Bruce Jancin

WAIKOLOA, HAWAII – In light of the U.S. Preventive Services Task Force’s recent rejection of population-based melanoma screening in a draft recommendation, the future of skin examination for early detection of melanoma most likely lies in the development of a targeted, risk-stratified screening approach, Dr. Michael A. Marchetti said at the Hawaii Dermatology Seminar.

The logical place to start would be in white men above age 50. They account for 50% of all melanoma deaths in the United States. Thus, this is a group where melanoma screening is most likely to bring significant demonstrable benefit with the least potential harm, according to Dr. Marchetti, a dermatologist at Memorial Sloan Kettering Cancer Center in New York.

In its December 2015 draft recommendation statement, the USPSTF declared “current evidence is insufficient to assess the balance of benefits and harms of visual skin cancer screening in adults.” The panel drew the same conclusion in its previous 2009 assessment, Dr. Marchetti noted at the seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Panelists did not find persuasive the German SCREEN study (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany), which initially generated enormous excitement among skin cancer experts worldwide. SCREEN investigators triumphantly reported a 48% drop in mortality from melanoma 5 years after the German state of Schleswig-Holstein instituted a population-based skin cancer screening program based upon total body skin examination by dermatologists and specially trained primary care physicians (J Am Acad Dermatol. 2012 Feb;66[2]:201-11).

However, the SCREEN study has since come under a variety of criticisms. The USPSTF took note, and in its December update declared the study had “important methodologic limitations” which “raise questions as to the plausibility of the observed effect.” In a best case scenario, according to the panelists, the benefit of the Schleswig-Holstein melanoma awareness campaign and free screening program worked out to at most one fewer melanoma death per 100,000 persons screened annually over a decade.

Dr. Marchetti noted that the German federal government found the SCREEN program initial results so impressive that a national program of free biannual skin cancer screening for all adults age 35 and older has been adopted. Disappointingly, however, investigators at the International Prevention Research Institute in Lyon, France, have reported that in the first 5 years of the national program, melanoma mortality rates not only didn’t decrease, they actually increased by 2.6% in men and 0.02% in women. Moreover, the same investigators determined that in the second 5-year period of screening in Schleswig-Holstein, melanoma mortality rates shot back up to levels seen before initiation of the screening program (BMJ Open. 2015 Sep 15;5[9]:e008158).

Dr. Marchetti said that based upon his reading of the USPSTF 2009 and December 2015 reports, he doesn’t think the panel takes issue with the concept that earlier detection of melanomas while they are thinner results in a much better prognosis. Their major concern is with the scarcity of data regarding the potential harms involved in population-based skin cancer screening, which include the cost and morbidity of the enormous number of skin biopsies which would result from such a screening program, with most of those biopsies coming back negative.

He added that he shares those reservations.

“I have a lot of concern about targeting low-risk populations for screening, particularly children and adolescents and dark-skinned individuals. I think in those circumstances we’re more likely to have greater harm,” the dermatologist said.

Indeed, he and his coinvestigators recently analyzed two large dermatopathology databases and concluded that during 2009-2013 in the United States, 1,035 biopsies of nevi were performed in patients age 19 years or younger in order to find one melanoma (JAMA Dermatol. 2015 Apr;151[4]:447-8).

Dr. Marchetti also recently published a viewpoint article in which he asserted that increased pressure to detect acral lentiginous melanoma in dark-skinned individuals could lead to significant harms with minimal return benefit (JAMA Dermatol. 2015 Oct;151[10]:1055-6).

The December 2015 update from USPSTF was the group’s draft document, with the final recommendations forthcoming this year. The public comment period has closed, and no major professional organization in the United States – not the American College of Physicians, the American Academy of Family Physicians, or even the American Academy of Dermatology – specifically recommends a clinical visual skin cancer screening examination.

In response to an audience question, session chair Dr. Ashfaq A. Marghoob commented that the USPSTF’s stance has big implications for physician reimbursement for skin cancer screening examinations in patients who have no symptoms or aren’t already under surveillance due to high risk of skin cancer.

“There is a code for screening, but by and large no insurance carrier will reimburse you if you use that code. In my experience, they’ll default to the U.S. Preventive Services Task Force that it’s a noncovered service. However, the minute you make your chief complaint ‘nevus,’ or ‘actinic keratosis,’ or ‘neoplasm undetermined’ and list skin cancer screening as a secondary service, then it’s covered,” said Dr. Marghoob, of Memorial Sloan Kettering Cancer Center, New York.

In addressing another audience question, he said he is not aware of any lawsuit ever having arisen directed at a physician who participated in “melanoma Monday” skin cancer screening using the American Academy of Dermatology forms with the examinee’s signature. Participating physicians are thoroughly protected.

Dr. Marchetti and Dr. Marghoob reported having no financial interests relevant to their presentations.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – In light of the U.S. Preventive Services Task Force’s recent rejection of population-based melanoma screening in a draft recommendation, the future of skin examination for early detection of melanoma most likely lies in the development of a targeted, risk-stratified screening approach, Dr. Michael A. Marchetti said at the Hawaii Dermatology Seminar.

The logical place to start would be in white men above age 50. They account for 50% of all melanoma deaths in the United States. Thus, this is a group where melanoma screening is most likely to bring significant demonstrable benefit with the least potential harm, according to Dr. Marchetti, a dermatologist at Memorial Sloan Kettering Cancer Center in New York.

In its December 2015 draft recommendation statement, the USPSTF declared “current evidence is insufficient to assess the balance of benefits and harms of visual skin cancer screening in adults.” The panel drew the same conclusion in its previous 2009 assessment, Dr. Marchetti noted at the seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Panelists did not find persuasive the German SCREEN study (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany), which initially generated enormous excitement among skin cancer experts worldwide. SCREEN investigators triumphantly reported a 48% drop in mortality from melanoma 5 years after the German state of Schleswig-Holstein instituted a population-based skin cancer screening program based upon total body skin examination by dermatologists and specially trained primary care physicians (J Am Acad Dermatol. 2012 Feb;66[2]:201-11).

However, the SCREEN study has since come under a variety of criticisms. The USPSTF took note, and in its December update declared the study had “important methodologic limitations” which “raise questions as to the plausibility of the observed effect.” In a best case scenario, according to the panelists, the benefit of the Schleswig-Holstein melanoma awareness campaign and free screening program worked out to at most one fewer melanoma death per 100,000 persons screened annually over a decade.

Dr. Marchetti noted that the German federal government found the SCREEN program initial results so impressive that a national program of free biannual skin cancer screening for all adults age 35 and older has been adopted. Disappointingly, however, investigators at the International Prevention Research Institute in Lyon, France, have reported that in the first 5 years of the national program, melanoma mortality rates not only didn’t decrease, they actually increased by 2.6% in men and 0.02% in women. Moreover, the same investigators determined that in the second 5-year period of screening in Schleswig-Holstein, melanoma mortality rates shot back up to levels seen before initiation of the screening program (BMJ Open. 2015 Sep 15;5[9]:e008158).

Dr. Marchetti said that based upon his reading of the USPSTF 2009 and December 2015 reports, he doesn’t think the panel takes issue with the concept that earlier detection of melanomas while they are thinner results in a much better prognosis. Their major concern is with the scarcity of data regarding the potential harms involved in population-based skin cancer screening, which include the cost and morbidity of the enormous number of skin biopsies which would result from such a screening program, with most of those biopsies coming back negative.

He added that he shares those reservations.

“I have a lot of concern about targeting low-risk populations for screening, particularly children and adolescents and dark-skinned individuals. I think in those circumstances we’re more likely to have greater harm,” the dermatologist said.

Indeed, he and his coinvestigators recently analyzed two large dermatopathology databases and concluded that during 2009-2013 in the United States, 1,035 biopsies of nevi were performed in patients age 19 years or younger in order to find one melanoma (JAMA Dermatol. 2015 Apr;151[4]:447-8).

Dr. Marchetti also recently published a viewpoint article in which he asserted that increased pressure to detect acral lentiginous melanoma in dark-skinned individuals could lead to significant harms with minimal return benefit (JAMA Dermatol. 2015 Oct;151[10]:1055-6).

The December 2015 update from USPSTF was the group’s draft document, with the final recommendations forthcoming this year. The public comment period has closed, and no major professional organization in the United States – not the American College of Physicians, the American Academy of Family Physicians, or even the American Academy of Dermatology – specifically recommends a clinical visual skin cancer screening examination.

In response to an audience question, session chair Dr. Ashfaq A. Marghoob commented that the USPSTF’s stance has big implications for physician reimbursement for skin cancer screening examinations in patients who have no symptoms or aren’t already under surveillance due to high risk of skin cancer.

“There is a code for screening, but by and large no insurance carrier will reimburse you if you use that code. In my experience, they’ll default to the U.S. Preventive Services Task Force that it’s a noncovered service. However, the minute you make your chief complaint ‘nevus,’ or ‘actinic keratosis,’ or ‘neoplasm undetermined’ and list skin cancer screening as a secondary service, then it’s covered,” said Dr. Marghoob, of Memorial Sloan Kettering Cancer Center, New York.

In addressing another audience question, he said he is not aware of any lawsuit ever having arisen directed at a physician who participated in “melanoma Monday” skin cancer screening using the American Academy of Dermatology forms with the examinee’s signature. Participating physicians are thoroughly protected.

Dr. Marchetti and Dr. Marghoob reported having no financial interests relevant to their presentations.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – In light of the U.S. Preventive Services Task Force’s recent rejection of population-based melanoma screening in a draft recommendation, the future of skin examination for early detection of melanoma most likely lies in the development of a targeted, risk-stratified screening approach, Dr. Michael A. Marchetti said at the Hawaii Dermatology Seminar.

The logical place to start would be in white men above age 50. They account for 50% of all melanoma deaths in the United States. Thus, this is a group where melanoma screening is most likely to bring significant demonstrable benefit with the least potential harm, according to Dr. Marchetti, a dermatologist at Memorial Sloan Kettering Cancer Center in New York.

In its December 2015 draft recommendation statement, the USPSTF declared “current evidence is insufficient to assess the balance of benefits and harms of visual skin cancer screening in adults.” The panel drew the same conclusion in its previous 2009 assessment, Dr. Marchetti noted at the seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

Panelists did not find persuasive the German SCREEN study (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany), which initially generated enormous excitement among skin cancer experts worldwide. SCREEN investigators triumphantly reported a 48% drop in mortality from melanoma 5 years after the German state of Schleswig-Holstein instituted a population-based skin cancer screening program based upon total body skin examination by dermatologists and specially trained primary care physicians (J Am Acad Dermatol. 2012 Feb;66[2]:201-11).

However, the SCREEN study has since come under a variety of criticisms. The USPSTF took note, and in its December update declared the study had “important methodologic limitations” which “raise questions as to the plausibility of the observed effect.” In a best case scenario, according to the panelists, the benefit of the Schleswig-Holstein melanoma awareness campaign and free screening program worked out to at most one fewer melanoma death per 100,000 persons screened annually over a decade.

Dr. Marchetti noted that the German federal government found the SCREEN program initial results so impressive that a national program of free biannual skin cancer screening for all adults age 35 and older has been adopted. Disappointingly, however, investigators at the International Prevention Research Institute in Lyon, France, have reported that in the first 5 years of the national program, melanoma mortality rates not only didn’t decrease, they actually increased by 2.6% in men and 0.02% in women. Moreover, the same investigators determined that in the second 5-year period of screening in Schleswig-Holstein, melanoma mortality rates shot back up to levels seen before initiation of the screening program (BMJ Open. 2015 Sep 15;5[9]:e008158).

Dr. Marchetti said that based upon his reading of the USPSTF 2009 and December 2015 reports, he doesn’t think the panel takes issue with the concept that earlier detection of melanomas while they are thinner results in a much better prognosis. Their major concern is with the scarcity of data regarding the potential harms involved in population-based skin cancer screening, which include the cost and morbidity of the enormous number of skin biopsies which would result from such a screening program, with most of those biopsies coming back negative.

He added that he shares those reservations.

“I have a lot of concern about targeting low-risk populations for screening, particularly children and adolescents and dark-skinned individuals. I think in those circumstances we’re more likely to have greater harm,” the dermatologist said.

Indeed, he and his coinvestigators recently analyzed two large dermatopathology databases and concluded that during 2009-2013 in the United States, 1,035 biopsies of nevi were performed in patients age 19 years or younger in order to find one melanoma (JAMA Dermatol. 2015 Apr;151[4]:447-8).

Dr. Marchetti also recently published a viewpoint article in which he asserted that increased pressure to detect acral lentiginous melanoma in dark-skinned individuals could lead to significant harms with minimal return benefit (JAMA Dermatol. 2015 Oct;151[10]:1055-6).

The December 2015 update from USPSTF was the group’s draft document, with the final recommendations forthcoming this year. The public comment period has closed, and no major professional organization in the United States – not the American College of Physicians, the American Academy of Family Physicians, or even the American Academy of Dermatology – specifically recommends a clinical visual skin cancer screening examination.

In response to an audience question, session chair Dr. Ashfaq A. Marghoob commented that the USPSTF’s stance has big implications for physician reimbursement for skin cancer screening examinations in patients who have no symptoms or aren’t already under surveillance due to high risk of skin cancer.

“There is a code for screening, but by and large no insurance carrier will reimburse you if you use that code. In my experience, they’ll default to the U.S. Preventive Services Task Force that it’s a noncovered service. However, the minute you make your chief complaint ‘nevus,’ or ‘actinic keratosis,’ or ‘neoplasm undetermined’ and list skin cancer screening as a secondary service, then it’s covered,” said Dr. Marghoob, of Memorial Sloan Kettering Cancer Center, New York.

In addressing another audience question, he said he is not aware of any lawsuit ever having arisen directed at a physician who participated in “melanoma Monday” skin cancer screening using the American Academy of Dermatology forms with the examinee’s signature. Participating physicians are thoroughly protected.

Dr. Marchetti and Dr. Marghoob reported having no financial interests relevant to their presentations.

The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Scrutiny of the number needed to treat with various systemic drugs to achieve a Psoriasis Area and Severity Index–90 (PASI-90) response in psoriasis highlights the folly of current stepwise treatment strategies imposed upon dermatologists by many payers, Dr. Craig L. Leonardi asserted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“It’s time to rethink our goals,” declared Dr. Leonardi, a dermatologist at Saint Louis University and a noted clinical trialist.

Bruce Jancin/Frontline Medical News

Most health plans insist that patients with moderate to severe psoriasis must have tried methotrexate and failed to achieve an adequate response before moving on to costlier biologic agents. But a PASI-90 response rate, indicative of 90% improvement in psoriasis area and severity, was achieved in only 13.6% of patients on methotrexate in the CHAMPION trial, compared with 59.2% and 70.9% of patients in phase III randomized trials of the interleukin-17 antagonists secukinumab (Cosentyx) and ixekizumab, respectively.

In other words, it is now routinely possible using highly effective medications to achieve a PASI-90 response in the majority of psoriasis patients, he noted.

Although statisticians say it isn’t appropriate to compare outcomes across clinical trials because study populations may differ, Dr. Leonardi decided it nevertheless would be illuminating to compare NNTs (the number of patients who needed to be treated with a medication instead of placebo to achieve one additional responder in a defined time period). In this analysis, he used data from phase III randomized, placebo-controlled clinical trials and Food and Drug Administration–regulated package inserts to calculate NNTs for systemic medications for psoriasis for the 10- to 16-week duration of phase III trials. The NNTs for a PASI-90 response ranged from a whopping 43.5 for methotrexate to 1.7 with secukinumab and 1.4 for ixekizumab.

“You can see immediately that methotrexate is outed as a weak and ineffective drug. And yet which drug are we usually asked to use first? Methotrexate. This is a structural problem that we have to solve in our specialty. We have to get with the insurance industry, we have to get with our guidelines of care and rewrite them. There is no reason that this drug should be placed in front of any of the other drugs, which are much more effective,” Dr. Leonardi said.

Viewing the data another way, the proportion of patients who achieved a PASI-75 response at the time of a major placebo-controlled clinical trial’s primary endpoint ranged from a low of 35.5% with methotrexate to 81.6% with secukinumab and 89.1% with ixekizumab. The NNTs to get a PASI-75 improvement with secukinumab and ixekizumab were, respectively, 1.3 and 1.2, compared to 6.0 for methotrexate.

“With an NNT of 1.2, if you treat 12 patients with ixekizumab, 10 of them are going to achieve PASI-75. This is a very different world than we had at the beginning of this adventure back in the early 2000s,” he observed.

In the modern era of highly effective biologic therapies for psoriasis, it makes sense to push as hard as possible in an effort to try to clear patients, according to Dr. Leonardi. That’s in part because the closer patients come to that once-nearly-unattainable goal, the better they actually feel, as underscored in the phase III results for ixekizumab.

In that study, the proportion of patients with a Dermatology Life Quality Index (DLQI) score of 0 or 1 at week 12 rose stepwise with the size of their PASI response. Among patients with a week-12 PASI response of 50 to less than 75, 18.8% had a DLQI of 0 or 1. For patients with a PASI-75 to less than PASI-90, it jumped to 52.3%. Among subjects with a PASI-90 to less than 100, 66.9% had a DLQI of 0 or 1. And among the 35.3% of ixekizumab-treated patients who had a PASI-100 response, the likelihood of a DLQI of 0 or 1 rose to 71.1%.

Noting that etanercept (Enbrel) is the only biologic on the market that achieves a PASI-75 response in less than half of treated patients, Dr. Leonardi said, “I’m over using etanercept as a first-line biologic. It’s the weakest biologic we can pick right now. I really like the highly efficacious drugs. I like adalimumab. I like the efficacy I see with ustekinumab. I like secukinumab. They are all preferred first-line drugs if I can get them, but it’s an insurance company world. I can’t tell you how many times I’ve heard, ‘Well, we’re not saying you can’t prescribe it, Dr. Leonardi, we’re just not going to pay for it.’ ”

Ixekizumab is under FDA review for psoriasis and a decision is expected within the first quarter of 2016, according to a spokesperson for Eli Lilly.

Dr. Leonardi is a recipient of research grants from well over a dozen pharmaceutical companies and is a consultant to and/or member of the speakers bureaus for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Janssen, Eli Lilly, Leo, Novartis, Pfizer, Sandoz, UCB, and Vitae.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Scrutiny of the number needed to treat with various systemic drugs to achieve a Psoriasis Area and Severity Index–90 (PASI-90) response in psoriasis highlights the folly of current stepwise treatment strategies imposed upon dermatologists by many payers, Dr. Craig L. Leonardi asserted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“It’s time to rethink our goals,” declared Dr. Leonardi, a dermatologist at Saint Louis University and a noted clinical trialist.

Bruce Jancin/Frontline Medical News

Most health plans insist that patients with moderate to severe psoriasis must have tried methotrexate and failed to achieve an adequate response before moving on to costlier biologic agents. But a PASI-90 response rate, indicative of 90% improvement in psoriasis area and severity, was achieved in only 13.6% of patients on methotrexate in the CHAMPION trial, compared with 59.2% and 70.9% of patients in phase III randomized trials of the interleukin-17 antagonists secukinumab (Cosentyx) and ixekizumab, respectively.

In other words, it is now routinely possible using highly effective medications to achieve a PASI-90 response in the majority of psoriasis patients, he noted.

Although statisticians say it isn’t appropriate to compare outcomes across clinical trials because study populations may differ, Dr. Leonardi decided it nevertheless would be illuminating to compare NNTs (the number of patients who needed to be treated with a medication instead of placebo to achieve one additional responder in a defined time period). In this analysis, he used data from phase III randomized, placebo-controlled clinical trials and Food and Drug Administration–regulated package inserts to calculate NNTs for systemic medications for psoriasis for the 10- to 16-week duration of phase III trials. The NNTs for a PASI-90 response ranged from a whopping 43.5 for methotrexate to 1.7 with secukinumab and 1.4 for ixekizumab.

“You can see immediately that methotrexate is outed as a weak and ineffective drug. And yet which drug are we usually asked to use first? Methotrexate. This is a structural problem that we have to solve in our specialty. We have to get with the insurance industry, we have to get with our guidelines of care and rewrite them. There is no reason that this drug should be placed in front of any of the other drugs, which are much more effective,” Dr. Leonardi said.

Viewing the data another way, the proportion of patients who achieved a PASI-75 response at the time of a major placebo-controlled clinical trial’s primary endpoint ranged from a low of 35.5% with methotrexate to 81.6% with secukinumab and 89.1% with ixekizumab. The NNTs to get a PASI-75 improvement with secukinumab and ixekizumab were, respectively, 1.3 and 1.2, compared to 6.0 for methotrexate.

“With an NNT of 1.2, if you treat 12 patients with ixekizumab, 10 of them are going to achieve PASI-75. This is a very different world than we had at the beginning of this adventure back in the early 2000s,” he observed.

In the modern era of highly effective biologic therapies for psoriasis, it makes sense to push as hard as possible in an effort to try to clear patients, according to Dr. Leonardi. That’s in part because the closer patients come to that once-nearly-unattainable goal, the better they actually feel, as underscored in the phase III results for ixekizumab.

In that study, the proportion of patients with a Dermatology Life Quality Index (DLQI) score of 0 or 1 at week 12 rose stepwise with the size of their PASI response. Among patients with a week-12 PASI response of 50 to less than 75, 18.8% had a DLQI of 0 or 1. For patients with a PASI-75 to less than PASI-90, it jumped to 52.3%. Among subjects with a PASI-90 to less than 100, 66.9% had a DLQI of 0 or 1. And among the 35.3% of ixekizumab-treated patients who had a PASI-100 response, the likelihood of a DLQI of 0 or 1 rose to 71.1%.

Noting that etanercept (Enbrel) is the only biologic on the market that achieves a PASI-75 response in less than half of treated patients, Dr. Leonardi said, “I’m over using etanercept as a first-line biologic. It’s the weakest biologic we can pick right now. I really like the highly efficacious drugs. I like adalimumab. I like the efficacy I see with ustekinumab. I like secukinumab. They are all preferred first-line drugs if I can get them, but it’s an insurance company world. I can’t tell you how many times I’ve heard, ‘Well, we’re not saying you can’t prescribe it, Dr. Leonardi, we’re just not going to pay for it.’ ”

Ixekizumab is under FDA review for psoriasis and a decision is expected within the first quarter of 2016, according to a spokesperson for Eli Lilly.

Dr. Leonardi is a recipient of research grants from well over a dozen pharmaceutical companies and is a consultant to and/or member of the speakers bureaus for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Janssen, Eli Lilly, Leo, Novartis, Pfizer, Sandoz, UCB, and Vitae.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – Scrutiny of the number needed to treat with various systemic drugs to achieve a Psoriasis Area and Severity Index–90 (PASI-90) response in psoriasis highlights the folly of current stepwise treatment strategies imposed upon dermatologists by many payers, Dr. Craig L. Leonardi asserted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“It’s time to rethink our goals,” declared Dr. Leonardi, a dermatologist at Saint Louis University and a noted clinical trialist.

Bruce Jancin/Frontline Medical News

Most health plans insist that patients with moderate to severe psoriasis must have tried methotrexate and failed to achieve an adequate response before moving on to costlier biologic agents. But a PASI-90 response rate, indicative of 90% improvement in psoriasis area and severity, was achieved in only 13.6% of patients on methotrexate in the CHAMPION trial, compared with 59.2% and 70.9% of patients in phase III randomized trials of the interleukin-17 antagonists secukinumab (Cosentyx) and ixekizumab, respectively.

In other words, it is now routinely possible using highly effective medications to achieve a PASI-90 response in the majority of psoriasis patients, he noted.

Although statisticians say it isn’t appropriate to compare outcomes across clinical trials because study populations may differ, Dr. Leonardi decided it nevertheless would be illuminating to compare NNTs (the number of patients who needed to be treated with a medication instead of placebo to achieve one additional responder in a defined time period). In this analysis, he used data from phase III randomized, placebo-controlled clinical trials and Food and Drug Administration–regulated package inserts to calculate NNTs for systemic medications for psoriasis for the 10- to 16-week duration of phase III trials. The NNTs for a PASI-90 response ranged from a whopping 43.5 for methotrexate to 1.7 with secukinumab and 1.4 for ixekizumab.

“You can see immediately that methotrexate is outed as a weak and ineffective drug. And yet which drug are we usually asked to use first? Methotrexate. This is a structural problem that we have to solve in our specialty. We have to get with the insurance industry, we have to get with our guidelines of care and rewrite them. There is no reason that this drug should be placed in front of any of the other drugs, which are much more effective,” Dr. Leonardi said.

Viewing the data another way, the proportion of patients who achieved a PASI-75 response at the time of a major placebo-controlled clinical trial’s primary endpoint ranged from a low of 35.5% with methotrexate to 81.6% with secukinumab and 89.1% with ixekizumab. The NNTs to get a PASI-75 improvement with secukinumab and ixekizumab were, respectively, 1.3 and 1.2, compared to 6.0 for methotrexate.

“With an NNT of 1.2, if you treat 12 patients with ixekizumab, 10 of them are going to achieve PASI-75. This is a very different world than we had at the beginning of this adventure back in the early 2000s,” he observed.

In the modern era of highly effective biologic therapies for psoriasis, it makes sense to push as hard as possible in an effort to try to clear patients, according to Dr. Leonardi. That’s in part because the closer patients come to that once-nearly-unattainable goal, the better they actually feel, as underscored in the phase III results for ixekizumab.

In that study, the proportion of patients with a Dermatology Life Quality Index (DLQI) score of 0 or 1 at week 12 rose stepwise with the size of their PASI response. Among patients with a week-12 PASI response of 50 to less than 75, 18.8% had a DLQI of 0 or 1. For patients with a PASI-75 to less than PASI-90, it jumped to 52.3%. Among subjects with a PASI-90 to less than 100, 66.9% had a DLQI of 0 or 1. And among the 35.3% of ixekizumab-treated patients who had a PASI-100 response, the likelihood of a DLQI of 0 or 1 rose to 71.1%.

Noting that etanercept (Enbrel) is the only biologic on the market that achieves a PASI-75 response in less than half of treated patients, Dr. Leonardi said, “I’m over using etanercept as a first-line biologic. It’s the weakest biologic we can pick right now. I really like the highly efficacious drugs. I like adalimumab. I like the efficacy I see with ustekinumab. I like secukinumab. They are all preferred first-line drugs if I can get them, but it’s an insurance company world. I can’t tell you how many times I’ve heard, ‘Well, we’re not saying you can’t prescribe it, Dr. Leonardi, we’re just not going to pay for it.’ ”

Ixekizumab is under FDA review for psoriasis and a decision is expected within the first quarter of 2016, according to a spokesperson for Eli Lilly.

Dr. Leonardi is a recipient of research grants from well over a dozen pharmaceutical companies and is a consultant to and/or member of the speakers bureaus for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Janssen, Eli Lilly, Leo, Novartis, Pfizer, Sandoz, UCB, and Vitae.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The latest update from the ongoing PSOLAR registry provides “very reassuring” evidence that the use of biologic agents to treat moderate to severe psoriasis doesn’t significantly increase malignancy risk other than for skin cancer, according to Dr. Kristina Callis Duffin.

Dr. Duffin of the department of dermatology at the University of Utah, Salt Lake City, cited a report presented by Dr. David Fiorentino, professor of dermatology at Stanford (Calif.) University, at the annual meeting of the European Academy of Dermatology and Venereology last October in Copenhagen. This update from the prospective international Psoriasis Longitudinal Assessment and Registry (PSOLAR) included 12,093 psoriasis patients deemed candidates for biologics, including 2,084 who did not go on a biologic agent while the rest did.

jancin

During 40,388 patient-years of prospective follow-up, or an average of 3.3 years, 455 patients were diagnosed with a malignancy other than skin cancer. The cumulative malignancy rate was 0.75 cases per 100 patient-years in patients on nonbiologic therapies, which was not significantly different from the rates of 0.51 per 100 patient-years in participants who started on ustekinumab (Stelara) at enrollment, 0.81 in patients on infliximab (Remicade), or 0.73 per 100 patient-years in those on other biologics, Dr. Duffin said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“These are all very low rates,” commented Dr. Duffin.

The PSOLAR data are particularly valuable because the registry was set up specifically to prospectively examine the long-term safety and efficacy of biologic agents in psoriasis patients. In contrast, the landmark epidemiologic study led by Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia, which concluded that mild psoriasis was associated with a 34% increased risk of lymphoma and that severe psoriasis carried a 59% greater risk than in nonpsoriatic controls (J Invest Dermatol. 2006 Oct;126[10]:2194-201), involved a retrospective analysis of the U.K. General Practice Research Database. And while that study had strength in numbers – it included more than 153,000 British psoriasis patients and nearly 800,000 controls – it wasn’t designed to look specifically at psoriasis patients.

It’s reassuring that the lymphoma rate of 0.47 cases per 100 patient-years in patients with severe psoriasis in the U.K. registry during the prebiologics era is virtually identical to the rates associated with biologic agents in PSOLAR to date, which ranged from 0.3 to 0.5 cases per 100 patient-years, Dr. Duffin said.

The PSOLAR findings are worth sharing with patients. As a result of direct-to-consumer advertising by pharmaceutical companies, psoriasis patients are typically quite concerned about the risk of cancer associated with biologic agents, she added.

“They hear the comment in the ad that serious infections and malignancies have been reported in patients on these drugs as ‘these drugs increase the risk of malignancy.’ So where I start this conversation is, ‘Actually, patients with psoriasis do have some increased risk of malignancy, but those malignancies are mostly nonmelanoma skin cancers and lymphoproliferative diseases,’” the dermatologist explained.

Much of this risk is probably related to the fact that patients with moderate to severe psoriasis often have an extensive history of exposure to immunosuppressive agents such as cyclosporine as well as UV light therapies, which increase the risk of skin cancer.

“You also have to consider the fact that psoriasis patients tend to have a lot of smoking behaviors and alcohol behaviors that increase cancer risk,” Dr. Duffin continued.

In shared decision making regarding the option of biologic therapy in psoriasis patients having a history of cancer or who develop cancer while on a biologic, she likes to pose a question: What scares you more: the risk of your cancer coming back or not being able to have a good quality of life?

“That gets them thinking,” she said.

She stressed that as part of discussions regarding the risk/benefit profile of biologic therapy in an individual with a history of cancer, or of continuing a biologic in someone diagnosed with a malignancy while on treatment, it’s important for the dermatologist to talk with the patient’s oncologist, who is best positioned to provide insight into the risk of cancer recurrence.

Dr. Duffin is a recipient of research grants from and a consultant to Janssen, which sponsors the PSOLAR registry, as well as to more than half a dozen other pharmaceutical companies. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The latest update from the ongoing PSOLAR registry provides “very reassuring” evidence that the use of biologic agents to treat moderate to severe psoriasis doesn’t significantly increase malignancy risk other than for skin cancer, according to Dr. Kristina Callis Duffin.

Dr. Duffin of the department of dermatology at the University of Utah, Salt Lake City, cited a report presented by Dr. David Fiorentino, professor of dermatology at Stanford (Calif.) University, at the annual meeting of the European Academy of Dermatology and Venereology last October in Copenhagen. This update from the prospective international Psoriasis Longitudinal Assessment and Registry (PSOLAR) included 12,093 psoriasis patients deemed candidates for biologics, including 2,084 who did not go on a biologic agent while the rest did.

jancin

During 40,388 patient-years of prospective follow-up, or an average of 3.3 years, 455 patients were diagnosed with a malignancy other than skin cancer. The cumulative malignancy rate was 0.75 cases per 100 patient-years in patients on nonbiologic therapies, which was not significantly different from the rates of 0.51 per 100 patient-years in participants who started on ustekinumab (Stelara) at enrollment, 0.81 in patients on infliximab (Remicade), or 0.73 per 100 patient-years in those on other biologics, Dr. Duffin said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“These are all very low rates,” commented Dr. Duffin.

The PSOLAR data are particularly valuable because the registry was set up specifically to prospectively examine the long-term safety and efficacy of biologic agents in psoriasis patients. In contrast, the landmark epidemiologic study led by Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia, which concluded that mild psoriasis was associated with a 34% increased risk of lymphoma and that severe psoriasis carried a 59% greater risk than in nonpsoriatic controls (J Invest Dermatol. 2006 Oct;126[10]:2194-201), involved a retrospective analysis of the U.K. General Practice Research Database. And while that study had strength in numbers – it included more than 153,000 British psoriasis patients and nearly 800,000 controls – it wasn’t designed to look specifically at psoriasis patients.

It’s reassuring that the lymphoma rate of 0.47 cases per 100 patient-years in patients with severe psoriasis in the U.K. registry during the prebiologics era is virtually identical to the rates associated with biologic agents in PSOLAR to date, which ranged from 0.3 to 0.5 cases per 100 patient-years, Dr. Duffin said.

The PSOLAR findings are worth sharing with patients. As a result of direct-to-consumer advertising by pharmaceutical companies, psoriasis patients are typically quite concerned about the risk of cancer associated with biologic agents, she added.

“They hear the comment in the ad that serious infections and malignancies have been reported in patients on these drugs as ‘these drugs increase the risk of malignancy.’ So where I start this conversation is, ‘Actually, patients with psoriasis do have some increased risk of malignancy, but those malignancies are mostly nonmelanoma skin cancers and lymphoproliferative diseases,’” the dermatologist explained.

Much of this risk is probably related to the fact that patients with moderate to severe psoriasis often have an extensive history of exposure to immunosuppressive agents such as cyclosporine as well as UV light therapies, which increase the risk of skin cancer.

“You also have to consider the fact that psoriasis patients tend to have a lot of smoking behaviors and alcohol behaviors that increase cancer risk,” Dr. Duffin continued.

In shared decision making regarding the option of biologic therapy in psoriasis patients having a history of cancer or who develop cancer while on a biologic, she likes to pose a question: What scares you more: the risk of your cancer coming back or not being able to have a good quality of life?

“That gets them thinking,” she said.

She stressed that as part of discussions regarding the risk/benefit profile of biologic therapy in an individual with a history of cancer, or of continuing a biologic in someone diagnosed with a malignancy while on treatment, it’s important for the dermatologist to talk with the patient’s oncologist, who is best positioned to provide insight into the risk of cancer recurrence.

Dr. Duffin is a recipient of research grants from and a consultant to Janssen, which sponsors the PSOLAR registry, as well as to more than half a dozen other pharmaceutical companies. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAIKOLOA, HAWAII – The latest update from the ongoing PSOLAR registry provides “very reassuring” evidence that the use of biologic agents to treat moderate to severe psoriasis doesn’t significantly increase malignancy risk other than for skin cancer, according to Dr. Kristina Callis Duffin.

Dr. Duffin of the department of dermatology at the University of Utah, Salt Lake City, cited a report presented by Dr. David Fiorentino, professor of dermatology at Stanford (Calif.) University, at the annual meeting of the European Academy of Dermatology and Venereology last October in Copenhagen. This update from the prospective international Psoriasis Longitudinal Assessment and Registry (PSOLAR) included 12,093 psoriasis patients deemed candidates for biologics, including 2,084 who did not go on a biologic agent while the rest did.

jancin

During 40,388 patient-years of prospective follow-up, or an average of 3.3 years, 455 patients were diagnosed with a malignancy other than skin cancer. The cumulative malignancy rate was 0.75 cases per 100 patient-years in patients on nonbiologic therapies, which was not significantly different from the rates of 0.51 per 100 patient-years in participants who started on ustekinumab (Stelara) at enrollment, 0.81 in patients on infliximab (Remicade), or 0.73 per 100 patient-years in those on other biologics, Dr. Duffin said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

“These are all very low rates,” commented Dr. Duffin.

The PSOLAR data are particularly valuable because the registry was set up specifically to prospectively examine the long-term safety and efficacy of biologic agents in psoriasis patients. In contrast, the landmark epidemiologic study led by Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia, which concluded that mild psoriasis was associated with a 34% increased risk of lymphoma and that severe psoriasis carried a 59% greater risk than in nonpsoriatic controls (J Invest Dermatol. 2006 Oct;126[10]:2194-201), involved a retrospective analysis of the U.K. General Practice Research Database. And while that study had strength in numbers – it included more than 153,000 British psoriasis patients and nearly 800,000 controls – it wasn’t designed to look specifically at psoriasis patients.

It’s reassuring that the lymphoma rate of 0.47 cases per 100 patient-years in patients with severe psoriasis in the U.K. registry during the prebiologics era is virtually identical to the rates associated with biologic agents in PSOLAR to date, which ranged from 0.3 to 0.5 cases per 100 patient-years, Dr. Duffin said.

The PSOLAR findings are worth sharing with patients. As a result of direct-to-consumer advertising by pharmaceutical companies, psoriasis patients are typically quite concerned about the risk of cancer associated with biologic agents, she added.

“They hear the comment in the ad that serious infections and malignancies have been reported in patients on these drugs as ‘these drugs increase the risk of malignancy.’ So where I start this conversation is, ‘Actually, patients with psoriasis do have some increased risk of malignancy, but those malignancies are mostly nonmelanoma skin cancers and lymphoproliferative diseases,’” the dermatologist explained.

Much of this risk is probably related to the fact that patients with moderate to severe psoriasis often have an extensive history of exposure to immunosuppressive agents such as cyclosporine as well as UV light therapies, which increase the risk of skin cancer.

“You also have to consider the fact that psoriasis patients tend to have a lot of smoking behaviors and alcohol behaviors that increase cancer risk,” Dr. Duffin continued.

In shared decision making regarding the option of biologic therapy in psoriasis patients having a history of cancer or who develop cancer while on a biologic, she likes to pose a question: What scares you more: the risk of your cancer coming back or not being able to have a good quality of life?

“That gets them thinking,” she said.

She stressed that as part of discussions regarding the risk/benefit profile of biologic therapy in an individual with a history of cancer, or of continuing a biologic in someone diagnosed with a malignancy while on treatment, it’s important for the dermatologist to talk with the patient’s oncologist, who is best positioned to provide insight into the risk of cancer recurrence.

Dr. Duffin is a recipient of research grants from and a consultant to Janssen, which sponsors the PSOLAR registry, as well as to more than half a dozen other pharmaceutical companies. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The Food and Drug Administration has approved the first-ever U.S. randomized clinical trial of transcatheter aortic valve replacement versus open surgical replacement in low–surgical risk patients with symptomatic severe aortic stenosis.

The PARTNER III trial will enroll roughly 1,200 patients age 65 or older, all with a Society of Thoracic Surgeons risk score of less than 4%, at 50 sites beginning this spring, Dr. Vinod H. Thourani said at the Annual Cardiovascular Conference at Snowmass.

This is a noninferiority trial with a primary endpoint comprising a 1-year composite of death, stroke, or rehospitalization. The study is sponsored by Edwards Lifesciences, and patients randomized to transcatheter aortic valve replacement (TAVR) will receive the company’s low-profile Sapien 3 valve.

Coprincipal investigators are Dr. Michael J. Mack of the Baylor Health Care System in Plano, Tex., and Dr. Martin B. Leon of Columbia University, New York. Dr. Thourani is a member of the PARTNER III executive committee.

This is a study that could upend clinical practice, he observed.

“Are we going to have within the next 5 years 80%-90% of all patients who present with severe symptomatic aortic stenosis treated with transcatheter valves? We’re really at a major crossroads here, I believe,” said Dr. Thourani, professor of surgery and medicine and codirector of the structural heart and valve center at Emory University in Atlanta.

He ran down the numbers: Today, roughly 80% of all surgical aortic valve replacements (SAVR) in the United States are performed in low–surgical risk patients. These low-risk patients comprise roughly 65% of the total operable population with severe aortic stenosis. If PARTNER III and other data show that TAVR provides results comparable to SAVR in this group, Dr. Thourani predicted that it’s likely most low–surgical risk patients will opt for the less invasive approach. The appeal is no surgical incision, less pain, a shorter or no ICU stay, and faster return to normal activity.

Right now, U.S. and European guidelines state that TAVR is the preferred or alternative strategy to SAVR only in the relatively small group comprised of inoperable or high–surgical risk patients. In clinical practice, TAVR has already supplanted SAVR in the 10% of operable patients with high surgical risk. And TAVR is poised to do so in the roughly 25% of patients who fall into the intermediate–surgical risk category, according to the cardiothoracic surgeon.

He predicted that the 1-year outcomes of TAVR in more than 1,000 intermediate-risk participants in the PARTNER II trial will create a stir when presented this year, as a late-breaker at the annual meeting of the American College of Cardiology in Chicago. Although he stressed that he doesn’t know the results, the 30-day outcomes presented at last year’s Transcatheter Cardiovascular Therapeutics conference are extremely promising: a 1.1% all-cause mortality rate in patients with an average Society of Thoracic Surgeons risk score of 5.3%, for a stunning observed-to-expected ratio of just 0.21. Plus, a 1.0% rate of disabling stroke in this large multicenter randomized experience.

“That becomes really compelling data for us to think we’re ready now to go to the next step,” Dr. Thourani said. “My belief is at the rate we’re going, we’ll see most intermediate-risk patients going to TAVR.”

To date there has been only one randomized trial of TAVR versus SAVR in low–surgical risk patients: the Nordic Aortic Valve Intervention Trial (NOTION), which included 280 randomized patients with an average Society of Thoracic Surgeons risk score of 3%.

In the 2-year results presented by Dr. Lars Søndergaard of the University of Copenhagen at TCT 2015, all-cause mortality was 2.1% with TAVR and 3.7% with SAVR at 30 days, 4.9% with TAVR and 7.5% with SAVR at 12 months, and 8.0% versus 9.8% at 24 months. The 30-day rates of major bleeding, cardiogenic shock, atrial fibrillation, and acute kidney injury were all substantially lower in the TAVR group. All very impressive. However, Dr. Thourani found the TAVR patients’ pacemaker-requirement rate troubling. At 30 days post TAVR, 34% of patients had a pacemaker, compared with 1.6% of the SAVR group. By 24 months, 41% of the TAVR group had received a pacemaker, compared with just 4% of the SAVR group.

“What’s the acceptable pacemaker rate for someone utilizing TAVR – 5%, 10%, 40%? That’s something we as a community have to look at,” the surgeon observed. He noted that his purchase price for a TAVR valve is roughly $32,500, whereas a SAVR valve costs him $4,500. And at Emory, putting in a pacemaker costs an added $10,000-$15,000 for the device.

“If I’m putting a pacemaker in 40% of my TAVR patients at a cost of $40,000-$45,000 per patient for the valve and pacemaker, that becomes an issue,” Dr. Thourani said.

Other concerns surrounding TAVR, in addition to reimbursement, include the uncertain long-term impact of residual minimal paravalvular leak, which is common.

“We’re not done talking about paravalvular leak rates. As cardiologists you’re not okay with me giving your patient a minimal paravalvular leak post-SAVR. Are we going to change the bar a little bit for TAVR?” he mused.

Another issue is thrombosis of TAVR valve leaflets, Dr. Thourani continued. In a large patient series reported last year, this event occurred in 0.6% of patients, with an average of 181 days from TAVR to confirmatory abnormal imaging (Circ Cardiovasc Interv. 2015 Apr;8[4]. pii: e001779). Two clinical trials are gearing up to examine various anticoagulant strategies to address the problem.

Despite the various concerns, however, Dr. Thourani is extremely optimistic about TAVR’s future. It’s a booming field, with 396 U.S. TAVR centers as of 2015. The indications appear to be on the verge of expansion. Technical progress continues, with half a dozen TAVR valves in development in addition to the two now FDA approved.

“We have just scratched the surface of what we’re going to do in the management of severe aortic stenosis,” the surgeon promised.

The latest results of minimalist TAVR provide another reason for optimism regarding TAVR’s future.

Emory University surgeons and interventional cardiologists have been pacesetters in the minimalist TAVR approach. The key elements of minimalist TAVR are that the procedure is performed in the cardiac catheterization laboratory via transfemoral access, under conscious sedation, with transthoracic echocardiographic guidance, no Swan-Ganz catheter, and no ICU stay for most patients.

Dr. Thourani presented as-yet unpublished data on a recent series of 111 high–surgical risk patients who underwent minimalist TAVR with implantation of a Sapien 3 valve at Emory. Although their Society of Thoracic Surgeons risk score was 8%, there was zero 30-day mortality in this group. One patient had a major stroke, two had major vascular complications, and the 30-day readmission rate was just 3.8%.

“Can we get to these results universally? We think we can. This is the bar we need to start thinking about,” Dr. Thourani said.

Dr. Thourani reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott, Boston Scientific, Medtronic, and Sorin.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The Food and Drug Administration has approved the first-ever U.S. randomized clinical trial of transcatheter aortic valve replacement versus open surgical replacement in low–surgical risk patients with symptomatic severe aortic stenosis.

The PARTNER III trial will enroll roughly 1,200 patients age 65 or older, all with a Society of Thoracic Surgeons risk score of less than 4%, at 50 sites beginning this spring, Dr. Vinod H. Thourani said at the Annual Cardiovascular Conference at Snowmass.

This is a noninferiority trial with a primary endpoint comprising a 1-year composite of death, stroke, or rehospitalization. The study is sponsored by Edwards Lifesciences, and patients randomized to transcatheter aortic valve replacement (TAVR) will receive the company’s low-profile Sapien 3 valve.

Coprincipal investigators are Dr. Michael J. Mack of the Baylor Health Care System in Plano, Tex., and Dr. Martin B. Leon of Columbia University, New York. Dr. Thourani is a member of the PARTNER III executive committee.

This is a study that could upend clinical practice, he observed.

“Are we going to have within the next 5 years 80%-90% of all patients who present with severe symptomatic aortic stenosis treated with transcatheter valves? We’re really at a major crossroads here, I believe,” said Dr. Thourani, professor of surgery and medicine and codirector of the structural heart and valve center at Emory University in Atlanta.

He ran down the numbers: Today, roughly 80% of all surgical aortic valve replacements (SAVR) in the United States are performed in low–surgical risk patients. These low-risk patients comprise roughly 65% of the total operable population with severe aortic stenosis. If PARTNER III and other data show that TAVR provides results comparable to SAVR in this group, Dr. Thourani predicted that it’s likely most low–surgical risk patients will opt for the less invasive approach. The appeal is no surgical incision, less pain, a shorter or no ICU stay, and faster return to normal activity.

Right now, U.S. and European guidelines state that TAVR is the preferred or alternative strategy to SAVR only in the relatively small group comprised of inoperable or high–surgical risk patients. In clinical practice, TAVR has already supplanted SAVR in the 10% of operable patients with high surgical risk. And TAVR is poised to do so in the roughly 25% of patients who fall into the intermediate–surgical risk category, according to the cardiothoracic surgeon.

He predicted that the 1-year outcomes of TAVR in more than 1,000 intermediate-risk participants in the PARTNER II trial will create a stir when presented this year, as a late-breaker at the annual meeting of the American College of Cardiology in Chicago. Although he stressed that he doesn’t know the results, the 30-day outcomes presented at last year’s Transcatheter Cardiovascular Therapeutics conference are extremely promising: a 1.1% all-cause mortality rate in patients with an average Society of Thoracic Surgeons risk score of 5.3%, for a stunning observed-to-expected ratio of just 0.21. Plus, a 1.0% rate of disabling stroke in this large multicenter randomized experience.

“That becomes really compelling data for us to think we’re ready now to go to the next step,” Dr. Thourani said. “My belief is at the rate we’re going, we’ll see most intermediate-risk patients going to TAVR.”

To date there has been only one randomized trial of TAVR versus SAVR in low–surgical risk patients: the Nordic Aortic Valve Intervention Trial (NOTION), which included 280 randomized patients with an average Society of Thoracic Surgeons risk score of 3%.

In the 2-year results presented by Dr. Lars Søndergaard of the University of Copenhagen at TCT 2015, all-cause mortality was 2.1% with TAVR and 3.7% with SAVR at 30 days, 4.9% with TAVR and 7.5% with SAVR at 12 months, and 8.0% versus 9.8% at 24 months. The 30-day rates of major bleeding, cardiogenic shock, atrial fibrillation, and acute kidney injury were all substantially lower in the TAVR group. All very impressive. However, Dr. Thourani found the TAVR patients’ pacemaker-requirement rate troubling. At 30 days post TAVR, 34% of patients had a pacemaker, compared with 1.6% of the SAVR group. By 24 months, 41% of the TAVR group had received a pacemaker, compared with just 4% of the SAVR group.

“What’s the acceptable pacemaker rate for someone utilizing TAVR – 5%, 10%, 40%? That’s something we as a community have to look at,” the surgeon observed. He noted that his purchase price for a TAVR valve is roughly $32,500, whereas a SAVR valve costs him $4,500. And at Emory, putting in a pacemaker costs an added $10,000-$15,000 for the device.

“If I’m putting a pacemaker in 40% of my TAVR patients at a cost of $40,000-$45,000 per patient for the valve and pacemaker, that becomes an issue,” Dr. Thourani said.

Other concerns surrounding TAVR, in addition to reimbursement, include the uncertain long-term impact of residual minimal paravalvular leak, which is common.

“We’re not done talking about paravalvular leak rates. As cardiologists you’re not okay with me giving your patient a minimal paravalvular leak post-SAVR. Are we going to change the bar a little bit for TAVR?” he mused.

Another issue is thrombosis of TAVR valve leaflets, Dr. Thourani continued. In a large patient series reported last year, this event occurred in 0.6% of patients, with an average of 181 days from TAVR to confirmatory abnormal imaging (Circ Cardiovasc Interv. 2015 Apr;8[4]. pii: e001779). Two clinical trials are gearing up to examine various anticoagulant strategies to address the problem.

Despite the various concerns, however, Dr. Thourani is extremely optimistic about TAVR’s future. It’s a booming field, with 396 U.S. TAVR centers as of 2015. The indications appear to be on the verge of expansion. Technical progress continues, with half a dozen TAVR valves in development in addition to the two now FDA approved.

“We have just scratched the surface of what we’re going to do in the management of severe aortic stenosis,” the surgeon promised.

The latest results of minimalist TAVR provide another reason for optimism regarding TAVR’s future.

Emory University surgeons and interventional cardiologists have been pacesetters in the minimalist TAVR approach. The key elements of minimalist TAVR are that the procedure is performed in the cardiac catheterization laboratory via transfemoral access, under conscious sedation, with transthoracic echocardiographic guidance, no Swan-Ganz catheter, and no ICU stay for most patients.

Dr. Thourani presented as-yet unpublished data on a recent series of 111 high–surgical risk patients who underwent minimalist TAVR with implantation of a Sapien 3 valve at Emory. Although their Society of Thoracic Surgeons risk score was 8%, there was zero 30-day mortality in this group. One patient had a major stroke, two had major vascular complications, and the 30-day readmission rate was just 3.8%.

“Can we get to these results universally? We think we can. This is the bar we need to start thinking about,” Dr. Thourani said.

Dr. Thourani reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott, Boston Scientific, Medtronic, and Sorin.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The Food and Drug Administration has approved the first-ever U.S. randomized clinical trial of transcatheter aortic valve replacement versus open surgical replacement in low–surgical risk patients with symptomatic severe aortic stenosis.

The PARTNER III trial will enroll roughly 1,200 patients age 65 or older, all with a Society of Thoracic Surgeons risk score of less than 4%, at 50 sites beginning this spring, Dr. Vinod H. Thourani said at the Annual Cardiovascular Conference at Snowmass.

This is a noninferiority trial with a primary endpoint comprising a 1-year composite of death, stroke, or rehospitalization. The study is sponsored by Edwards Lifesciences, and patients randomized to transcatheter aortic valve replacement (TAVR) will receive the company’s low-profile Sapien 3 valve.

Coprincipal investigators are Dr. Michael J. Mack of the Baylor Health Care System in Plano, Tex., and Dr. Martin B. Leon of Columbia University, New York. Dr. Thourani is a member of the PARTNER III executive committee.

This is a study that could upend clinical practice, he observed.

“Are we going to have within the next 5 years 80%-90% of all patients who present with severe symptomatic aortic stenosis treated with transcatheter valves? We’re really at a major crossroads here, I believe,” said Dr. Thourani, professor of surgery and medicine and codirector of the structural heart and valve center at Emory University in Atlanta.

He ran down the numbers: Today, roughly 80% of all surgical aortic valve replacements (SAVR) in the United States are performed in low–surgical risk patients. These low-risk patients comprise roughly 65% of the total operable population with severe aortic stenosis. If PARTNER III and other data show that TAVR provides results comparable to SAVR in this group, Dr. Thourani predicted that it’s likely most low–surgical risk patients will opt for the less invasive approach. The appeal is no surgical incision, less pain, a shorter or no ICU stay, and faster return to normal activity.

Right now, U.S. and European guidelines state that TAVR is the preferred or alternative strategy to SAVR only in the relatively small group comprised of inoperable or high–surgical risk patients. In clinical practice, TAVR has already supplanted SAVR in the 10% of operable patients with high surgical risk. And TAVR is poised to do so in the roughly 25% of patients who fall into the intermediate–surgical risk category, according to the cardiothoracic surgeon.

He predicted that the 1-year outcomes of TAVR in more than 1,000 intermediate-risk participants in the PARTNER II trial will create a stir when presented this year, as a late-breaker at the annual meeting of the American College of Cardiology in Chicago. Although he stressed that he doesn’t know the results, the 30-day outcomes presented at last year’s Transcatheter Cardiovascular Therapeutics conference are extremely promising: a 1.1% all-cause mortality rate in patients with an average Society of Thoracic Surgeons risk score of 5.3%, for a stunning observed-to-expected ratio of just 0.21. Plus, a 1.0% rate of disabling stroke in this large multicenter randomized experience.

“That becomes really compelling data for us to think we’re ready now to go to the next step,” Dr. Thourani said. “My belief is at the rate we’re going, we’ll see most intermediate-risk patients going to TAVR.”

To date there has been only one randomized trial of TAVR versus SAVR in low–surgical risk patients: the Nordic Aortic Valve Intervention Trial (NOTION), which included 280 randomized patients with an average Society of Thoracic Surgeons risk score of 3%.

In the 2-year results presented by Dr. Lars Søndergaard of the University of Copenhagen at TCT 2015, all-cause mortality was 2.1% with TAVR and 3.7% with SAVR at 30 days, 4.9% with TAVR and 7.5% with SAVR at 12 months, and 8.0% versus 9.8% at 24 months. The 30-day rates of major bleeding, cardiogenic shock, atrial fibrillation, and acute kidney injury were all substantially lower in the TAVR group. All very impressive. However, Dr. Thourani found the TAVR patients’ pacemaker-requirement rate troubling. At 30 days post TAVR, 34% of patients had a pacemaker, compared with 1.6% of the SAVR group. By 24 months, 41% of the TAVR group had received a pacemaker, compared with just 4% of the SAVR group.

“What’s the acceptable pacemaker rate for someone utilizing TAVR – 5%, 10%, 40%? That’s something we as a community have to look at,” the surgeon observed. He noted that his purchase price for a TAVR valve is roughly $32,500, whereas a SAVR valve costs him $4,500. And at Emory, putting in a pacemaker costs an added $10,000-$15,000 for the device.

“If I’m putting a pacemaker in 40% of my TAVR patients at a cost of $40,000-$45,000 per patient for the valve and pacemaker, that becomes an issue,” Dr. Thourani said.

Other concerns surrounding TAVR, in addition to reimbursement, include the uncertain long-term impact of residual minimal paravalvular leak, which is common.

“We’re not done talking about paravalvular leak rates. As cardiologists you’re not okay with me giving your patient a minimal paravalvular leak post-SAVR. Are we going to change the bar a little bit for TAVR?” he mused.

Another issue is thrombosis of TAVR valve leaflets, Dr. Thourani continued. In a large patient series reported last year, this event occurred in 0.6% of patients, with an average of 181 days from TAVR to confirmatory abnormal imaging (Circ Cardiovasc Interv. 2015 Apr;8[4]. pii: e001779). Two clinical trials are gearing up to examine various anticoagulant strategies to address the problem.

Despite the various concerns, however, Dr. Thourani is extremely optimistic about TAVR’s future. It’s a booming field, with 396 U.S. TAVR centers as of 2015. The indications appear to be on the verge of expansion. Technical progress continues, with half a dozen TAVR valves in development in addition to the two now FDA approved.

“We have just scratched the surface of what we’re going to do in the management of severe aortic stenosis,” the surgeon promised.

The latest results of minimalist TAVR provide another reason for optimism regarding TAVR’s future.

Emory University surgeons and interventional cardiologists have been pacesetters in the minimalist TAVR approach. The key elements of minimalist TAVR are that the procedure is performed in the cardiac catheterization laboratory via transfemoral access, under conscious sedation, with transthoracic echocardiographic guidance, no Swan-Ganz catheter, and no ICU stay for most patients.

Dr. Thourani presented as-yet unpublished data on a recent series of 111 high–surgical risk patients who underwent minimalist TAVR with implantation of a Sapien 3 valve at Emory. Although their Society of Thoracic Surgeons risk score was 8%, there was zero 30-day mortality in this group. One patient had a major stroke, two had major vascular complications, and the 30-day readmission rate was just 3.8%.

“Can we get to these results universally? We think we can. This is the bar we need to start thinking about,” Dr. Thourani said.

Dr. Thourani reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott, Boston Scientific, Medtronic, and Sorin.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Current American Heart Association consensus recommendations for noninvasive testing of women with suspected ischemic heart disease utilize a novel and simplified approach to pretest risk stratification.

The writing committee’s thinking was that a new risk assessment method specific to symptomatic women was needed. Conventional risk scores, such as the Framingham and American College of Cardiology/AHA atherosclerotic cardiovascular disease risk calculator, are weighted for risk evaluation in the general population of asymptomatic men and women, committee cochair Dr. Jennifer H. Mieres explained at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

The pretest risk assessment strategy for ischemic heart disease (IHD) described in the AHA consensus statement (Circulation. 2014 Jul 22;130[4]:350-79) is applicable only in women who present with chest pain symptoms or an ischemic equivalent such as excessive shortness of breath not attributable to underlying pulmonary disease. It’s designed to avoid overuse of costly noninvasive and invasive diagnostic testing, which has become common in concert with increasing physician awareness that the pattern of symptom presentation is broader in women than men with IHD.

Given the epidemiologic evidence that coronary heart disease tends to occur a decade later in women than men, the female-specific risk assessment method utilizes age as its starting point. In general, women who present with symptoms suggestive of IHD in their 50s are classified as low risk. Those in their 60s are deemed intermediate risk. And symptomatic women in their 70s are categorized as high risk. A patient gets bumped up one risk category if she has multiple cardiac risk factors or functional disability, according to Dr. Mieres, professor of cardiology and population health at Hofstra University in Hempstead, N.Y.

Functional disability is defined as inability to perform activities of daily living or as a limited exercise capacity estimated at less than 5 metabolic equivalents (METs) using the Duke Activities Status Index (DASI), a validated brief 12-item questionnaire suitable for patients to complete in the waiting room.

A symptomatic woman’s baseline fitness level is important for a couple of reasons. If she can’t perform basic activities of daily living or do more than 5 METs of exercise then the exercise treadmill test is not the initial diagnostic test of choice because she won’t be able to achieve maximum stress.

Plus, the landmark Women’s Ischemia Syndrome Evaluation (WISE) study showed that a symptomatic woman’s baseline fitness level is a powerful predictor of her prognosis: Participants who had an estimated exercise capacity of 4.7 METs or less based upon their DASI score had a 3.7-fold greater risk of death or nonfatal MI during follow-up did than those with a DASI score of 10 METs or more. Those with a DASI score of 4.8-7.4 METs were 2.1-fold more likely to experience death or MI, and women with an estimated exercise capacity of 7.5-9.9 METs based upon DASI were at 1.9-fold increased risk of death or MI, compared with those having a DASI score of at least 10 METs (J Am Coll Cardiol. 2006 Feb 7;47[3 Suppl]:S36-43).

In addition, the women’s IHD risk evaluation utilizes several high-risk equivalents which automatically move a symptomatic woman into the high-risk category regardless of her age. These are peripheral artery disease, longstanding poorly controlled diabetes, and a history of cerebrovascular accident, Dr. Mieres continued.

She stressed that most low-risk symptomatic women are not candidates for diagnostic testing. The exercise treadmill test is the first-line diagnostic test for women at intermediate risk for IHD who are functionally capable and have a normal resting ECG.

Stress imaging studies are reserved for intermediate- and high-risk women with resting ST-segment abnormalities, inability to exercise adequately, or an indeterminate exercise treadmill test.

Stress echocardiography gets a class I recommendation in these situations. So does stress myocardial perfusion imaging with SPECT or PET except in premenopausal women, where concerns about radiation exposure dictate that stress echo or stress cardiac magnetic resonance imaging is preferable.

Otherwise, stress cardiac magnetic resonance gets a class IIb – “may be reasonable” – recommendation as an initial imaging test in these situations.

Coronary artery calcium measurement via CT angiography gets a class IIb recommendation in intermediate-risk symptomatic women. This imaging method is unique in that it not only provides accurate information about the obstructive burden of CAD, but it measures the nonobstructive burden as well. That’s particularly important in women because they have a greater burden of nonobstructive CAD, defined as 1%-49% stenosis, than do men. Women with stress test abnormalities and nonobstructive CAD are no longer defined as having a false-positive test, as was traditionally the case; instead, their test is categorized as abnormal because the WISE study has shown they are at elevated IHD risk, Dr. Mieres said.

She reported having no financial conflicts regarding her presentation.

SNOWMASS, COLO. – Current American Heart Association consensus recommendations for noninvasive testing of women with suspected ischemic heart disease utilize a novel and simplified approach to pretest risk stratification.

The writing committee’s thinking was that a new risk assessment method specific to symptomatic women was needed. Conventional risk scores, such as the Framingham and American College of Cardiology/AHA atherosclerotic cardiovascular disease risk calculator, are weighted for risk evaluation in the general population of asymptomatic men and women, committee cochair Dr. Jennifer H. Mieres explained at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

The pretest risk assessment strategy for ischemic heart disease (IHD) described in the AHA consensus statement (Circulation. 2014 Jul 22;130[4]:350-79) is applicable only in women who present with chest pain symptoms or an ischemic equivalent such as excessive shortness of breath not attributable to underlying pulmonary disease. It’s designed to avoid overuse of costly noninvasive and invasive diagnostic testing, which has become common in concert with increasing physician awareness that the pattern of symptom presentation is broader in women than men with IHD.

Given the epidemiologic evidence that coronary heart disease tends to occur a decade later in women than men, the female-specific risk assessment method utilizes age as its starting point. In general, women who present with symptoms suggestive of IHD in their 50s are classified as low risk. Those in their 60s are deemed intermediate risk. And symptomatic women in their 70s are categorized as high risk. A patient gets bumped up one risk category if she has multiple cardiac risk factors or functional disability, according to Dr. Mieres, professor of cardiology and population health at Hofstra University in Hempstead, N.Y.

Functional disability is defined as inability to perform activities of daily living or as a limited exercise capacity estimated at less than 5 metabolic equivalents (METs) using the Duke Activities Status Index (DASI), a validated brief 12-item questionnaire suitable for patients to complete in the waiting room.

A symptomatic woman’s baseline fitness level is important for a couple of reasons. If she can’t perform basic activities of daily living or do more than 5 METs of exercise then the exercise treadmill test is not the initial diagnostic test of choice because she won’t be able to achieve maximum stress.

Plus, the landmark Women’s Ischemia Syndrome Evaluation (WISE) study showed that a symptomatic woman’s baseline fitness level is a powerful predictor of her prognosis: Participants who had an estimated exercise capacity of 4.7 METs or less based upon their DASI score had a 3.7-fold greater risk of death or nonfatal MI during follow-up did than those with a DASI score of 10 METs or more. Those with a DASI score of 4.8-7.4 METs were 2.1-fold more likely to experience death or MI, and women with an estimated exercise capacity of 7.5-9.9 METs based upon DASI were at 1.9-fold increased risk of death or MI, compared with those having a DASI score of at least 10 METs (J Am Coll Cardiol. 2006 Feb 7;47[3 Suppl]:S36-43).

In addition, the women’s IHD risk evaluation utilizes several high-risk equivalents which automatically move a symptomatic woman into the high-risk category regardless of her age. These are peripheral artery disease, longstanding poorly controlled diabetes, and a history of cerebrovascular accident, Dr. Mieres continued.

She stressed that most low-risk symptomatic women are not candidates for diagnostic testing. The exercise treadmill test is the first-line diagnostic test for women at intermediate risk for IHD who are functionally capable and have a normal resting ECG.

Stress imaging studies are reserved for intermediate- and high-risk women with resting ST-segment abnormalities, inability to exercise adequately, or an indeterminate exercise treadmill test.

Stress echocardiography gets a class I recommendation in these situations. So does stress myocardial perfusion imaging with SPECT or PET except in premenopausal women, where concerns about radiation exposure dictate that stress echo or stress cardiac magnetic resonance imaging is preferable.

Otherwise, stress cardiac magnetic resonance gets a class IIb – “may be reasonable” – recommendation as an initial imaging test in these situations.

Coronary artery calcium measurement via CT angiography gets a class IIb recommendation in intermediate-risk symptomatic women. This imaging method is unique in that it not only provides accurate information about the obstructive burden of CAD, but it measures the nonobstructive burden as well. That’s particularly important in women because they have a greater burden of nonobstructive CAD, defined as 1%-49% stenosis, than do men. Women with stress test abnormalities and nonobstructive CAD are no longer defined as having a false-positive test, as was traditionally the case; instead, their test is categorized as abnormal because the WISE study has shown they are at elevated IHD risk, Dr. Mieres said.

She reported having no financial conflicts regarding her presentation.

SNOWMASS, COLO. – Current American Heart Association consensus recommendations for noninvasive testing of women with suspected ischemic heart disease utilize a novel and simplified approach to pretest risk stratification.

The writing committee’s thinking was that a new risk assessment method specific to symptomatic women was needed. Conventional risk scores, such as the Framingham and American College of Cardiology/AHA atherosclerotic cardiovascular disease risk calculator, are weighted for risk evaluation in the general population of asymptomatic men and women, committee cochair Dr. Jennifer H. Mieres explained at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

The pretest risk assessment strategy for ischemic heart disease (IHD) described in the AHA consensus statement (Circulation. 2014 Jul 22;130[4]:350-79) is applicable only in women who present with chest pain symptoms or an ischemic equivalent such as excessive shortness of breath not attributable to underlying pulmonary disease. It’s designed to avoid overuse of costly noninvasive and invasive diagnostic testing, which has become common in concert with increasing physician awareness that the pattern of symptom presentation is broader in women than men with IHD.

Given the epidemiologic evidence that coronary heart disease tends to occur a decade later in women than men, the female-specific risk assessment method utilizes age as its starting point. In general, women who present with symptoms suggestive of IHD in their 50s are classified as low risk. Those in their 60s are deemed intermediate risk. And symptomatic women in their 70s are categorized as high risk. A patient gets bumped up one risk category if she has multiple cardiac risk factors or functional disability, according to Dr. Mieres, professor of cardiology and population health at Hofstra University in Hempstead, N.Y.

Functional disability is defined as inability to perform activities of daily living or as a limited exercise capacity estimated at less than 5 metabolic equivalents (METs) using the Duke Activities Status Index (DASI), a validated brief 12-item questionnaire suitable for patients to complete in the waiting room.

A symptomatic woman’s baseline fitness level is important for a couple of reasons. If she can’t perform basic activities of daily living or do more than 5 METs of exercise then the exercise treadmill test is not the initial diagnostic test of choice because she won’t be able to achieve maximum stress.

Plus, the landmark Women’s Ischemia Syndrome Evaluation (WISE) study showed that a symptomatic woman’s baseline fitness level is a powerful predictor of her prognosis: Participants who had an estimated exercise capacity of 4.7 METs or less based upon their DASI score had a 3.7-fold greater risk of death or nonfatal MI during follow-up did than those with a DASI score of 10 METs or more. Those with a DASI score of 4.8-7.4 METs were 2.1-fold more likely to experience death or MI, and women with an estimated exercise capacity of 7.5-9.9 METs based upon DASI were at 1.9-fold increased risk of death or MI, compared with those having a DASI score of at least 10 METs (J Am Coll Cardiol. 2006 Feb 7;47[3 Suppl]:S36-43).

In addition, the women’s IHD risk evaluation utilizes several high-risk equivalents which automatically move a symptomatic woman into the high-risk category regardless of her age. These are peripheral artery disease, longstanding poorly controlled diabetes, and a history of cerebrovascular accident, Dr. Mieres continued.

She stressed that most low-risk symptomatic women are not candidates for diagnostic testing. The exercise treadmill test is the first-line diagnostic test for women at intermediate risk for IHD who are functionally capable and have a normal resting ECG.

Stress imaging studies are reserved for intermediate- and high-risk women with resting ST-segment abnormalities, inability to exercise adequately, or an indeterminate exercise treadmill test.

Stress echocardiography gets a class I recommendation in these situations. So does stress myocardial perfusion imaging with SPECT or PET except in premenopausal women, where concerns about radiation exposure dictate that stress echo or stress cardiac magnetic resonance imaging is preferable.

Otherwise, stress cardiac magnetic resonance gets a class IIb – “may be reasonable” – recommendation as an initial imaging test in these situations.

Coronary artery calcium measurement via CT angiography gets a class IIb recommendation in intermediate-risk symptomatic women. This imaging method is unique in that it not only provides accurate information about the obstructive burden of CAD, but it measures the nonobstructive burden as well. That’s particularly important in women because they have a greater burden of nonobstructive CAD, defined as 1%-49% stenosis, than do men. Women with stress test abnormalities and nonobstructive CAD are no longer defined as having a false-positive test, as was traditionally the case; instead, their test is categorized as abnormal because the WISE study has shown they are at elevated IHD risk, Dr. Mieres said.

She reported having no financial conflicts regarding her presentation.

SNOWMASS, COLO. – Current American Heart Association consensus recommendations for noninvasive testing of women with suspected ischemic heart disease utilize a novel and simplified approach to pretest risk stratification.

The writing committee’s thinking was that a new risk assessment method specific to symptomatic women was needed. Conventional risk scores, such as the Framingham and American College of Cardiology/AHA atherosclerotic cardiovascular disease risk calculator, are weighted for risk evaluation in the general population of asymptomatic men and women, committee cochair Dr. Jennifer H. Mieres explained at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

The pretest risk assessment strategy for ischemic heart disease (IHD) described in the AHA consensus statement (Circulation. 2014 Jul 22;130[4]:350-79) is applicable only in women who present with chest pain symptoms or an ischemic equivalent such as excessive shortness of breath not attributable to underlying pulmonary disease. It’s designed to avoid overuse of costly noninvasive and invasive diagnostic testing, which has become common in concert with increasing physician awareness that the pattern of symptom presentation is broader in women than men with IHD.

Given the epidemiologic evidence that coronary heart disease tends to occur a decade later in women than men, the female-specific risk assessment method utilizes age as its starting point. In general, women who present with symptoms suggestive of IHD in their 50s are classified as low risk. Those in their 60s are deemed intermediate risk. And symptomatic women in their 70s are categorized as high risk. A patient gets bumped up one risk category if she has multiple cardiac risk factors or functional disability, according to Dr. Mieres, professor of cardiology and population health at Hofstra University in Hempstead, N.Y.

Functional disability is defined as inability to perform activities of daily living or as a limited exercise capacity estimated at less than 5 metabolic equivalents (METs) using the Duke Activities Status Index (DASI), a validated brief 12-item questionnaire suitable for patients to complete in the waiting room.

A symptomatic woman’s baseline fitness level is important for a couple of reasons. If she can’t perform basic activities of daily living or do more than 5 METs of exercise then the exercise treadmill test is not the initial diagnostic test of choice because she won’t be able to achieve maximum stress.

Plus, the landmark Women’s Ischemia Syndrome Evaluation (WISE) study showed that a symptomatic woman’s baseline fitness level is a powerful predictor of her prognosis: Participants who had an estimated exercise capacity of 4.7 METs or less based upon their DASI score had a 3.7-fold greater risk of death or nonfatal MI during follow-up did than those with a DASI score of 10 METs or more. Those with a DASI score of 4.8-7.4 METs were 2.1-fold more likely to experience death or MI, and women with an estimated exercise capacity of 7.5-9.9 METs based upon DASI were at 1.9-fold increased risk of death or MI, compared with those having a DASI score of at least 10 METs (J Am Coll Cardiol. 2006 Feb 7;47[3 Suppl]:S36-43).

In addition, the women’s IHD risk evaluation utilizes several high-risk equivalents which automatically move a symptomatic woman into the high-risk category regardless of her age. These are peripheral artery disease, longstanding poorly controlled diabetes, and a history of cerebrovascular accident, Dr. Mieres continued.

She stressed that most low-risk symptomatic women are not candidates for diagnostic testing. The exercise treadmill test is the first-line diagnostic test for women at intermediate risk for IHD who are functionally capable and have a normal resting ECG.

Stress imaging studies are reserved for intermediate- and high-risk women with resting ST-segment abnormalities, inability to exercise adequately, or an indeterminate exercise treadmill test.

Stress echocardiography gets a class I recommendation in these situations. So does stress myocardial perfusion imaging with SPECT or PET except in premenopausal women, where concerns about radiation exposure dictate that stress echo or stress cardiac magnetic resonance imaging is preferable.

Otherwise, stress cardiac magnetic resonance gets a class IIb – “may be reasonable” – recommendation as an initial imaging test in these situations.

Coronary artery calcium measurement via CT angiography gets a class IIb recommendation in intermediate-risk symptomatic women. This imaging method is unique in that it not only provides accurate information about the obstructive burden of CAD, but it measures the nonobstructive burden as well. That’s particularly important in women because they have a greater burden of nonobstructive CAD, defined as 1%-49% stenosis, than do men. Women with stress test abnormalities and nonobstructive CAD are no longer defined as having a false-positive test, as was traditionally the case; instead, their test is categorized as abnormal because the WISE study has shown they are at elevated IHD risk, Dr. Mieres said.

She reported having no financial conflicts regarding her presentation.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Current American Heart Association consensus recommendations for noninvasive testing of women with suspected ischemic heart disease utilize a novel and simplified approach to pretest risk stratification.

The writing committee’s thinking was that a new risk assessment method specific to symptomatic women was needed. Conventional risk scores, such as the Framingham and American College of Cardiology/AHA atherosclerotic cardiovascular disease risk calculator, are weighted for risk evaluation in the general population of asymptomatic men and women, committee cochair Dr. Jennifer H. Mieres explained at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

The pretest risk assessment strategy for ischemic heart disease (IHD) described in the AHA consensus statement (Circulation. 2014 Jul 22;130[4]:350-79) is applicable only in women who present with chest pain symptoms or an ischemic equivalent such as excessive shortness of breath not attributable to underlying pulmonary disease. It’s designed to avoid overuse of costly noninvasive and invasive diagnostic testing, which has become common in concert with increasing physician awareness that the pattern of symptom presentation is broader in women than men with IHD.

Given the epidemiologic evidence that coronary heart disease tends to occur a decade later in women than men, the female-specific risk assessment method utilizes age as its starting point. In general, women who present with symptoms suggestive of IHD in their 50s are classified as low risk. Those in their 60s are deemed intermediate risk. And symptomatic women in their 70s are categorized as high risk. A patient gets bumped up one risk category if she has multiple cardiac risk factors or functional disability, according to Dr. Mieres, professor of cardiology and population health at Hofstra University in Hempstead, N.Y.

Functional disability is defined as inability to perform activities of daily living or as a limited exercise capacity estimated at less than 5 metabolic equivalents (METs) using the Duke Activities Status Index (DASI), a validated brief 12-item questionnaire suitable for patients to complete in the waiting room.

A symptomatic woman’s baseline fitness level is important for a couple of reasons. If she can’t perform basic activities of daily living or do more than 5 METs of exercise then the exercise treadmill test is not the initial diagnostic test of choice because she won’t be able to achieve maximum stress.

Plus, the landmark Women’s Ischemia Syndrome Evaluation (WISE) study showed that a symptomatic woman’s baseline fitness level is a powerful predictor of her prognosis: Participants who had an estimated exercise capacity of 4.7 METs or less based upon their DASI score had a 3.7-fold greater risk of death or nonfatal MI during follow-up did than those with a DASI score of 10 METs or more. Those with a DASI score of 4.8-7.4 METs were 2.1-fold more likely to experience death or MI, and women with an estimated exercise capacity of 7.5-9.9 METs based upon DASI were at 1.9-fold increased risk of death or MI, compared with those having a DASI score of at least 10 METs (J Am Coll Cardiol. 2006 Feb 7;47[3 Suppl]:S36-43).

In addition, the women’s IHD risk evaluation utilizes several high-risk equivalents which automatically move a symptomatic woman into the high-risk category regardless of her age. These are peripheral artery disease, longstanding poorly controlled diabetes, and a history of cerebrovascular accident, Dr. Mieres continued.

She stressed that most low-risk symptomatic women are not candidates for diagnostic testing. The exercise treadmill test is the first-line diagnostic test for women at intermediate risk for IHD who are functionally capable and have a normal resting ECG.

Stress imaging studies are reserved for intermediate- and high-risk women with resting ST-segment abnormalities, inability to exercise adequately, or an indeterminate exercise treadmill test.

Stress echocardiography gets a class I recommendation in these situations. So does stress myocardial perfusion imaging with SPECT or PET except in premenopausal women, where concerns about radiation exposure dictate that stress echo or stress cardiac magnetic resonance imaging is preferable.

Otherwise, stress cardiac magnetic resonance gets a class IIb – “may be reasonable” – recommendation as an initial imaging test in these situations.

Coronary artery calcium measurement via CT angiography gets a class IIb recommendation in intermediate-risk symptomatic women. This imaging method is unique in that it not only provides accurate information about the obstructive burden of CAD, but it measures the nonobstructive burden as well. That’s particularly important in women because they have a greater burden of nonobstructive CAD, defined as 1%-49% stenosis, than do men. Women with stress test abnormalities and nonobstructive CAD are no longer defined as having a false-positive test, as was traditionally the case; instead, their test is categorized as abnormal because the WISE study has shown they are at elevated IHD risk, Dr. Mieres said.

She reported having no financial conflicts regarding her presentation.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Current American Heart Association consensus recommendations for noninvasive testing of women with suspected ischemic heart disease utilize a novel and simplified approach to pretest risk stratification.

The writing committee’s thinking was that a new risk assessment method specific to symptomatic women was needed. Conventional risk scores, such as the Framingham and American College of Cardiology/AHA atherosclerotic cardiovascular disease risk calculator, are weighted for risk evaluation in the general population of asymptomatic men and women, committee cochair Dr. Jennifer H. Mieres explained at the Annual Cardiovascular Conference at Snowmass.

Bruce Jancin/Frontline Medical News

The pretest risk assessment strategy for ischemic heart disease (IHD) described in the AHA consensus statement (Circulation. 2014 Jul 22;130[4]:350-79) is applicable only in women who present with chest pain symptoms or an ischemic equivalent such as excessive shortness of breath not attributable to underlying pulmonary disease. It’s designed to avoid overuse of costly noninvasive and invasive diagnostic testing, which has become common in concert with increasing physician awareness that the pattern of symptom presentation is broader in women than men with IHD.

Given the epidemiologic evidence that coronary heart disease tends to occur a decade later in women than men, the female-specific risk assessment method utilizes age as its starting point. In general, women who present with symptoms suggestive of IHD in their 50s are classified as low risk. Those in their 60s are deemed intermediate risk. And symptomatic women in their 70s are categorized as high risk. A patient gets bumped up one risk category if she has multiple cardiac risk factors or functional disability, according to Dr. Mieres, professor of cardiology and population health at Hofstra University in Hempstead, N.Y.

Functional disability is defined as inability to perform activities of daily living or as a limited exercise capacity estimated at less than 5 metabolic equivalents (METs) using the Duke Activities Status Index (DASI), a validated brief 12-item questionnaire suitable for patients to complete in the waiting room.

A symptomatic woman’s baseline fitness level is important for a couple of reasons. If she can’t perform basic activities of daily living or do more than 5 METs of exercise then the exercise treadmill test is not the initial diagnostic test of choice because she won’t be able to achieve maximum stress.

Plus, the landmark Women’s Ischemia Syndrome Evaluation (WISE) study showed that a symptomatic woman’s baseline fitness level is a powerful predictor of her prognosis: Participants who had an estimated exercise capacity of 4.7 METs or less based upon their DASI score had a 3.7-fold greater risk of death or nonfatal MI during follow-up did than those with a DASI score of 10 METs or more. Those with a DASI score of 4.8-7.4 METs were 2.1-fold more likely to experience death or MI, and women with an estimated exercise capacity of 7.5-9.9 METs based upon DASI were at 1.9-fold increased risk of death or MI, compared with those having a DASI score of at least 10 METs (J Am Coll Cardiol. 2006 Feb 7;47[3 Suppl]:S36-43).

In addition, the women’s IHD risk evaluation utilizes several high-risk equivalents which automatically move a symptomatic woman into the high-risk category regardless of her age. These are peripheral artery disease, longstanding poorly controlled diabetes, and a history of cerebrovascular accident, Dr. Mieres continued.

She stressed that most low-risk symptomatic women are not candidates for diagnostic testing. The exercise treadmill test is the first-line diagnostic test for women at intermediate risk for IHD who are functionally capable and have a normal resting ECG.

Stress imaging studies are reserved for intermediate- and high-risk women with resting ST-segment abnormalities, inability to exercise adequately, or an indeterminate exercise treadmill test.

Stress echocardiography gets a class I recommendation in these situations. So does stress myocardial perfusion imaging with SPECT or PET except in premenopausal women, where concerns about radiation exposure dictate that stress echo or stress cardiac magnetic resonance imaging is preferable.

Otherwise, stress cardiac magnetic resonance gets a class IIb – “may be reasonable” – recommendation as an initial imaging test in these situations.

Coronary artery calcium measurement via CT angiography gets a class IIb recommendation in intermediate-risk symptomatic women. This imaging method is unique in that it not only provides accurate information about the obstructive burden of CAD, but it measures the nonobstructive burden as well. That’s particularly important in women because they have a greater burden of nonobstructive CAD, defined as 1%-49% stenosis, than do men. Women with stress test abnormalities and nonobstructive CAD are no longer defined as having a false-positive test, as was traditionally the case; instead, their test is categorized as abnormal because the WISE study has shown they are at elevated IHD risk, Dr. Mieres said.

She reported having no financial conflicts regarding her presentation.

bjancin@frontlinemedcom.com