254 patients with mild psoriasis and psoriatic arthritis were at 1.3-fold increased risk of CKD and 2.5-fold increased risk of incident ESRD, compared with controls. Moreover, among the 93 patients with severe psoriasis plus psoriatic arthritis, the risks of incident CKD and ESRD were increased by 2.6- and 6.7-fold over the control subjects.
The new Taiwanese national study confirms earlier work by Dr. Joel M. Gelfand and his coinvestigators at the University of Pennsylvania, Philadelphia. Their population-based cohort study and nested cross-sectional study utilizing a huge U.K. electronic medical records database analyzed 136,529 patients with mild psoriasis, 7,354 with severe psoriasis, and nearly 690,000 matched controls and concluded that moderate to severe psoriasis is associated with an increased risk of stage 3-5 chronic kidney disease (BMJ. 2013 Oct 15;347:f5961).
He reported having no financial conflicts regarding this study.
This article was updated October 29, 2015.
AT THE EADV CONGRESS
Key clinical point: Patients with severe but not mild psoriasis are at increased risk of new-onset chronic kidney disease and end-stage renal disease.
Major finding: Severe psoriasis was independently associated with a 1.9-fold increased risk of new-onset CKD and a 3-fold increased risk of ESRD. Comorbid psoriatic arthritis further boosted those risks.
Data source: This retrospective cohort study included 4,633 consecutive patients diagnosed with psoriasis in Taiwan.
Disclosures: Dr. Chi reported having no financial conflicts regarding this government-funded study.
EADV: Long-term weight loss curbs psoriasis severity
COPENHAGEN – Long-term weight loss achieved by obese patients with psoriasis provides long-lasting reductions in psoriasis severity, Dr. Peter Jensen reported at the annual congress of the European Academy of Dermatology and Venereology.
He presented a prospective 64-week observational study that was a follow-up to his earlier 16-week randomized, controlled clinical trial. The earlier study (JAMA Dermatol. 2013 Jul;149[7]:795-801) generated enormous interest because it provided the first level I evidence that weight loss by obese psoriasis patients brings clinically meaningful improvement in their skin disease as well as achieving well-established metabolic and cardiovascular risk reduction benefits.
In the randomized trial, 60 consecutive obese patients with psoriasis and a mean baseline Psoriasis Area and Severity Index (PASI) of 5.4 and a body mass index of 34.4 kg/m2 were assigned to a dietary intervention or given general advice to eat healthy foods. The intervention entailed 8 weeks of a low-energy liquid diet featuring a daily total nutrition intake of 800-1,000 kcal in the form of fortified drinks and soups. This was followed by 8 weeks in which regular foods were reintroduced at 1,200 kcal/day. At week 16, the intervention group had lost an average of 15.4 kg more body weight than controls. Their mean PASI was 2.0 points lower as well, according to Dr. Jensen, a dermatologist at the University of Copenhagen.
In the observational follow-up study, the original control group was offered the opportunity to participate in the 16-week weight loss intervention. All patients were then prospectively followed for 48 weeks after completing the dietary intervention. Psoriasis medications weren’t changed during the study period. The questions Dr. Jensen and coinvestigators sought to answer through the follow-up study were, first, can patients keep the weight off long term without a structured maintenance program and, if so, do their PASI scores stay low or do they creep back up?
Only 32 of the original 60 patients completed the full 64-week study. Among the completers, as is typical in weight loss studies, there was a gradual weight regain. Nonetheless, at 64 weeks, patients still maintained a mean 10-kg weight loss, compared with baseline, or two-thirds of the weight loss achieved during the 16-week dietary intervention.
Most importantly from a dermatologic perspective, the positive effect upon disease severity was maintained despite the regain of one-third of the initial weight loss, with patients showing a clinically important mean 3-point reduction in PASI, compared with baseline, Dr. Jensen noted.
Audience members were enthusiastic about the study findings but asked if the results are widely applicable. In other words, was this an unusually highly motivated group of patients?
“Our experience is that people really would like to try this. It was no problem to get participation,” according to Dr. Jensen.
Study limitations included the small sample size and the fact that this was a patient cohort with relatively mild psoriasis. In the future, it would be informative to study the effects of weight loss in obese patients with higher baseline PASI scores, the dermatologist said.
The study was funded by the Danish Academy of Dermatology and various research foundations. Dr. Jensen reported having no financial conflicts.
COPENHAGEN – Long-term weight loss achieved by obese patients with psoriasis provides long-lasting reductions in psoriasis severity, Dr. Peter Jensen reported at the annual congress of the European Academy of Dermatology and Venereology.
He presented a prospective 64-week observational study that was a follow-up to his earlier 16-week randomized, controlled clinical trial. The earlier study (JAMA Dermatol. 2013 Jul;149[7]:795-801) generated enormous interest because it provided the first level I evidence that weight loss by obese psoriasis patients brings clinically meaningful improvement in their skin disease as well as achieving well-established metabolic and cardiovascular risk reduction benefits.
In the randomized trial, 60 consecutive obese patients with psoriasis and a mean baseline Psoriasis Area and Severity Index (PASI) of 5.4 and a body mass index of 34.4 kg/m2 were assigned to a dietary intervention or given general advice to eat healthy foods. The intervention entailed 8 weeks of a low-energy liquid diet featuring a daily total nutrition intake of 800-1,000 kcal in the form of fortified drinks and soups. This was followed by 8 weeks in which regular foods were reintroduced at 1,200 kcal/day. At week 16, the intervention group had lost an average of 15.4 kg more body weight than controls. Their mean PASI was 2.0 points lower as well, according to Dr. Jensen, a dermatologist at the University of Copenhagen.
In the observational follow-up study, the original control group was offered the opportunity to participate in the 16-week weight loss intervention. All patients were then prospectively followed for 48 weeks after completing the dietary intervention. Psoriasis medications weren’t changed during the study period. The questions Dr. Jensen and coinvestigators sought to answer through the follow-up study were, first, can patients keep the weight off long term without a structured maintenance program and, if so, do their PASI scores stay low or do they creep back up?
Only 32 of the original 60 patients completed the full 64-week study. Among the completers, as is typical in weight loss studies, there was a gradual weight regain. Nonetheless, at 64 weeks, patients still maintained a mean 10-kg weight loss, compared with baseline, or two-thirds of the weight loss achieved during the 16-week dietary intervention.
Most importantly from a dermatologic perspective, the positive effect upon disease severity was maintained despite the regain of one-third of the initial weight loss, with patients showing a clinically important mean 3-point reduction in PASI, compared with baseline, Dr. Jensen noted.
Audience members were enthusiastic about the study findings but asked if the results are widely applicable. In other words, was this an unusually highly motivated group of patients?
“Our experience is that people really would like to try this. It was no problem to get participation,” according to Dr. Jensen.
Study limitations included the small sample size and the fact that this was a patient cohort with relatively mild psoriasis. In the future, it would be informative to study the effects of weight loss in obese patients with higher baseline PASI scores, the dermatologist said.
The study was funded by the Danish Academy of Dermatology and various research foundations. Dr. Jensen reported having no financial conflicts.
COPENHAGEN – Long-term weight loss achieved by obese patients with psoriasis provides long-lasting reductions in psoriasis severity, Dr. Peter Jensen reported at the annual congress of the European Academy of Dermatology and Venereology.
He presented a prospective 64-week observational study that was a follow-up to his earlier 16-week randomized, controlled clinical trial. The earlier study (JAMA Dermatol. 2013 Jul;149[7]:795-801) generated enormous interest because it provided the first level I evidence that weight loss by obese psoriasis patients brings clinically meaningful improvement in their skin disease as well as achieving well-established metabolic and cardiovascular risk reduction benefits.
In the randomized trial, 60 consecutive obese patients with psoriasis and a mean baseline Psoriasis Area and Severity Index (PASI) of 5.4 and a body mass index of 34.4 kg/m2 were assigned to a dietary intervention or given general advice to eat healthy foods. The intervention entailed 8 weeks of a low-energy liquid diet featuring a daily total nutrition intake of 800-1,000 kcal in the form of fortified drinks and soups. This was followed by 8 weeks in which regular foods were reintroduced at 1,200 kcal/day. At week 16, the intervention group had lost an average of 15.4 kg more body weight than controls. Their mean PASI was 2.0 points lower as well, according to Dr. Jensen, a dermatologist at the University of Copenhagen.
In the observational follow-up study, the original control group was offered the opportunity to participate in the 16-week weight loss intervention. All patients were then prospectively followed for 48 weeks after completing the dietary intervention. Psoriasis medications weren’t changed during the study period. The questions Dr. Jensen and coinvestigators sought to answer through the follow-up study were, first, can patients keep the weight off long term without a structured maintenance program and, if so, do their PASI scores stay low or do they creep back up?
Only 32 of the original 60 patients completed the full 64-week study. Among the completers, as is typical in weight loss studies, there was a gradual weight regain. Nonetheless, at 64 weeks, patients still maintained a mean 10-kg weight loss, compared with baseline, or two-thirds of the weight loss achieved during the 16-week dietary intervention.
Most importantly from a dermatologic perspective, the positive effect upon disease severity was maintained despite the regain of one-third of the initial weight loss, with patients showing a clinically important mean 3-point reduction in PASI, compared with baseline, Dr. Jensen noted.
Audience members were enthusiastic about the study findings but asked if the results are widely applicable. In other words, was this an unusually highly motivated group of patients?
“Our experience is that people really would like to try this. It was no problem to get participation,” according to Dr. Jensen.
Study limitations included the small sample size and the fact that this was a patient cohort with relatively mild psoriasis. In the future, it would be informative to study the effects of weight loss in obese patients with higher baseline PASI scores, the dermatologist said.
The study was funded by the Danish Academy of Dermatology and various research foundations. Dr. Jensen reported having no financial conflicts.
AT THE EADV CONGRESS
Key clinical point: Long-term weight loss by obese patients with psoriasi pays dividends in terms of sustained clinically meaningful reduction in PASI scores.
Major finding: At 64 weeks of follow-up, obese patients were able to maintain two-thirds of the mean 15.4-kg weight loss achieved through a 16-week dietary intervention, and their mean PASI scores were 3 points lower than the mean score of 5.4 points at baseline.
Data source: This was a prospective observational study of 32 obese psoriasis patients who completed 48 weeks of additional follow-up after a 16-week low-energy dietary intervention.
Disclosures: The study was funded by the Danish Academy of Dermatology and various research foundations. The presenter reported having no financial conflicts.
EADV: Novel topical crisaborole shines in atopic dermatitis
COPENHAGEN – The nonsteroidal phosphodiesterase-4 inhibitor crisaborole aced all Food and Drug Administration–required efficacy and safety endpoints as a topical treatment for atopic dermatitis, according to results from a pair of pivotal phase III randomized trials.
“This is a fairly rapidly effective treatment,” explained Dr. Mark G. Lebwohl, who presented the findings at the annual congress of the European Academy of Dermatology and Venereology. “It has a favorable safety profile and has been studied in patients as young as 2 years of age. It may represent a new, safe, and efficacious treatment for patients 2 years of age and older with mild to moderate atopic dermatitis.”
Atopic dermatitis (AD) experts have long complained of a major unmet need for new, safe, and effective topical agents for AD, a condition that affects an estimated 18%-20% of children and 2%-10% of adults. Current treatment options all have drawbacks.
Topical steroids, long a treatment mainstay, are viewed by many parents with phobic mistrust of safety. And both FDA-approved topical calcineurin inhibitors carry black box warnings of possible cancer risk.
The two pivotal phase III studies, identical in design, included a total of 1,522 patients aged 2 years through adulthood with mild to moderate AD. Roughly 60% of patients had moderate disease, as defined by an Investigator’s Static Global Assessment (ISGA) score of 3 on a 0-4 scale; the other 40% had mild AD. The mean involved body surface area was 18%.
Participants were randomized two to one to crisaborole ointment 2% b.i.d. or vehicle for 28 days. Physicians assessed patients at baseline on day 1 of the study and again on days 8, 15, 22, 29, and 36. The primary endpoint was the proportion of patients on day 29 who had an ISGA of 0 or 1 – clear or almost clear – as well as at least a 2-point improvement from baseline on that scale.
In one of the trials, that endpoint was achieved in 32.8% of the crisaborole group, compared with 25.4% of controls.
“That 25% placebo response is actually fairly typical for atopic dermatitis studies,” according to Dr. Lebwohl, professor and chairman of the department of dermatology at Mount Sinai School of Medicine, New York.
In the other study, 31.4% of the crisaborole group and 18% of controls achieved the primary endpoint. In both studies, the difference was statistically significant in favor of topical crisaborole.
There were two prespecified secondary endpoints. One was time to treatment success, as defined by clear or almost clear. A “striking” significant difference between the study arms appeared as early as the first assessment, just 1 week into the trial, Dr. Lebwohl observed.
The other secondary endpoint was the FDA’s former efficacy standard, which required being clear or almost clear without the additional need for at least a 2-point ISGA improvement. That endpoint was achieved by 51.7% and 48.5% of crisaborole-treated patients in the two studies, compared with 40.6% and 29.7% of controls. Again, both differences were statistically significant.
No treatment-related serious adverse events occurred in either study. Mild application-site pain was slightly more common in the crisaborole-treated patients. But the rate of study discontinuations because of adverse events was identical between the crisaborole and control groups, at 1.2%. No differences in laboratory values, ECGs, or vital signs were noted between the two groups.
Dr. Lebwohl explained that boron is an essential element in crisaborole. The boron stimulates an increase in cyclic adenosine monophosphate levels, which in turn results in a steep reduction in production of inflammatory cytokines, including interleukins-4, -2, and -31, as well as tumor necrosis factor-alpha.
One audience member asked if it’s possible that crisaborole acts systemically rather than topically, given that patients averaged 18% body surface area involvement, and such a large area of damaged skin could conceivably allow the topical agent ready access to the circulation.
Dr. Lebwohl replied that systemic absorption of the drug was minor. “If you break down the results into patients with very low body surface areas – the lowest was 5% – those patients improved as well. So, I think it would be unlikely that this was a systemic effect.”
Anacor, which is developing the drug as a treatment for AD and other skin diseases, plans to file for marketing approval during the first half of 2016.
Anacor sponsored the two pivotal phase III randomized trials. Dr. Lebwohl declared having no financial conflicts of interest, because all funds went directly to the medical center in which he practices.
COPENHAGEN – The nonsteroidal phosphodiesterase-4 inhibitor crisaborole aced all Food and Drug Administration–required efficacy and safety endpoints as a topical treatment for atopic dermatitis, according to results from a pair of pivotal phase III randomized trials.
“This is a fairly rapidly effective treatment,” explained Dr. Mark G. Lebwohl, who presented the findings at the annual congress of the European Academy of Dermatology and Venereology. “It has a favorable safety profile and has been studied in patients as young as 2 years of age. It may represent a new, safe, and efficacious treatment for patients 2 years of age and older with mild to moderate atopic dermatitis.”
Atopic dermatitis (AD) experts have long complained of a major unmet need for new, safe, and effective topical agents for AD, a condition that affects an estimated 18%-20% of children and 2%-10% of adults. Current treatment options all have drawbacks.
Topical steroids, long a treatment mainstay, are viewed by many parents with phobic mistrust of safety. And both FDA-approved topical calcineurin inhibitors carry black box warnings of possible cancer risk.
The two pivotal phase III studies, identical in design, included a total of 1,522 patients aged 2 years through adulthood with mild to moderate AD. Roughly 60% of patients had moderate disease, as defined by an Investigator’s Static Global Assessment (ISGA) score of 3 on a 0-4 scale; the other 40% had mild AD. The mean involved body surface area was 18%.
Participants were randomized two to one to crisaborole ointment 2% b.i.d. or vehicle for 28 days. Physicians assessed patients at baseline on day 1 of the study and again on days 8, 15, 22, 29, and 36. The primary endpoint was the proportion of patients on day 29 who had an ISGA of 0 or 1 – clear or almost clear – as well as at least a 2-point improvement from baseline on that scale.
In one of the trials, that endpoint was achieved in 32.8% of the crisaborole group, compared with 25.4% of controls.
“That 25% placebo response is actually fairly typical for atopic dermatitis studies,” according to Dr. Lebwohl, professor and chairman of the department of dermatology at Mount Sinai School of Medicine, New York.
In the other study, 31.4% of the crisaborole group and 18% of controls achieved the primary endpoint. In both studies, the difference was statistically significant in favor of topical crisaborole.
There were two prespecified secondary endpoints. One was time to treatment success, as defined by clear or almost clear. A “striking” significant difference between the study arms appeared as early as the first assessment, just 1 week into the trial, Dr. Lebwohl observed.
The other secondary endpoint was the FDA’s former efficacy standard, which required being clear or almost clear without the additional need for at least a 2-point ISGA improvement. That endpoint was achieved by 51.7% and 48.5% of crisaborole-treated patients in the two studies, compared with 40.6% and 29.7% of controls. Again, both differences were statistically significant.
No treatment-related serious adverse events occurred in either study. Mild application-site pain was slightly more common in the crisaborole-treated patients. But the rate of study discontinuations because of adverse events was identical between the crisaborole and control groups, at 1.2%. No differences in laboratory values, ECGs, or vital signs were noted between the two groups.
Dr. Lebwohl explained that boron is an essential element in crisaborole. The boron stimulates an increase in cyclic adenosine monophosphate levels, which in turn results in a steep reduction in production of inflammatory cytokines, including interleukins-4, -2, and -31, as well as tumor necrosis factor-alpha.
One audience member asked if it’s possible that crisaborole acts systemically rather than topically, given that patients averaged 18% body surface area involvement, and such a large area of damaged skin could conceivably allow the topical agent ready access to the circulation.
Dr. Lebwohl replied that systemic absorption of the drug was minor. “If you break down the results into patients with very low body surface areas – the lowest was 5% – those patients improved as well. So, I think it would be unlikely that this was a systemic effect.”
Anacor, which is developing the drug as a treatment for AD and other skin diseases, plans to file for marketing approval during the first half of 2016.
Anacor sponsored the two pivotal phase III randomized trials. Dr. Lebwohl declared having no financial conflicts of interest, because all funds went directly to the medical center in which he practices.
COPENHAGEN – The nonsteroidal phosphodiesterase-4 inhibitor crisaborole aced all Food and Drug Administration–required efficacy and safety endpoints as a topical treatment for atopic dermatitis, according to results from a pair of pivotal phase III randomized trials.
“This is a fairly rapidly effective treatment,” explained Dr. Mark G. Lebwohl, who presented the findings at the annual congress of the European Academy of Dermatology and Venereology. “It has a favorable safety profile and has been studied in patients as young as 2 years of age. It may represent a new, safe, and efficacious treatment for patients 2 years of age and older with mild to moderate atopic dermatitis.”
Atopic dermatitis (AD) experts have long complained of a major unmet need for new, safe, and effective topical agents for AD, a condition that affects an estimated 18%-20% of children and 2%-10% of adults. Current treatment options all have drawbacks.
Topical steroids, long a treatment mainstay, are viewed by many parents with phobic mistrust of safety. And both FDA-approved topical calcineurin inhibitors carry black box warnings of possible cancer risk.
The two pivotal phase III studies, identical in design, included a total of 1,522 patients aged 2 years through adulthood with mild to moderate AD. Roughly 60% of patients had moderate disease, as defined by an Investigator’s Static Global Assessment (ISGA) score of 3 on a 0-4 scale; the other 40% had mild AD. The mean involved body surface area was 18%.
Participants were randomized two to one to crisaborole ointment 2% b.i.d. or vehicle for 28 days. Physicians assessed patients at baseline on day 1 of the study and again on days 8, 15, 22, 29, and 36. The primary endpoint was the proportion of patients on day 29 who had an ISGA of 0 or 1 – clear or almost clear – as well as at least a 2-point improvement from baseline on that scale.
In one of the trials, that endpoint was achieved in 32.8% of the crisaborole group, compared with 25.4% of controls.
“That 25% placebo response is actually fairly typical for atopic dermatitis studies,” according to Dr. Lebwohl, professor and chairman of the department of dermatology at Mount Sinai School of Medicine, New York.
In the other study, 31.4% of the crisaborole group and 18% of controls achieved the primary endpoint. In both studies, the difference was statistically significant in favor of topical crisaborole.
There were two prespecified secondary endpoints. One was time to treatment success, as defined by clear or almost clear. A “striking” significant difference between the study arms appeared as early as the first assessment, just 1 week into the trial, Dr. Lebwohl observed.
The other secondary endpoint was the FDA’s former efficacy standard, which required being clear or almost clear without the additional need for at least a 2-point ISGA improvement. That endpoint was achieved by 51.7% and 48.5% of crisaborole-treated patients in the two studies, compared with 40.6% and 29.7% of controls. Again, both differences were statistically significant.
No treatment-related serious adverse events occurred in either study. Mild application-site pain was slightly more common in the crisaborole-treated patients. But the rate of study discontinuations because of adverse events was identical between the crisaborole and control groups, at 1.2%. No differences in laboratory values, ECGs, or vital signs were noted between the two groups.
Dr. Lebwohl explained that boron is an essential element in crisaborole. The boron stimulates an increase in cyclic adenosine monophosphate levels, which in turn results in a steep reduction in production of inflammatory cytokines, including interleukins-4, -2, and -31, as well as tumor necrosis factor-alpha.
One audience member asked if it’s possible that crisaborole acts systemically rather than topically, given that patients averaged 18% body surface area involvement, and such a large area of damaged skin could conceivably allow the topical agent ready access to the circulation.
Dr. Lebwohl replied that systemic absorption of the drug was minor. “If you break down the results into patients with very low body surface areas – the lowest was 5% – those patients improved as well. So, I think it would be unlikely that this was a systemic effect.”
Anacor, which is developing the drug as a treatment for AD and other skin diseases, plans to file for marketing approval during the first half of 2016.
Anacor sponsored the two pivotal phase III randomized trials. Dr. Lebwohl declared having no financial conflicts of interest, because all funds went directly to the medical center in which he practices.
AT THE EADV CONGRESS
Key clinical point: Crisaborole topical ointment 2% b.i.d. appeared to be a safe and effective treatment for mild to moderate atopic dermatitis in children and adults.
Major finding: The primary combined efficacy endpoint was met by 32.8% and 31.4% of crisaborole-treated patients in two randomized trials, compared with 25.4% and 18% of vehicle-treated patients.
Data source: The two identically designed pivotal phase III clinical trials included 759 patients and 763 patients aged 2 years through adulthood with mild to moderate atopic dermatitis.
Disclosures: Anacor sponsored the two pivotal phase III randomized trials. Dr. Lebwohl declared having no financial conflicts of interest, because all funds went directly to the medical center in which he practices.
ESC: What’s the hottest recent advance in cardiology? And the winner is …
LONDON – What was the top development in all of cardiology during the past year, the advance that holds the most far-reaching implications for clinical practice?
At the annual congress of the European Society of Cardiology, six experts each made a case for the biggest game changer in their discipline – risk prevention, electrophysiology, imaging, heart failure, percutaneous coronary intervention, and acute cardiac care. And when the audience of perhaps 400-strong had cast their votes, the winner was … the novel angiotensin receptor neprilysin inhibitor (ARNI) known as LCZ696 or valsartan/sacubitril. In the landmark PARADIGM-HF trial, the drug reduced the risk of cardiovascular death by 20% and heart failure hospitalization by 21% over and above what’s achieved with enalapril plus the other current guideline-recommended heart failure medications. “I’m a device person, but I’ve decided a device is not the most important recent innovation in heart failure,” Dr. Cecilia Linde said in her winning argument.
“This ARNI is the first new drug in years with a very clear impact on morbidity and mortality. This is why I believe PARADIGM-HF is the most important study result of the last year in heart failure. It will directly impact treatment and will change the ESC guidelines for heart failure therapy. The PARADIGM-HF results suggest that the ARNI should be given as first-line therapy instead of an ACE inhibitor or angiotensin receptor blocker,” said Dr. Linde, professor and head of cardiology at the Karolinska Institute, Stockholm.
In the double-blind, randomized 8,399-patient PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371[11]:993-1004), the number needed to treat with LCZ696 instead of enalapril for 27 months in order to avoid one cardiovascular death or heart failure hospitalization was 21. The number needed to treat to avoid one cardiovascular death was 32.
Electrophysiology
The big news here is the concept of the autonomic nervous system as the master controller of atrial fibrillation, governing both the firing of arrhythmic triggers and the change in the arrhythmogenic substrate over time, according to Dr. Sabine Ernst of the National Heart and Lung Institute at Imperial College, London.
“There is a new recognition of how the sympathetic and parasympathetic nervous systems interact to initiate and maintain arrhythmias. This will change the electrophysiology world forever,” she predicted.
Indeed, the future of antiarrhythmic therapy lies in neuromodulation of the autonomic nervous system, and it’s a lot closer than most cardiologists realize, according to the electrophysiologist.
She pointed to a recent study in which investigators at the University of Oklahoma Heart Rhythm Institute randomized 40 patients with paroxysmal atrial fibrillation to noninvasive low-level electrical stimulation of the vagus nerve or to sham treatment. The stimulation at 20 Hz suppressed atrial fibrillation and reduced levels of inflammatory cytokines (J Am Coll Cardiol. 2015 Mar 10;65[9]:867-75).
Vagus nerve stimulation was accomplished using a pair of clips attached to the external ear in order to access the tragus nerve. At just 20 Hz, participants felt no discomfort.
“This is just the very first step. It’s probably not the right frequency or intensity yet. But maybe – and I just want you to start to dream about this – just maybe this could be easily implanted in something we put in our ears. How nice it would be if we could add it to a hearing aid for a patient with atrial fibrillation; we would not need to bother with rate control anymore. Or to prevent atrial fibrillation, [we could put] a low-level vagus stimulator in the headphones for a smartphone,” Dr. Ernst said.
The noninvasiveness of this novel approach is what she finds most appealing.
“I want to stop putting catheters in other people’s hearts. I want to use a method I can ideally apply in the outpatient setting. I think we’ve got to move away from just destroying myocardium in patients with arrhythmias,” she said.
Cardiovascular prevention
Dr. Joep Perk nominated as the most important development of the past year in this field a new set of refined ECG screening criteria for asymptomatic hypertrophic cardiomyopathy (HCM) in athletes. Previous criteria – both the 2010 ESC criteria and the recently published Seattle criteria developed by an international collaborative group (Br J Sports Med. 2013 Feb;47[3]:122-4) – have unacceptably high false-positive rates, which lead to further testing, particularly in black athletes.
“In my personal experience, these young athletes start to think there is something wrong with their heart. They’ll be worried and might be erroneously disqualified. So even though we mean well, it does a lot of psychological harm,” said Dr. Perk, head of the department of internal medicine at Oskarshamn (Sweden) Hospital.
The so-called refined criteria (Circulation. 2014 Apr 22;129[16]:1637-49) were designed to improve upon the specificity of the ESC and Seattle criteria by excluding several isolated ECG patterns that have been shown not relevant in black athletes.
When the developers of the refined criteria applied all three sets of criteria to a large population of black and white athletes, including 103 young athletes with HCM, all three showed 98% sensitivity for the detection of HCM. However, the false-positive ECG rate in black athletes improved from 40.4% using the ESC criteria, to 18.4% with the Seattle criteria, to 11.5% using the refined criteria. Among white athletes, the false-positive rates using the three sets of criteria were 16.2%, 7.1%, and 5.3%.
“These new refined criteria should be incorporated into guidelines for the screening of athletes. They provide a 71% reduction in positive ECGs in black athletes, compared with the ESC recommendations,” Dr. Perk said.
Cardiac imaging
“I really think 3-D printing is going to revolutionize every aspect of medicine,” asserted Dr. Luigi Badano of the University of Padua (Italy).
At the ESC congress, his research group presented a study in which they used custom software to create an exact model of a real patient’s tricuspid valve out of liquid resin based on transthoracic echo images. It took 90 minutes.
“This technology allows us to hold the physical structure of the heart in our hands,” he noted. “We can use it to teach anatomy to medical students without a corpse, plan surgical interventions, and communicate with patients, showing them exact structures and revolutionizing the concept of informed consent.”
And that’s just scratching the surface. He noted that investigators at Wake Forest Baptist Medical Center Institute for Regenerative Medicine in North Carolina recently utilized 3-D printing with bio-ink and bio-paper to print 3-D beating cardiac cells clustered into “organoids.” It’s the first step toward creating a prototype beating heart.
“Can you dream about that? The donor heart shortage could in the future be solved by printing a beating heart for insertion into the patient. The investigators predict they’ll have a functional beating heart within 20 years,” Dr. Badano said.
Acute cardiac care
Dr. Maddalena Lettino and her fellow leaders of the European Acute Cardiac Care Association agreed that the breakthrough of the year in their field was validation of a novel 1-hour rule-in/rule-out algorithm using high-sensitivity cardiac troponin T to accelerate management of patients who present to the emergency department with chest pain. According to studies totaling more than 3,000 patients with more than 600 MIs in which the assay and algorithm were tested, roughly 75% of patients can safely and accurately have acute MI ruled out or ruled in within 1 hour.
Given that close to 10% of all emergency department visits are for chest pain, adoption of this algorithm will reduce ED overcrowding, speed physician workflow, save health care systems money, and spare patients and families the anxiety that comes with a delayed diagnosis, said Dr. Lettino, director of the clinical cardiology unit at Humanitas Research Hospital in Milan.
Coronary intervention
The 15%-20% of coronary stent recipients who are at high bleeding risk constitute “the forgotten patient population,” said Dr. Philippe Garot of the Paris South Cardiovascular Institute.
He noted that the key question of whether such patients can be managed safely with a mere 1-month course of dual antiplatelet therapy will finally be answered this fall with the release of the LEADERS FREE trial results. This large, randomized double-blind trial compares safety and efficacy outcomes in patients assigned to a bare metal stent or the novel drug-eluting BioFreedom stent.
Stay tuned, because LEADERS FREE could be a game changer in interventional cardiology, he said.
The six presenters indicated they had no relevant financial conflicts.
LONDON – What was the top development in all of cardiology during the past year, the advance that holds the most far-reaching implications for clinical practice?
At the annual congress of the European Society of Cardiology, six experts each made a case for the biggest game changer in their discipline – risk prevention, electrophysiology, imaging, heart failure, percutaneous coronary intervention, and acute cardiac care. And when the audience of perhaps 400-strong had cast their votes, the winner was … the novel angiotensin receptor neprilysin inhibitor (ARNI) known as LCZ696 or valsartan/sacubitril. In the landmark PARADIGM-HF trial, the drug reduced the risk of cardiovascular death by 20% and heart failure hospitalization by 21% over and above what’s achieved with enalapril plus the other current guideline-recommended heart failure medications. “I’m a device person, but I’ve decided a device is not the most important recent innovation in heart failure,” Dr. Cecilia Linde said in her winning argument.
“This ARNI is the first new drug in years with a very clear impact on morbidity and mortality. This is why I believe PARADIGM-HF is the most important study result of the last year in heart failure. It will directly impact treatment and will change the ESC guidelines for heart failure therapy. The PARADIGM-HF results suggest that the ARNI should be given as first-line therapy instead of an ACE inhibitor or angiotensin receptor blocker,” said Dr. Linde, professor and head of cardiology at the Karolinska Institute, Stockholm.
In the double-blind, randomized 8,399-patient PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371[11]:993-1004), the number needed to treat with LCZ696 instead of enalapril for 27 months in order to avoid one cardiovascular death or heart failure hospitalization was 21. The number needed to treat to avoid one cardiovascular death was 32.
Electrophysiology
The big news here is the concept of the autonomic nervous system as the master controller of atrial fibrillation, governing both the firing of arrhythmic triggers and the change in the arrhythmogenic substrate over time, according to Dr. Sabine Ernst of the National Heart and Lung Institute at Imperial College, London.
“There is a new recognition of how the sympathetic and parasympathetic nervous systems interact to initiate and maintain arrhythmias. This will change the electrophysiology world forever,” she predicted.
Indeed, the future of antiarrhythmic therapy lies in neuromodulation of the autonomic nervous system, and it’s a lot closer than most cardiologists realize, according to the electrophysiologist.
She pointed to a recent study in which investigators at the University of Oklahoma Heart Rhythm Institute randomized 40 patients with paroxysmal atrial fibrillation to noninvasive low-level electrical stimulation of the vagus nerve or to sham treatment. The stimulation at 20 Hz suppressed atrial fibrillation and reduced levels of inflammatory cytokines (J Am Coll Cardiol. 2015 Mar 10;65[9]:867-75).
Vagus nerve stimulation was accomplished using a pair of clips attached to the external ear in order to access the tragus nerve. At just 20 Hz, participants felt no discomfort.
“This is just the very first step. It’s probably not the right frequency or intensity yet. But maybe – and I just want you to start to dream about this – just maybe this could be easily implanted in something we put in our ears. How nice it would be if we could add it to a hearing aid for a patient with atrial fibrillation; we would not need to bother with rate control anymore. Or to prevent atrial fibrillation, [we could put] a low-level vagus stimulator in the headphones for a smartphone,” Dr. Ernst said.
The noninvasiveness of this novel approach is what she finds most appealing.
“I want to stop putting catheters in other people’s hearts. I want to use a method I can ideally apply in the outpatient setting. I think we’ve got to move away from just destroying myocardium in patients with arrhythmias,” she said.
Cardiovascular prevention
Dr. Joep Perk nominated as the most important development of the past year in this field a new set of refined ECG screening criteria for asymptomatic hypertrophic cardiomyopathy (HCM) in athletes. Previous criteria – both the 2010 ESC criteria and the recently published Seattle criteria developed by an international collaborative group (Br J Sports Med. 2013 Feb;47[3]:122-4) – have unacceptably high false-positive rates, which lead to further testing, particularly in black athletes.
“In my personal experience, these young athletes start to think there is something wrong with their heart. They’ll be worried and might be erroneously disqualified. So even though we mean well, it does a lot of psychological harm,” said Dr. Perk, head of the department of internal medicine at Oskarshamn (Sweden) Hospital.
The so-called refined criteria (Circulation. 2014 Apr 22;129[16]:1637-49) were designed to improve upon the specificity of the ESC and Seattle criteria by excluding several isolated ECG patterns that have been shown not relevant in black athletes.
When the developers of the refined criteria applied all three sets of criteria to a large population of black and white athletes, including 103 young athletes with HCM, all three showed 98% sensitivity for the detection of HCM. However, the false-positive ECG rate in black athletes improved from 40.4% using the ESC criteria, to 18.4% with the Seattle criteria, to 11.5% using the refined criteria. Among white athletes, the false-positive rates using the three sets of criteria were 16.2%, 7.1%, and 5.3%.
“These new refined criteria should be incorporated into guidelines for the screening of athletes. They provide a 71% reduction in positive ECGs in black athletes, compared with the ESC recommendations,” Dr. Perk said.
Cardiac imaging
“I really think 3-D printing is going to revolutionize every aspect of medicine,” asserted Dr. Luigi Badano of the University of Padua (Italy).
At the ESC congress, his research group presented a study in which they used custom software to create an exact model of a real patient’s tricuspid valve out of liquid resin based on transthoracic echo images. It took 90 minutes.
“This technology allows us to hold the physical structure of the heart in our hands,” he noted. “We can use it to teach anatomy to medical students without a corpse, plan surgical interventions, and communicate with patients, showing them exact structures and revolutionizing the concept of informed consent.”
And that’s just scratching the surface. He noted that investigators at Wake Forest Baptist Medical Center Institute for Regenerative Medicine in North Carolina recently utilized 3-D printing with bio-ink and bio-paper to print 3-D beating cardiac cells clustered into “organoids.” It’s the first step toward creating a prototype beating heart.
“Can you dream about that? The donor heart shortage could in the future be solved by printing a beating heart for insertion into the patient. The investigators predict they’ll have a functional beating heart within 20 years,” Dr. Badano said.
Acute cardiac care
Dr. Maddalena Lettino and her fellow leaders of the European Acute Cardiac Care Association agreed that the breakthrough of the year in their field was validation of a novel 1-hour rule-in/rule-out algorithm using high-sensitivity cardiac troponin T to accelerate management of patients who present to the emergency department with chest pain. According to studies totaling more than 3,000 patients with more than 600 MIs in which the assay and algorithm were tested, roughly 75% of patients can safely and accurately have acute MI ruled out or ruled in within 1 hour.
Given that close to 10% of all emergency department visits are for chest pain, adoption of this algorithm will reduce ED overcrowding, speed physician workflow, save health care systems money, and spare patients and families the anxiety that comes with a delayed diagnosis, said Dr. Lettino, director of the clinical cardiology unit at Humanitas Research Hospital in Milan.
Coronary intervention
The 15%-20% of coronary stent recipients who are at high bleeding risk constitute “the forgotten patient population,” said Dr. Philippe Garot of the Paris South Cardiovascular Institute.
He noted that the key question of whether such patients can be managed safely with a mere 1-month course of dual antiplatelet therapy will finally be answered this fall with the release of the LEADERS FREE trial results. This large, randomized double-blind trial compares safety and efficacy outcomes in patients assigned to a bare metal stent or the novel drug-eluting BioFreedom stent.
Stay tuned, because LEADERS FREE could be a game changer in interventional cardiology, he said.
The six presenters indicated they had no relevant financial conflicts.
LONDON – What was the top development in all of cardiology during the past year, the advance that holds the most far-reaching implications for clinical practice?
At the annual congress of the European Society of Cardiology, six experts each made a case for the biggest game changer in their discipline – risk prevention, electrophysiology, imaging, heart failure, percutaneous coronary intervention, and acute cardiac care. And when the audience of perhaps 400-strong had cast their votes, the winner was … the novel angiotensin receptor neprilysin inhibitor (ARNI) known as LCZ696 or valsartan/sacubitril. In the landmark PARADIGM-HF trial, the drug reduced the risk of cardiovascular death by 20% and heart failure hospitalization by 21% over and above what’s achieved with enalapril plus the other current guideline-recommended heart failure medications. “I’m a device person, but I’ve decided a device is not the most important recent innovation in heart failure,” Dr. Cecilia Linde said in her winning argument.
“This ARNI is the first new drug in years with a very clear impact on morbidity and mortality. This is why I believe PARADIGM-HF is the most important study result of the last year in heart failure. It will directly impact treatment and will change the ESC guidelines for heart failure therapy. The PARADIGM-HF results suggest that the ARNI should be given as first-line therapy instead of an ACE inhibitor or angiotensin receptor blocker,” said Dr. Linde, professor and head of cardiology at the Karolinska Institute, Stockholm.
In the double-blind, randomized 8,399-patient PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371[11]:993-1004), the number needed to treat with LCZ696 instead of enalapril for 27 months in order to avoid one cardiovascular death or heart failure hospitalization was 21. The number needed to treat to avoid one cardiovascular death was 32.
Electrophysiology
The big news here is the concept of the autonomic nervous system as the master controller of atrial fibrillation, governing both the firing of arrhythmic triggers and the change in the arrhythmogenic substrate over time, according to Dr. Sabine Ernst of the National Heart and Lung Institute at Imperial College, London.
“There is a new recognition of how the sympathetic and parasympathetic nervous systems interact to initiate and maintain arrhythmias. This will change the electrophysiology world forever,” she predicted.
Indeed, the future of antiarrhythmic therapy lies in neuromodulation of the autonomic nervous system, and it’s a lot closer than most cardiologists realize, according to the electrophysiologist.
She pointed to a recent study in which investigators at the University of Oklahoma Heart Rhythm Institute randomized 40 patients with paroxysmal atrial fibrillation to noninvasive low-level electrical stimulation of the vagus nerve or to sham treatment. The stimulation at 20 Hz suppressed atrial fibrillation and reduced levels of inflammatory cytokines (J Am Coll Cardiol. 2015 Mar 10;65[9]:867-75).
Vagus nerve stimulation was accomplished using a pair of clips attached to the external ear in order to access the tragus nerve. At just 20 Hz, participants felt no discomfort.
“This is just the very first step. It’s probably not the right frequency or intensity yet. But maybe – and I just want you to start to dream about this – just maybe this could be easily implanted in something we put in our ears. How nice it would be if we could add it to a hearing aid for a patient with atrial fibrillation; we would not need to bother with rate control anymore. Or to prevent atrial fibrillation, [we could put] a low-level vagus stimulator in the headphones for a smartphone,” Dr. Ernst said.
The noninvasiveness of this novel approach is what she finds most appealing.
“I want to stop putting catheters in other people’s hearts. I want to use a method I can ideally apply in the outpatient setting. I think we’ve got to move away from just destroying myocardium in patients with arrhythmias,” she said.
Cardiovascular prevention
Dr. Joep Perk nominated as the most important development of the past year in this field a new set of refined ECG screening criteria for asymptomatic hypertrophic cardiomyopathy (HCM) in athletes. Previous criteria – both the 2010 ESC criteria and the recently published Seattle criteria developed by an international collaborative group (Br J Sports Med. 2013 Feb;47[3]:122-4) – have unacceptably high false-positive rates, which lead to further testing, particularly in black athletes.
“In my personal experience, these young athletes start to think there is something wrong with their heart. They’ll be worried and might be erroneously disqualified. So even though we mean well, it does a lot of psychological harm,” said Dr. Perk, head of the department of internal medicine at Oskarshamn (Sweden) Hospital.
The so-called refined criteria (Circulation. 2014 Apr 22;129[16]:1637-49) were designed to improve upon the specificity of the ESC and Seattle criteria by excluding several isolated ECG patterns that have been shown not relevant in black athletes.
When the developers of the refined criteria applied all three sets of criteria to a large population of black and white athletes, including 103 young athletes with HCM, all three showed 98% sensitivity for the detection of HCM. However, the false-positive ECG rate in black athletes improved from 40.4% using the ESC criteria, to 18.4% with the Seattle criteria, to 11.5% using the refined criteria. Among white athletes, the false-positive rates using the three sets of criteria were 16.2%, 7.1%, and 5.3%.
“These new refined criteria should be incorporated into guidelines for the screening of athletes. They provide a 71% reduction in positive ECGs in black athletes, compared with the ESC recommendations,” Dr. Perk said.
Cardiac imaging
“I really think 3-D printing is going to revolutionize every aspect of medicine,” asserted Dr. Luigi Badano of the University of Padua (Italy).
At the ESC congress, his research group presented a study in which they used custom software to create an exact model of a real patient’s tricuspid valve out of liquid resin based on transthoracic echo images. It took 90 minutes.
“This technology allows us to hold the physical structure of the heart in our hands,” he noted. “We can use it to teach anatomy to medical students without a corpse, plan surgical interventions, and communicate with patients, showing them exact structures and revolutionizing the concept of informed consent.”
And that’s just scratching the surface. He noted that investigators at Wake Forest Baptist Medical Center Institute for Regenerative Medicine in North Carolina recently utilized 3-D printing with bio-ink and bio-paper to print 3-D beating cardiac cells clustered into “organoids.” It’s the first step toward creating a prototype beating heart.
“Can you dream about that? The donor heart shortage could in the future be solved by printing a beating heart for insertion into the patient. The investigators predict they’ll have a functional beating heart within 20 years,” Dr. Badano said.
Acute cardiac care
Dr. Maddalena Lettino and her fellow leaders of the European Acute Cardiac Care Association agreed that the breakthrough of the year in their field was validation of a novel 1-hour rule-in/rule-out algorithm using high-sensitivity cardiac troponin T to accelerate management of patients who present to the emergency department with chest pain. According to studies totaling more than 3,000 patients with more than 600 MIs in which the assay and algorithm were tested, roughly 75% of patients can safely and accurately have acute MI ruled out or ruled in within 1 hour.
Given that close to 10% of all emergency department visits are for chest pain, adoption of this algorithm will reduce ED overcrowding, speed physician workflow, save health care systems money, and spare patients and families the anxiety that comes with a delayed diagnosis, said Dr. Lettino, director of the clinical cardiology unit at Humanitas Research Hospital in Milan.
Coronary intervention
The 15%-20% of coronary stent recipients who are at high bleeding risk constitute “the forgotten patient population,” said Dr. Philippe Garot of the Paris South Cardiovascular Institute.
He noted that the key question of whether such patients can be managed safely with a mere 1-month course of dual antiplatelet therapy will finally be answered this fall with the release of the LEADERS FREE trial results. This large, randomized double-blind trial compares safety and efficacy outcomes in patients assigned to a bare metal stent or the novel drug-eluting BioFreedom stent.
Stay tuned, because LEADERS FREE could be a game changer in interventional cardiology, he said.
The six presenters indicated they had no relevant financial conflicts.
EXPERT ANALYSIS FROM THE ESC CONGRESS 2015
ESC: LV response to exercise differs in women
LONDON – Left ventricular adaptation to intensive exercise is gender specific, and this novel observation could be useful in identifying female athletes who harbor a serious cardiac condition such as hypertrophic cardiomyopathy, Dr. Sanjay Sharma said at the annual congress of the European Society of Cardiology.
“Although the presence of concentric remodeling or hypertrophy in male athletes engaged in dynamic sports is a common phenotype, it should raise suspicion of underlying cardiomyopathy in female athletes,” declared Dr. Sharma, professor of inherited cardiac diseases in sports cardiology at St. George’s University of London and medical director of the London Marathon.
He drew this conclusion from a study he and his coinvestigators conducted in 1,082 white elite athletes, including 439 females, all of whom had an ECG and underwent echocardiography. The athletes were placed into one of three groups based upon the nature of the exercise entailed in their sport: dynamic exercise, as in endurance events such as distance running or bicycle racing; static exercise, such as weight lifting and wrestling; and sports involving a mix of both.
Normal left ventricular geometry was seen in 70% of male and female athletes. However, important gender-based differences in LV geometry were noted in the athletes participating in dynamic sports. The male athletes were far more likely to exhibit concentric hypertrophy or remodeling, which takes the form of increased LV wall thickness with little or no increase in LV mass, compared with norms. Indeed, 15% of male athletes specializing in dynamic sports had echocardiographic evidence of concentric hypertrophy or remodeling, compared with a mere 4% of female athletes in dynamic sports. In contrast, female athletes were far more likely to exhibit eccentric hypertrophy, featuring a normal LV relative wall thickness with an increased LV cavity size – although not to an extreme degree – when scaled for body surface area.
“In our study, a relative wall thickness greater than 0.5 or an LV mass greater than 145 g/m2 was not detected in any female. These data could be very important in differentiating between physiology and pathology in female athletes presenting potential cardiac symptoms,” according to Dr. Sharma.
He noted that people who exercise intensively for about 4 hours per week or more develop a constellation of structural and functional changes in the heart that allow generation of the large stroke volumes required to deliver sustained high cardiac output. Age and the type of sport play a large role in the magnitude of these changes. And it now appears that gender influences the form these changes will take.
Why do gender differences exist in remodeling in response to exercise? Dr. Sharma speculated that male athletes’ much higher levels of testosterone – an anabolic hormone – might explain their proclivity for LV wall thickening. Also, males are known to have a higher blood pressure response to exercise, which might promote wall thickening.
“An important point I want to make is that death in sport amongst females is extremely rare. The male to female ratio for death in competitive sports is 10:1, and among recreational athletes it’s 20:1,” the cardiologist said.
To help put that in perspective, he noted that among the 1 million runners of the London Marathon during the last 35 years there have been 14 cardiac deaths among male participants and none among females.
LONDON – Left ventricular adaptation to intensive exercise is gender specific, and this novel observation could be useful in identifying female athletes who harbor a serious cardiac condition such as hypertrophic cardiomyopathy, Dr. Sanjay Sharma said at the annual congress of the European Society of Cardiology.
“Although the presence of concentric remodeling or hypertrophy in male athletes engaged in dynamic sports is a common phenotype, it should raise suspicion of underlying cardiomyopathy in female athletes,” declared Dr. Sharma, professor of inherited cardiac diseases in sports cardiology at St. George’s University of London and medical director of the London Marathon.
He drew this conclusion from a study he and his coinvestigators conducted in 1,082 white elite athletes, including 439 females, all of whom had an ECG and underwent echocardiography. The athletes were placed into one of three groups based upon the nature of the exercise entailed in their sport: dynamic exercise, as in endurance events such as distance running or bicycle racing; static exercise, such as weight lifting and wrestling; and sports involving a mix of both.
Normal left ventricular geometry was seen in 70% of male and female athletes. However, important gender-based differences in LV geometry were noted in the athletes participating in dynamic sports. The male athletes were far more likely to exhibit concentric hypertrophy or remodeling, which takes the form of increased LV wall thickness with little or no increase in LV mass, compared with norms. Indeed, 15% of male athletes specializing in dynamic sports had echocardiographic evidence of concentric hypertrophy or remodeling, compared with a mere 4% of female athletes in dynamic sports. In contrast, female athletes were far more likely to exhibit eccentric hypertrophy, featuring a normal LV relative wall thickness with an increased LV cavity size – although not to an extreme degree – when scaled for body surface area.
“In our study, a relative wall thickness greater than 0.5 or an LV mass greater than 145 g/m2 was not detected in any female. These data could be very important in differentiating between physiology and pathology in female athletes presenting potential cardiac symptoms,” according to Dr. Sharma.
He noted that people who exercise intensively for about 4 hours per week or more develop a constellation of structural and functional changes in the heart that allow generation of the large stroke volumes required to deliver sustained high cardiac output. Age and the type of sport play a large role in the magnitude of these changes. And it now appears that gender influences the form these changes will take.
Why do gender differences exist in remodeling in response to exercise? Dr. Sharma speculated that male athletes’ much higher levels of testosterone – an anabolic hormone – might explain their proclivity for LV wall thickening. Also, males are known to have a higher blood pressure response to exercise, which might promote wall thickening.
“An important point I want to make is that death in sport amongst females is extremely rare. The male to female ratio for death in competitive sports is 10:1, and among recreational athletes it’s 20:1,” the cardiologist said.
To help put that in perspective, he noted that among the 1 million runners of the London Marathon during the last 35 years there have been 14 cardiac deaths among male participants and none among females.
LONDON – Left ventricular adaptation to intensive exercise is gender specific, and this novel observation could be useful in identifying female athletes who harbor a serious cardiac condition such as hypertrophic cardiomyopathy, Dr. Sanjay Sharma said at the annual congress of the European Society of Cardiology.
“Although the presence of concentric remodeling or hypertrophy in male athletes engaged in dynamic sports is a common phenotype, it should raise suspicion of underlying cardiomyopathy in female athletes,” declared Dr. Sharma, professor of inherited cardiac diseases in sports cardiology at St. George’s University of London and medical director of the London Marathon.
He drew this conclusion from a study he and his coinvestigators conducted in 1,082 white elite athletes, including 439 females, all of whom had an ECG and underwent echocardiography. The athletes were placed into one of three groups based upon the nature of the exercise entailed in their sport: dynamic exercise, as in endurance events such as distance running or bicycle racing; static exercise, such as weight lifting and wrestling; and sports involving a mix of both.
Normal left ventricular geometry was seen in 70% of male and female athletes. However, important gender-based differences in LV geometry were noted in the athletes participating in dynamic sports. The male athletes were far more likely to exhibit concentric hypertrophy or remodeling, which takes the form of increased LV wall thickness with little or no increase in LV mass, compared with norms. Indeed, 15% of male athletes specializing in dynamic sports had echocardiographic evidence of concentric hypertrophy or remodeling, compared with a mere 4% of female athletes in dynamic sports. In contrast, female athletes were far more likely to exhibit eccentric hypertrophy, featuring a normal LV relative wall thickness with an increased LV cavity size – although not to an extreme degree – when scaled for body surface area.
“In our study, a relative wall thickness greater than 0.5 or an LV mass greater than 145 g/m2 was not detected in any female. These data could be very important in differentiating between physiology and pathology in female athletes presenting potential cardiac symptoms,” according to Dr. Sharma.
He noted that people who exercise intensively for about 4 hours per week or more develop a constellation of structural and functional changes in the heart that allow generation of the large stroke volumes required to deliver sustained high cardiac output. Age and the type of sport play a large role in the magnitude of these changes. And it now appears that gender influences the form these changes will take.
Why do gender differences exist in remodeling in response to exercise? Dr. Sharma speculated that male athletes’ much higher levels of testosterone – an anabolic hormone – might explain their proclivity for LV wall thickening. Also, males are known to have a higher blood pressure response to exercise, which might promote wall thickening.
“An important point I want to make is that death in sport amongst females is extremely rare. The male to female ratio for death in competitive sports is 10:1, and among recreational athletes it’s 20:1,” the cardiologist said.
To help put that in perspective, he noted that among the 1 million runners of the London Marathon during the last 35 years there have been 14 cardiac deaths among male participants and none among females.
AT THE ESC CONGRESS 2015
Key clinical point: Cardiac adaptation to exercise differs by gender, a finding that may help in identifying female athletes with occult cardiomyopathy.
Major finding: The prevalence of left ventricular concentric hypertrophy or remodeling among female elite endurance-sport athletes was just 4%, compared with 15% among their male counterparts.
Data source: This study compared left ventricular geometry in 644 male and 439 female elite athletes.
Disclosures: The presenter reported having no financial conflicts regarding this study.
EADV: Atopic dermatitis boosts MI risk
COPENHAGEN – Adults with atopic dermatitis are at significantly increased risk of acute MI compared with the general population, according to a Danish national population-based case-control study.
Indeed, Danish adults with atopic dermatitis (AD) were at a 1.67-fold increased risk for an MI in a Cox regression analysis adjusted for age, gender, education level, and cardiovascular risk factors, Dr. Jette Lindorff Riis reported at the annual congress of the European Academy of Dermatology and Venereology.
“The associated MI risk is comparable to that of Danish patients with psoriasis, another inflammatory skin disease, which has been associated with increased cardiovascular risk,” said Dr. Riis of Aarhus (Denmark) University Hospital.
Her study included all 5,278 Danish adult AD patients who met the study enrollment criteria: born in 1900-1983, received a hospital discharge diagnosis of AD during 1977-2012, and had at least one additional hospital inpatient or outpatient visit for AD during follow-up. Three-quarters of patients were born in 1960-1983, the rest earlier. The follow-up period began at the time of hospital diagnosis of AD and continued to the time of MI, death, or the end of 2012.
The requirement that participants had to be diagnosed as having AD by a hospital-based physician, in most cases a dermatologist, and that they had to have a second hospital encounter for AD was created to minimize the likelihood of misdiagnosis, a not uncommon occurrence in the primary care setting, she explained.
Each of the 5,278 adults with AD was matched based upon age and gender with 10 controls. Follow-up was accomplished through linkages between Denmark’s comprehensive cradle-to-grave population-wide registries.
During a maximum follow-up of 35 years, the AD patients were at a 1.67-fold greater risk than that of controls after adjustment for potential confounders, including standard cardiovascular risk factors, stroke, and the use of antihypertensive, lipid-lowering, and antidiabetic medications.
The Danish registry data do not contain specific information about patients’ AD disease severity, so as a crude proxy the investigators looked at the number of hospital inpatient or outpatient visits for AD. They found that patients with 2-4 visits had an adjusted 1.31-fold increased risk of acute MI compared with controls, those with 5-9 visits had a 1.83-fold increased risk, and those with 10 or more hospital encounters for AD during follow-up had a 2.42-fold increased risk.
When Dr. Riis and coinvestigators compared adult Danes with AD to a Danish national cohort of psoriasis patients, they found the AD patients were at an adjusted 15% increased risk of MI, a nonsignificant difference. That’s an important finding, since a link between psoriasis and increased cardiovascular risk was first reported nearly a decade ago and has since been confirmed in multiple studies. Given that AD is quite common among adults – various studies have reported prevalence rates of 2%-10% – and that the skin disease appears to boost the risk of what is already the No. 1 cause of mortality in developed countries, the new findings have major implications for clinical practice.
“We might have to think more about cardiovascular risk factor reduction on a daily basis in order to take good care of our atopic dermatitis patients,” Dr. Riis observed.
The Danish study is the latest in a very recent flurry of research pointing for the first time to increased cardiovascular risk in adult AD. Earlier this year investigators at Northwestern University, Chicago, reported finding that adult atopic dermatitis patients have increased levels of cardiovascular risk factors (J Allergy Clin Immunol. 2015 Mar;135[3]:721-8.e6), and even more recently they reported increased rates of coronary artery disease and MI in adults with self-reported AD in analyses of the National Health and Nutrition Examination Survey and the 2010 and 2012 Health Interview Survey (Allergy. 2015 Oct;70[10]:1300-8).
Moreover, earlier this year, Dr. Riis’ colleagues at Aarhus reported a significantly increased rate of asymptomatic coronary artery stenosis in AD patients compared with controls (Am J Med. 2015 Jun 18. pii: S0002-9343[15]00545-8).
Dr. Riis said she’s eager to see studies evaluating whether systemic treatments for AD, which dampen systemic inflammation, also curb the elevated acute MI risk.
Audience comments centered around the issue of whether the Danish results apply to the many less-severe cases of adult AD that never necessitate a trip to the hospital. Are those patients also at increased risk of MI? Dr. Riis said that remains an unanswered question, given that the investigators couldn’t find a reliable indicator of disease severity in the databases. They tried using systemic therapy as a proxy, but it turned out too few AD patients used systemic agents to be able to draw conclusions, which suggests the study population wasn’t at the extreme end of the AD severity spectrum.
She reported having no financial conflicts regarding the study, conducted free of commercial support.
COPENHAGEN – Adults with atopic dermatitis are at significantly increased risk of acute MI compared with the general population, according to a Danish national population-based case-control study.
Indeed, Danish adults with atopic dermatitis (AD) were at a 1.67-fold increased risk for an MI in a Cox regression analysis adjusted for age, gender, education level, and cardiovascular risk factors, Dr. Jette Lindorff Riis reported at the annual congress of the European Academy of Dermatology and Venereology.
“The associated MI risk is comparable to that of Danish patients with psoriasis, another inflammatory skin disease, which has been associated with increased cardiovascular risk,” said Dr. Riis of Aarhus (Denmark) University Hospital.
Her study included all 5,278 Danish adult AD patients who met the study enrollment criteria: born in 1900-1983, received a hospital discharge diagnosis of AD during 1977-2012, and had at least one additional hospital inpatient or outpatient visit for AD during follow-up. Three-quarters of patients were born in 1960-1983, the rest earlier. The follow-up period began at the time of hospital diagnosis of AD and continued to the time of MI, death, or the end of 2012.
The requirement that participants had to be diagnosed as having AD by a hospital-based physician, in most cases a dermatologist, and that they had to have a second hospital encounter for AD was created to minimize the likelihood of misdiagnosis, a not uncommon occurrence in the primary care setting, she explained.
Each of the 5,278 adults with AD was matched based upon age and gender with 10 controls. Follow-up was accomplished through linkages between Denmark’s comprehensive cradle-to-grave population-wide registries.
During a maximum follow-up of 35 years, the AD patients were at a 1.67-fold greater risk than that of controls after adjustment for potential confounders, including standard cardiovascular risk factors, stroke, and the use of antihypertensive, lipid-lowering, and antidiabetic medications.
The Danish registry data do not contain specific information about patients’ AD disease severity, so as a crude proxy the investigators looked at the number of hospital inpatient or outpatient visits for AD. They found that patients with 2-4 visits had an adjusted 1.31-fold increased risk of acute MI compared with controls, those with 5-9 visits had a 1.83-fold increased risk, and those with 10 or more hospital encounters for AD during follow-up had a 2.42-fold increased risk.
When Dr. Riis and coinvestigators compared adult Danes with AD to a Danish national cohort of psoriasis patients, they found the AD patients were at an adjusted 15% increased risk of MI, a nonsignificant difference. That’s an important finding, since a link between psoriasis and increased cardiovascular risk was first reported nearly a decade ago and has since been confirmed in multiple studies. Given that AD is quite common among adults – various studies have reported prevalence rates of 2%-10% – and that the skin disease appears to boost the risk of what is already the No. 1 cause of mortality in developed countries, the new findings have major implications for clinical practice.
“We might have to think more about cardiovascular risk factor reduction on a daily basis in order to take good care of our atopic dermatitis patients,” Dr. Riis observed.
The Danish study is the latest in a very recent flurry of research pointing for the first time to increased cardiovascular risk in adult AD. Earlier this year investigators at Northwestern University, Chicago, reported finding that adult atopic dermatitis patients have increased levels of cardiovascular risk factors (J Allergy Clin Immunol. 2015 Mar;135[3]:721-8.e6), and even more recently they reported increased rates of coronary artery disease and MI in adults with self-reported AD in analyses of the National Health and Nutrition Examination Survey and the 2010 and 2012 Health Interview Survey (Allergy. 2015 Oct;70[10]:1300-8).
Moreover, earlier this year, Dr. Riis’ colleagues at Aarhus reported a significantly increased rate of asymptomatic coronary artery stenosis in AD patients compared with controls (Am J Med. 2015 Jun 18. pii: S0002-9343[15]00545-8).
Dr. Riis said she’s eager to see studies evaluating whether systemic treatments for AD, which dampen systemic inflammation, also curb the elevated acute MI risk.
Audience comments centered around the issue of whether the Danish results apply to the many less-severe cases of adult AD that never necessitate a trip to the hospital. Are those patients also at increased risk of MI? Dr. Riis said that remains an unanswered question, given that the investigators couldn’t find a reliable indicator of disease severity in the databases. They tried using systemic therapy as a proxy, but it turned out too few AD patients used systemic agents to be able to draw conclusions, which suggests the study population wasn’t at the extreme end of the AD severity spectrum.
She reported having no financial conflicts regarding the study, conducted free of commercial support.
COPENHAGEN – Adults with atopic dermatitis are at significantly increased risk of acute MI compared with the general population, according to a Danish national population-based case-control study.
Indeed, Danish adults with atopic dermatitis (AD) were at a 1.67-fold increased risk for an MI in a Cox regression analysis adjusted for age, gender, education level, and cardiovascular risk factors, Dr. Jette Lindorff Riis reported at the annual congress of the European Academy of Dermatology and Venereology.
“The associated MI risk is comparable to that of Danish patients with psoriasis, another inflammatory skin disease, which has been associated with increased cardiovascular risk,” said Dr. Riis of Aarhus (Denmark) University Hospital.
Her study included all 5,278 Danish adult AD patients who met the study enrollment criteria: born in 1900-1983, received a hospital discharge diagnosis of AD during 1977-2012, and had at least one additional hospital inpatient or outpatient visit for AD during follow-up. Three-quarters of patients were born in 1960-1983, the rest earlier. The follow-up period began at the time of hospital diagnosis of AD and continued to the time of MI, death, or the end of 2012.
The requirement that participants had to be diagnosed as having AD by a hospital-based physician, in most cases a dermatologist, and that they had to have a second hospital encounter for AD was created to minimize the likelihood of misdiagnosis, a not uncommon occurrence in the primary care setting, she explained.
Each of the 5,278 adults with AD was matched based upon age and gender with 10 controls. Follow-up was accomplished through linkages between Denmark’s comprehensive cradle-to-grave population-wide registries.
During a maximum follow-up of 35 years, the AD patients were at a 1.67-fold greater risk than that of controls after adjustment for potential confounders, including standard cardiovascular risk factors, stroke, and the use of antihypertensive, lipid-lowering, and antidiabetic medications.
The Danish registry data do not contain specific information about patients’ AD disease severity, so as a crude proxy the investigators looked at the number of hospital inpatient or outpatient visits for AD. They found that patients with 2-4 visits had an adjusted 1.31-fold increased risk of acute MI compared with controls, those with 5-9 visits had a 1.83-fold increased risk, and those with 10 or more hospital encounters for AD during follow-up had a 2.42-fold increased risk.
When Dr. Riis and coinvestigators compared adult Danes with AD to a Danish national cohort of psoriasis patients, they found the AD patients were at an adjusted 15% increased risk of MI, a nonsignificant difference. That’s an important finding, since a link between psoriasis and increased cardiovascular risk was first reported nearly a decade ago and has since been confirmed in multiple studies. Given that AD is quite common among adults – various studies have reported prevalence rates of 2%-10% – and that the skin disease appears to boost the risk of what is already the No. 1 cause of mortality in developed countries, the new findings have major implications for clinical practice.
“We might have to think more about cardiovascular risk factor reduction on a daily basis in order to take good care of our atopic dermatitis patients,” Dr. Riis observed.
The Danish study is the latest in a very recent flurry of research pointing for the first time to increased cardiovascular risk in adult AD. Earlier this year investigators at Northwestern University, Chicago, reported finding that adult atopic dermatitis patients have increased levels of cardiovascular risk factors (J Allergy Clin Immunol. 2015 Mar;135[3]:721-8.e6), and even more recently they reported increased rates of coronary artery disease and MI in adults with self-reported AD in analyses of the National Health and Nutrition Examination Survey and the 2010 and 2012 Health Interview Survey (Allergy. 2015 Oct;70[10]:1300-8).
Moreover, earlier this year, Dr. Riis’ colleagues at Aarhus reported a significantly increased rate of asymptomatic coronary artery stenosis in AD patients compared with controls (Am J Med. 2015 Jun 18. pii: S0002-9343[15]00545-8).
Dr. Riis said she’s eager to see studies evaluating whether systemic treatments for AD, which dampen systemic inflammation, also curb the elevated acute MI risk.
Audience comments centered around the issue of whether the Danish results apply to the many less-severe cases of adult AD that never necessitate a trip to the hospital. Are those patients also at increased risk of MI? Dr. Riis said that remains an unanswered question, given that the investigators couldn’t find a reliable indicator of disease severity in the databases. They tried using systemic therapy as a proxy, but it turned out too few AD patients used systemic agents to be able to draw conclusions, which suggests the study population wasn’t at the extreme end of the AD severity spectrum.
She reported having no financial conflicts regarding the study, conducted free of commercial support.
AT THE EADV CONGRESS
Key clinical point: Like psoriasis patients, adults with atopic dermatitis appear to be at increased risk for acute MI.
Major finding: Adults with atopic dermatitis were at an adjusted 1.67-fold increased risk of acute MI compared with matched controls after researchers controlled for potential confounders.
Data source: This Danish national case-control study of 5,278 adult atopic dermatitis patients and 52,780 matched controls followed for up to 35 years.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was conducted free of commercial support.
ESC: A novel ‘win-win’ combo for hypertension
LONDON – The combination of two old diuretics – amiloride and hydrochlorothiazide – at half-doses provides synergistic blood pressure lowering beyond the full doses of either drug alone while neutralizing the thiazide diuretic’s blood glucose– and uric acid–raising side effects, according to the results of the PATHWAY-3 trial.
“We think this combination of amiloride and hydrochlorothiazide at equipotent doses is a ‘win win,’ ” Dr. Morris J. Brown said in presenting the study findings at the annual congress of the European Society of Cardiology.
“Since unlocking the data, we’ve scarcely been able to contain our excitement at the results. I believe these results will return potassium-sparing diuretics to prominence,” said Dr. Brown, professor of clinical pharmacology at the University of Cambridge (England).
The thiazide diuretics as a group have fallen out of favor because of their adverse metabolic effects, including increased risks of diabetes and gout. But the PATHWAY-3 trial demonstrates that, with the half-dose combination approach, amiloride cancels those side effects, while hydrochlorothiazide (HCTZ) neutralizes amiloride’s tendency to boost serum potassium, he explained.
PATHWAY-3 was a 13-center, 24-week randomized trial involving 399 hypertensive patients with at least one additional component of the metabolic syndrome. They were assigned to 12 weeks of amiloride at 10 mg/day, HCTZ at 25 mg/day, or the combination at half-doses, followed by another 12 weeks at twice the dose in all three groups.
The primary outcome was a safety endpoint: the change from baseline in 2-hour oral glucose tolerance tests conducted at 12 and 24 weeks. Blood glucose levels rose in patients on HCTZ and fell significantly in patients on amiloride or the combination. At 24 weeks, the 2-hour blood glucose level was 0.71 mmol/L lower in the amiloride group and 0.58 mmol/L lower in the combination group than in the HCTZ group.
A key secondary endpoint was change in home systolic blood pressure levels. Averaged over 24 weeks, systolic blood pressure was reduced from baseline by 14.7 mm Hg with amiloride monotherapy, by 14.0 mm Hg with HCTZ, and by 17.5 mm Hg with half-dose combination therapy.
Serum potassium levels rose over time with amiloride, fell with HCTZ, and remained unchanged with combination therapy. But full-dose amiloride monotherapy was well tolerated, with no instances of hyperkalemia as defined by a level above 5.8 mmol/L, even though virtually all patients were on background therapy with an ACE inhibitor or angiotensin receptor blocker, Dr. Brown reported.
He noted that the amiloride-HCTZ combination is the only diuretic that has demonstrated superiority in terms of morbidity and mortality in long-term clinical trials versus a calcium channel blocker in the INSIGHT trial (Lancet. 2000 Jul 29;356[9227]:366-72) and versus beta blocker therapy in the MRC-Elderly trial (BMJ. 1992 Feb 15;304:405-12).
PATHWAY-3 is part of an ongoing program developed by the British Heart Foundation to reexamine old, inexpensive drugs that have been pushed aside by newer and far costlier alternatives.
“The continuing famine of new small molecules makes reappraisal and repurposing of old drugs even more important,” Dr. Brown noted.
Discussant Dr. Antonio Coca found the PATHWAY-3 results compelling.
“On the basis of PATHWAY-3, the combination of amiloride and hydrochlorothiazide in equivalent doses becomes the preferred choice for diuretic treatment in patients with insulin resistance, such as obese hypertensives or those with elevated fasting plasma glucose. These findings together with previous morbidity and mortality data from INSIGHT and MRC-Elderly support its first-line use in patients requiring diuretic therapy for hypertension, alone or in combination with other antihypertensive drugs,” said Dr. Coca of the University of Barcelona.
In an interview, Dr. Elliott M. Antmann, immediate past president of the American Heart Association, said he found the PATHWAY-3 study “very impressive.”
“I personally am going to be prescribing more amiloride, which I haven’t prescribed in years,” said Dr. Antmann of Harvard Medical School, Boston.
Dr. Brown reported no financial conflicts regarding the PATHWAY-3 trial, funded by the British Heart Foundation and the National Institute for Health Research.
LONDON – The combination of two old diuretics – amiloride and hydrochlorothiazide – at half-doses provides synergistic blood pressure lowering beyond the full doses of either drug alone while neutralizing the thiazide diuretic’s blood glucose– and uric acid–raising side effects, according to the results of the PATHWAY-3 trial.
“We think this combination of amiloride and hydrochlorothiazide at equipotent doses is a ‘win win,’ ” Dr. Morris J. Brown said in presenting the study findings at the annual congress of the European Society of Cardiology.
“Since unlocking the data, we’ve scarcely been able to contain our excitement at the results. I believe these results will return potassium-sparing diuretics to prominence,” said Dr. Brown, professor of clinical pharmacology at the University of Cambridge (England).
The thiazide diuretics as a group have fallen out of favor because of their adverse metabolic effects, including increased risks of diabetes and gout. But the PATHWAY-3 trial demonstrates that, with the half-dose combination approach, amiloride cancels those side effects, while hydrochlorothiazide (HCTZ) neutralizes amiloride’s tendency to boost serum potassium, he explained.
PATHWAY-3 was a 13-center, 24-week randomized trial involving 399 hypertensive patients with at least one additional component of the metabolic syndrome. They were assigned to 12 weeks of amiloride at 10 mg/day, HCTZ at 25 mg/day, or the combination at half-doses, followed by another 12 weeks at twice the dose in all three groups.
The primary outcome was a safety endpoint: the change from baseline in 2-hour oral glucose tolerance tests conducted at 12 and 24 weeks. Blood glucose levels rose in patients on HCTZ and fell significantly in patients on amiloride or the combination. At 24 weeks, the 2-hour blood glucose level was 0.71 mmol/L lower in the amiloride group and 0.58 mmol/L lower in the combination group than in the HCTZ group.
A key secondary endpoint was change in home systolic blood pressure levels. Averaged over 24 weeks, systolic blood pressure was reduced from baseline by 14.7 mm Hg with amiloride monotherapy, by 14.0 mm Hg with HCTZ, and by 17.5 mm Hg with half-dose combination therapy.
Serum potassium levels rose over time with amiloride, fell with HCTZ, and remained unchanged with combination therapy. But full-dose amiloride monotherapy was well tolerated, with no instances of hyperkalemia as defined by a level above 5.8 mmol/L, even though virtually all patients were on background therapy with an ACE inhibitor or angiotensin receptor blocker, Dr. Brown reported.
He noted that the amiloride-HCTZ combination is the only diuretic that has demonstrated superiority in terms of morbidity and mortality in long-term clinical trials versus a calcium channel blocker in the INSIGHT trial (Lancet. 2000 Jul 29;356[9227]:366-72) and versus beta blocker therapy in the MRC-Elderly trial (BMJ. 1992 Feb 15;304:405-12).
PATHWAY-3 is part of an ongoing program developed by the British Heart Foundation to reexamine old, inexpensive drugs that have been pushed aside by newer and far costlier alternatives.
“The continuing famine of new small molecules makes reappraisal and repurposing of old drugs even more important,” Dr. Brown noted.
Discussant Dr. Antonio Coca found the PATHWAY-3 results compelling.
“On the basis of PATHWAY-3, the combination of amiloride and hydrochlorothiazide in equivalent doses becomes the preferred choice for diuretic treatment in patients with insulin resistance, such as obese hypertensives or those with elevated fasting plasma glucose. These findings together with previous morbidity and mortality data from INSIGHT and MRC-Elderly support its first-line use in patients requiring diuretic therapy for hypertension, alone or in combination with other antihypertensive drugs,” said Dr. Coca of the University of Barcelona.
In an interview, Dr. Elliott M. Antmann, immediate past president of the American Heart Association, said he found the PATHWAY-3 study “very impressive.”
“I personally am going to be prescribing more amiloride, which I haven’t prescribed in years,” said Dr. Antmann of Harvard Medical School, Boston.
Dr. Brown reported no financial conflicts regarding the PATHWAY-3 trial, funded by the British Heart Foundation and the National Institute for Health Research.
LONDON – The combination of two old diuretics – amiloride and hydrochlorothiazide – at half-doses provides synergistic blood pressure lowering beyond the full doses of either drug alone while neutralizing the thiazide diuretic’s blood glucose– and uric acid–raising side effects, according to the results of the PATHWAY-3 trial.
“We think this combination of amiloride and hydrochlorothiazide at equipotent doses is a ‘win win,’ ” Dr. Morris J. Brown said in presenting the study findings at the annual congress of the European Society of Cardiology.
“Since unlocking the data, we’ve scarcely been able to contain our excitement at the results. I believe these results will return potassium-sparing diuretics to prominence,” said Dr. Brown, professor of clinical pharmacology at the University of Cambridge (England).
The thiazide diuretics as a group have fallen out of favor because of their adverse metabolic effects, including increased risks of diabetes and gout. But the PATHWAY-3 trial demonstrates that, with the half-dose combination approach, amiloride cancels those side effects, while hydrochlorothiazide (HCTZ) neutralizes amiloride’s tendency to boost serum potassium, he explained.
PATHWAY-3 was a 13-center, 24-week randomized trial involving 399 hypertensive patients with at least one additional component of the metabolic syndrome. They were assigned to 12 weeks of amiloride at 10 mg/day, HCTZ at 25 mg/day, or the combination at half-doses, followed by another 12 weeks at twice the dose in all three groups.
The primary outcome was a safety endpoint: the change from baseline in 2-hour oral glucose tolerance tests conducted at 12 and 24 weeks. Blood glucose levels rose in patients on HCTZ and fell significantly in patients on amiloride or the combination. At 24 weeks, the 2-hour blood glucose level was 0.71 mmol/L lower in the amiloride group and 0.58 mmol/L lower in the combination group than in the HCTZ group.
A key secondary endpoint was change in home systolic blood pressure levels. Averaged over 24 weeks, systolic blood pressure was reduced from baseline by 14.7 mm Hg with amiloride monotherapy, by 14.0 mm Hg with HCTZ, and by 17.5 mm Hg with half-dose combination therapy.
Serum potassium levels rose over time with amiloride, fell with HCTZ, and remained unchanged with combination therapy. But full-dose amiloride monotherapy was well tolerated, with no instances of hyperkalemia as defined by a level above 5.8 mmol/L, even though virtually all patients were on background therapy with an ACE inhibitor or angiotensin receptor blocker, Dr. Brown reported.
He noted that the amiloride-HCTZ combination is the only diuretic that has demonstrated superiority in terms of morbidity and mortality in long-term clinical trials versus a calcium channel blocker in the INSIGHT trial (Lancet. 2000 Jul 29;356[9227]:366-72) and versus beta blocker therapy in the MRC-Elderly trial (BMJ. 1992 Feb 15;304:405-12).
PATHWAY-3 is part of an ongoing program developed by the British Heart Foundation to reexamine old, inexpensive drugs that have been pushed aside by newer and far costlier alternatives.
“The continuing famine of new small molecules makes reappraisal and repurposing of old drugs even more important,” Dr. Brown noted.
Discussant Dr. Antonio Coca found the PATHWAY-3 results compelling.
“On the basis of PATHWAY-3, the combination of amiloride and hydrochlorothiazide in equivalent doses becomes the preferred choice for diuretic treatment in patients with insulin resistance, such as obese hypertensives or those with elevated fasting plasma glucose. These findings together with previous morbidity and mortality data from INSIGHT and MRC-Elderly support its first-line use in patients requiring diuretic therapy for hypertension, alone or in combination with other antihypertensive drugs,” said Dr. Coca of the University of Barcelona.
In an interview, Dr. Elliott M. Antmann, immediate past president of the American Heart Association, said he found the PATHWAY-3 study “very impressive.”
“I personally am going to be prescribing more amiloride, which I haven’t prescribed in years,” said Dr. Antmann of Harvard Medical School, Boston.
Dr. Brown reported no financial conflicts regarding the PATHWAY-3 trial, funded by the British Heart Foundation and the National Institute for Health Research.
AT THE ESC CONGRESS 2015
Key clinical point: Half-doses of the diuretics amiloride and hydrochlorothiazide given in combination had a synergistic effect on blood pressure lowering and were associated with fewer metabolic side effects than were full doses.
Major finding: The combination of amiloride and hydrochlorothiazide reduced systolic blood pressure by 17.5 mm Hg while leaving blood glucose, uric acid, and serum potassium levels unchanged.
Data source: A multicenter, prospective randomized trial involving 399 patients with hypertension and at least one other component of the metabolic syndrome.
Disclosures: The PATHWAY-3 trial was funded by the British Heart Foundation and the National Institute for Health Research. The presenter reported having no relevant financial conflicts.
Big declines seen in aspergillosis mortality
SAN DIEGO – In-hospital mortality in patients with aspergillosis plummeted nationally, according to data from 2001-2011, with the biggest improvement seen in immunocompromised patients traditionally considered at high mortality risk, Dr. Masako Mizusawa reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The decline in in-hospital mortality wasn’t linear. Rather, it followed a stepwise pattern, and those steps occurred in association with three major advances during the study years: Food and Drug Administration approval of voriconazole in 2002, the FDA’s 2003 approval of the galactomannan serologic assay allowing for speedier diagnosis of aspergillosis, and the 2008 Infectious Diseases Society of America clinical practice guidelines on the treatment of aspergillosis (Clin Infect Dis. 2008 Feb 1;46[3]:327-60).
“This was an observational study and we can’t actually say that these events are causative. But just looking at the time relationship, it certainly looks plausible,” Dr. Mizusawa said.
In addition, the median hospital length of stay decreased from 9 to 7 days in patients with this potentially life-threatening infection, noted Dr. Mizusawa of Tufts Medical Center, Boston.
She presented what she believes is the largest U.S. longitudinal study of hospital care for aspergillosis. The retrospective study used nationally representative data from the Agency for Healthcare Research and Quality’s Healthcare Utilization and Cost Project–Nationwide Inpatient Sample.
Dr. Mizusawa and coinvestigators defined aspergillosis patients as being at high mortality risk if they had established risk factors indicative of immunocompromise, including hematologic malignancy, neutropenia, recent stem cell or solid organ transplantation, HIV, or rheumatologic disease. Patients at lower mortality risk included those with asthma, COPD, diabetes, malnutrition, pulmonary tuberculosis, or non-TB mycobacterial infection.
The proportion of patients who were high risk climbed over the years, from 41% among the 892 patients with aspergillosis-related hospitalization in the 2001 sample to 50% among 1,420 patients in 2011. Yet in-hospital mortality in high-risk patients fell from 26.4% in 2001 to 9.1% in 2011. Meanwhile, the mortality rate in lower-risk patients improved from 14.6% to 6.6%. The overall in-hospital mortality rate went from 18.8% to 7.7%.
Of note, the proportion of aspergillosis patients with renal failure jumped from 9.8% in 2001 to 21.5% in 2011, even though the treatments for aspergillosis are relatively non-nephrotoxic, with the exception of amphotericin B. The outlook for these patients has improved greatly: In-hospital mortality for aspergillosis patients in renal failure went from 40.2% in 2001 to 16.1% in 2011.
While in-hospital mortality and length of stay were decreasing during the study years, total hospital charges for patients with aspergillosis were going up: from a median of $29,998 in 2001 to $44,888 in 2001 dollars a decade later. This cost-of-care increase was confined to patients at lower baseline risk or with no risk factors. Somewhat surprisingly, the high-risk group didn’t have a significant increase in hospital charges over the 10-year period.
“Maybe we’re just doing a better job of treating them, so they may not necessarily have to use a lot of resources,” Dr. Mizusawa offered as explanation.
She reported having no financial conflicts regarding this unfunded study.
SAN DIEGO – In-hospital mortality in patients with aspergillosis plummeted nationally, according to data from 2001-2011, with the biggest improvement seen in immunocompromised patients traditionally considered at high mortality risk, Dr. Masako Mizusawa reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The decline in in-hospital mortality wasn’t linear. Rather, it followed a stepwise pattern, and those steps occurred in association with three major advances during the study years: Food and Drug Administration approval of voriconazole in 2002, the FDA’s 2003 approval of the galactomannan serologic assay allowing for speedier diagnosis of aspergillosis, and the 2008 Infectious Diseases Society of America clinical practice guidelines on the treatment of aspergillosis (Clin Infect Dis. 2008 Feb 1;46[3]:327-60).
“This was an observational study and we can’t actually say that these events are causative. But just looking at the time relationship, it certainly looks plausible,” Dr. Mizusawa said.
In addition, the median hospital length of stay decreased from 9 to 7 days in patients with this potentially life-threatening infection, noted Dr. Mizusawa of Tufts Medical Center, Boston.
She presented what she believes is the largest U.S. longitudinal study of hospital care for aspergillosis. The retrospective study used nationally representative data from the Agency for Healthcare Research and Quality’s Healthcare Utilization and Cost Project–Nationwide Inpatient Sample.
Dr. Mizusawa and coinvestigators defined aspergillosis patients as being at high mortality risk if they had established risk factors indicative of immunocompromise, including hematologic malignancy, neutropenia, recent stem cell or solid organ transplantation, HIV, or rheumatologic disease. Patients at lower mortality risk included those with asthma, COPD, diabetes, malnutrition, pulmonary tuberculosis, or non-TB mycobacterial infection.
The proportion of patients who were high risk climbed over the years, from 41% among the 892 patients with aspergillosis-related hospitalization in the 2001 sample to 50% among 1,420 patients in 2011. Yet in-hospital mortality in high-risk patients fell from 26.4% in 2001 to 9.1% in 2011. Meanwhile, the mortality rate in lower-risk patients improved from 14.6% to 6.6%. The overall in-hospital mortality rate went from 18.8% to 7.7%.
Of note, the proportion of aspergillosis patients with renal failure jumped from 9.8% in 2001 to 21.5% in 2011, even though the treatments for aspergillosis are relatively non-nephrotoxic, with the exception of amphotericin B. The outlook for these patients has improved greatly: In-hospital mortality for aspergillosis patients in renal failure went from 40.2% in 2001 to 16.1% in 2011.
While in-hospital mortality and length of stay were decreasing during the study years, total hospital charges for patients with aspergillosis were going up: from a median of $29,998 in 2001 to $44,888 in 2001 dollars a decade later. This cost-of-care increase was confined to patients at lower baseline risk or with no risk factors. Somewhat surprisingly, the high-risk group didn’t have a significant increase in hospital charges over the 10-year period.
“Maybe we’re just doing a better job of treating them, so they may not necessarily have to use a lot of resources,” Dr. Mizusawa offered as explanation.
She reported having no financial conflicts regarding this unfunded study.
SAN DIEGO – In-hospital mortality in patients with aspergillosis plummeted nationally, according to data from 2001-2011, with the biggest improvement seen in immunocompromised patients traditionally considered at high mortality risk, Dr. Masako Mizusawa reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The decline in in-hospital mortality wasn’t linear. Rather, it followed a stepwise pattern, and those steps occurred in association with three major advances during the study years: Food and Drug Administration approval of voriconazole in 2002, the FDA’s 2003 approval of the galactomannan serologic assay allowing for speedier diagnosis of aspergillosis, and the 2008 Infectious Diseases Society of America clinical practice guidelines on the treatment of aspergillosis (Clin Infect Dis. 2008 Feb 1;46[3]:327-60).
“This was an observational study and we can’t actually say that these events are causative. But just looking at the time relationship, it certainly looks plausible,” Dr. Mizusawa said.
In addition, the median hospital length of stay decreased from 9 to 7 days in patients with this potentially life-threatening infection, noted Dr. Mizusawa of Tufts Medical Center, Boston.
She presented what she believes is the largest U.S. longitudinal study of hospital care for aspergillosis. The retrospective study used nationally representative data from the Agency for Healthcare Research and Quality’s Healthcare Utilization and Cost Project–Nationwide Inpatient Sample.
Dr. Mizusawa and coinvestigators defined aspergillosis patients as being at high mortality risk if they had established risk factors indicative of immunocompromise, including hematologic malignancy, neutropenia, recent stem cell or solid organ transplantation, HIV, or rheumatologic disease. Patients at lower mortality risk included those with asthma, COPD, diabetes, malnutrition, pulmonary tuberculosis, or non-TB mycobacterial infection.
The proportion of patients who were high risk climbed over the years, from 41% among the 892 patients with aspergillosis-related hospitalization in the 2001 sample to 50% among 1,420 patients in 2011. Yet in-hospital mortality in high-risk patients fell from 26.4% in 2001 to 9.1% in 2011. Meanwhile, the mortality rate in lower-risk patients improved from 14.6% to 6.6%. The overall in-hospital mortality rate went from 18.8% to 7.7%.
Of note, the proportion of aspergillosis patients with renal failure jumped from 9.8% in 2001 to 21.5% in 2011, even though the treatments for aspergillosis are relatively non-nephrotoxic, with the exception of amphotericin B. The outlook for these patients has improved greatly: In-hospital mortality for aspergillosis patients in renal failure went from 40.2% in 2001 to 16.1% in 2011.
While in-hospital mortality and length of stay were decreasing during the study years, total hospital charges for patients with aspergillosis were going up: from a median of $29,998 in 2001 to $44,888 in 2001 dollars a decade later. This cost-of-care increase was confined to patients at lower baseline risk or with no risk factors. Somewhat surprisingly, the high-risk group didn’t have a significant increase in hospital charges over the 10-year period.
“Maybe we’re just doing a better job of treating them, so they may not necessarily have to use a lot of resources,” Dr. Mizusawa offered as explanation.
She reported having no financial conflicts regarding this unfunded study.
AT ICAAC 2015
Key clinical point: In-hospital mortality has more than halved for patients with aspergillosis-related hospitalization during a recent 10-year period.
Major finding: In-hospital mortality among patients with an aspergillosis-related hospitalization fell nationally from 18.8% in 2001 to 7.7% in 2011, with the biggest drop occurring in those at high risk.
Data source: A retrospective study of nationally representative data from the Healthcare Utilization and Cost Project–Nationwide Inpatient Sample for 2001-2011.
Disclosures: The presenter reported having no financial conflicts regarding this unfunded study.
ESC: Coronary artery calcium score gets an upgrade
LONDON – Coronary artery calcium as assessed by CT scan, widely considered the best marker of cardiovascular risk, just got significantly better.
The standard measure of coronary artery calcium (CAC) has been the Agatson score, which evaluates plaque calcium volume. But new evidence from the large, multicenter, prospective, observational Multi-Ethnic Study of Atherosclerosis (MESA) demonstrates that plaque calcium density is independently and inversely associated with both CHD and stroke risk. In other words, greater calcium density is protective against cardiovascular disease and counteracts the increased risk associated with greater calcium volume, Dr. Michael H. Criqui said at the annual congress of the European Society of Cardiology.
“We no longer believe in the Agatson score. We took a look at it and found out that at any given level of plaque calcium volume, a higher density score is protective. So when we look at our scans now, we no longer use the Agatson. We take the volume, then measure density separately, and we calculate a score that’s based on both,” explained Dr. Criqui, professor and chief of the division of preventive medicine at the University of California, San Diego.
Session moderator Dr. Sidney C. Smith Jr., was favorably impressed by the new analysis.
“Somehow we need to get this information in front of the guideline committees for the ESC, ACC [American College of Cardiology], and AHA [American Heart Association], because this is very interesting,” said Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.
The MESA analysis included 3,398 adults followed for an average of 10.3 years. During that time 264 incident CHD events and 126 hard stroke events occurred.
“You find that as the calcium volume gets higher, the CHD risk gets much higher – up to fourfold higher for the fourth quartile. But we all knew that before. The new concept is that as your density score gets higher your risk goes way down. In the fourth quartile of density, you have only half the risk of developing a coronary event at any given calcium volume,” according to Dr. Criqui.
This confirms an earlier preliminary report by Dr. Criqui and coinvestigators based upon 7.6 years of MESA follow-up (JAMA. 2014 Jan 15;311[3]:271-8). The number of cardiovascular events in the update is 47% greater than in the initial report, considerably strengthening the findings.
The predictive power of the combined CAC volume and density score was underscored by the finding that the area under the receiver operating curve for CHD events was 0.674. To put that in perspective, when the investigators applied the ACC/AHA risk calculator tool to the MESA data, the area under the receiver operating characteristic curve was less impressive at 0.654. Combining the risk prediction score and the CAC volume/density score further increases the predictive power, he noted.
Plaque calcium density was similarly predictive in men and women, in younger and older adults, and in all four ethnic groups participating in MESA: Hispanics, African Americans, non-Hispanic whites, and Asians.
For CHD, the hazard ratio was 1.83 for each standard deviation of CAC volume and 0.71 for each standard deviation of CAC density. For stroke, the impacts were slightly less: a hazard ratio of 1.46 for each standard deviation of CAC volume and 0.83 for each standard deviation of density.
Asked if any biomarkers are related to CAC density, Dr. Criqui replied, “Preliminary data show that most of the risk factors we know are bad for us, like diabetes and smoking, are associated with lower CAC density. And the things that are good for us, like exercise and statins, are associated with higher density.”
He and his coworkers are now looking at plaque calcium density versus volume in the abdominal and thoracic aorta to learn if the same relationships seen in the coronary arteries hold true.
MESA is funded by the National Heart, Lung, and Blood Institute. Dr. Criqui reported having no financial conflicts of interest.
LONDON – Coronary artery calcium as assessed by CT scan, widely considered the best marker of cardiovascular risk, just got significantly better.
The standard measure of coronary artery calcium (CAC) has been the Agatson score, which evaluates plaque calcium volume. But new evidence from the large, multicenter, prospective, observational Multi-Ethnic Study of Atherosclerosis (MESA) demonstrates that plaque calcium density is independently and inversely associated with both CHD and stroke risk. In other words, greater calcium density is protective against cardiovascular disease and counteracts the increased risk associated with greater calcium volume, Dr. Michael H. Criqui said at the annual congress of the European Society of Cardiology.
“We no longer believe in the Agatson score. We took a look at it and found out that at any given level of plaque calcium volume, a higher density score is protective. So when we look at our scans now, we no longer use the Agatson. We take the volume, then measure density separately, and we calculate a score that’s based on both,” explained Dr. Criqui, professor and chief of the division of preventive medicine at the University of California, San Diego.
Session moderator Dr. Sidney C. Smith Jr., was favorably impressed by the new analysis.
“Somehow we need to get this information in front of the guideline committees for the ESC, ACC [American College of Cardiology], and AHA [American Heart Association], because this is very interesting,” said Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.
The MESA analysis included 3,398 adults followed for an average of 10.3 years. During that time 264 incident CHD events and 126 hard stroke events occurred.
“You find that as the calcium volume gets higher, the CHD risk gets much higher – up to fourfold higher for the fourth quartile. But we all knew that before. The new concept is that as your density score gets higher your risk goes way down. In the fourth quartile of density, you have only half the risk of developing a coronary event at any given calcium volume,” according to Dr. Criqui.
This confirms an earlier preliminary report by Dr. Criqui and coinvestigators based upon 7.6 years of MESA follow-up (JAMA. 2014 Jan 15;311[3]:271-8). The number of cardiovascular events in the update is 47% greater than in the initial report, considerably strengthening the findings.
The predictive power of the combined CAC volume and density score was underscored by the finding that the area under the receiver operating curve for CHD events was 0.674. To put that in perspective, when the investigators applied the ACC/AHA risk calculator tool to the MESA data, the area under the receiver operating characteristic curve was less impressive at 0.654. Combining the risk prediction score and the CAC volume/density score further increases the predictive power, he noted.
Plaque calcium density was similarly predictive in men and women, in younger and older adults, and in all four ethnic groups participating in MESA: Hispanics, African Americans, non-Hispanic whites, and Asians.
For CHD, the hazard ratio was 1.83 for each standard deviation of CAC volume and 0.71 for each standard deviation of CAC density. For stroke, the impacts were slightly less: a hazard ratio of 1.46 for each standard deviation of CAC volume and 0.83 for each standard deviation of density.
Asked if any biomarkers are related to CAC density, Dr. Criqui replied, “Preliminary data show that most of the risk factors we know are bad for us, like diabetes and smoking, are associated with lower CAC density. And the things that are good for us, like exercise and statins, are associated with higher density.”
He and his coworkers are now looking at plaque calcium density versus volume in the abdominal and thoracic aorta to learn if the same relationships seen in the coronary arteries hold true.
MESA is funded by the National Heart, Lung, and Blood Institute. Dr. Criqui reported having no financial conflicts of interest.
LONDON – Coronary artery calcium as assessed by CT scan, widely considered the best marker of cardiovascular risk, just got significantly better.
The standard measure of coronary artery calcium (CAC) has been the Agatson score, which evaluates plaque calcium volume. But new evidence from the large, multicenter, prospective, observational Multi-Ethnic Study of Atherosclerosis (MESA) demonstrates that plaque calcium density is independently and inversely associated with both CHD and stroke risk. In other words, greater calcium density is protective against cardiovascular disease and counteracts the increased risk associated with greater calcium volume, Dr. Michael H. Criqui said at the annual congress of the European Society of Cardiology.
“We no longer believe in the Agatson score. We took a look at it and found out that at any given level of plaque calcium volume, a higher density score is protective. So when we look at our scans now, we no longer use the Agatson. We take the volume, then measure density separately, and we calculate a score that’s based on both,” explained Dr. Criqui, professor and chief of the division of preventive medicine at the University of California, San Diego.
Session moderator Dr. Sidney C. Smith Jr., was favorably impressed by the new analysis.
“Somehow we need to get this information in front of the guideline committees for the ESC, ACC [American College of Cardiology], and AHA [American Heart Association], because this is very interesting,” said Dr. Smith, professor of medicine at the University of North Carolina, Chapel Hill.
The MESA analysis included 3,398 adults followed for an average of 10.3 years. During that time 264 incident CHD events and 126 hard stroke events occurred.
“You find that as the calcium volume gets higher, the CHD risk gets much higher – up to fourfold higher for the fourth quartile. But we all knew that before. The new concept is that as your density score gets higher your risk goes way down. In the fourth quartile of density, you have only half the risk of developing a coronary event at any given calcium volume,” according to Dr. Criqui.
This confirms an earlier preliminary report by Dr. Criqui and coinvestigators based upon 7.6 years of MESA follow-up (JAMA. 2014 Jan 15;311[3]:271-8). The number of cardiovascular events in the update is 47% greater than in the initial report, considerably strengthening the findings.
The predictive power of the combined CAC volume and density score was underscored by the finding that the area under the receiver operating curve for CHD events was 0.674. To put that in perspective, when the investigators applied the ACC/AHA risk calculator tool to the MESA data, the area under the receiver operating characteristic curve was less impressive at 0.654. Combining the risk prediction score and the CAC volume/density score further increases the predictive power, he noted.
Plaque calcium density was similarly predictive in men and women, in younger and older adults, and in all four ethnic groups participating in MESA: Hispanics, African Americans, non-Hispanic whites, and Asians.
For CHD, the hazard ratio was 1.83 for each standard deviation of CAC volume and 0.71 for each standard deviation of CAC density. For stroke, the impacts were slightly less: a hazard ratio of 1.46 for each standard deviation of CAC volume and 0.83 for each standard deviation of density.
Asked if any biomarkers are related to CAC density, Dr. Criqui replied, “Preliminary data show that most of the risk factors we know are bad for us, like diabetes and smoking, are associated with lower CAC density. And the things that are good for us, like exercise and statins, are associated with higher density.”
He and his coworkers are now looking at plaque calcium density versus volume in the abdominal and thoracic aorta to learn if the same relationships seen in the coronary arteries hold true.
MESA is funded by the National Heart, Lung, and Blood Institute. Dr. Criqui reported having no financial conflicts of interest.
AT THE ESC CONGRESS 2015
Key clinical point: Greater coronary artery plaque calcium density protects against cardiovascular events.
Major finding: The risk of a coronary heart disease event decreases by 29% for each standard deviation increase in coronary artery calcium plaque density and rises by 83% with each standard deviation increase in plaque volume.
Data source: This analysis from the multicenter, prospective, observational Multi-Ethnic Study of Atherosclerosis included 3,398 adults followed for an average of 10.3 years.
Disclosures: The MESA study is funded by the National Heart, Lung, and Blood Institute. The presenter reported having no financial conflicts.
