Bruce Jancin

GOTHENBURG, SWEDEN - Compliance with topical dermatologic therapies is worse than most physicians realize, according to a new study.

Through a series of Danish studies utilizing the nation’s comprehensive electronic medical and pharmacy records system, investigators concluded that more than one in three new prescriptions for creams and ointments for dermatologic diseases is never picked up. And for those who actually do fill their prescriptions, treatment adherence just goes downhill from there.

"I would say that even an optimistic estimate would be that only one in five patients truly follows the treatment advice and takes their treatment at home. It's really an alarming figure. The typical result is that the patient comes in complaining, 'It didn't work, doctor,' and now they expect another prescription," Dr. Jørgen Serup said.

"Creams and ointments are truly messy, greasy, cumbersome, and patients can only treat a limited number of lesions on a limited area, and only on certain anatomic sites. These are serious limitations. This is a lot more difficult than just taking a pill," added Dr. Serup, professor of dermatology at Copenhagen University. "Maybe the creams and ointments are really obsolete because they are so difficult to use in clinical practice. Maybe we should be using much more systemic therapy."

He and his colleagues examined all new prescriptions for previously untried medications issued for dermatologic outpatients at Copenhagen University Hospital every 15th day during 2006. Thirty-one percent of the 322 eligible patients exhibited what Dr. Serup termed "primary nonadherence," meaning they never collected their medication. Patients with psoriasis were the biggest offenders; they failed to pick up their medications 44% of the time. This was also the case for 31% of atopic dermatitis patients, 12% being treated for skin infections, and 9% of acne patients.

Thirty-five percent of prescriptions for topical preparations remained behind the pharmacy counter. Prescriptions for systemic agents fared much better; only 14% went unredeemed (J. Am. Acad. Dermatol. 2008;59:27-33).

In another study, the Danish dermatologists visited the homes of 17 first-time dermatologic outpatients who had been given prescriptions for previously untried topical medications. Upon weighing the patients' drug containers, the investigators found only 1 of the 17 patients used the directed dosage. Two patients never picked up their prescriptions, 13 used too little drug, and 1 patient used too much (J. Am. Acad. Dermatol. 2008;59:975-80).

Inadequate application of topical agents is another problem. In a joint study conducted with Swedish dermatologists, the Danish investigators found that highly motivated volunteers applied a fluorescent test cream to only 69% of the skin surface as directed. Areas prone to neglect included the upper breast, axilla and surrounding skin, posterior trunk, legs, and soles of the feet (Br. J. Dermatol. 2007;156:974-8).

Yet another form of treatment noncompliance results from patients’ failure to show up for scheduled appointments. Dr. Serup and coworkers recently reviewed 3,592 patient appointments at the university hospital’s outpatient dermatology clinic and found that 13% of patients didn’t keep their appointments. Patients failed to show for about 10% of all appointments because of forgetfulness or a variety of excuses; this was most common in patients under age 30. The rest of the no-shows were caused by booking mistakes by the clinic staff.

Poor physician-patient communication plays a role in noncompliance as well, as underscored in a study in which Dr. Serup’s colleagues taped and studied 57 dermatologic consultations with 17 dermatology patients, all of whom received new prescriptions for topical agents. At follow-up 2 weeks later, only 41% of patients were familiar with their diagnosis, 71% understood the recommended number of treatment applications per day, and 35% knew the planned duration of treatment. Just 12% of patients understood the proper quantity of the topical agent to be applied; their ignorance on this score was understandable, since dermatologists covered that key issue in only 18% of the recorded clinic visits. Moreover, dermatologists provided a clear explanation of the diagnosis in only 65% of cases (J. Dermatolog. Treat. 2009;20:190-3).

On a more optimistic note, Dr. Serup believes mobile phones and other modern tools can be better utilized to boost compliance among dermatology patients, especially the younger ones, who tend to have the lowest compliance rates. The literature shows that text message reminders and email consultations are effective in this regard, at least within general medicine. A system recently developed in Sweden allows patients to install software on their mobile phone so they can monitor their disease and phone their physician for data transfer and to communicate about therapy. Dr. Serup has utilized this technology to follow the course of treatment in patients with atopic dermatitis.

"It is exactly the language of the [younger generation] to have the information displayed on a mobile phone screen. This can't be used in the elderly, though," he said.

He declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Compliance with topical dermatologic therapies is worse than most physicians realize, according to a new study.

Through a series of Danish studies utilizing the nation’s comprehensive electronic medical and pharmacy records system, investigators concluded that more than one in three new prescriptions for creams and ointments for dermatologic diseases is never picked up. And for those who actually do fill their prescriptions, treatment adherence just goes downhill from there.

"I would say that even an optimistic estimate would be that only one in five patients truly follows the treatment advice and takes their treatment at home. It's really an alarming figure. The typical result is that the patient comes in complaining, 'It didn't work, doctor,' and now they expect another prescription," Dr. Jørgen Serup said.

"Creams and ointments are truly messy, greasy, cumbersome, and patients can only treat a limited number of lesions on a limited area, and only on certain anatomic sites. These are serious limitations. This is a lot more difficult than just taking a pill," added Dr. Serup, professor of dermatology at Copenhagen University. "Maybe the creams and ointments are really obsolete because they are so difficult to use in clinical practice. Maybe we should be using much more systemic therapy."

He and his colleagues examined all new prescriptions for previously untried medications issued for dermatologic outpatients at Copenhagen University Hospital every 15th day during 2006. Thirty-one percent of the 322 eligible patients exhibited what Dr. Serup termed "primary nonadherence," meaning they never collected their medication. Patients with psoriasis were the biggest offenders; they failed to pick up their medications 44% of the time. This was also the case for 31% of atopic dermatitis patients, 12% being treated for skin infections, and 9% of acne patients.

Thirty-five percent of prescriptions for topical preparations remained behind the pharmacy counter. Prescriptions for systemic agents fared much better; only 14% went unredeemed (J. Am. Acad. Dermatol. 2008;59:27-33).

In another study, the Danish dermatologists visited the homes of 17 first-time dermatologic outpatients who had been given prescriptions for previously untried topical medications. Upon weighing the patients' drug containers, the investigators found only 1 of the 17 patients used the directed dosage. Two patients never picked up their prescriptions, 13 used too little drug, and 1 patient used too much (J. Am. Acad. Dermatol. 2008;59:975-80).

Inadequate application of topical agents is another problem. In a joint study conducted with Swedish dermatologists, the Danish investigators found that highly motivated volunteers applied a fluorescent test cream to only 69% of the skin surface as directed. Areas prone to neglect included the upper breast, axilla and surrounding skin, posterior trunk, legs, and soles of the feet (Br. J. Dermatol. 2007;156:974-8).

Yet another form of treatment noncompliance results from patients’ failure to show up for scheduled appointments. Dr. Serup and coworkers recently reviewed 3,592 patient appointments at the university hospital’s outpatient dermatology clinic and found that 13% of patients didn’t keep their appointments. Patients failed to show for about 10% of all appointments because of forgetfulness or a variety of excuses; this was most common in patients under age 30. The rest of the no-shows were caused by booking mistakes by the clinic staff.

Poor physician-patient communication plays a role in noncompliance as well, as underscored in a study in which Dr. Serup’s colleagues taped and studied 57 dermatologic consultations with 17 dermatology patients, all of whom received new prescriptions for topical agents. At follow-up 2 weeks later, only 41% of patients were familiar with their diagnosis, 71% understood the recommended number of treatment applications per day, and 35% knew the planned duration of treatment. Just 12% of patients understood the proper quantity of the topical agent to be applied; their ignorance on this score was understandable, since dermatologists covered that key issue in only 18% of the recorded clinic visits. Moreover, dermatologists provided a clear explanation of the diagnosis in only 65% of cases (J. Dermatolog. Treat. 2009;20:190-3).

On a more optimistic note, Dr. Serup believes mobile phones and other modern tools can be better utilized to boost compliance among dermatology patients, especially the younger ones, who tend to have the lowest compliance rates. The literature shows that text message reminders and email consultations are effective in this regard, at least within general medicine. A system recently developed in Sweden allows patients to install software on their mobile phone so they can monitor their disease and phone their physician for data transfer and to communicate about therapy. Dr. Serup has utilized this technology to follow the course of treatment in patients with atopic dermatitis.

"It is exactly the language of the [younger generation] to have the information displayed on a mobile phone screen. This can't be used in the elderly, though," he said.

He declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Compliance with topical dermatologic therapies is worse than most physicians realize, according to a new study.

Through a series of Danish studies utilizing the nation’s comprehensive electronic medical and pharmacy records system, investigators concluded that more than one in three new prescriptions for creams and ointments for dermatologic diseases is never picked up. And for those who actually do fill their prescriptions, treatment adherence just goes downhill from there.

"I would say that even an optimistic estimate would be that only one in five patients truly follows the treatment advice and takes their treatment at home. It's really an alarming figure. The typical result is that the patient comes in complaining, 'It didn't work, doctor,' and now they expect another prescription," Dr. Jørgen Serup said.

"Creams and ointments are truly messy, greasy, cumbersome, and patients can only treat a limited number of lesions on a limited area, and only on certain anatomic sites. These are serious limitations. This is a lot more difficult than just taking a pill," added Dr. Serup, professor of dermatology at Copenhagen University. "Maybe the creams and ointments are really obsolete because they are so difficult to use in clinical practice. Maybe we should be using much more systemic therapy."

He and his colleagues examined all new prescriptions for previously untried medications issued for dermatologic outpatients at Copenhagen University Hospital every 15th day during 2006. Thirty-one percent of the 322 eligible patients exhibited what Dr. Serup termed "primary nonadherence," meaning they never collected their medication. Patients with psoriasis were the biggest offenders; they failed to pick up their medications 44% of the time. This was also the case for 31% of atopic dermatitis patients, 12% being treated for skin infections, and 9% of acne patients.

Thirty-five percent of prescriptions for topical preparations remained behind the pharmacy counter. Prescriptions for systemic agents fared much better; only 14% went unredeemed (J. Am. Acad. Dermatol. 2008;59:27-33).

In another study, the Danish dermatologists visited the homes of 17 first-time dermatologic outpatients who had been given prescriptions for previously untried topical medications. Upon weighing the patients' drug containers, the investigators found only 1 of the 17 patients used the directed dosage. Two patients never picked up their prescriptions, 13 used too little drug, and 1 patient used too much (J. Am. Acad. Dermatol. 2008;59:975-80).

Inadequate application of topical agents is another problem. In a joint study conducted with Swedish dermatologists, the Danish investigators found that highly motivated volunteers applied a fluorescent test cream to only 69% of the skin surface as directed. Areas prone to neglect included the upper breast, axilla and surrounding skin, posterior trunk, legs, and soles of the feet (Br. J. Dermatol. 2007;156:974-8).

Yet another form of treatment noncompliance results from patients’ failure to show up for scheduled appointments. Dr. Serup and coworkers recently reviewed 3,592 patient appointments at the university hospital’s outpatient dermatology clinic and found that 13% of patients didn’t keep their appointments. Patients failed to show for about 10% of all appointments because of forgetfulness or a variety of excuses; this was most common in patients under age 30. The rest of the no-shows were caused by booking mistakes by the clinic staff.

Poor physician-patient communication plays a role in noncompliance as well, as underscored in a study in which Dr. Serup’s colleagues taped and studied 57 dermatologic consultations with 17 dermatology patients, all of whom received new prescriptions for topical agents. At follow-up 2 weeks later, only 41% of patients were familiar with their diagnosis, 71% understood the recommended number of treatment applications per day, and 35% knew the planned duration of treatment. Just 12% of patients understood the proper quantity of the topical agent to be applied; their ignorance on this score was understandable, since dermatologists covered that key issue in only 18% of the recorded clinic visits. Moreover, dermatologists provided a clear explanation of the diagnosis in only 65% of cases (J. Dermatolog. Treat. 2009;20:190-3).

On a more optimistic note, Dr. Serup believes mobile phones and other modern tools can be better utilized to boost compliance among dermatology patients, especially the younger ones, who tend to have the lowest compliance rates. The literature shows that text message reminders and email consultations are effective in this regard, at least within general medicine. A system recently developed in Sweden allows patients to install software on their mobile phone so they can monitor their disease and phone their physician for data transfer and to communicate about therapy. Dr. Serup has utilized this technology to follow the course of treatment in patients with atopic dermatitis.

"It is exactly the language of the [younger generation] to have the information displayed on a mobile phone screen. This can't be used in the elderly, though," he said.

He declared having no relevant financial interests.

SAN ANTONIO – Compliance with mammographic screening guidelines is considerably less than would be expected based upon the public sound and fury that greeted the U.S. Preventive Services Task Force’s November 2009 updated guidelines recommending a cutback from annual to biennial screening in 50- to 74-year-olds and dropping the routine screening of women aged 40-49.

"When the U.S. Preventive Services Task Force guidelines came out, there was a large outcry. We heard, ‘Don’t take away our right, our ability, to have a mammogram regularly.’ So we thought we’d take a look at our database and see what women are actually doing, what the compliance is with the guidelines," Dr. Milayna Subar explained at the San Antonio Breast Cancer Symposium.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

Her study involved nearly 1.6 million American women aged 40 or older with full health insurance coverage and no history of breast cancer. It showed that only 50% got annual mammograms during the study years 2006-2009, as was widely recommended by most major guidelines during that period, including the since-revised USPSTF guidelines.

Moreover, 40% of insured women with access to the full range of preventive health care services did not even get the biennial mammographic screening as recommended in the USPSTF guidelines operative today, reported Dr. Subar, vice president and national practice leader for oncology at Medco Health Solutions.

Of note, the widely cited American Cancer Society guidelines still recommend annual mammography in women aged 40 or older, and American College of Obstetricians and Gynecologists guidelines recommend annual mammography in women aged 50 and older, and every 1-2 years in 40- to 49-year-olds. The reality demonstrated by the Medco study is that compliance with these more-stringent guidelines falls even further short of adherence to the cutback USPSTF guidelines, she observed.

During 2006-2009, the rate of annual screening mammography remained fairly constant over the years at 47% among women aged 40-49 years, compared with 54% in 50- to 64-year-olds, and 45% among those women aged 65 or older.

Screening every 2 years was obtained by 57% of women aged 40-49, 65% of those aged 50-64 years – the age when all of the guidelines (despite their other differences) agree on screening at a minimum of every 2 years – and in 53% of insured women aged 65 or older.

This study didn’t examine reasons for noncompliance with mammographic guidelines among insured women. But Dr. Subar offered several theories as to the low screening rates: fear, procedure-related discomfort, simple forgetfulness, the declining number of mammographic facilities, and the inconsistency of the guidelines.

"I think there could be some confusion about what to do," she said.

Some women may have been put off by debate among experts as to the net benefit of screening mammography. For Dr. Alan Coates, that issue has been well answered by a recent published analysis of the Norwegian breast cancer screening program experience.

The Norwegian investigators found that during a recent 20-year period mortality due to breast cancer declined by 28% in that country, as has also been true in most other Western countries. Since the Norwegian national mammographic screening was introduced in stages regionally, the investigators were able to determine that of the 28% drop in breast cancer mortality, 18% was attributable to improved patient management, most notably the introduction of adjuvant tamoxifen and better multidisciplinary care, while the other 10% was due to the effects of earlier diagnosis through mammographic screening (N. Engl. J. Med. 2010;363:1203-10), noted Dr. Coates of the University of Sydney in his conference-closing summary of the year’s highlights in early breast cancer.

Dr. Subar’s study was sponsored by Medco Health Solutions.

SAN ANTONIO – Compliance with mammographic screening guidelines is considerably less than would be expected based upon the public sound and fury that greeted the U.S. Preventive Services Task Force’s November 2009 updated guidelines recommending a cutback from annual to biennial screening in 50- to 74-year-olds and dropping the routine screening of women aged 40-49.

"When the U.S. Preventive Services Task Force guidelines came out, there was a large outcry. We heard, ‘Don’t take away our right, our ability, to have a mammogram regularly.’ So we thought we’d take a look at our database and see what women are actually doing, what the compliance is with the guidelines," Dr. Milayna Subar explained at the San Antonio Breast Cancer Symposium.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

Her study involved nearly 1.6 million American women aged 40 or older with full health insurance coverage and no history of breast cancer. It showed that only 50% got annual mammograms during the study years 2006-2009, as was widely recommended by most major guidelines during that period, including the since-revised USPSTF guidelines.

Moreover, 40% of insured women with access to the full range of preventive health care services did not even get the biennial mammographic screening as recommended in the USPSTF guidelines operative today, reported Dr. Subar, vice president and national practice leader for oncology at Medco Health Solutions.

Of note, the widely cited American Cancer Society guidelines still recommend annual mammography in women aged 40 or older, and American College of Obstetricians and Gynecologists guidelines recommend annual mammography in women aged 50 and older, and every 1-2 years in 40- to 49-year-olds. The reality demonstrated by the Medco study is that compliance with these more-stringent guidelines falls even further short of adherence to the cutback USPSTF guidelines, she observed.

During 2006-2009, the rate of annual screening mammography remained fairly constant over the years at 47% among women aged 40-49 years, compared with 54% in 50- to 64-year-olds, and 45% among those women aged 65 or older.

Screening every 2 years was obtained by 57% of women aged 40-49, 65% of those aged 50-64 years – the age when all of the guidelines (despite their other differences) agree on screening at a minimum of every 2 years – and in 53% of insured women aged 65 or older.

This study didn’t examine reasons for noncompliance with mammographic guidelines among insured women. But Dr. Subar offered several theories as to the low screening rates: fear, procedure-related discomfort, simple forgetfulness, the declining number of mammographic facilities, and the inconsistency of the guidelines.

"I think there could be some confusion about what to do," she said.

Some women may have been put off by debate among experts as to the net benefit of screening mammography. For Dr. Alan Coates, that issue has been well answered by a recent published analysis of the Norwegian breast cancer screening program experience.

The Norwegian investigators found that during a recent 20-year period mortality due to breast cancer declined by 28% in that country, as has also been true in most other Western countries. Since the Norwegian national mammographic screening was introduced in stages regionally, the investigators were able to determine that of the 28% drop in breast cancer mortality, 18% was attributable to improved patient management, most notably the introduction of adjuvant tamoxifen and better multidisciplinary care, while the other 10% was due to the effects of earlier diagnosis through mammographic screening (N. Engl. J. Med. 2010;363:1203-10), noted Dr. Coates of the University of Sydney in his conference-closing summary of the year’s highlights in early breast cancer.

Dr. Subar’s study was sponsored by Medco Health Solutions.

SAN ANTONIO – Compliance with mammographic screening guidelines is considerably less than would be expected based upon the public sound and fury that greeted the U.S. Preventive Services Task Force’s November 2009 updated guidelines recommending a cutback from annual to biennial screening in 50- to 74-year-olds and dropping the routine screening of women aged 40-49.

"When the U.S. Preventive Services Task Force guidelines came out, there was a large outcry. We heard, ‘Don’t take away our right, our ability, to have a mammogram regularly.’ So we thought we’d take a look at our database and see what women are actually doing, what the compliance is with the guidelines," Dr. Milayna Subar explained at the San Antonio Breast Cancer Symposium.

[Check out our comprehensive coverage of the San Antonio Breast Cancer Symposium.]

Her study involved nearly 1.6 million American women aged 40 or older with full health insurance coverage and no history of breast cancer. It showed that only 50% got annual mammograms during the study years 2006-2009, as was widely recommended by most major guidelines during that period, including the since-revised USPSTF guidelines.

Moreover, 40% of insured women with access to the full range of preventive health care services did not even get the biennial mammographic screening as recommended in the USPSTF guidelines operative today, reported Dr. Subar, vice president and national practice leader for oncology at Medco Health Solutions.

Of note, the widely cited American Cancer Society guidelines still recommend annual mammography in women aged 40 or older, and American College of Obstetricians and Gynecologists guidelines recommend annual mammography in women aged 50 and older, and every 1-2 years in 40- to 49-year-olds. The reality demonstrated by the Medco study is that compliance with these more-stringent guidelines falls even further short of adherence to the cutback USPSTF guidelines, she observed.

During 2006-2009, the rate of annual screening mammography remained fairly constant over the years at 47% among women aged 40-49 years, compared with 54% in 50- to 64-year-olds, and 45% among those women aged 65 or older.

Screening every 2 years was obtained by 57% of women aged 40-49, 65% of those aged 50-64 years – the age when all of the guidelines (despite their other differences) agree on screening at a minimum of every 2 years – and in 53% of insured women aged 65 or older.

This study didn’t examine reasons for noncompliance with mammographic guidelines among insured women. But Dr. Subar offered several theories as to the low screening rates: fear, procedure-related discomfort, simple forgetfulness, the declining number of mammographic facilities, and the inconsistency of the guidelines.

"I think there could be some confusion about what to do," she said.

Some women may have been put off by debate among experts as to the net benefit of screening mammography. For Dr. Alan Coates, that issue has been well answered by a recent published analysis of the Norwegian breast cancer screening program experience.

The Norwegian investigators found that during a recent 20-year period mortality due to breast cancer declined by 28% in that country, as has also been true in most other Western countries. Since the Norwegian national mammographic screening was introduced in stages regionally, the investigators were able to determine that of the 28% drop in breast cancer mortality, 18% was attributable to improved patient management, most notably the introduction of adjuvant tamoxifen and better multidisciplinary care, while the other 10% was due to the effects of earlier diagnosis through mammographic screening (N. Engl. J. Med. 2010;363:1203-10), noted Dr. Coates of the University of Sydney in his conference-closing summary of the year’s highlights in early breast cancer.

Dr. Subar’s study was sponsored by Medco Health Solutions.

SAN ANTONIO – The combination of two anti-HER2 therapies, together with chemotherapy, may be markedly better than one, according to watershed randomized clinical trials presented at the San Antonio Breast Cancer Symposium.

"This is data that is preliminary; it’s not to be used today in practice. But this is the way things are going to go," predicted Dr. José Baselga, chief of hematology/oncology at Massachusetts General Hospital, Boston, and professor of medicine at Harvard Medical School and the Autonomous University of Barcelona.

He presented the results of the Neo-ALTTO trial, a phase III, open-label, triple-arm study that randomized 455 women with HER2-positive early breast cancer to 18 weeks of neoadjuvant anti-HER2 therapy with trastuzumab (Herceptin), lapatinib (Tykerb), or both. After the first 6 weeks of anti-HER2 therapy, 12 weeks of paclitaxel was added to each study arm prior to surgery.

Pathological complete response (pCR), which was the primary study end point, occurred in 24.7% of patients in the lapatinib/paclitaxel arm, 29.5% in the trastuzumab/paclitaxel arm, and a significantly higher 51.3% in the lapatinib/trastuzumab/paclitaxel arm.

[Trastuzumab/Pertuzumab Doublet Eradicates Some Early Breast Cancer]

Grade 3 or worse adverse events occurred most frequently in the two lapatinib-containing arms. The most common of these was grade 3 or higher diarrhea, which occurred in 21% of the dual anti-HER2 group, 23% in the lapatinib arm, and just 2% in the trastuzumab arm. Grade 3 or higher hepatotoxicity occurred in 9% on dual anti-HER2 therapy, 13% on lapatinib, and 1% on trastuzumab. Grade 3 or higher neutropenia and skin rash followed the same pattern.

Largely as a result of toxicities, 39% and 34% of patients in the dual anti-HER2 and lapatinib arms, respectively, didn’t complete neoadjuvant treatment as planned. This was the case for only 8% in the trastuzumab arm.

Based upon the success of Neo-ALLT, Dr. Baselga and coinvestigators have launched the companion ALTTO trial. Nearly 8,200 of a planned 8,400 patients with HER2-positive breast cancer have been enrolled in the trial, which will feature four adjuvant therapy arms: lapatinib, trastuzumab, both agents, and sequential trastuzumab followed by lapatinib. Study end points will include overall and disease-free survival.

Although the numerically superior pCR rate with trastuzumab/paclitaxel, compared with lapatinib/paclitaxel, didn’t achieve statistical significance in Neo-ALTTO, it did in another randomized trial that was presented during the same session. Dr. Michael Untch of the Helios Clinic in Berlin presented the results of the phase II GeparQuinto study led by the German Breast Group, in which 620 patients with HER2-positive primary breast cancer were randomized to neoadjuvant therapy with either trastuzumab or lapatinib, both given in conjunction with neoadjuvant anthracycline/taxane-based chemotherapy.

The pCR rate (defined as no invasive or noninvasive residual disease in the breast or nodes) was 31.3% in the trastuzumab/chemotherapy arm, compared with 21.7% with lapatinib/chemotherapy (P less than .05).

These study results prompted extensive discussion during the conference. Dr. Eric P. Winer served as formal discussant of Neo-ALTTO, GeparQuinto, and a third neoadjuvant trial – NeoSphere – in which docetaxel plus dual anti-HER2 therapy with trastuzumab and the investigational agent pertuzumab produced a significantly higher pCR rate than did docetaxel plus either anti-HER2 biologic agent alone.

Dr. Winer argued that even though Neo-ALTTO is a phase III trial, he doesn’t consider pCR rate an appropriate end point for drug approval or change in clinical practice. As a surrogate for the key end points of overall and disease-free survival, pCR simply isn’t reliable enough, he said. A classic case in point was the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-27 trial, in which a doubling of the pCR rate didn’t lead to improvement in overall or disease-free survival.

"In my view, [the combination of] trastuzumab, lapatinib, and paclitaxel looks like a regimen of great interest. It’s not ready for adjuvant therapy. It isn’t ready for neoadjuvant therapy outside of a clinical trial. But we all eagerly await the results of ALTTO," said Dr. Winer, director of the breast oncology center at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.

As for trastuzumab vs. lapatinib as single-agent anti-HER2 neoadjuvant therapy in conjunction with neoadjuvant chemotherapy, the evidence from Neo-ALTTO and GeparQuinto makes it "hard to escape the conclusion that [the combination of] lapatinib and chemotherapy is a little less active and a little more toxic than trastuzumab and chemotherapy," the oncologist observed.

Dr. Baselga later commented that clinical practice in the management of HER2-positive breast cancer could change as early as next year, when the results of the ongoing CLEOPATRA trial are due to be reported. That study is comparing first-line therapy for HER2-positive metastatic breast cancer with trastuzumab plus docetaxel vs. trastuzumab, pertuzumab, and docetaxel.

In a plenary lecture, Dr. Neil L. Spector of Duke University, Durham, N.C., said that if two anti-HER2 drugs are better than one, it’s entirely possible that complete blockade of HER2 via triple therapy with trastuzumab, pertuzumab, and lapatinib would be the most effective of all, albeit with an astronomical price tag.

"Total blockade may be feasible, but we’re going to bust the economy," he argued. "If we’re going to develop these things, and only 5 patients out of 100 can afford them, we have to rethink what the hell we’re doing."

Dr. Spector said that although 15 years ago he was a major skeptic about tumor vaccines, he has recently changed his mind in response to preclinical and early clinical evidence that vaccines now in development can generate good titers of polyclonal antibodies. "What if we could generate trastuzumab- and pertuzumablike antibodies directly in patients, making total HER2 blockade more affordable?" he said. "I think vaccines have come of age."

An ongoing clinical trial at Duke shows evidence that a polyclonal HER2 vaccine in combination with lapatinib provides an enhanced anti-tumor effect, the oncologist added.

The Neo-ALTTO and GeparQuinto trials were supported by GlaxoSmithKline. Dr. Baselga and Dr. Untch declared that they have no relevant financial relationships to disclose.

Correction: An earlier version of this article described imprecisely the CLEOPATRA trial. The trial compares first-line therapies for HER-2 positive metastatic breast cancer.

SAN ANTONIO – The combination of two anti-HER2 therapies, together with chemotherapy, may be markedly better than one, according to watershed randomized clinical trials presented at the San Antonio Breast Cancer Symposium.

"This is data that is preliminary; it’s not to be used today in practice. But this is the way things are going to go," predicted Dr. José Baselga, chief of hematology/oncology at Massachusetts General Hospital, Boston, and professor of medicine at Harvard Medical School and the Autonomous University of Barcelona.

He presented the results of the Neo-ALTTO trial, a phase III, open-label, triple-arm study that randomized 455 women with HER2-positive early breast cancer to 18 weeks of neoadjuvant anti-HER2 therapy with trastuzumab (Herceptin), lapatinib (Tykerb), or both. After the first 6 weeks of anti-HER2 therapy, 12 weeks of paclitaxel was added to each study arm prior to surgery.

Pathological complete response (pCR), which was the primary study end point, occurred in 24.7% of patients in the lapatinib/paclitaxel arm, 29.5% in the trastuzumab/paclitaxel arm, and a significantly higher 51.3% in the lapatinib/trastuzumab/paclitaxel arm.

[Trastuzumab/Pertuzumab Doublet Eradicates Some Early Breast Cancer]

Grade 3 or worse adverse events occurred most frequently in the two lapatinib-containing arms. The most common of these was grade 3 or higher diarrhea, which occurred in 21% of the dual anti-HER2 group, 23% in the lapatinib arm, and just 2% in the trastuzumab arm. Grade 3 or higher hepatotoxicity occurred in 9% on dual anti-HER2 therapy, 13% on lapatinib, and 1% on trastuzumab. Grade 3 or higher neutropenia and skin rash followed the same pattern.

Largely as a result of toxicities, 39% and 34% of patients in the dual anti-HER2 and lapatinib arms, respectively, didn’t complete neoadjuvant treatment as planned. This was the case for only 8% in the trastuzumab arm.

Based upon the success of Neo-ALLT, Dr. Baselga and coinvestigators have launched the companion ALTTO trial. Nearly 8,200 of a planned 8,400 patients with HER2-positive breast cancer have been enrolled in the trial, which will feature four adjuvant therapy arms: lapatinib, trastuzumab, both agents, and sequential trastuzumab followed by lapatinib. Study end points will include overall and disease-free survival.

Although the numerically superior pCR rate with trastuzumab/paclitaxel, compared with lapatinib/paclitaxel, didn’t achieve statistical significance in Neo-ALTTO, it did in another randomized trial that was presented during the same session. Dr. Michael Untch of the Helios Clinic in Berlin presented the results of the phase II GeparQuinto study led by the German Breast Group, in which 620 patients with HER2-positive primary breast cancer were randomized to neoadjuvant therapy with either trastuzumab or lapatinib, both given in conjunction with neoadjuvant anthracycline/taxane-based chemotherapy.

The pCR rate (defined as no invasive or noninvasive residual disease in the breast or nodes) was 31.3% in the trastuzumab/chemotherapy arm, compared with 21.7% with lapatinib/chemotherapy (P less than .05).

These study results prompted extensive discussion during the conference. Dr. Eric P. Winer served as formal discussant of Neo-ALTTO, GeparQuinto, and a third neoadjuvant trial – NeoSphere – in which docetaxel plus dual anti-HER2 therapy with trastuzumab and the investigational agent pertuzumab produced a significantly higher pCR rate than did docetaxel plus either anti-HER2 biologic agent alone.

Dr. Winer argued that even though Neo-ALTTO is a phase III trial, he doesn’t consider pCR rate an appropriate end point for drug approval or change in clinical practice. As a surrogate for the key end points of overall and disease-free survival, pCR simply isn’t reliable enough, he said. A classic case in point was the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-27 trial, in which a doubling of the pCR rate didn’t lead to improvement in overall or disease-free survival.

"In my view, [the combination of] trastuzumab, lapatinib, and paclitaxel looks like a regimen of great interest. It’s not ready for adjuvant therapy. It isn’t ready for neoadjuvant therapy outside of a clinical trial. But we all eagerly await the results of ALTTO," said Dr. Winer, director of the breast oncology center at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.

As for trastuzumab vs. lapatinib as single-agent anti-HER2 neoadjuvant therapy in conjunction with neoadjuvant chemotherapy, the evidence from Neo-ALTTO and GeparQuinto makes it "hard to escape the conclusion that [the combination of] lapatinib and chemotherapy is a little less active and a little more toxic than trastuzumab and chemotherapy," the oncologist observed.

Dr. Baselga later commented that clinical practice in the management of HER2-positive breast cancer could change as early as next year, when the results of the ongoing CLEOPATRA trial are due to be reported. That study is comparing first-line therapy for HER2-positive metastatic breast cancer with trastuzumab plus docetaxel vs. trastuzumab, pertuzumab, and docetaxel.

In a plenary lecture, Dr. Neil L. Spector of Duke University, Durham, N.C., said that if two anti-HER2 drugs are better than one, it’s entirely possible that complete blockade of HER2 via triple therapy with trastuzumab, pertuzumab, and lapatinib would be the most effective of all, albeit with an astronomical price tag.

"Total blockade may be feasible, but we’re going to bust the economy," he argued. "If we’re going to develop these things, and only 5 patients out of 100 can afford them, we have to rethink what the hell we’re doing."

Dr. Spector said that although 15 years ago he was a major skeptic about tumor vaccines, he has recently changed his mind in response to preclinical and early clinical evidence that vaccines now in development can generate good titers of polyclonal antibodies. "What if we could generate trastuzumab- and pertuzumablike antibodies directly in patients, making total HER2 blockade more affordable?" he said. "I think vaccines have come of age."

An ongoing clinical trial at Duke shows evidence that a polyclonal HER2 vaccine in combination with lapatinib provides an enhanced anti-tumor effect, the oncologist added.

The Neo-ALTTO and GeparQuinto trials were supported by GlaxoSmithKline. Dr. Baselga and Dr. Untch declared that they have no relevant financial relationships to disclose.

Correction: An earlier version of this article described imprecisely the CLEOPATRA trial. The trial compares first-line therapies for HER-2 positive metastatic breast cancer.

SAN ANTONIO – The combination of two anti-HER2 therapies, together with chemotherapy, may be markedly better than one, according to watershed randomized clinical trials presented at the San Antonio Breast Cancer Symposium.

"This is data that is preliminary; it’s not to be used today in practice. But this is the way things are going to go," predicted Dr. José Baselga, chief of hematology/oncology at Massachusetts General Hospital, Boston, and professor of medicine at Harvard Medical School and the Autonomous University of Barcelona.

He presented the results of the Neo-ALTTO trial, a phase III, open-label, triple-arm study that randomized 455 women with HER2-positive early breast cancer to 18 weeks of neoadjuvant anti-HER2 therapy with trastuzumab (Herceptin), lapatinib (Tykerb), or both. After the first 6 weeks of anti-HER2 therapy, 12 weeks of paclitaxel was added to each study arm prior to surgery.

Pathological complete response (pCR), which was the primary study end point, occurred in 24.7% of patients in the lapatinib/paclitaxel arm, 29.5% in the trastuzumab/paclitaxel arm, and a significantly higher 51.3% in the lapatinib/trastuzumab/paclitaxel arm.

[Trastuzumab/Pertuzumab Doublet Eradicates Some Early Breast Cancer]

Grade 3 or worse adverse events occurred most frequently in the two lapatinib-containing arms. The most common of these was grade 3 or higher diarrhea, which occurred in 21% of the dual anti-HER2 group, 23% in the lapatinib arm, and just 2% in the trastuzumab arm. Grade 3 or higher hepatotoxicity occurred in 9% on dual anti-HER2 therapy, 13% on lapatinib, and 1% on trastuzumab. Grade 3 or higher neutropenia and skin rash followed the same pattern.

Largely as a result of toxicities, 39% and 34% of patients in the dual anti-HER2 and lapatinib arms, respectively, didn’t complete neoadjuvant treatment as planned. This was the case for only 8% in the trastuzumab arm.

Based upon the success of Neo-ALLT, Dr. Baselga and coinvestigators have launched the companion ALTTO trial. Nearly 8,200 of a planned 8,400 patients with HER2-positive breast cancer have been enrolled in the trial, which will feature four adjuvant therapy arms: lapatinib, trastuzumab, both agents, and sequential trastuzumab followed by lapatinib. Study end points will include overall and disease-free survival.

Although the numerically superior pCR rate with trastuzumab/paclitaxel, compared with lapatinib/paclitaxel, didn’t achieve statistical significance in Neo-ALTTO, it did in another randomized trial that was presented during the same session. Dr. Michael Untch of the Helios Clinic in Berlin presented the results of the phase II GeparQuinto study led by the German Breast Group, in which 620 patients with HER2-positive primary breast cancer were randomized to neoadjuvant therapy with either trastuzumab or lapatinib, both given in conjunction with neoadjuvant anthracycline/taxane-based chemotherapy.

The pCR rate (defined as no invasive or noninvasive residual disease in the breast or nodes) was 31.3% in the trastuzumab/chemotherapy arm, compared with 21.7% with lapatinib/chemotherapy (P less than .05).

These study results prompted extensive discussion during the conference. Dr. Eric P. Winer served as formal discussant of Neo-ALTTO, GeparQuinto, and a third neoadjuvant trial – NeoSphere – in which docetaxel plus dual anti-HER2 therapy with trastuzumab and the investigational agent pertuzumab produced a significantly higher pCR rate than did docetaxel plus either anti-HER2 biologic agent alone.

Dr. Winer argued that even though Neo-ALTTO is a phase III trial, he doesn’t consider pCR rate an appropriate end point for drug approval or change in clinical practice. As a surrogate for the key end points of overall and disease-free survival, pCR simply isn’t reliable enough, he said. A classic case in point was the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-27 trial, in which a doubling of the pCR rate didn’t lead to improvement in overall or disease-free survival.

"In my view, [the combination of] trastuzumab, lapatinib, and paclitaxel looks like a regimen of great interest. It’s not ready for adjuvant therapy. It isn’t ready for neoadjuvant therapy outside of a clinical trial. But we all eagerly await the results of ALTTO," said Dr. Winer, director of the breast oncology center at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston.

As for trastuzumab vs. lapatinib as single-agent anti-HER2 neoadjuvant therapy in conjunction with neoadjuvant chemotherapy, the evidence from Neo-ALTTO and GeparQuinto makes it "hard to escape the conclusion that [the combination of] lapatinib and chemotherapy is a little less active and a little more toxic than trastuzumab and chemotherapy," the oncologist observed.

Dr. Baselga later commented that clinical practice in the management of HER2-positive breast cancer could change as early as next year, when the results of the ongoing CLEOPATRA trial are due to be reported. That study is comparing first-line therapy for HER2-positive metastatic breast cancer with trastuzumab plus docetaxel vs. trastuzumab, pertuzumab, and docetaxel.

In a plenary lecture, Dr. Neil L. Spector of Duke University, Durham, N.C., said that if two anti-HER2 drugs are better than one, it’s entirely possible that complete blockade of HER2 via triple therapy with trastuzumab, pertuzumab, and lapatinib would be the most effective of all, albeit with an astronomical price tag.

"Total blockade may be feasible, but we’re going to bust the economy," he argued. "If we’re going to develop these things, and only 5 patients out of 100 can afford them, we have to rethink what the hell we’re doing."

Dr. Spector said that although 15 years ago he was a major skeptic about tumor vaccines, he has recently changed his mind in response to preclinical and early clinical evidence that vaccines now in development can generate good titers of polyclonal antibodies. "What if we could generate trastuzumab- and pertuzumablike antibodies directly in patients, making total HER2 blockade more affordable?" he said. "I think vaccines have come of age."

An ongoing clinical trial at Duke shows evidence that a polyclonal HER2 vaccine in combination with lapatinib provides an enhanced anti-tumor effect, the oncologist added.

The Neo-ALTTO and GeparQuinto trials were supported by GlaxoSmithKline. Dr. Baselga and Dr. Untch declared that they have no relevant financial relationships to disclose.

Correction: An earlier version of this article described imprecisely the CLEOPATRA trial. The trial compares first-line therapies for HER-2 positive metastatic breast cancer.

CHICAGO – Pacemaker-detected asymptomatic atrial high-rate episodes in patients with no history of atrial fibrillation were associated with a 2.5-fold increased risk of subsequent ischemic stroke or systemic embolism in the large, multicenter ASSERT study.

These device-detected asymptomatic episodes of atrial tachyarrhythmia are quite common in pacemaker recipients who have no history of atrial fibrillation. Indeed, 36% of the 2,580 participants in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) had at least one such episode lasting for more than 6 minutes at an atrial rate of greater than 190 minutes during a mean 2.8 years of follow-up. Among the minority of patients who were followed out to 5 years, the rate was 50%, Dr. Jeff S. Healey reported at the annual scientific sessions of the American Heart Association.

The primary outcome in ASSERT was the incidence of ischemic stroke or systemic embolism. This occurred at a rate of 0.69% per year in patients with no device-detected atrial high-rate episodes (AHREs), and 1.61% per year in those with one or more such episodes, for a 2.5-fold increased risk, said Dr. Healey of McMaster University in Hamilton, Ont.

In the ASSERT population with no history of atrial fibrillation, 35% of all strokes or systemic emboli were preceded by at least one episode of device-detected AHRE.

The incidence of clinical atrial fibrillation or atrial flutter (a secondary end point) was 1.22% per year in patients without AHREs and 6.29% per year in those with an AHRE, for a 5.6-fold increased relative risk.

Eliminating from consideration those patients who developed clinical atrial fibrillation or atrial fibrillation as documented by surface ECG did not substantially change the study results, he added.

Among the roughly 80% of ASSERT participants with a baseline CHADS2 score of at least 2, the incidence of ischemic stroke or systemic embolism was 0.7% annually in those without an AHRE and 2.14% per year in those with an AHRE, for a 2.67-fold increased relative risk. This 2.1% per year stroke rate warrants physician attention, the cardiologist said.

"The risk of stroke among patients with device-detected atrial tachyarrhythmias and a CHADS2 score of 2 or more is similar to that in patients with atrial fibrillation, where guidelines recommend physicians begin to consider use of oral anticoagulation," Dr. Healey noted.

ASSERT participants averaged 76 years of age. In all, 15% had heart failure, 28% had diabetes, and 7% had a history of stroke.

Discussant Dr. John Camm said that ASSERT has important clinical ramifications, including the need to consider oral anticoagulation therapy for stroke prevention in pacemaker patients with no history of atrial fibrillation if their device records an AHRE lasting for more than 6 minutes in excess of 190 beats per minute. What to do about lesser episodes remains a question for the future.

Physicians will have to wait another 4 years for the next major developments regarding pacemaker-detected AHREs. The year 2014 will bring results from Biotronik’s 2,718-patient IMPACT trial, in which patients with episodes of atrial tachyarrhythmia detected by home monitoring will be placed on anticoagulation, as well as St. Jude Medical’s 5,000-patient RATE registry, said Dr. Camm, professor of cardiology at St. George’s, University of London.

The ASSERT study was sponsored by St. Jude Medical. Dr. Healey disclosed serving on the advisory boards of Sanofi-Aventis and Boehringer Ingelheim.

CHICAGO – Pacemaker-detected asymptomatic atrial high-rate episodes in patients with no history of atrial fibrillation were associated with a 2.5-fold increased risk of subsequent ischemic stroke or systemic embolism in the large, multicenter ASSERT study.

These device-detected asymptomatic episodes of atrial tachyarrhythmia are quite common in pacemaker recipients who have no history of atrial fibrillation. Indeed, 36% of the 2,580 participants in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) had at least one such episode lasting for more than 6 minutes at an atrial rate of greater than 190 minutes during a mean 2.8 years of follow-up. Among the minority of patients who were followed out to 5 years, the rate was 50%, Dr. Jeff S. Healey reported at the annual scientific sessions of the American Heart Association.

The primary outcome in ASSERT was the incidence of ischemic stroke or systemic embolism. This occurred at a rate of 0.69% per year in patients with no device-detected atrial high-rate episodes (AHREs), and 1.61% per year in those with one or more such episodes, for a 2.5-fold increased risk, said Dr. Healey of McMaster University in Hamilton, Ont.

In the ASSERT population with no history of atrial fibrillation, 35% of all strokes or systemic emboli were preceded by at least one episode of device-detected AHRE.

The incidence of clinical atrial fibrillation or atrial flutter (a secondary end point) was 1.22% per year in patients without AHREs and 6.29% per year in those with an AHRE, for a 5.6-fold increased relative risk.

Eliminating from consideration those patients who developed clinical atrial fibrillation or atrial fibrillation as documented by surface ECG did not substantially change the study results, he added.

Among the roughly 80% of ASSERT participants with a baseline CHADS2 score of at least 2, the incidence of ischemic stroke or systemic embolism was 0.7% annually in those without an AHRE and 2.14% per year in those with an AHRE, for a 2.67-fold increased relative risk. This 2.1% per year stroke rate warrants physician attention, the cardiologist said.

"The risk of stroke among patients with device-detected atrial tachyarrhythmias and a CHADS2 score of 2 or more is similar to that in patients with atrial fibrillation, where guidelines recommend physicians begin to consider use of oral anticoagulation," Dr. Healey noted.

ASSERT participants averaged 76 years of age. In all, 15% had heart failure, 28% had diabetes, and 7% had a history of stroke.

Discussant Dr. John Camm said that ASSERT has important clinical ramifications, including the need to consider oral anticoagulation therapy for stroke prevention in pacemaker patients with no history of atrial fibrillation if their device records an AHRE lasting for more than 6 minutes in excess of 190 beats per minute. What to do about lesser episodes remains a question for the future.

Physicians will have to wait another 4 years for the next major developments regarding pacemaker-detected AHREs. The year 2014 will bring results from Biotronik’s 2,718-patient IMPACT trial, in which patients with episodes of atrial tachyarrhythmia detected by home monitoring will be placed on anticoagulation, as well as St. Jude Medical’s 5,000-patient RATE registry, said Dr. Camm, professor of cardiology at St. George’s, University of London.

The ASSERT study was sponsored by St. Jude Medical. Dr. Healey disclosed serving on the advisory boards of Sanofi-Aventis and Boehringer Ingelheim.

CHICAGO – Pacemaker-detected asymptomatic atrial high-rate episodes in patients with no history of atrial fibrillation were associated with a 2.5-fold increased risk of subsequent ischemic stroke or systemic embolism in the large, multicenter ASSERT study.

These device-detected asymptomatic episodes of atrial tachyarrhythmia are quite common in pacemaker recipients who have no history of atrial fibrillation. Indeed, 36% of the 2,580 participants in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) had at least one such episode lasting for more than 6 minutes at an atrial rate of greater than 190 minutes during a mean 2.8 years of follow-up. Among the minority of patients who were followed out to 5 years, the rate was 50%, Dr. Jeff S. Healey reported at the annual scientific sessions of the American Heart Association.

The primary outcome in ASSERT was the incidence of ischemic stroke or systemic embolism. This occurred at a rate of 0.69% per year in patients with no device-detected atrial high-rate episodes (AHREs), and 1.61% per year in those with one or more such episodes, for a 2.5-fold increased risk, said Dr. Healey of McMaster University in Hamilton, Ont.

In the ASSERT population with no history of atrial fibrillation, 35% of all strokes or systemic emboli were preceded by at least one episode of device-detected AHRE.

The incidence of clinical atrial fibrillation or atrial flutter (a secondary end point) was 1.22% per year in patients without AHREs and 6.29% per year in those with an AHRE, for a 5.6-fold increased relative risk.

Eliminating from consideration those patients who developed clinical atrial fibrillation or atrial fibrillation as documented by surface ECG did not substantially change the study results, he added.

Among the roughly 80% of ASSERT participants with a baseline CHADS2 score of at least 2, the incidence of ischemic stroke or systemic embolism was 0.7% annually in those without an AHRE and 2.14% per year in those with an AHRE, for a 2.67-fold increased relative risk. This 2.1% per year stroke rate warrants physician attention, the cardiologist said.

"The risk of stroke among patients with device-detected atrial tachyarrhythmias and a CHADS2 score of 2 or more is similar to that in patients with atrial fibrillation, where guidelines recommend physicians begin to consider use of oral anticoagulation," Dr. Healey noted.

ASSERT participants averaged 76 years of age. In all, 15% had heart failure, 28% had diabetes, and 7% had a history of stroke.

Discussant Dr. John Camm said that ASSERT has important clinical ramifications, including the need to consider oral anticoagulation therapy for stroke prevention in pacemaker patients with no history of atrial fibrillation if their device records an AHRE lasting for more than 6 minutes in excess of 190 beats per minute. What to do about lesser episodes remains a question for the future.

Physicians will have to wait another 4 years for the next major developments regarding pacemaker-detected AHREs. The year 2014 will bring results from Biotronik’s 2,718-patient IMPACT trial, in which patients with episodes of atrial tachyarrhythmia detected by home monitoring will be placed on anticoagulation, as well as St. Jude Medical’s 5,000-patient RATE registry, said Dr. Camm, professor of cardiology at St. George’s, University of London.

The ASSERT study was sponsored by St. Jude Medical. Dr. Healey disclosed serving on the advisory boards of Sanofi-Aventis and Boehringer Ingelheim.

CHICAGO – Pacemaker-detected asymptomatic atrial high-rate episodes in patients with no history of atrial fibrillation were associated with a 2.5-fold increased risk of subsequent ischemic stroke or systemic embolism in the large, multicenter ASSERT study.

These device-detected asymptomatic episodes of atrial tachyarrhythmia are quite common in pacemaker recipients who have no history of atrial fibrillation. Indeed, 36% of the 2,580 participants in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) had at least one such episode lasting for more than 6 minutes at an atrial rate of greater than 190 minutes during a mean 2.8 years of follow-up. Among the minority of patients who were followed out to 5 years, the rate was 50%, Dr. Jeff S. Healey reported at the annual scientific sessions of the American Heart Association.

The primary outcome in ASSERT was the incidence of ischemic stroke or systemic embolism. This occurred at a rate of 0.69% per year in patients with no device-detected atrial high-rate episodes (AHREs), and 1.61% per year in those with one or more such episodes, for a 2.5-fold increased risk, said Dr. Healey of McMaster University in Hamilton, Ont.

In the ASSERT population with no history of atrial fibrillation, 35% of all strokes or systemic emboli were preceded by at least one episode of device-detected AHRE.

The incidence of clinical atrial fibrillation or atrial flutter (a secondary end point) was 1.22% per year in patients without AHREs and 6.29% per year in those with an AHRE, for a 5.6-fold increased relative risk.

Eliminating from consideration those patients who developed clinical atrial fibrillation or atrial fibrillation as documented by surface ECG did not substantially change the study results, he added.

Among the roughly 80% of ASSERT participants with a baseline CHADS2 score of at least 2, the incidence of ischemic stroke or systemic embolism was 0.7% annually in those without an AHRE and 2.14% per year in those with an AHRE, for a 2.67-fold increased relative risk. This 2.1% per year stroke rate warrants physician attention, the cardiologist said.

"The risk of stroke among patients with device-detected atrial tachyarrhythmias and a CHADS2 score of 2 or more is similar to that in patients with atrial fibrillation, where guidelines recommend physicians begin to consider use of oral anticoagulation," Dr. Healey noted.

ASSERT participants averaged 76 years of age. In all, 15% had heart failure, 28% had diabetes, and 7% had a history of stroke.

Discussant Dr. John Camm said that ASSERT has important clinical ramifications, including the need to consider oral anticoagulation therapy for stroke prevention in pacemaker patients with no history of atrial fibrillation if their device records an AHRE lasting for more than 6 minutes in excess of 190 beats per minute. What to do about lesser episodes remains a question for the future.

Physicians will have to wait another 4 years for the next major developments regarding pacemaker-detected AHREs. The year 2014 will bring results from Biotronik’s 2,718-patient IMPACT trial, in which patients with episodes of atrial tachyarrhythmia detected by home monitoring will be placed on anticoagulation, as well as St. Jude Medical’s 5,000-patient RATE registry, said Dr. Camm, professor of cardiology at St. George’s, University of London.

The ASSERT study was sponsored by St. Jude Medical. Dr. Healey disclosed serving on the advisory boards of Sanofi-Aventis and Boehringer Ingelheim.

CHICAGO – Pacemaker-detected asymptomatic atrial high-rate episodes in patients with no history of atrial fibrillation were associated with a 2.5-fold increased risk of subsequent ischemic stroke or systemic embolism in the large, multicenter ASSERT study.

These device-detected asymptomatic episodes of atrial tachyarrhythmia are quite common in pacemaker recipients who have no history of atrial fibrillation. Indeed, 36% of the 2,580 participants in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) had at least one such episode lasting for more than 6 minutes at an atrial rate of greater than 190 minutes during a mean 2.8 years of follow-up. Among the minority of patients who were followed out to 5 years, the rate was 50%, Dr. Jeff S. Healey reported at the annual scientific sessions of the American Heart Association.

The primary outcome in ASSERT was the incidence of ischemic stroke or systemic embolism. This occurred at a rate of 0.69% per year in patients with no device-detected atrial high-rate episodes (AHREs), and 1.61% per year in those with one or more such episodes, for a 2.5-fold increased risk, said Dr. Healey of McMaster University in Hamilton, Ont.

In the ASSERT population with no history of atrial fibrillation, 35% of all strokes or systemic emboli were preceded by at least one episode of device-detected AHRE.

The incidence of clinical atrial fibrillation or atrial flutter (a secondary end point) was 1.22% per year in patients without AHREs and 6.29% per year in those with an AHRE, for a 5.6-fold increased relative risk.

Eliminating from consideration those patients who developed clinical atrial fibrillation or atrial fibrillation as documented by surface ECG did not substantially change the study results, he added.

Among the roughly 80% of ASSERT participants with a baseline CHADS2 score of at least 2, the incidence of ischemic stroke or systemic embolism was 0.7% annually in those without an AHRE and 2.14% per year in those with an AHRE, for a 2.67-fold increased relative risk. This 2.1% per year stroke rate warrants physician attention, the cardiologist said.

"The risk of stroke among patients with device-detected atrial tachyarrhythmias and a CHADS2 score of 2 or more is similar to that in patients with atrial fibrillation, where guidelines recommend physicians begin to consider use of oral anticoagulation," Dr. Healey noted.

ASSERT participants averaged 76 years of age. In all, 15% had heart failure, 28% had diabetes, and 7% had a history of stroke.

Discussant Dr. John Camm said that ASSERT has important clinical ramifications, including the need to consider oral anticoagulation therapy for stroke prevention in pacemaker patients with no history of atrial fibrillation if their device records an AHRE lasting for more than 6 minutes in excess of 190 beats per minute. What to do about lesser episodes remains a question for the future.

Physicians will have to wait another 4 years for the next major developments regarding pacemaker-detected AHREs. The year 2014 will bring results from Biotronik’s 2,718-patient IMPACT trial, in which patients with episodes of atrial tachyarrhythmia detected by home monitoring will be placed on anticoagulation, as well as St. Jude Medical’s 5,000-patient RATE registry, said Dr. Camm, professor of cardiology at St. George’s, University of London.

The ASSERT study was sponsored by St. Jude Medical. Dr. Healey disclosed serving on the advisory boards of Sanofi-Aventis and Boehringer Ingelheim.

CHICAGO – Pacemaker-detected asymptomatic atrial high-rate episodes in patients with no history of atrial fibrillation were associated with a 2.5-fold increased risk of subsequent ischemic stroke or systemic embolism in the large, multicenter ASSERT study.

These device-detected asymptomatic episodes of atrial tachyarrhythmia are quite common in pacemaker recipients who have no history of atrial fibrillation. Indeed, 36% of the 2,580 participants in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) had at least one such episode lasting for more than 6 minutes at an atrial rate of greater than 190 minutes during a mean 2.8 years of follow-up. Among the minority of patients who were followed out to 5 years, the rate was 50%, Dr. Jeff S. Healey reported at the annual scientific sessions of the American Heart Association.

The primary outcome in ASSERT was the incidence of ischemic stroke or systemic embolism. This occurred at a rate of 0.69% per year in patients with no device-detected atrial high-rate episodes (AHREs), and 1.61% per year in those with one or more such episodes, for a 2.5-fold increased risk, said Dr. Healey of McMaster University in Hamilton, Ont.

In the ASSERT population with no history of atrial fibrillation, 35% of all strokes or systemic emboli were preceded by at least one episode of device-detected AHRE.

The incidence of clinical atrial fibrillation or atrial flutter (a secondary end point) was 1.22% per year in patients without AHREs and 6.29% per year in those with an AHRE, for a 5.6-fold increased relative risk.

Eliminating from consideration those patients who developed clinical atrial fibrillation or atrial fibrillation as documented by surface ECG did not substantially change the study results, he added.

Among the roughly 80% of ASSERT participants with a baseline CHADS2 score of at least 2, the incidence of ischemic stroke or systemic embolism was 0.7% annually in those without an AHRE and 2.14% per year in those with an AHRE, for a 2.67-fold increased relative risk. This 2.1% per year stroke rate warrants physician attention, the cardiologist said.

"The risk of stroke among patients with device-detected atrial tachyarrhythmias and a CHADS2 score of 2 or more is similar to that in patients with atrial fibrillation, where guidelines recommend physicians begin to consider use of oral anticoagulation," Dr. Healey noted.

ASSERT participants averaged 76 years of age. In all, 15% had heart failure, 28% had diabetes, and 7% had a history of stroke.

Discussant Dr. John Camm said that ASSERT has important clinical ramifications, including the need to consider oral anticoagulation therapy for stroke prevention in pacemaker patients with no history of atrial fibrillation if their device records an AHRE lasting for more than 6 minutes in excess of 190 beats per minute. What to do about lesser episodes remains a question for the future.

Physicians will have to wait another 4 years for the next major developments regarding pacemaker-detected AHREs. The year 2014 will bring results from Biotronik’s 2,718-patient IMPACT trial, in which patients with episodes of atrial tachyarrhythmia detected by home monitoring will be placed on anticoagulation, as well as St. Jude Medical’s 5,000-patient RATE registry, said Dr. Camm, professor of cardiology at St. George’s, University of London.

The ASSERT study was sponsored by St. Jude Medical. Dr. Healey disclosed serving on the advisory boards of Sanofi-Aventis and Boehringer Ingelheim.

CHICAGO– Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It’s well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the annual scientific sessions of the American Heart Association.

[Vitamin D Deficiency Linked to Risk of Heart Failure Death]

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES-III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

"We were surprised by this finding. I’m not exactly sure how to explain it, except that we’ve seen something similar before. It’s possible that blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites," she observed.

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What’s badly needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women’s Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2x2 factorial design to learn if these supplements prevent the development of these diseases over the course of a planned 5-year follow-up.

[Dietary Reference Intakes for Vitamin D Caution Against Excess]

"I’m not sure that they’re going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I’m glad that we’re finally having a clinical trial because this is an important question. We really need some evidence-based data to help guide our treatment decisions for patients," Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

"Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, ‘We think we’re helping with your bones, and we may also be helping with your heart.’ But we’re certainly waiting on future clinical trial evidence to confirm this," she said.

[Low Vitamin D Tied to Mortality in Diabetes]

The NHANES-III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

CHICAGO– Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It’s well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the annual scientific sessions of the American Heart Association.

[Vitamin D Deficiency Linked to Risk of Heart Failure Death]

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES-III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

"We were surprised by this finding. I’m not exactly sure how to explain it, except that we’ve seen something similar before. It’s possible that blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites," she observed.

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What’s badly needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women’s Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2x2 factorial design to learn if these supplements prevent the development of these diseases over the course of a planned 5-year follow-up.

[Dietary Reference Intakes for Vitamin D Caution Against Excess]

"I’m not sure that they’re going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I’m glad that we’re finally having a clinical trial because this is an important question. We really need some evidence-based data to help guide our treatment decisions for patients," Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

"Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, ‘We think we’re helping with your bones, and we may also be helping with your heart.’ But we’re certainly waiting on future clinical trial evidence to confirm this," she said.

[Low Vitamin D Tied to Mortality in Diabetes]

The NHANES-III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

CHICAGO– Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It’s well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the annual scientific sessions of the American Heart Association.

[Vitamin D Deficiency Linked to Risk of Heart Failure Death]

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES-III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

"We were surprised by this finding. I’m not exactly sure how to explain it, except that we’ve seen something similar before. It’s possible that blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites," she observed.

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What’s badly needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women’s Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2x2 factorial design to learn if these supplements prevent the development of these diseases over the course of a planned 5-year follow-up.

[Dietary Reference Intakes for Vitamin D Caution Against Excess]

"I’m not sure that they’re going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I’m glad that we’re finally having a clinical trial because this is an important question. We really need some evidence-based data to help guide our treatment decisions for patients," Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

"Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, ‘We think we’re helping with your bones, and we may also be helping with your heart.’ But we’re certainly waiting on future clinical trial evidence to confirm this," she said.

[Low Vitamin D Tied to Mortality in Diabetes]

The NHANES-III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

CHICAGO– Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It’s well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the annual scientific sessions of the American Heart Association.

[Vitamin D Deficiency Linked to Risk of Heart Failure Death]

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES-III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

"We were surprised by this finding. I’m not exactly sure how to explain it, except that we’ve seen something similar before. It’s possible that blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites," she observed.

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What’s badly needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women’s Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2x2 factorial design to learn if these supplements prevent the development of these diseases over the course of a planned 5-year follow-up.

[Dietary Reference Intakes for Vitamin D Caution Against Excess]

"I’m not sure that they’re going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I’m glad that we’re finally having a clinical trial because this is an important question. We really need some evidence-based data to help guide our treatment decisions for patients," Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

"Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, ‘We think we’re helping with your bones, and we may also be helping with your heart.’ But we’re certainly waiting on future clinical trial evidence to confirm this," she said.

[Low Vitamin D Tied to Mortality in Diabetes]

The NHANES-III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

CHICAGO– Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It’s well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the annual scientific sessions of the American Heart Association.

[Vitamin D Deficiency Linked to Risk of Heart Failure Death]

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES-III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

"We were surprised by this finding. I’m not exactly sure how to explain it, except that we’ve seen something similar before. It’s possible that blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites," she observed.

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What’s badly needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women’s Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2x2 factorial design to learn if these supplements prevent the development of these diseases over the course of a planned 5-year follow-up.

[Dietary Reference Intakes for Vitamin D Caution Against Excess]

"I’m not sure that they’re going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I’m glad that we’re finally having a clinical trial because this is an important question. We really need some evidence-based data to help guide our treatment decisions for patients," Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

"Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, ‘We think we’re helping with your bones, and we may also be helping with your heart.’ But we’re certainly waiting on future clinical trial evidence to confirm this," she said.

[Low Vitamin D Tied to Mortality in Diabetes]

The NHANES-III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

CHICAGO– Vitamin D deficiency is an independent risk factor for fatal stroke in whites but not in blacks.

This finding in a study of nearly 8,000 white and black adults followed for more than 14 years came as a surprise. It’s well established that both stroke rates and vitamin D deficiency are markedly higher in blacks than in whites. The study hypothesis was that low vitamin D levels contribute to the increased risk of stroke in the black population. Not so, Dr. Erin D. Michos reported at the annual scientific sessions of the American Heart Association.

[Vitamin D Deficiency Linked to Risk of Heart Failure Death]

The study involved a nationally representative group of 7,981 white and black participants in the Third National Health and Nutrition Examination Survey (NHANES-III) conducted during 1988-1994. At that time, vitamin D deficiency as defined by a serum 25-hydroxyvitamin D level less than 15 ng/mL was present in 32% of blacks and 7% of whites.

Death certificate data accrued during a median 14.1 years of follow-up listed stroke as the cause of death in 116 whites and 60 blacks. As expected, blacks had a higher rate of fatal stroke, with a 65% increased risk after adjustment for traditional stroke risk factors and socioeconomic variables.

In a multivariate analysis adjusted for the standard cardiovascular and stroke risk factors, vitamin D deficiency in whites was associated with a 2.2-fold increased risk of fatal stroke compared with whites who had adequate vitamin D levels. Unexpectedly, however, vitamin D–deficient blacks had an adjusted 6% lower risk of fatal stroke than did blacks with adequate vitamin D levels, a nonsignificant difference, said Dr. Michos, a cardiologist at Johns Hopkins University, Baltimore.

"We were surprised by this finding. I’m not exactly sure how to explain it, except that we’ve seen something similar before. It’s possible that blacks may have an adaptive resistance to the adverse effects of low vitamin D. For example, even though blacks have lower vitamin D levels, they are less likely to have fractures and osteoporosis than whites," she observed.

Limitations of this study include the fact that the one-time measurements of serum vitamin D at baseline may not reflect lifetime vitamin D status, and only fatal strokes were assessed.

What’s badly needed now is clinical trial data to show whether identification and treatment of vitamin D deficiency actually prevents strokes and heart disease, Dr. Michos noted. Fortunately, such a trial is underway. The National Institutes of Health–sponsored Vitamin D and Omega-3 Trial (VITAL), led by investigators at Brigham and Women’s Hospital in Boston, is randomizing 20,000 older adults without a history of heart disease, stroke, or cancer to 2,000 IU/day of vitamin D, fish oil, or placebo in a 2x2 factorial design to learn if these supplements prevent the development of these diseases over the course of a planned 5-year follow-up.

[Dietary Reference Intakes for Vitamin D Caution Against Excess]

"I’m not sure that they’re going to be able to show that one dose fits all. Blood levels of vitamin D vary in response to a given dose based on sun exposure, genetics, and body mass index. But I’m glad that we’re finally having a clinical trial because this is an important question. We really need some evidence-based data to help guide our treatment decisions for patients," Dr. Michos said.

While awaiting the VITAL outcomes data, screen for vitamin D deficiency, she recommended.

"Vitamin D deficiency is very common. Doses of 1,000-2,000 IU/day appear safe, with little downside, and we know it has good benefits for the bones. So I tell my patients, ‘We think we’re helping with your bones, and we may also be helping with your heart.’ But we’re certainly waiting on future clinical trial evidence to confirm this," she said.

[Low Vitamin D Tied to Mortality in Diabetes]

The NHANES-III study was sponsored by the Centers for Disease Control and Prevention. Dr. Michos declared having no conflicts of interest.

SAN ANTONIO – Early maternal and infant outcomes in a large German registry of women diagnosed with breast cancer during pregnancy argue in favor of treating breast cancer while continuing the pregnancy rather than resorting to early delivery by cesarean section in order to begin chemotherapy after the baby is born, according to Dr. Sibylle Loibl.

"Patients should be treated as closely as possible to standard recommendations for nonpregnant women," declared Dr. Loibl of University Women’s Hospital, Frankfurt.

[Surgical Excision Can Spread Tumor Cells to Sentinel Node]

In this regard, the experience gleaned from the combined prospective and retrospective registry, which is supported by the Breast International Group and German Breast Group, supports newly published recommendations (Eur. J. Cancer 2010;46:3,158-68) issued by an international expert consensus panel of which Dr. Loibl was a member.

About 2% of all breast cancers are diagnosed during pregnancy. These are difficult cases that generate anxiety because of the need to weigh treatment of the mother and the interests of her developing child. With many women delaying childbirth until later in life, breast cancers in pregnancy may be increasing, according to Dr. Loibl.

The Breast Cancer During Pregnancy (BCP) registry to date includes 313 women with breast cancer of various stages and subtypes diagnosed during pregnancy. Forty-two percent of women were in their second trimester at the time of diagnosis, 23% were in the first trimester, and the rest were in the third.

Twenty-nine women miscarried or elected to have an abortion. Of the remainder, 49% were delivered by cesarean section. Half of women underwent mastectomy, and half had breast-conserving surgery, Dr. Loibl reported at the San Antonio Breast Cancer Symposium.

[Women's Health Initiative: New Findings on Big-Three Cancer Rates]

A total of 142 women in the BCP registry underwent chemotherapy during pregnancy, and 118 others had chemotherapy after delivery. Patients who underwent chemotherapy during pregnancy were diagnosed with breast cancer at a median gestational age of 20 weeks, compared with 28 weeks for those who had chemotherapy after delivery.

Of note, 17% of women who underwent chemotherapy during pregnancy delivered before gestational week 35, compared with fully 33% of those who didn’t start chemotherapy until after delivery. The high rate of early delivery in the latter group was largely the consequence of a management strategy seeking to start chemotherapy as soon as possible without a fetus on board. But it’s well-established that preterm delivery carries a price in terms of infant morbidity – and the BCG registry data indicate there is no reason to go that route, according to Dr. Loibl.

Patients who underwent chemotherapy during pregnancy received a median of four cycles. Seventy-seven percent received an anthracycline-based regimen. Only six women received a taxane during pregnancy.

The median birth weight in babies in the chemotherapy-during-pregnancy group was 2,810 g, compared with 2,730 g in those for whom chemotherapy was delayed until after delivery.

Neonatal outcomes 4 weeks after delivery were similar in the groups with and without chemotherapy during pregnancy. However, there were three babies with congenital malformations in the chemotherapy-during-pregnancy group – one each of rectal atresia, hypospadias, and polydactyly – compared with one in the group not exposed to chemotherapy, although this difference wasn’t significant.

Median disease-free survival was closely similar in the two groups of women at 29 months. Session cochair Dr. Daniel F. Hayes of the University of Michigan, Ann Arbor, commented that these women had a strikingly poor prognosis with a high recurrence rate. Dr. Loibl said she and her colleagues think so, too, and plan to conduct a matched-pair outcomes comparison with a group of nonpregnant breast cancer patients of the same age, cancer stage, and treatment in order to look into this further.

One audience member rose to say he, for one, is quite worried about exposing a developing fetus to anthracyclines or taxanes, and that he’ll continue to feel that way until Dr. Loibl returns to San Antonio with reassuring follow-up data on the children at age 5 years and beyond.

"I would be one who in a patient diagnosed at 28 weeks would take her to week 34 and then deliver the baby, sparing the baby the rigors of chemotherapy until you show me it’s safe," he added.

Dr. Loibl replied that the limited longer-term follow-up data available thus far on children in the BCG registry show "nothing suspicious so far."

Further evidence in support of her point that premature delivery before commencing chemotherapy is unnecessary was provided in two other studies presented by Dr. Elyce Cardonick of the Robert Wood Johnson Medical School in New Brunswick, N.J.

In one, Dr. Cardonick reported on maternal and neonatal outcomes in 109 women diagnosed with breast cancer during pregnancy. Ten received dose-dense chemotherapy and the rest underwent conventional chemotherapy.

One neonate in the dose-dense chemotherapy group experienced transient neutropenia, as did one of nine treated mothers. None of the neonates in the conventional chemotherapy group experienced neutropenia, although 5.4% of the mothers did. Neonatal birth weight and gestational age at delivery were similar in the two groups. At a mean follow-up of 3.5 years, the mean time to recurrent breast cancer was 17.6 months in the dose-dense chemotherapy group and not significantly different at 19.8 months with conventional chemotherapy.

Dr. Cardonick concluded that there’s no reason to discourage consideration of dose-dense chemotherapy in pregnant women fitting the profile of those who benefit from it in the nonpregnant population.

In the other study, Dr. Cardonick and coworkers performed echocardiography on 23 children who had been exposed in utero to anthracycline-based chemotherapy for maternal breast cancer. The cardiac imaging was performed at a mean age of 15 months, with a range from postnatal day 3 to 9 years of age.

Any toxic chemotherapy effects on fetal cardiac myocytes weren’t apparent on postnatal echocardiography, which reassuringly showed no functional or structural defects in any of the children.

Dr. Loibl and Dr. Cardonick reported having no relevant financial disclosures.

[Bevacizumab Short of Mark in First Neoadjuvant Breast Cancer Trial]

SAN ANTONIO – Early maternal and infant outcomes in a large German registry of women diagnosed with breast cancer during pregnancy argue in favor of treating breast cancer while continuing the pregnancy rather than resorting to early delivery by cesarean section in order to begin chemotherapy after the baby is born, according to Dr. Sibylle Loibl.

"Patients should be treated as closely as possible to standard recommendations for nonpregnant women," declared Dr. Loibl of University Women’s Hospital, Frankfurt.

[Surgical Excision Can Spread Tumor Cells to Sentinel Node]

In this regard, the experience gleaned from the combined prospective and retrospective registry, which is supported by the Breast International Group and German Breast Group, supports newly published recommendations (Eur. J. Cancer 2010;46:3,158-68) issued by an international expert consensus panel of which Dr. Loibl was a member.

About 2% of all breast cancers are diagnosed during pregnancy. These are difficult cases that generate anxiety because of the need to weigh treatment of the mother and the interests of her developing child. With many women delaying childbirth until later in life, breast cancers in pregnancy may be increasing, according to Dr. Loibl.

The Breast Cancer During Pregnancy (BCP) registry to date includes 313 women with breast cancer of various stages and subtypes diagnosed during pregnancy. Forty-two percent of women were in their second trimester at the time of diagnosis, 23% were in the first trimester, and the rest were in the third.

Twenty-nine women miscarried or elected to have an abortion. Of the remainder, 49% were delivered by cesarean section. Half of women underwent mastectomy, and half had breast-conserving surgery, Dr. Loibl reported at the San Antonio Breast Cancer Symposium.

[Women's Health Initiative: New Findings on Big-Three Cancer Rates]

A total of 142 women in the BCP registry underwent chemotherapy during pregnancy, and 118 others had chemotherapy after delivery. Patients who underwent chemotherapy during pregnancy were diagnosed with breast cancer at a median gestational age of 20 weeks, compared with 28 weeks for those who had chemotherapy after delivery.

Of note, 17% of women who underwent chemotherapy during pregnancy delivered before gestational week 35, compared with fully 33% of those who didn’t start chemotherapy until after delivery. The high rate of early delivery in the latter group was largely the consequence of a management strategy seeking to start chemotherapy as soon as possible without a fetus on board. But it’s well-established that preterm delivery carries a price in terms of infant morbidity – and the BCG registry data indicate there is no reason to go that route, according to Dr. Loibl.

Patients who underwent chemotherapy during pregnancy received a median of four cycles. Seventy-seven percent received an anthracycline-based regimen. Only six women received a taxane during pregnancy.

The median birth weight in babies in the chemotherapy-during-pregnancy group was 2,810 g, compared with 2,730 g in those for whom chemotherapy was delayed until after delivery.

Neonatal outcomes 4 weeks after delivery were similar in the groups with and without chemotherapy during pregnancy. However, there were three babies with congenital malformations in the chemotherapy-during-pregnancy group – one each of rectal atresia, hypospadias, and polydactyly – compared with one in the group not exposed to chemotherapy, although this difference wasn’t significant.

Median disease-free survival was closely similar in the two groups of women at 29 months. Session cochair Dr. Daniel F. Hayes of the University of Michigan, Ann Arbor, commented that these women had a strikingly poor prognosis with a high recurrence rate. Dr. Loibl said she and her colleagues think so, too, and plan to conduct a matched-pair outcomes comparison with a group of nonpregnant breast cancer patients of the same age, cancer stage, and treatment in order to look into this further.

One audience member rose to say he, for one, is quite worried about exposing a developing fetus to anthracyclines or taxanes, and that he’ll continue to feel that way until Dr. Loibl returns to San Antonio with reassuring follow-up data on the children at age 5 years and beyond.

"I would be one who in a patient diagnosed at 28 weeks would take her to week 34 and then deliver the baby, sparing the baby the rigors of chemotherapy until you show me it’s safe," he added.

Dr. Loibl replied that the limited longer-term follow-up data available thus far on children in the BCG registry show "nothing suspicious so far."

Further evidence in support of her point that premature delivery before commencing chemotherapy is unnecessary was provided in two other studies presented by Dr. Elyce Cardonick of the Robert Wood Johnson Medical School in New Brunswick, N.J.

In one, Dr. Cardonick reported on maternal and neonatal outcomes in 109 women diagnosed with breast cancer during pregnancy. Ten received dose-dense chemotherapy and the rest underwent conventional chemotherapy.

One neonate in the dose-dense chemotherapy group experienced transient neutropenia, as did one of nine treated mothers. None of the neonates in the conventional chemotherapy group experienced neutropenia, although 5.4% of the mothers did. Neonatal birth weight and gestational age at delivery were similar in the two groups. At a mean follow-up of 3.5 years, the mean time to recurrent breast cancer was 17.6 months in the dose-dense chemotherapy group and not significantly different at 19.8 months with conventional chemotherapy.

Dr. Cardonick concluded that there’s no reason to discourage consideration of dose-dense chemotherapy in pregnant women fitting the profile of those who benefit from it in the nonpregnant population.

In the other study, Dr. Cardonick and coworkers performed echocardiography on 23 children who had been exposed in utero to anthracycline-based chemotherapy for maternal breast cancer. The cardiac imaging was performed at a mean age of 15 months, with a range from postnatal day 3 to 9 years of age.

Any toxic chemotherapy effects on fetal cardiac myocytes weren’t apparent on postnatal echocardiography, which reassuringly showed no functional or structural defects in any of the children.

Dr. Loibl and Dr. Cardonick reported having no relevant financial disclosures.

[Bevacizumab Short of Mark in First Neoadjuvant Breast Cancer Trial]

SAN ANTONIO – Early maternal and infant outcomes in a large German registry of women diagnosed with breast cancer during pregnancy argue in favor of treating breast cancer while continuing the pregnancy rather than resorting to early delivery by cesarean section in order to begin chemotherapy after the baby is born, according to Dr. Sibylle Loibl.

"Patients should be treated as closely as possible to standard recommendations for nonpregnant women," declared Dr. Loibl of University Women’s Hospital, Frankfurt.

[Surgical Excision Can Spread Tumor Cells to Sentinel Node]

In this regard, the experience gleaned from the combined prospective and retrospective registry, which is supported by the Breast International Group and German Breast Group, supports newly published recommendations (Eur. J. Cancer 2010;46:3,158-68) issued by an international expert consensus panel of which Dr. Loibl was a member.

About 2% of all breast cancers are diagnosed during pregnancy. These are difficult cases that generate anxiety because of the need to weigh treatment of the mother and the interests of her developing child. With many women delaying childbirth until later in life, breast cancers in pregnancy may be increasing, according to Dr. Loibl.

The Breast Cancer During Pregnancy (BCP) registry to date includes 313 women with breast cancer of various stages and subtypes diagnosed during pregnancy. Forty-two percent of women were in their second trimester at the time of diagnosis, 23% were in the first trimester, and the rest were in the third.

Twenty-nine women miscarried or elected to have an abortion. Of the remainder, 49% were delivered by cesarean section. Half of women underwent mastectomy, and half had breast-conserving surgery, Dr. Loibl reported at the San Antonio Breast Cancer Symposium.

[Women's Health Initiative: New Findings on Big-Three Cancer Rates]

A total of 142 women in the BCP registry underwent chemotherapy during pregnancy, and 118 others had chemotherapy after delivery. Patients who underwent chemotherapy during pregnancy were diagnosed with breast cancer at a median gestational age of 20 weeks, compared with 28 weeks for those who had chemotherapy after delivery.

Of note, 17% of women who underwent chemotherapy during pregnancy delivered before gestational week 35, compared with fully 33% of those who didn’t start chemotherapy until after delivery. The high rate of early delivery in the latter group was largely the consequence of a management strategy seeking to start chemotherapy as soon as possible without a fetus on board. But it’s well-established that preterm delivery carries a price in terms of infant morbidity – and the BCG registry data indicate there is no reason to go that route, according to Dr. Loibl.

Patients who underwent chemotherapy during pregnancy received a median of four cycles. Seventy-seven percent received an anthracycline-based regimen. Only six women received a taxane during pregnancy.

The median birth weight in babies in the chemotherapy-during-pregnancy group was 2,810 g, compared with 2,730 g in those for whom chemotherapy was delayed until after delivery.

Neonatal outcomes 4 weeks after delivery were similar in the groups with and without chemotherapy during pregnancy. However, there were three babies with congenital malformations in the chemotherapy-during-pregnancy group – one each of rectal atresia, hypospadias, and polydactyly – compared with one in the group not exposed to chemotherapy, although this difference wasn’t significant.

Median disease-free survival was closely similar in the two groups of women at 29 months. Session cochair Dr. Daniel F. Hayes of the University of Michigan, Ann Arbor, commented that these women had a strikingly poor prognosis with a high recurrence rate. Dr. Loibl said she and her colleagues think so, too, and plan to conduct a matched-pair outcomes comparison with a group of nonpregnant breast cancer patients of the same age, cancer stage, and treatment in order to look into this further.

One audience member rose to say he, for one, is quite worried about exposing a developing fetus to anthracyclines or taxanes, and that he’ll continue to feel that way until Dr. Loibl returns to San Antonio with reassuring follow-up data on the children at age 5 years and beyond.

"I would be one who in a patient diagnosed at 28 weeks would take her to week 34 and then deliver the baby, sparing the baby the rigors of chemotherapy until you show me it’s safe," he added.

Dr. Loibl replied that the limited longer-term follow-up data available thus far on children in the BCG registry show "nothing suspicious so far."

Further evidence in support of her point that premature delivery before commencing chemotherapy is unnecessary was provided in two other studies presented by Dr. Elyce Cardonick of the Robert Wood Johnson Medical School in New Brunswick, N.J.

In one, Dr. Cardonick reported on maternal and neonatal outcomes in 109 women diagnosed with breast cancer during pregnancy. Ten received dose-dense chemotherapy and the rest underwent conventional chemotherapy.

One neonate in the dose-dense chemotherapy group experienced transient neutropenia, as did one of nine treated mothers. None of the neonates in the conventional chemotherapy group experienced neutropenia, although 5.4% of the mothers did. Neonatal birth weight and gestational age at delivery were similar in the two groups. At a mean follow-up of 3.5 years, the mean time to recurrent breast cancer was 17.6 months in the dose-dense chemotherapy group and not significantly different at 19.8 months with conventional chemotherapy.

Dr. Cardonick concluded that there’s no reason to discourage consideration of dose-dense chemotherapy in pregnant women fitting the profile of those who benefit from it in the nonpregnant population.

In the other study, Dr. Cardonick and coworkers performed echocardiography on 23 children who had been exposed in utero to anthracycline-based chemotherapy for maternal breast cancer. The cardiac imaging was performed at a mean age of 15 months, with a range from postnatal day 3 to 9 years of age.

Any toxic chemotherapy effects on fetal cardiac myocytes weren’t apparent on postnatal echocardiography, which reassuringly showed no functional or structural defects in any of the children.

Dr. Loibl and Dr. Cardonick reported having no relevant financial disclosures.

[Bevacizumab Short of Mark in First Neoadjuvant Breast Cancer Trial]

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the annual scientific sessions of the American Heart Association.

[Current and Former Smoking Pose Large PAD Risks in Women]

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the annual scientific sessions of the American Heart Association.

[Current and Former Smoking Pose Large PAD Risks in Women]

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the annual scientific sessions of the American Heart Association.

[Current and Former Smoking Pose Large PAD Risks in Women]

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the annual scientific sessions of the American Heart Association.

[Current and Former Smoking Pose Large PAD Risks in Women]

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the annual scientific sessions of the American Heart Association.

[Current and Former Smoking Pose Large PAD Risks in Women]

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.

CHICAGO – Women who report high psychological job strain have a 40% increased risk of cardiovascular disease, according to a large, 10-year prospective study.

High job strain is defined by a demanding job, often involving time pressure and conflict, coupled with little decision-making authority or opportunity for personal growth.

But women with high job strain weren’t the only group at increased risk for acute MI and other cardiovascular events in this analysis of more than 17,000 working women participating in the Women’s Health Study. Those with active job strain defined as high-demand work featuring a high sense of control, based on Robert Karasek’s 14-item job strain model used in this study, had a 60% increase in total cardiovascular events compared with those reporting low job strain, Natalie Slopen, Sc.D., reported at the annual scientific sessions of the American Heart Association.

[Current and Former Smoking Pose Large PAD Risks in Women]

This last point regarding the cardiovascular risks associated with active job strain should be near and dear to the hearts of female physicians. Many, perhaps most, physicians fit within the Karasek active job strain category, noted Dr. Slopen, a postdoctoral research fellow in the department of society, human development, and health at Harvard School of Public Health, Boston.

The Women’s Health Study involves 17,415 female, mostly white, health professionals in good health at an average age of 57 years at enrollment in what was initially a randomized, placebo-controlled clinical trial of vitamin E and aspirin for primary prevention of cancer and cardiovascular disease. The study is now in the observational phase with 10 years of follow-up, during which 517 clinically verified nonfatal MIs, strokes, coronary revascularization procedures, and cardiovascular deaths have occurred.

In a Cox proportional hazards model adjusted for age, race, socioeconomic status, and study drug assignment, the 3,529 women who reported high job strain at baseline had a 90% increased risk of MI, a 40% increase in coronary revascularization, and a 40% increase in total cardiovascular events, compared with the 4,161 female health professionals with low job strain.

The 3,736 women who reported active job strain had a 60% increase in total cardiovascular events compared with the low job strain group.

The investigators also inquired about job insecurity. At baseline, 19% of Women’s Health Study participants indicated they were concerned about future job loss. Contrary to the study hypothesis, however, no independent association was found between job insecurity and subsequent development of cardiovascular disease.

An important clinical implication of this study is that it may be useful for physicians to ask about job stress as part of their total health assessment of women employed outside the home. Women with high job strain or active job strain can be counseled that there are data to support several beneficial interventions. These include maintaining a physically active lifestyle to help burn off psychological stress, engaging in social support networks to aid in coping with work strain, and reserving time every day – as little as 10-15 minutes – for some form of relaxation. It’s also important to limit the intrusion of work activities outside the workplace; e-mail is a big offender in this regard, according to Dr. Slopen.

The Women’s Health Study is funded by the National Institutes of Health. Dr. Slopen declared having no relevant financial disclosures.