Sherry Boschert

SAN FRANCISCO – Close adherence to guidelines for deciding when to do endometrial biopsies in women with abnormal uterine bleeding could mean ordering biopsies in 88% of perimenopausal women with bleeding, according to Dr. Rebecca Jackson.

Irregular uterine bleeding is "incredibly common," endometrial cancer is "relatively common," and models to predict which women with abnormal bleeding are at risk for endometrial cancer "have been examined and are not useful," said Dr. Jackson, professor of obstetrics and gynecology at the University of California, San Francisco, and chief of obstetrics and gynecology at San Francisco General Hospital. Without much data to go on, "we’re left with expert opinion," she said.

She offered the following approach employed at her institution in a presentation at a conference on women’s health sponsored by the university. "We’re heartened to see that UpToDate has the same approach," Dr. Jackson said, referring to the digital evidence-based clinical decision support tool.

American College of Obstetricians and Gynecologists Practice Bulletin 128 on the Diagnosis of Abnormal Uterine Bleeding in Reproductive-Aged Women recommends that endometrial tissue sampling be done in patients with abnormal uterine bleeding who are older than 45 years and in younger patients who have a history of unopposed estrogen exposure, failed medical management, and persistent abnormal uterine bleeding (Obstet. Gynecol. 2012;120:197-206).

During an average 4-year perimenopause, however, only 12% of women completely stop menstruating; 70% have short, irregular menses; and 18% have longer, heavier menses, studies have shown (Int. J. Fertil 1967;12:77-126; Acta Obstet. Gynecol. Scand. 1966;45:320-51).A close application of the ACOG guidelines could mean biopsies in all but 12% of perimenopausal women, she said.

Dr. Jackson said she takes endometrial biopsies in all postmenopausal women with any abnormal uterine bleeding except for bleeding that starts 4-6 months after initiating hormone therapy. Approximately 10% of postmenopausal women with bleeding have cancer. "That’s a very high pretest probability when you’re talking about cancer, way higher than when you think about an abnormal mammogram," she said. Offering a postmenopausal patient a choice between a biopsy and a transvaginal ultrasound is reasonable as long as either procedure is available quickly and the patient understands that she still may need an endometrial biopsy after an ultrasound.

In women with a recent onset of irregular bleeding, don’t jump to a biopsy too quickly for this very common phenomenon. "Consider treating her, and if it normalizes, there’s no need for an endometrial biopsy," she said.

She recommended a low threshold for biopsy in women older than 50 years who have recurrent irregular bleeding because the risk of cancer is going up with age, but consider not getting a biopsy if the periods are light and spacing out. Periods that happen every 2-3 months and last 2-3 days are "not a very worrisome pattern," she said. Endometrial cancer presents most commonly with menometrorrhagia and sometimes with intermenstrual bleeding, but rarely with regularly timed menses.

Dr. Jackson said she biopsies women aged 45-50 years if they have recurrent irregular bleeding plus at least one risk factor for endometrial cancer or they’ve had more than 6 months of menometrorrhagia.

In younger women, consider a biopsy if they’ve had a "long history" of untreated anovulatory bleeding, which could be 2 years or 5 years, she suggested. "We have a hard time getting consensus on that [definition of] long," she noted.

A Pap smear result showing atypical glandular cells or endometrial cells would be another reason to biopsy if the Pap smear was not done at the time of menses.

An endometrial biopsy is not perfectly sensitive, so "keep your radar up" even if the biopsy result is negative, and evaluate further if abnormal bleeding persists, she said.

Her search of the literature on less-aggressive strategies for endometrial biopsies turned up just one small prospective cohort study of 1,000 women with abnormal uterine bleeding who were eligible for endometrial biopsy under ACOG guidelines. Biopsies were performed in only 570 women who were postmenopausal or who had at least one risk factor for endometrial cancer (such as obesity or polycystic ovarian syndrome), and all were followed for 2 years. None of the women who did not undergo biopsy developed cancer or hyperplasia, but the study was underpowered to assess outcomes in those women, she said (J. Reprod. Med. 2001;46:831-4).

Dr. Jackson reported having no relevant financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Close adherence to guidelines for deciding when to do endometrial biopsies in women with abnormal uterine bleeding could mean ordering biopsies in 88% of perimenopausal women with bleeding, according to Dr. Rebecca Jackson.

Irregular uterine bleeding is "incredibly common," endometrial cancer is "relatively common," and models to predict which women with abnormal bleeding are at risk for endometrial cancer "have been examined and are not useful," said Dr. Jackson, professor of obstetrics and gynecology at the University of California, San Francisco, and chief of obstetrics and gynecology at San Francisco General Hospital. Without much data to go on, "we’re left with expert opinion," she said.

She offered the following approach employed at her institution in a presentation at a conference on women’s health sponsored by the university. "We’re heartened to see that UpToDate has the same approach," Dr. Jackson said, referring to the digital evidence-based clinical decision support tool.

American College of Obstetricians and Gynecologists Practice Bulletin 128 on the Diagnosis of Abnormal Uterine Bleeding in Reproductive-Aged Women recommends that endometrial tissue sampling be done in patients with abnormal uterine bleeding who are older than 45 years and in younger patients who have a history of unopposed estrogen exposure, failed medical management, and persistent abnormal uterine bleeding (Obstet. Gynecol. 2012;120:197-206).

During an average 4-year perimenopause, however, only 12% of women completely stop menstruating; 70% have short, irregular menses; and 18% have longer, heavier menses, studies have shown (Int. J. Fertil 1967;12:77-126; Acta Obstet. Gynecol. Scand. 1966;45:320-51).A close application of the ACOG guidelines could mean biopsies in all but 12% of perimenopausal women, she said.

Dr. Jackson said she takes endometrial biopsies in all postmenopausal women with any abnormal uterine bleeding except for bleeding that starts 4-6 months after initiating hormone therapy. Approximately 10% of postmenopausal women with bleeding have cancer. "That’s a very high pretest probability when you’re talking about cancer, way higher than when you think about an abnormal mammogram," she said. Offering a postmenopausal patient a choice between a biopsy and a transvaginal ultrasound is reasonable as long as either procedure is available quickly and the patient understands that she still may need an endometrial biopsy after an ultrasound.

In women with a recent onset of irregular bleeding, don’t jump to a biopsy too quickly for this very common phenomenon. "Consider treating her, and if it normalizes, there’s no need for an endometrial biopsy," she said.

She recommended a low threshold for biopsy in women older than 50 years who have recurrent irregular bleeding because the risk of cancer is going up with age, but consider not getting a biopsy if the periods are light and spacing out. Periods that happen every 2-3 months and last 2-3 days are "not a very worrisome pattern," she said. Endometrial cancer presents most commonly with menometrorrhagia and sometimes with intermenstrual bleeding, but rarely with regularly timed menses.

Dr. Jackson said she biopsies women aged 45-50 years if they have recurrent irregular bleeding plus at least one risk factor for endometrial cancer or they’ve had more than 6 months of menometrorrhagia.

In younger women, consider a biopsy if they’ve had a "long history" of untreated anovulatory bleeding, which could be 2 years or 5 years, she suggested. "We have a hard time getting consensus on that [definition of] long," she noted.

A Pap smear result showing atypical glandular cells or endometrial cells would be another reason to biopsy if the Pap smear was not done at the time of menses.

An endometrial biopsy is not perfectly sensitive, so "keep your radar up" even if the biopsy result is negative, and evaluate further if abnormal bleeding persists, she said.

Her search of the literature on less-aggressive strategies for endometrial biopsies turned up just one small prospective cohort study of 1,000 women with abnormal uterine bleeding who were eligible for endometrial biopsy under ACOG guidelines. Biopsies were performed in only 570 women who were postmenopausal or who had at least one risk factor for endometrial cancer (such as obesity or polycystic ovarian syndrome), and all were followed for 2 years. None of the women who did not undergo biopsy developed cancer or hyperplasia, but the study was underpowered to assess outcomes in those women, she said (J. Reprod. Med. 2001;46:831-4).

Dr. Jackson reported having no relevant financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Close adherence to guidelines for deciding when to do endometrial biopsies in women with abnormal uterine bleeding could mean ordering biopsies in 88% of perimenopausal women with bleeding, according to Dr. Rebecca Jackson.

Irregular uterine bleeding is "incredibly common," endometrial cancer is "relatively common," and models to predict which women with abnormal bleeding are at risk for endometrial cancer "have been examined and are not useful," said Dr. Jackson, professor of obstetrics and gynecology at the University of California, San Francisco, and chief of obstetrics and gynecology at San Francisco General Hospital. Without much data to go on, "we’re left with expert opinion," she said.

She offered the following approach employed at her institution in a presentation at a conference on women’s health sponsored by the university. "We’re heartened to see that UpToDate has the same approach," Dr. Jackson said, referring to the digital evidence-based clinical decision support tool.

American College of Obstetricians and Gynecologists Practice Bulletin 128 on the Diagnosis of Abnormal Uterine Bleeding in Reproductive-Aged Women recommends that endometrial tissue sampling be done in patients with abnormal uterine bleeding who are older than 45 years and in younger patients who have a history of unopposed estrogen exposure, failed medical management, and persistent abnormal uterine bleeding (Obstet. Gynecol. 2012;120:197-206).

During an average 4-year perimenopause, however, only 12% of women completely stop menstruating; 70% have short, irregular menses; and 18% have longer, heavier menses, studies have shown (Int. J. Fertil 1967;12:77-126; Acta Obstet. Gynecol. Scand. 1966;45:320-51).A close application of the ACOG guidelines could mean biopsies in all but 12% of perimenopausal women, she said.

Dr. Jackson said she takes endometrial biopsies in all postmenopausal women with any abnormal uterine bleeding except for bleeding that starts 4-6 months after initiating hormone therapy. Approximately 10% of postmenopausal women with bleeding have cancer. "That’s a very high pretest probability when you’re talking about cancer, way higher than when you think about an abnormal mammogram," she said. Offering a postmenopausal patient a choice between a biopsy and a transvaginal ultrasound is reasonable as long as either procedure is available quickly and the patient understands that she still may need an endometrial biopsy after an ultrasound.

In women with a recent onset of irregular bleeding, don’t jump to a biopsy too quickly for this very common phenomenon. "Consider treating her, and if it normalizes, there’s no need for an endometrial biopsy," she said.

She recommended a low threshold for biopsy in women older than 50 years who have recurrent irregular bleeding because the risk of cancer is going up with age, but consider not getting a biopsy if the periods are light and spacing out. Periods that happen every 2-3 months and last 2-3 days are "not a very worrisome pattern," she said. Endometrial cancer presents most commonly with menometrorrhagia and sometimes with intermenstrual bleeding, but rarely with regularly timed menses.

Dr. Jackson said she biopsies women aged 45-50 years if they have recurrent irregular bleeding plus at least one risk factor for endometrial cancer or they’ve had more than 6 months of menometrorrhagia.

In younger women, consider a biopsy if they’ve had a "long history" of untreated anovulatory bleeding, which could be 2 years or 5 years, she suggested. "We have a hard time getting consensus on that [definition of] long," she noted.

A Pap smear result showing atypical glandular cells or endometrial cells would be another reason to biopsy if the Pap smear was not done at the time of menses.

An endometrial biopsy is not perfectly sensitive, so "keep your radar up" even if the biopsy result is negative, and evaluate further if abnormal bleeding persists, she said.

Her search of the literature on less-aggressive strategies for endometrial biopsies turned up just one small prospective cohort study of 1,000 women with abnormal uterine bleeding who were eligible for endometrial biopsy under ACOG guidelines. Biopsies were performed in only 570 women who were postmenopausal or who had at least one risk factor for endometrial cancer (such as obesity or polycystic ovarian syndrome), and all were followed for 2 years. None of the women who did not undergo biopsy developed cancer or hyperplasia, but the study was underpowered to assess outcomes in those women, she said (J. Reprod. Med. 2001;46:831-4).

Dr. Jackson reported having no relevant financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Low-risk toddlers who screened positive on the revised version of a widely used autism screening tool were 114 times more likely to be diagnosed with autism spectrum disorder, compared with those who screened negative in a validation study of 15,612 children.

The Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) reduced the number of toddlers needing follow-up and increased detection of autism spectrum disorder, compared with the original checklist with follow-up (M-CHAT-F). The screen-positive rate decreased significantly from 9% with the M-CHAT-R to 7% with the M-CHAT-R/F. The rate of detecting autism spectrum disorder significantly increased from 45 to 67 cases per 10,000 children screened, Diana L. Robins, Ph.D., of Georgia State University, Atlanta, and her associates reported (Pediatrics 2014;133:37-45).

In the two-stage screening tool, parents first answer 20 yes-or-no questions, which typically takes less than 5 minutes. In the study, 92% scored 0-2 at this stage, indicating low risk with no further evaluation needed unless other risk factors are present. One percent of toddlers were considered high risk based on scores of 8 or higher, and all of these were later diagnosed with some kind of development delay or concern, which justifies immediate referral for formal evaluation and possible early intervention, the investigators reported.

Six percent of toddlers scored 3-7, indicating medium risk for autism spectrum disorder, and their parents were invited to complete a second stage of screening by answering structured follow-up questions to obtain more information, a process that takes 5-10 minutes by phone with a nurse, physician assistant, or other health professional. Approximately one-third of toddlers whose parents complete the follow-up continue to show risk for autism spectrum disorder on subsequent evaluation and deserve referral, the investigators said.

Autism spectrum disorder was diagnosed in 48% of all toddlers who screened positive, making them 114 times more likely than screen-negative children to be diagnosed with the disorder. Among the rest of those who screened positive, 36% had other developmental delays, 11% had developmental concerns but no formal diagnosis, and 5% were deemed to be typically developing.

Subjects were screened in Georgia and Connecticut during the children’s 18- or 24-month well-child care visits with pediatricians. The pediatricians also were asked to check a box at the top of the form if they had concern about autism spectrum disorder based on their clinical judgment. Among the 64 toddlers flagged by physicians, 30 were diagnosed with autism spectrum disorder and 12 had developmental delays or concerns. Pediatricians were more likely to indicate concern about possible autism in toddlers of highly educated parents, and the overall sensitivity of physician concern alone for detecting autism spectrum disorder was 24%.

Combining M-CHAT-R/F results and pediatricians’ clinical judgment provided a very high detection rate for autism spectrum disorder, "indicating that standardized screening in conjunction with routine developmental surveillance optimizes early detection for autism spectrum disorder," Dr. Robins reported.

She and her associates revised the original M-CHAT-F by eliminating three items (peek-a-boo, playing with toys, and wandering without purpose), reorganizing the remaining 20 items, simplifying the language, giving examples for developmental context and clarity, simplifying the scoring, and making other changes.

Toddlers with autism spectrum disorder in the study were diagnosed on average just after their second birthday, 2 years earlier than the median age of diagnosis in national data.

The M-CHAT-R/F can be downloaded for free in multiple languages from www.mchatscreen.com.

The investigators are studying the validity of using the M-CHAT-R/F in high-risk toddlers and looking at various ways to find cases of autism missed by the screening tool.

The National Institutes of Health funded the study. Dr. Robins and two of her coinvestigators are co-owners of M-CHAT LLC and receive royalties from the licensing of M-CHAT in electronic products, although her coinvestigators allocate all their royalties to research and clinical training expenditures. Three other coinvestigators reported having no financial disclosures.

[email protected] On Twitter @sherryboschert

SAN FRANCISCO – Low-risk toddlers who screened positive on the revised version of a widely used autism screening tool were 114 times more likely to be diagnosed with autism spectrum disorder, compared with those who screened negative in a validation study of 15,612 children.

The Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) reduced the number of toddlers needing follow-up and increased detection of autism spectrum disorder, compared with the original checklist with follow-up (M-CHAT-F). The screen-positive rate decreased significantly from 9% with the M-CHAT-R to 7% with the M-CHAT-R/F. The rate of detecting autism spectrum disorder significantly increased from 45 to 67 cases per 10,000 children screened, Diana L. Robins, Ph.D., of Georgia State University, Atlanta, and her associates reported (Pediatrics 2014;133:37-45).

In the two-stage screening tool, parents first answer 20 yes-or-no questions, which typically takes less than 5 minutes. In the study, 92% scored 0-2 at this stage, indicating low risk with no further evaluation needed unless other risk factors are present. One percent of toddlers were considered high risk based on scores of 8 or higher, and all of these were later diagnosed with some kind of development delay or concern, which justifies immediate referral for formal evaluation and possible early intervention, the investigators reported.

Six percent of toddlers scored 3-7, indicating medium risk for autism spectrum disorder, and their parents were invited to complete a second stage of screening by answering structured follow-up questions to obtain more information, a process that takes 5-10 minutes by phone with a nurse, physician assistant, or other health professional. Approximately one-third of toddlers whose parents complete the follow-up continue to show risk for autism spectrum disorder on subsequent evaluation and deserve referral, the investigators said.

Autism spectrum disorder was diagnosed in 48% of all toddlers who screened positive, making them 114 times more likely than screen-negative children to be diagnosed with the disorder. Among the rest of those who screened positive, 36% had other developmental delays, 11% had developmental concerns but no formal diagnosis, and 5% were deemed to be typically developing.

Subjects were screened in Georgia and Connecticut during the children’s 18- or 24-month well-child care visits with pediatricians. The pediatricians also were asked to check a box at the top of the form if they had concern about autism spectrum disorder based on their clinical judgment. Among the 64 toddlers flagged by physicians, 30 were diagnosed with autism spectrum disorder and 12 had developmental delays or concerns. Pediatricians were more likely to indicate concern about possible autism in toddlers of highly educated parents, and the overall sensitivity of physician concern alone for detecting autism spectrum disorder was 24%.

Combining M-CHAT-R/F results and pediatricians’ clinical judgment provided a very high detection rate for autism spectrum disorder, "indicating that standardized screening in conjunction with routine developmental surveillance optimizes early detection for autism spectrum disorder," Dr. Robins reported.

She and her associates revised the original M-CHAT-F by eliminating three items (peek-a-boo, playing with toys, and wandering without purpose), reorganizing the remaining 20 items, simplifying the language, giving examples for developmental context and clarity, simplifying the scoring, and making other changes.

Toddlers with autism spectrum disorder in the study were diagnosed on average just after their second birthday, 2 years earlier than the median age of diagnosis in national data.

The M-CHAT-R/F can be downloaded for free in multiple languages from www.mchatscreen.com.

The investigators are studying the validity of using the M-CHAT-R/F in high-risk toddlers and looking at various ways to find cases of autism missed by the screening tool.

The National Institutes of Health funded the study. Dr. Robins and two of her coinvestigators are co-owners of M-CHAT LLC and receive royalties from the licensing of M-CHAT in electronic products, although her coinvestigators allocate all their royalties to research and clinical training expenditures. Three other coinvestigators reported having no financial disclosures.

[email protected] On Twitter @sherryboschert

SAN FRANCISCO – Low-risk toddlers who screened positive on the revised version of a widely used autism screening tool were 114 times more likely to be diagnosed with autism spectrum disorder, compared with those who screened negative in a validation study of 15,612 children.

The Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) reduced the number of toddlers needing follow-up and increased detection of autism spectrum disorder, compared with the original checklist with follow-up (M-CHAT-F). The screen-positive rate decreased significantly from 9% with the M-CHAT-R to 7% with the M-CHAT-R/F. The rate of detecting autism spectrum disorder significantly increased from 45 to 67 cases per 10,000 children screened, Diana L. Robins, Ph.D., of Georgia State University, Atlanta, and her associates reported (Pediatrics 2014;133:37-45).

In the two-stage screening tool, parents first answer 20 yes-or-no questions, which typically takes less than 5 minutes. In the study, 92% scored 0-2 at this stage, indicating low risk with no further evaluation needed unless other risk factors are present. One percent of toddlers were considered high risk based on scores of 8 or higher, and all of these were later diagnosed with some kind of development delay or concern, which justifies immediate referral for formal evaluation and possible early intervention, the investigators reported.

Six percent of toddlers scored 3-7, indicating medium risk for autism spectrum disorder, and their parents were invited to complete a second stage of screening by answering structured follow-up questions to obtain more information, a process that takes 5-10 minutes by phone with a nurse, physician assistant, or other health professional. Approximately one-third of toddlers whose parents complete the follow-up continue to show risk for autism spectrum disorder on subsequent evaluation and deserve referral, the investigators said.

Autism spectrum disorder was diagnosed in 48% of all toddlers who screened positive, making them 114 times more likely than screen-negative children to be diagnosed with the disorder. Among the rest of those who screened positive, 36% had other developmental delays, 11% had developmental concerns but no formal diagnosis, and 5% were deemed to be typically developing.

Subjects were screened in Georgia and Connecticut during the children’s 18- or 24-month well-child care visits with pediatricians. The pediatricians also were asked to check a box at the top of the form if they had concern about autism spectrum disorder based on their clinical judgment. Among the 64 toddlers flagged by physicians, 30 were diagnosed with autism spectrum disorder and 12 had developmental delays or concerns. Pediatricians were more likely to indicate concern about possible autism in toddlers of highly educated parents, and the overall sensitivity of physician concern alone for detecting autism spectrum disorder was 24%.

Combining M-CHAT-R/F results and pediatricians’ clinical judgment provided a very high detection rate for autism spectrum disorder, "indicating that standardized screening in conjunction with routine developmental surveillance optimizes early detection for autism spectrum disorder," Dr. Robins reported.

She and her associates revised the original M-CHAT-F by eliminating three items (peek-a-boo, playing with toys, and wandering without purpose), reorganizing the remaining 20 items, simplifying the language, giving examples for developmental context and clarity, simplifying the scoring, and making other changes.

Toddlers with autism spectrum disorder in the study were diagnosed on average just after their second birthday, 2 years earlier than the median age of diagnosis in national data.

The M-CHAT-R/F can be downloaded for free in multiple languages from www.mchatscreen.com.

The investigators are studying the validity of using the M-CHAT-R/F in high-risk toddlers and looking at various ways to find cases of autism missed by the screening tool.

The National Institutes of Health funded the study. Dr. Robins and two of her coinvestigators are co-owners of M-CHAT LLC and receive royalties from the licensing of M-CHAT in electronic products, although her coinvestigators allocate all their royalties to research and clinical training expenditures. Three other coinvestigators reported having no financial disclosures.

[email protected] On Twitter @sherryboschert

SAN FRANCISCO – Hospitalists are the most logical source of physicians to fill a shortage of intensive care providers. Or, maybe it’s emergency physicians. But it could be internists, depending on which of three speakers at the Critical Care Congress you find most persuasive.

Whether it’s any of those specialties or all three, there are barriers to be overcome with each strategy, the speakers said in a session on critical care practitioners.

Hospitalists already are doing critical care, Dr. Andrew D. Auerbach said. "Even if not hired primarily for that, they’re doing it anyway," said Dr. Auerbach, a hospitalist and researcher at the University of California, San Francisco. A 2010 study found that 34 of 72 open intensive care units in Michigan had hospitalists as ICU attending physicians (J. Hosp. Med. 2010;5:4-9). These included smaller hospitals outside major population centers, not just small community hospitals, he said at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

Hospitalists in those settings become "the first-line providers in critical care" when, for example, a patient with respiratory failure and sepsis needs to go to the ICU at 2 a.m. "The pulmonologist is trying to do their best, but is at home. The emergency physician is in the emergency department trying to take care of broken legs and car crashes. The anesthesiologist is doing airways and epidurals up on the obstetrics floor."

These hospitalists need to be supported in their intensivist roles by "giving them the training – whether it be for an added certification or board certification, I don’t care," Dr. Auerbach said. Intensivists also could benefit by forging clinical partnerships with hospitalists to tap hospitalists’ expertise in sepsis care, patient monitoring, antimicrobial stewardship, comanaging surgical patients, and transitioning patient care, he suggested.

"Hospitalists want to go into critical care medicine but have been at times in limbo because there is no pathway for them except to do the 2 years of fellowship training," Dr. Stephen M. Pastores agreed in a separate presentation. "We need to help our hospitalists get to the promised land of the ICU," either by creating a shortened training pathway or by offering new incentives.

Community hospitals that want more intensivists could pay for hospitalists to pursue fellowship training and guarantee them an intensivist job when training is finished, said Dr. Pastores, director of the critical care fellowship program at Memorial Sloan-Kettering Cancer Center, New York, and a board-certified internist, pulmonologist, and intensivist there.

Hospitals that are determined to have intensivists run the ICU might consider that approach, which could offset the hassle of leaving one’s job and taking a temporary pay cut in order to pursue a critical care fellowship, Dr. Franklin A. Michota agreed in a phone interview. Or, they simply could offer higher salaries to recruit intensivists. "It’s a supply-and-demand phenomenon," said Dr. Michota, director of academic affairs in the department of hospitalist medicine at the Cleveland Clinic.

On the other hand, intensive care is within the scope and training of hospitalists, and any hospitalists working in ICUs should be pursuing critical care CME already, he added. Doing a 2-year critical care fellowship "on top of that won’t change the skill set" but will increase the salary that a physician can command, he said.

Besides hospitalists, Dr. Pastores sees greater possibilities from expanding the pipeline of internists into critical care.

"I’d argue that the internal medicine–based trained intensivists really have no competing responsibilities" compared with pulmonologists, surgeons, or other specialists and thus are more likely to work full-time in an ICU, he said. "From that perspective, why are there only 34 stand-alone programs in internal medicine critical care compared to 134 programs in pulmonary critical care? Maybe that could be addressed in a more efficient way."

Pulmonary critical care medicine programs also could be doing more. Although it’s not well known, the Accreditation Council for Graduate Medical Education (ACGME) allows pulmonary critical care programs every other year to train a fellow who does not want to be certified in pulmonary medicine but only wants to do critical care medicine, Dr. Pastores said. If the programs took advantage of that, the number of full-time critical care providers would increase.

A paper to be published by Dr. Pastores and his colleagues this spring in the journal Critical Care Medicine will propose that the ACGME relax some "very restrictive mandates" on internal medicine–based critical care medicine training programs.

One hurdle requires the critical care medicine program’s primary site to offer at least three out of five key fellowship programs. "That can be very difficult for many of the smaller programs that are not major academic centers, where they may not have things like fellowships in infectious diseases, nephrology, pulmonary, et cetera," he said.

Another barrier excludes physicians who are not certified in internal medicine from being counted as key faculty in internal medicine–based critical care training programs. "In my program, we have anesthesiologists and surgeons who are teaching our fellows, and there’s no good reason they shouldn’t be counted as key faculty," he said.

He and Dr. Brian Wessman, who also spoke at the meeting, cited another ACGME barrier, this one blocking the pipeline of emergency medicine physicians. Internal medicine–based critical care medicine training programs must limit the proportion of emergency medicine trainees to 25% of their programs.

Emergency medicine physicians are the ideal candidates for critical care medicine because their training already includes exposure to undifferentiated critical care patients and development of a "robust procedural acumen applicable to critical care," said Dr. Wessman, an emergency medicine physician and codirector of the critical care fellowship program at Washington University, St. Louis.

There now are three paths to obtaining certification in emergency medicine/critical care medicine, he said. Medicine-based critical care programs limit trainees from emergency medicine to 25% of slots. As of July 2013, emergency medicine physicians could enter surgical critical care fellowships at three institutions. And beginning in the 2014 academic year, 10 anesthesiology critical care medicine fellowship programs will offer an emergency medicine/critical care medicine training tract.

"If you haven’t run across an emergency medicine intensivist yet, you will," Dr. Wessman said. "I think you will see our numbers grow exponentially now that there are ways for us to go forward, if we can remove some of the barriers."

None of the speakers had financial disclosures relevant to this topic. Dr. Pastores reported receiving research grants from Spectral Diagnostics and Bayer Healthcare. Dr. Michota reported financial associations with Boehringer Ingelheim, Daiichi-Sankyo, and other companies. Dr. Wessman and Dr. Auerbach reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Hospitalists are the most logical source of physicians to fill a shortage of intensive care providers. Or, maybe it’s emergency physicians. But it could be internists, depending on which of three speakers at the Critical Care Congress you find most persuasive.

Whether it’s any of those specialties or all three, there are barriers to be overcome with each strategy, the speakers said in a session on critical care practitioners.

Hospitalists already are doing critical care, Dr. Andrew D. Auerbach said. "Even if not hired primarily for that, they’re doing it anyway," said Dr. Auerbach, a hospitalist and researcher at the University of California, San Francisco. A 2010 study found that 34 of 72 open intensive care units in Michigan had hospitalists as ICU attending physicians (J. Hosp. Med. 2010;5:4-9). These included smaller hospitals outside major population centers, not just small community hospitals, he said at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

Hospitalists in those settings become "the first-line providers in critical care" when, for example, a patient with respiratory failure and sepsis needs to go to the ICU at 2 a.m. "The pulmonologist is trying to do their best, but is at home. The emergency physician is in the emergency department trying to take care of broken legs and car crashes. The anesthesiologist is doing airways and epidurals up on the obstetrics floor."

These hospitalists need to be supported in their intensivist roles by "giving them the training – whether it be for an added certification or board certification, I don’t care," Dr. Auerbach said. Intensivists also could benefit by forging clinical partnerships with hospitalists to tap hospitalists’ expertise in sepsis care, patient monitoring, antimicrobial stewardship, comanaging surgical patients, and transitioning patient care, he suggested.

"Hospitalists want to go into critical care medicine but have been at times in limbo because there is no pathway for them except to do the 2 years of fellowship training," Dr. Stephen M. Pastores agreed in a separate presentation. "We need to help our hospitalists get to the promised land of the ICU," either by creating a shortened training pathway or by offering new incentives.

Community hospitals that want more intensivists could pay for hospitalists to pursue fellowship training and guarantee them an intensivist job when training is finished, said Dr. Pastores, director of the critical care fellowship program at Memorial Sloan-Kettering Cancer Center, New York, and a board-certified internist, pulmonologist, and intensivist there.

Hospitals that are determined to have intensivists run the ICU might consider that approach, which could offset the hassle of leaving one’s job and taking a temporary pay cut in order to pursue a critical care fellowship, Dr. Franklin A. Michota agreed in a phone interview. Or, they simply could offer higher salaries to recruit intensivists. "It’s a supply-and-demand phenomenon," said Dr. Michota, director of academic affairs in the department of hospitalist medicine at the Cleveland Clinic.

On the other hand, intensive care is within the scope and training of hospitalists, and any hospitalists working in ICUs should be pursuing critical care CME already, he added. Doing a 2-year critical care fellowship "on top of that won’t change the skill set" but will increase the salary that a physician can command, he said.

Besides hospitalists, Dr. Pastores sees greater possibilities from expanding the pipeline of internists into critical care.

"I’d argue that the internal medicine–based trained intensivists really have no competing responsibilities" compared with pulmonologists, surgeons, or other specialists and thus are more likely to work full-time in an ICU, he said. "From that perspective, why are there only 34 stand-alone programs in internal medicine critical care compared to 134 programs in pulmonary critical care? Maybe that could be addressed in a more efficient way."

Pulmonary critical care medicine programs also could be doing more. Although it’s not well known, the Accreditation Council for Graduate Medical Education (ACGME) allows pulmonary critical care programs every other year to train a fellow who does not want to be certified in pulmonary medicine but only wants to do critical care medicine, Dr. Pastores said. If the programs took advantage of that, the number of full-time critical care providers would increase.

A paper to be published by Dr. Pastores and his colleagues this spring in the journal Critical Care Medicine will propose that the ACGME relax some "very restrictive mandates" on internal medicine–based critical care medicine training programs.

One hurdle requires the critical care medicine program’s primary site to offer at least three out of five key fellowship programs. "That can be very difficult for many of the smaller programs that are not major academic centers, where they may not have things like fellowships in infectious diseases, nephrology, pulmonary, et cetera," he said.

Another barrier excludes physicians who are not certified in internal medicine from being counted as key faculty in internal medicine–based critical care training programs. "In my program, we have anesthesiologists and surgeons who are teaching our fellows, and there’s no good reason they shouldn’t be counted as key faculty," he said.

He and Dr. Brian Wessman, who also spoke at the meeting, cited another ACGME barrier, this one blocking the pipeline of emergency medicine physicians. Internal medicine–based critical care medicine training programs must limit the proportion of emergency medicine trainees to 25% of their programs.

Emergency medicine physicians are the ideal candidates for critical care medicine because their training already includes exposure to undifferentiated critical care patients and development of a "robust procedural acumen applicable to critical care," said Dr. Wessman, an emergency medicine physician and codirector of the critical care fellowship program at Washington University, St. Louis.

There now are three paths to obtaining certification in emergency medicine/critical care medicine, he said. Medicine-based critical care programs limit trainees from emergency medicine to 25% of slots. As of July 2013, emergency medicine physicians could enter surgical critical care fellowships at three institutions. And beginning in the 2014 academic year, 10 anesthesiology critical care medicine fellowship programs will offer an emergency medicine/critical care medicine training tract.

"If you haven’t run across an emergency medicine intensivist yet, you will," Dr. Wessman said. "I think you will see our numbers grow exponentially now that there are ways for us to go forward, if we can remove some of the barriers."

None of the speakers had financial disclosures relevant to this topic. Dr. Pastores reported receiving research grants from Spectral Diagnostics and Bayer Healthcare. Dr. Michota reported financial associations with Boehringer Ingelheim, Daiichi-Sankyo, and other companies. Dr. Wessman and Dr. Auerbach reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Hospitalists are the most logical source of physicians to fill a shortage of intensive care providers. Or, maybe it’s emergency physicians. But it could be internists, depending on which of three speakers at the Critical Care Congress you find most persuasive.

Whether it’s any of those specialties or all three, there are barriers to be overcome with each strategy, the speakers said in a session on critical care practitioners.

Hospitalists already are doing critical care, Dr. Andrew D. Auerbach said. "Even if not hired primarily for that, they’re doing it anyway," said Dr. Auerbach, a hospitalist and researcher at the University of California, San Francisco. A 2010 study found that 34 of 72 open intensive care units in Michigan had hospitalists as ICU attending physicians (J. Hosp. Med. 2010;5:4-9). These included smaller hospitals outside major population centers, not just small community hospitals, he said at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

Hospitalists in those settings become "the first-line providers in critical care" when, for example, a patient with respiratory failure and sepsis needs to go to the ICU at 2 a.m. "The pulmonologist is trying to do their best, but is at home. The emergency physician is in the emergency department trying to take care of broken legs and car crashes. The anesthesiologist is doing airways and epidurals up on the obstetrics floor."

These hospitalists need to be supported in their intensivist roles by "giving them the training – whether it be for an added certification or board certification, I don’t care," Dr. Auerbach said. Intensivists also could benefit by forging clinical partnerships with hospitalists to tap hospitalists’ expertise in sepsis care, patient monitoring, antimicrobial stewardship, comanaging surgical patients, and transitioning patient care, he suggested.

"Hospitalists want to go into critical care medicine but have been at times in limbo because there is no pathway for them except to do the 2 years of fellowship training," Dr. Stephen M. Pastores agreed in a separate presentation. "We need to help our hospitalists get to the promised land of the ICU," either by creating a shortened training pathway or by offering new incentives.

Community hospitals that want more intensivists could pay for hospitalists to pursue fellowship training and guarantee them an intensivist job when training is finished, said Dr. Pastores, director of the critical care fellowship program at Memorial Sloan-Kettering Cancer Center, New York, and a board-certified internist, pulmonologist, and intensivist there.

Hospitals that are determined to have intensivists run the ICU might consider that approach, which could offset the hassle of leaving one’s job and taking a temporary pay cut in order to pursue a critical care fellowship, Dr. Franklin A. Michota agreed in a phone interview. Or, they simply could offer higher salaries to recruit intensivists. "It’s a supply-and-demand phenomenon," said Dr. Michota, director of academic affairs in the department of hospitalist medicine at the Cleveland Clinic.

On the other hand, intensive care is within the scope and training of hospitalists, and any hospitalists working in ICUs should be pursuing critical care CME already, he added. Doing a 2-year critical care fellowship "on top of that won’t change the skill set" but will increase the salary that a physician can command, he said.

Besides hospitalists, Dr. Pastores sees greater possibilities from expanding the pipeline of internists into critical care.

"I’d argue that the internal medicine–based trained intensivists really have no competing responsibilities" compared with pulmonologists, surgeons, or other specialists and thus are more likely to work full-time in an ICU, he said. "From that perspective, why are there only 34 stand-alone programs in internal medicine critical care compared to 134 programs in pulmonary critical care? Maybe that could be addressed in a more efficient way."

Pulmonary critical care medicine programs also could be doing more. Although it’s not well known, the Accreditation Council for Graduate Medical Education (ACGME) allows pulmonary critical care programs every other year to train a fellow who does not want to be certified in pulmonary medicine but only wants to do critical care medicine, Dr. Pastores said. If the programs took advantage of that, the number of full-time critical care providers would increase.

A paper to be published by Dr. Pastores and his colleagues this spring in the journal Critical Care Medicine will propose that the ACGME relax some "very restrictive mandates" on internal medicine–based critical care medicine training programs.

One hurdle requires the critical care medicine program’s primary site to offer at least three out of five key fellowship programs. "That can be very difficult for many of the smaller programs that are not major academic centers, where they may not have things like fellowships in infectious diseases, nephrology, pulmonary, et cetera," he said.

Another barrier excludes physicians who are not certified in internal medicine from being counted as key faculty in internal medicine–based critical care training programs. "In my program, we have anesthesiologists and surgeons who are teaching our fellows, and there’s no good reason they shouldn’t be counted as key faculty," he said.

He and Dr. Brian Wessman, who also spoke at the meeting, cited another ACGME barrier, this one blocking the pipeline of emergency medicine physicians. Internal medicine–based critical care medicine training programs must limit the proportion of emergency medicine trainees to 25% of their programs.

Emergency medicine physicians are the ideal candidates for critical care medicine because their training already includes exposure to undifferentiated critical care patients and development of a "robust procedural acumen applicable to critical care," said Dr. Wessman, an emergency medicine physician and codirector of the critical care fellowship program at Washington University, St. Louis.

There now are three paths to obtaining certification in emergency medicine/critical care medicine, he said. Medicine-based critical care programs limit trainees from emergency medicine to 25% of slots. As of July 2013, emergency medicine physicians could enter surgical critical care fellowships at three institutions. And beginning in the 2014 academic year, 10 anesthesiology critical care medicine fellowship programs will offer an emergency medicine/critical care medicine training tract.

"If you haven’t run across an emergency medicine intensivist yet, you will," Dr. Wessman said. "I think you will see our numbers grow exponentially now that there are ways for us to go forward, if we can remove some of the barriers."

None of the speakers had financial disclosures relevant to this topic. Dr. Pastores reported receiving research grants from Spectral Diagnostics and Bayer Healthcare. Dr. Michota reported financial associations with Boehringer Ingelheim, Daiichi-Sankyo, and other companies. Dr. Wessman and Dr. Auerbach reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Meeting the goals of the Surviving Sepsis Campaign's resuscitation care bundle significantly decreased the risk for in-hospital mortality, even when the goals were met beyond the recommended 6-hour window after diagnosis of severe sepsis, a study of 395 patients found.

In-hospital mortality rates were 88% lower in the 85 patients who met the resuscitation bundle goals 6-18 hours after diagnosis and 55% lower in the 95 patients who met the goals within the desired 6 hours after diagnosis compared with 216 patients who didn’t reach the goals within 18 hours of diagnosis, Dr. Zerihun A. Bunaye reported at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

For resuscitation care in severe sepsis, it’s better late than never, he said. "Definitely this is showing that there’s a benefit if we continue to aggressively resuscitate the patients beyond 6 hours and try to achieve the goals," said Dr. Bunaye of Mercy Hospital, St. Louis. The lead investigator in the study was Dr. Farid Sadaka, also of the hospital.

Better survival in the group that complied with resuscitation bundle goals in 6-18 hours compared with the 6-hour compliance group surprised the investigators and may be due to several confounding factors that were not analyzed in the study, he said.

The Surviving Sepsis Campaign recommends two sets of "bundles" of care (sets of elements of care selected from evidence-based practice guidelines that have an effect on outcomes when implemented as a group that’s beyond the effect of individual implementation), some to be completed within 3 hours and other goals to be met within 6 hours.

The resuscitation bundle of care aims to prescribe appropriate antibiotics within 3 hours and within 6 hours to get the patient’s mean arterial pressure above 65 mm Hg, get central venous pressure above 8 mm Hg, achieve central venous oxygen saturation greater than 70%, and measure lactic acid, Dr. Bunaye said.

The investigators prospectively collected data as part of a performance improvement project with feedback mechanisms for alerting physicians when bundle goals were not being met so they could continue efforts to meet the goals beyond the recommended deadlines.

The study included patients with septic shock treated between July 2011 and January 2013 in a 54-bed ICU at the large university-affiliated hospital. It compared compliance with the resuscitation bundles within 18 hours of diagnosis and survival rates during approximately 31 days in the hospital.

Compared with the 54% of cases that did not comply with the resuscitation bundles within 18 hours, the hazard ratio for mortality was 0.45 in the 24% of cases that complied within 6 hours and 0.12 in the 22% that complied within 18 hours, Dr. Bunaye reported. Patients in the three groups did not differ significantly at baseline by age, weight, or Sequential Organ Failure Assessment score.

Previous studies have suggested that only 30%-40% of hospitals adhere to the Surviving Sepsis Campaign guidelines. The current study suggests that continuing efforts to meet the goals beyond 6 hours are beneficial, he said.

The findings are limited by the small sample size and the focus on a single institution. The study also did not account for potential confounding variables.

Severe sepsis in the United States is more common than AIDS, colon cancer, and breast cancer combined and is the leading cause of death in noncoronary ICUs, the literature suggests. The United States sees more than 500,000 cases of severe sepsis and septic shock each year, leading to death in 20% of patients with severe sepsis and 45% of those with septic shock, Dr. Bunaye said.

Financial disclosures for the investigators were not available at press time.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Meeting the goals of the Surviving Sepsis Campaign's resuscitation care bundle significantly decreased the risk for in-hospital mortality, even when the goals were met beyond the recommended 6-hour window after diagnosis of severe sepsis, a study of 395 patients found.

In-hospital mortality rates were 88% lower in the 85 patients who met the resuscitation bundle goals 6-18 hours after diagnosis and 55% lower in the 95 patients who met the goals within the desired 6 hours after diagnosis compared with 216 patients who didn’t reach the goals within 18 hours of diagnosis, Dr. Zerihun A. Bunaye reported at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

For resuscitation care in severe sepsis, it’s better late than never, he said. "Definitely this is showing that there’s a benefit if we continue to aggressively resuscitate the patients beyond 6 hours and try to achieve the goals," said Dr. Bunaye of Mercy Hospital, St. Louis. The lead investigator in the study was Dr. Farid Sadaka, also of the hospital.

Better survival in the group that complied with resuscitation bundle goals in 6-18 hours compared with the 6-hour compliance group surprised the investigators and may be due to several confounding factors that were not analyzed in the study, he said.

The Surviving Sepsis Campaign recommends two sets of "bundles" of care (sets of elements of care selected from evidence-based practice guidelines that have an effect on outcomes when implemented as a group that’s beyond the effect of individual implementation), some to be completed within 3 hours and other goals to be met within 6 hours.

The resuscitation bundle of care aims to prescribe appropriate antibiotics within 3 hours and within 6 hours to get the patient’s mean arterial pressure above 65 mm Hg, get central venous pressure above 8 mm Hg, achieve central venous oxygen saturation greater than 70%, and measure lactic acid, Dr. Bunaye said.

The investigators prospectively collected data as part of a performance improvement project with feedback mechanisms for alerting physicians when bundle goals were not being met so they could continue efforts to meet the goals beyond the recommended deadlines.

The study included patients with septic shock treated between July 2011 and January 2013 in a 54-bed ICU at the large university-affiliated hospital. It compared compliance with the resuscitation bundles within 18 hours of diagnosis and survival rates during approximately 31 days in the hospital.

Compared with the 54% of cases that did not comply with the resuscitation bundles within 18 hours, the hazard ratio for mortality was 0.45 in the 24% of cases that complied within 6 hours and 0.12 in the 22% that complied within 18 hours, Dr. Bunaye reported. Patients in the three groups did not differ significantly at baseline by age, weight, or Sequential Organ Failure Assessment score.

Previous studies have suggested that only 30%-40% of hospitals adhere to the Surviving Sepsis Campaign guidelines. The current study suggests that continuing efforts to meet the goals beyond 6 hours are beneficial, he said.

The findings are limited by the small sample size and the focus on a single institution. The study also did not account for potential confounding variables.

Severe sepsis in the United States is more common than AIDS, colon cancer, and breast cancer combined and is the leading cause of death in noncoronary ICUs, the literature suggests. The United States sees more than 500,000 cases of severe sepsis and septic shock each year, leading to death in 20% of patients with severe sepsis and 45% of those with septic shock, Dr. Bunaye said.

Financial disclosures for the investigators were not available at press time.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Meeting the goals of the Surviving Sepsis Campaign's resuscitation care bundle significantly decreased the risk for in-hospital mortality, even when the goals were met beyond the recommended 6-hour window after diagnosis of severe sepsis, a study of 395 patients found.

In-hospital mortality rates were 88% lower in the 85 patients who met the resuscitation bundle goals 6-18 hours after diagnosis and 55% lower in the 95 patients who met the goals within the desired 6 hours after diagnosis compared with 216 patients who didn’t reach the goals within 18 hours of diagnosis, Dr. Zerihun A. Bunaye reported at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

For resuscitation care in severe sepsis, it’s better late than never, he said. "Definitely this is showing that there’s a benefit if we continue to aggressively resuscitate the patients beyond 6 hours and try to achieve the goals," said Dr. Bunaye of Mercy Hospital, St. Louis. The lead investigator in the study was Dr. Farid Sadaka, also of the hospital.

Better survival in the group that complied with resuscitation bundle goals in 6-18 hours compared with the 6-hour compliance group surprised the investigators and may be due to several confounding factors that were not analyzed in the study, he said.

The Surviving Sepsis Campaign recommends two sets of "bundles" of care (sets of elements of care selected from evidence-based practice guidelines that have an effect on outcomes when implemented as a group that’s beyond the effect of individual implementation), some to be completed within 3 hours and other goals to be met within 6 hours.

The resuscitation bundle of care aims to prescribe appropriate antibiotics within 3 hours and within 6 hours to get the patient’s mean arterial pressure above 65 mm Hg, get central venous pressure above 8 mm Hg, achieve central venous oxygen saturation greater than 70%, and measure lactic acid, Dr. Bunaye said.

The investigators prospectively collected data as part of a performance improvement project with feedback mechanisms for alerting physicians when bundle goals were not being met so they could continue efforts to meet the goals beyond the recommended deadlines.

The study included patients with septic shock treated between July 2011 and January 2013 in a 54-bed ICU at the large university-affiliated hospital. It compared compliance with the resuscitation bundles within 18 hours of diagnosis and survival rates during approximately 31 days in the hospital.

Compared with the 54% of cases that did not comply with the resuscitation bundles within 18 hours, the hazard ratio for mortality was 0.45 in the 24% of cases that complied within 6 hours and 0.12 in the 22% that complied within 18 hours, Dr. Bunaye reported. Patients in the three groups did not differ significantly at baseline by age, weight, or Sequential Organ Failure Assessment score.

Previous studies have suggested that only 30%-40% of hospitals adhere to the Surviving Sepsis Campaign guidelines. The current study suggests that continuing efforts to meet the goals beyond 6 hours are beneficial, he said.

The findings are limited by the small sample size and the focus on a single institution. The study also did not account for potential confounding variables.

Severe sepsis in the United States is more common than AIDS, colon cancer, and breast cancer combined and is the leading cause of death in noncoronary ICUs, the literature suggests. The United States sees more than 500,000 cases of severe sepsis and septic shock each year, leading to death in 20% of patients with severe sepsis and 45% of those with septic shock, Dr. Bunaye said.

Financial disclosures for the investigators were not available at press time.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Trans-catheter aortic valve replacement with the self-expanding CoreValve in patients at extreme surgical risk significantly reduced the rate of death or major stroke at 1 year, from 43% to 26%, in a 487-patient pivotal trial.

The CoreValve Extreme Risk study gathered data from a registry of patients with symptomatic severe aortic stenosis who attempted an iliofemoral implantation procedure with the CoreValve at 40 U.S. sites. Results were compared with an "objective performance goal" derived from two sources: a meta-analysis of five contemporary balloon valvuloplasty series that found a 43% mortality and major stroke rate at 1 year, and the 1-year rate from the PARTNER B trial in inoperable patients (Placement of Aortic Transcatheter Valves, Cohort B), which was 50% but had a lower confidence bound of 43%.

The performance-goal comparison was necessary in the current study because randomizing these patients to medical therapy in a control group is no longer an acceptable option in the United States, Dr. Jeffrey J. Popma said at the Transcatheter Cardiovascular Therapeutics annual meeting.

The 1-year all-cause mortality rate was 24%, and the cardiovascular mortality was 18%, reported Dr. Popma, professor of medicine at Harvard Medical School, Boston.

Two percent of patients developed a major stroke within 1 month and 4% did so within 1 year.

Data from a continued access study involving another 830 extreme-risk patients who received the CoreValve through an iliofemoral approach are showing even better results, with a 16% rate of mortality or major stroke at 6 months.

Among secondary endpoints at 1 year in the main study, 7% of patients developed any kind of stroke, 2% had an MI, 2% needed reintervention, 41% had bleeding that met Valve Academic Research Consortium criteria, 8% had major vascular complications, and 27% required implantation of a permanent pacemaker, Dr. Popma reported at the meeting, cosponsored by the American College of Cardiology. Ninety percent of patients improved by at least one New York Heart Association functional class and 60% improved by at least two classes at 1 year of follow-up.

Paravalvular regurgitation of any severity was seen in 53% of patients 1 month after implantation and in 33% at 1 year. Moderate paravalvular leakage (PVL) affected 9% at 1 month and 4% at 1 year, and severe PVL affected 1.6% at 1 month and no patients at 1 year, Dr. Popma said. Among the 11% of patients with moderate PVL at 1 month, 80% of those who survived to 1 year had a reduction in leakage over time.

"We believe that’s why we did not find an association in the study between mild or moderate aortic regurgitation with respect to late-term mortality," though mortality risk was substantially higher with severe regurgitation, he said. One-year mortality rates were 86% with severe PVL and 24% with either moderate or mild PVL, compared with 18% in patients with no PVL.

The improvement in PVL rates over time may be due to use of CT angiography to select appropriate valve sizes for patients and continued expansion of the self-expanding frame over time. "That’s a remarkable finding, and it needs to be confirmed," Dr. Popma said.

The study focused on patients whose severe frailty, comorbidity, or disability put them at extreme risk of at least a 50% chance of death or irreversible morbidity within 30 days had they undergone surgical aortic valve replacement. A second U.S. pivotal trial of the CoreValve is focusing on patients at high (but not extreme) risk.

Most of the sites in the study had no experience with CoreValve before this study, Dr. Michael J. Mack noted at a press briefing. "The results are outstanding, but especially putting it in that light," said Dr. Mack, a member of the steering committee for the PARTNER trial.

Dr. Popma reported financial ties with Medtronic, which sponsored the study and makes CoreValve.

[email protected]

SAN FRANCISCO – Trans-catheter aortic valve replacement with the self-expanding CoreValve in patients at extreme surgical risk significantly reduced the rate of death or major stroke at 1 year, from 43% to 26%, in a 487-patient pivotal trial.

The CoreValve Extreme Risk study gathered data from a registry of patients with symptomatic severe aortic stenosis who attempted an iliofemoral implantation procedure with the CoreValve at 40 U.S. sites. Results were compared with an "objective performance goal" derived from two sources: a meta-analysis of five contemporary balloon valvuloplasty series that found a 43% mortality and major stroke rate at 1 year, and the 1-year rate from the PARTNER B trial in inoperable patients (Placement of Aortic Transcatheter Valves, Cohort B), which was 50% but had a lower confidence bound of 43%.

The performance-goal comparison was necessary in the current study because randomizing these patients to medical therapy in a control group is no longer an acceptable option in the United States, Dr. Jeffrey J. Popma said at the Transcatheter Cardiovascular Therapeutics annual meeting.

The 1-year all-cause mortality rate was 24%, and the cardiovascular mortality was 18%, reported Dr. Popma, professor of medicine at Harvard Medical School, Boston.

Two percent of patients developed a major stroke within 1 month and 4% did so within 1 year.

Data from a continued access study involving another 830 extreme-risk patients who received the CoreValve through an iliofemoral approach are showing even better results, with a 16% rate of mortality or major stroke at 6 months.

Among secondary endpoints at 1 year in the main study, 7% of patients developed any kind of stroke, 2% had an MI, 2% needed reintervention, 41% had bleeding that met Valve Academic Research Consortium criteria, 8% had major vascular complications, and 27% required implantation of a permanent pacemaker, Dr. Popma reported at the meeting, cosponsored by the American College of Cardiology. Ninety percent of patients improved by at least one New York Heart Association functional class and 60% improved by at least two classes at 1 year of follow-up.

Paravalvular regurgitation of any severity was seen in 53% of patients 1 month after implantation and in 33% at 1 year. Moderate paravalvular leakage (PVL) affected 9% at 1 month and 4% at 1 year, and severe PVL affected 1.6% at 1 month and no patients at 1 year, Dr. Popma said. Among the 11% of patients with moderate PVL at 1 month, 80% of those who survived to 1 year had a reduction in leakage over time.

"We believe that’s why we did not find an association in the study between mild or moderate aortic regurgitation with respect to late-term mortality," though mortality risk was substantially higher with severe regurgitation, he said. One-year mortality rates were 86% with severe PVL and 24% with either moderate or mild PVL, compared with 18% in patients with no PVL.

The improvement in PVL rates over time may be due to use of CT angiography to select appropriate valve sizes for patients and continued expansion of the self-expanding frame over time. "That’s a remarkable finding, and it needs to be confirmed," Dr. Popma said.

The study focused on patients whose severe frailty, comorbidity, or disability put them at extreme risk of at least a 50% chance of death or irreversible morbidity within 30 days had they undergone surgical aortic valve replacement. A second U.S. pivotal trial of the CoreValve is focusing on patients at high (but not extreme) risk.

Most of the sites in the study had no experience with CoreValve before this study, Dr. Michael J. Mack noted at a press briefing. "The results are outstanding, but especially putting it in that light," said Dr. Mack, a member of the steering committee for the PARTNER trial.

Dr. Popma reported financial ties with Medtronic, which sponsored the study and makes CoreValve.

[email protected]

SAN FRANCISCO – Trans-catheter aortic valve replacement with the self-expanding CoreValve in patients at extreme surgical risk significantly reduced the rate of death or major stroke at 1 year, from 43% to 26%, in a 487-patient pivotal trial.

The CoreValve Extreme Risk study gathered data from a registry of patients with symptomatic severe aortic stenosis who attempted an iliofemoral implantation procedure with the CoreValve at 40 U.S. sites. Results were compared with an "objective performance goal" derived from two sources: a meta-analysis of five contemporary balloon valvuloplasty series that found a 43% mortality and major stroke rate at 1 year, and the 1-year rate from the PARTNER B trial in inoperable patients (Placement of Aortic Transcatheter Valves, Cohort B), which was 50% but had a lower confidence bound of 43%.

The performance-goal comparison was necessary in the current study because randomizing these patients to medical therapy in a control group is no longer an acceptable option in the United States, Dr. Jeffrey J. Popma said at the Transcatheter Cardiovascular Therapeutics annual meeting.

The 1-year all-cause mortality rate was 24%, and the cardiovascular mortality was 18%, reported Dr. Popma, professor of medicine at Harvard Medical School, Boston.

Two percent of patients developed a major stroke within 1 month and 4% did so within 1 year.

Data from a continued access study involving another 830 extreme-risk patients who received the CoreValve through an iliofemoral approach are showing even better results, with a 16% rate of mortality or major stroke at 6 months.

Among secondary endpoints at 1 year in the main study, 7% of patients developed any kind of stroke, 2% had an MI, 2% needed reintervention, 41% had bleeding that met Valve Academic Research Consortium criteria, 8% had major vascular complications, and 27% required implantation of a permanent pacemaker, Dr. Popma reported at the meeting, cosponsored by the American College of Cardiology. Ninety percent of patients improved by at least one New York Heart Association functional class and 60% improved by at least two classes at 1 year of follow-up.

Paravalvular regurgitation of any severity was seen in 53% of patients 1 month after implantation and in 33% at 1 year. Moderate paravalvular leakage (PVL) affected 9% at 1 month and 4% at 1 year, and severe PVL affected 1.6% at 1 month and no patients at 1 year, Dr. Popma said. Among the 11% of patients with moderate PVL at 1 month, 80% of those who survived to 1 year had a reduction in leakage over time.

"We believe that’s why we did not find an association in the study between mild or moderate aortic regurgitation with respect to late-term mortality," though mortality risk was substantially higher with severe regurgitation, he said. One-year mortality rates were 86% with severe PVL and 24% with either moderate or mild PVL, compared with 18% in patients with no PVL.

The improvement in PVL rates over time may be due to use of CT angiography to select appropriate valve sizes for patients and continued expansion of the self-expanding frame over time. "That’s a remarkable finding, and it needs to be confirmed," Dr. Popma said.

The study focused on patients whose severe frailty, comorbidity, or disability put them at extreme risk of at least a 50% chance of death or irreversible morbidity within 30 days had they undergone surgical aortic valve replacement. A second U.S. pivotal trial of the CoreValve is focusing on patients at high (but not extreme) risk.

Most of the sites in the study had no experience with CoreValve before this study, Dr. Michael J. Mack noted at a press briefing. "The results are outstanding, but especially putting it in that light," said Dr. Mack, a member of the steering committee for the PARTNER trial.

Dr. Popma reported financial ties with Medtronic, which sponsored the study and makes CoreValve.

[email protected]

SAN FRANCISCO – Because of significant limitations in the Food and Drug Administration’s pregnancy categories, it’s important to have another reliable resource handy to guide prescribing during pregnancy, Dr. Elizabeth S. Harleman believes.

Three out of four attendees at a conference on women’s health sponsored by the University of California, San Francisco, said that they use the FDA categories to determine a drug’s safety during pregnancy, an informal electronic poll at the meeting showed. There are good reasons for that, Dr. Harleman told the audience. The FDA categories are easily accessible, quick to read, and provide some information.

But they’re also hard to remember and don’t provide sufficient information, she added. "I think it’s going to become increasingly important, as we take care of more women with chronic diseases earlier in life, to think about the implications of conceiving while on the medications that we’re prescribing," said Dr. Harleman, of the department of medicine at the university.

The FDA categories do not provide any gradation of risk. Drugs in the A or B categories are not necessarily safer than category D drugs, she said. A medication can get a B categorization without any human data. The FDA categories give no information about dosing or the timing of administration. "If you give a drug in the first trimester, there may be very different implications than if you give a drug in the third trimester, and you can’t get that information from this classification system," she said.

There’s also no information on the change in risk from one category to another. "We don’t know if this increases the risk from 1% to 5% or from 1% to 80%," Dr. Harleman said. "It’s very hard to make an informed decision about prescribing a medication just using the FDA classification."

Approximately 60% of drugs in category X have no human data behind that classification. A drug can end up in category X simply because it has no utility during pregnancy, such as oral contraceptives. Physicians who don’t know that, however, may erroneously tell a woman who conceived while on an oral contraceptive that the drug increases her baby’s risk for malformation.

The FDA categories rarely get updated. "It’s really more of a legal system" than a helpful clinical tool, she said.

Half of pregnant women who are on medications take category C, D, or X drugs, studies have shown. One in six women of reproductive age receives a category D or X drug, mainly antibiotics, anticonvulsants, statins, benzodiazepines, or warfarin. A study of 488,175 women found that those taking category D or X drugs were no more likely to have documentation in their physicians’ charts of a discussion about contraception.

"In our hurried practices, sometimes it’s hard to remember this, but we need to think about which drugs are absolutely contraindicated and make sure that we are discussing them with our patients," Dr. Harleman said.

The main drugs to avoid during pregnancy are ACE inhibitors, tetracycline, fluoroquinolones, systemic retinoids, warfarin, valproic acid, nonsteroidal anti-inflammatory drugs, and live vaccines. "It’s a pretty short list," she said. "A lot of other drugs are safe in pregnancy; we may just not have as much familiarity with using them."

Dr. Harleman gave three pieces of advice on prescribing during pregnancy: Think hard before starting or stopping any medication. Remember that changes in blood volume and metabolism during pregnancy may mandate increased frequency of dosing or higher doses. And keep one of the following pregnancy prescribing resources available instead of relying solely on the FDA categories:

• The clinical reference tool Micromedex. It has an excellent "ReproRisk" section, she said (micromedex.com).

• Reprotox, a service of the nonprofit Reproductive Toxicology Center, Washington. It synthesizes all the published information on drug safety and provides quick-take summaries that Dr. Harleman believes are worth the low fee for use (reprotox.org/Default.aspx).

• The American College of Physicians’ "Medical Care of the Pregnant Patient," 2nd ed. (Hanover, Pa.: Sheridan Press, 2008) is a good source.

• Motherisk is a service affiliated with the Hospital for Sick Children, Toronto (motherisk.org).

• MotherToBaby is a service of the Organization of Teratology Information Specialists (mothertobaby.org).

• The reference guide "Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk," 9th ed. (Philadelphia: Lippincott Williams and Wilkins, 2011) is a good source.

• The book "Medications and Mother’s Milk" (Amarillo, Tex.: Hale Publishing, 2012) is helpful.

Dr. Harleman reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Because of significant limitations in the Food and Drug Administration’s pregnancy categories, it’s important to have another reliable resource handy to guide prescribing during pregnancy, Dr. Elizabeth S. Harleman believes.

Three out of four attendees at a conference on women’s health sponsored by the University of California, San Francisco, said that they use the FDA categories to determine a drug’s safety during pregnancy, an informal electronic poll at the meeting showed. There are good reasons for that, Dr. Harleman told the audience. The FDA categories are easily accessible, quick to read, and provide some information.

But they’re also hard to remember and don’t provide sufficient information, she added. "I think it’s going to become increasingly important, as we take care of more women with chronic diseases earlier in life, to think about the implications of conceiving while on the medications that we’re prescribing," said Dr. Harleman, of the department of medicine at the university.

The FDA categories do not provide any gradation of risk. Drugs in the A or B categories are not necessarily safer than category D drugs, she said. A medication can get a B categorization without any human data. The FDA categories give no information about dosing or the timing of administration. "If you give a drug in the first trimester, there may be very different implications than if you give a drug in the third trimester, and you can’t get that information from this classification system," she said.

There’s also no information on the change in risk from one category to another. "We don’t know if this increases the risk from 1% to 5% or from 1% to 80%," Dr. Harleman said. "It’s very hard to make an informed decision about prescribing a medication just using the FDA classification."

Approximately 60% of drugs in category X have no human data behind that classification. A drug can end up in category X simply because it has no utility during pregnancy, such as oral contraceptives. Physicians who don’t know that, however, may erroneously tell a woman who conceived while on an oral contraceptive that the drug increases her baby’s risk for malformation.

The FDA categories rarely get updated. "It’s really more of a legal system" than a helpful clinical tool, she said.

Half of pregnant women who are on medications take category C, D, or X drugs, studies have shown. One in six women of reproductive age receives a category D or X drug, mainly antibiotics, anticonvulsants, statins, benzodiazepines, or warfarin. A study of 488,175 women found that those taking category D or X drugs were no more likely to have documentation in their physicians’ charts of a discussion about contraception.

"In our hurried practices, sometimes it’s hard to remember this, but we need to think about which drugs are absolutely contraindicated and make sure that we are discussing them with our patients," Dr. Harleman said.

The main drugs to avoid during pregnancy are ACE inhibitors, tetracycline, fluoroquinolones, systemic retinoids, warfarin, valproic acid, nonsteroidal anti-inflammatory drugs, and live vaccines. "It’s a pretty short list," she said. "A lot of other drugs are safe in pregnancy; we may just not have as much familiarity with using them."

Dr. Harleman gave three pieces of advice on prescribing during pregnancy: Think hard before starting or stopping any medication. Remember that changes in blood volume and metabolism during pregnancy may mandate increased frequency of dosing or higher doses. And keep one of the following pregnancy prescribing resources available instead of relying solely on the FDA categories:

• The clinical reference tool Micromedex. It has an excellent "ReproRisk" section, she said (micromedex.com).

• Reprotox, a service of the nonprofit Reproductive Toxicology Center, Washington. It synthesizes all the published information on drug safety and provides quick-take summaries that Dr. Harleman believes are worth the low fee for use (reprotox.org/Default.aspx).

• The American College of Physicians’ "Medical Care of the Pregnant Patient," 2nd ed. (Hanover, Pa.: Sheridan Press, 2008) is a good source.

• Motherisk is a service affiliated with the Hospital for Sick Children, Toronto (motherisk.org).

• MotherToBaby is a service of the Organization of Teratology Information Specialists (mothertobaby.org).

• The reference guide "Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk," 9th ed. (Philadelphia: Lippincott Williams and Wilkins, 2011) is a good source.

• The book "Medications and Mother’s Milk" (Amarillo, Tex.: Hale Publishing, 2012) is helpful.

Dr. Harleman reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Because of significant limitations in the Food and Drug Administration’s pregnancy categories, it’s important to have another reliable resource handy to guide prescribing during pregnancy, Dr. Elizabeth S. Harleman believes.

Three out of four attendees at a conference on women’s health sponsored by the University of California, San Francisco, said that they use the FDA categories to determine a drug’s safety during pregnancy, an informal electronic poll at the meeting showed. There are good reasons for that, Dr. Harleman told the audience. The FDA categories are easily accessible, quick to read, and provide some information.

But they’re also hard to remember and don’t provide sufficient information, she added. "I think it’s going to become increasingly important, as we take care of more women with chronic diseases earlier in life, to think about the implications of conceiving while on the medications that we’re prescribing," said Dr. Harleman, of the department of medicine at the university.

The FDA categories do not provide any gradation of risk. Drugs in the A or B categories are not necessarily safer than category D drugs, she said. A medication can get a B categorization without any human data. The FDA categories give no information about dosing or the timing of administration. "If you give a drug in the first trimester, there may be very different implications than if you give a drug in the third trimester, and you can’t get that information from this classification system," she said.

There’s also no information on the change in risk from one category to another. "We don’t know if this increases the risk from 1% to 5% or from 1% to 80%," Dr. Harleman said. "It’s very hard to make an informed decision about prescribing a medication just using the FDA classification."

Approximately 60% of drugs in category X have no human data behind that classification. A drug can end up in category X simply because it has no utility during pregnancy, such as oral contraceptives. Physicians who don’t know that, however, may erroneously tell a woman who conceived while on an oral contraceptive that the drug increases her baby’s risk for malformation.

The FDA categories rarely get updated. "It’s really more of a legal system" than a helpful clinical tool, she said.

Half of pregnant women who are on medications take category C, D, or X drugs, studies have shown. One in six women of reproductive age receives a category D or X drug, mainly antibiotics, anticonvulsants, statins, benzodiazepines, or warfarin. A study of 488,175 women found that those taking category D or X drugs were no more likely to have documentation in their physicians’ charts of a discussion about contraception.

"In our hurried practices, sometimes it’s hard to remember this, but we need to think about which drugs are absolutely contraindicated and make sure that we are discussing them with our patients," Dr. Harleman said.

The main drugs to avoid during pregnancy are ACE inhibitors, tetracycline, fluoroquinolones, systemic retinoids, warfarin, valproic acid, nonsteroidal anti-inflammatory drugs, and live vaccines. "It’s a pretty short list," she said. "A lot of other drugs are safe in pregnancy; we may just not have as much familiarity with using them."

Dr. Harleman gave three pieces of advice on prescribing during pregnancy: Think hard before starting or stopping any medication. Remember that changes in blood volume and metabolism during pregnancy may mandate increased frequency of dosing or higher doses. And keep one of the following pregnancy prescribing resources available instead of relying solely on the FDA categories:

• The clinical reference tool Micromedex. It has an excellent "ReproRisk" section, she said (micromedex.com).

• Reprotox, a service of the nonprofit Reproductive Toxicology Center, Washington. It synthesizes all the published information on drug safety and provides quick-take summaries that Dr. Harleman believes are worth the low fee for use (reprotox.org/Default.aspx).

• The American College of Physicians’ "Medical Care of the Pregnant Patient," 2nd ed. (Hanover, Pa.: Sheridan Press, 2008) is a good source.

• Motherisk is a service affiliated with the Hospital for Sick Children, Toronto (motherisk.org).

• MotherToBaby is a service of the Organization of Teratology Information Specialists (mothertobaby.org).

• The reference guide "Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk," 9th ed. (Philadelphia: Lippincott Williams and Wilkins, 2011) is a good source.

• The book "Medications and Mother’s Milk" (Amarillo, Tex.: Hale Publishing, 2012) is helpful.

Dr. Harleman reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – The medical abortion regimen approved by the Food and Drug Administration is less effective and less convenient than an alternative evidence-based regimen, yet in some areas women are being denied access to the more effective regimen, Dr. Jody Steinauer said.

Some U.S. states are mandating that only the FDA-approved regimen be offered to women. "That is going to have a real impact on women’s care," she said at a conference on women’s health sponsored by the University of California, San Francisco.

The FDA-approved regimen is 92%-96% effective in causing abortions in pregnancies of less than 49 days, and in 50% of cases the abortion will be complete within 4 hours. The alternative regimen is 96%-99% effective for gestations of less than 63 days, with complete abortions in less than 4 hours in 93% of cases, said Dr. Steinauer of the university.

Sherry Boschert/Frontline Medical News

Two states – Arizona and Ohio – require that the FDA-approved regimen be used when prescribing the progesterone antagonist mifepristone for abortion, according to the Guttmacher Institute, which seeks to advance reproductive rights. Two other states – North Dakota and Oklahoma – passed similar laws that have been stayed by the courts.

Under the FDA-approved regimen, the woman is given 600 mg of mifepristone orally (three tablets of Mifeprex) in the clinic. That’s a higher dose than the 200 mg (one tablet) of mifepristone that has been shown to be effective and is also is taken in the clinic under the alternative regimen, Dr. Steinauer said. In both scenarios, the woman then goes home with pain medications to use as needed.

Two days later, according to the FDA-approved regimen, the woman is given 400 mcg of the prostaglandin misoprostol orally in the clinic to induce bleeding over the next 4-24 hours or more. "In the FDA-approved regimen as modeled by France, women have to pass the pregnancy in the clinic, so you would have to have a place for her to be bleeding," Dr. Steinauer said.

Under the alternative regimen, the woman places 800 mcg of misoprostol pills in the vagina or buccally to induce bleeding, but she can decide to take it anywhere from 6 hours to 3 days after taking the mifepristone and she can take the misoprostol at home. "There’s a lot of flexibility in when women take `miso,’ so they can decide when they will have bleeding," which can happen at home, she said.

The vaginal or buccal administration of misoprostol in the alternative regimen is "much more effective" than oral administration, she added.

The FDA regimen calls for follow-up on day 14. The alternative regimen again is more flexible, allowing follow-up in the range of days 3-14. The FDA says that the approved regimen can be used for gestations up to 7 weeks, while the gestational limit for the alternative regimen is 9 weeks.

Dr. Steinauer’s institution follows the alternative regimen. Patients may return for follow-up as soon as 3 days after taking the misoprostol, and they are instructed to call earlier if they experience unexpected symptoms.

Both the FDA regimen and the alternative regimen are safe, "and, given the higher efficacy of the evidence-based regimen," it might be safer than the FDA-approved one, she said.

On average, the alternative regimen is 97% effective, with incomplete abortion in 2% and continuing pregnancy in 1%, Dr. Steinauer said.

Studies on side effects from medical abortions show bleeding longer than 30 days in 9% of cases, bleeding before misoprostol (after mifepristone) in 21%-47%, abdominal pain requiring narcotics in 29%-73%, nausea in 20%-65%, vomiting in 10%-44%, diarrhea in 3%-29%, chills or fever in 7%-44%, headache in 27%-32%, dizziness in 12%-38%, and passage of the pregnancy before misoprostol in 4%, she said.

When asked to comment on the comparison of regimens, Dr. Eve Espey said that fewer side effects are seen with buccal or vaginal administration of misoprostol compared with taking the drug orally, and that the lower dose of mifepristone in the alternative regimen also may reduce side effects.

The comparison of regimens "is useful to clinicians who may be confused about the legal challenges to the ‘alternative’ or ‘evidence-based’ medical abortion regimen. Dr. Steinauer highlights the superiority of the alternative regimen: it uses less medication, making it less expensive with fewer side effects, and offers a more convenient schedule with fewer total visits for the patient," said Dr. Espey, an ob.gyn. at the University of New Mexico, Albuquerque. "Legal restrictions on the alternative medical abortion regimen are non–evidence based and are harmful to women."

When asked why the alternative regimen has not been reviewed by the FDA, an FDA spokeswoman responded in an e-mail, “The Agency reviews applications for changes to approved applications that are submitted by drug manufacturers.” The FDA cannot comment on whether or not it has received an application, added Andrea Fischer of the FDA’s Office of Media Affairs.

When asked to comment on moves by some politicians to restrict medical abortions to the FDA-approved regimen, she wrote, “FDA works to ensure that approved products are appropriately labeled based on data submitted in applications for the drugs’ approvals; this provides health care practitioners with accurate information about the safety and effectiveness data supporting each approval.”*

Dr. Steinauer and Dr. Espey reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

* This story was updated 1/27/2014

SAN FRANCISCO – The medical abortion regimen approved by the Food and Drug Administration is less effective and less convenient than an alternative evidence-based regimen, yet in some areas women are being denied access to the more effective regimen, Dr. Jody Steinauer said.

Some U.S. states are mandating that only the FDA-approved regimen be offered to women. "That is going to have a real impact on women’s care," she said at a conference on women’s health sponsored by the University of California, San Francisco.

The FDA-approved regimen is 92%-96% effective in causing abortions in pregnancies of less than 49 days, and in 50% of cases the abortion will be complete within 4 hours. The alternative regimen is 96%-99% effective for gestations of less than 63 days, with complete abortions in less than 4 hours in 93% of cases, said Dr. Steinauer of the university.

Sherry Boschert/Frontline Medical News

Two states – Arizona and Ohio – require that the FDA-approved regimen be used when prescribing the progesterone antagonist mifepristone for abortion, according to the Guttmacher Institute, which seeks to advance reproductive rights. Two other states – North Dakota and Oklahoma – passed similar laws that have been stayed by the courts.

Under the FDA-approved regimen, the woman is given 600 mg of mifepristone orally (three tablets of Mifeprex) in the clinic. That’s a higher dose than the 200 mg (one tablet) of mifepristone that has been shown to be effective and is also is taken in the clinic under the alternative regimen, Dr. Steinauer said. In both scenarios, the woman then goes home with pain medications to use as needed.

Two days later, according to the FDA-approved regimen, the woman is given 400 mcg of the prostaglandin misoprostol orally in the clinic to induce bleeding over the next 4-24 hours or more. "In the FDA-approved regimen as modeled by France, women have to pass the pregnancy in the clinic, so you would have to have a place for her to be bleeding," Dr. Steinauer said.

Under the alternative regimen, the woman places 800 mcg of misoprostol pills in the vagina or buccally to induce bleeding, but she can decide to take it anywhere from 6 hours to 3 days after taking the mifepristone and she can take the misoprostol at home. "There’s a lot of flexibility in when women take `miso,’ so they can decide when they will have bleeding," which can happen at home, she said.

The vaginal or buccal administration of misoprostol in the alternative regimen is "much more effective" than oral administration, she added.

The FDA regimen calls for follow-up on day 14. The alternative regimen again is more flexible, allowing follow-up in the range of days 3-14. The FDA says that the approved regimen can be used for gestations up to 7 weeks, while the gestational limit for the alternative regimen is 9 weeks.

Dr. Steinauer’s institution follows the alternative regimen. Patients may return for follow-up as soon as 3 days after taking the misoprostol, and they are instructed to call earlier if they experience unexpected symptoms.

Both the FDA regimen and the alternative regimen are safe, "and, given the higher efficacy of the evidence-based regimen," it might be safer than the FDA-approved one, she said.

On average, the alternative regimen is 97% effective, with incomplete abortion in 2% and continuing pregnancy in 1%, Dr. Steinauer said.

Studies on side effects from medical abortions show bleeding longer than 30 days in 9% of cases, bleeding before misoprostol (after mifepristone) in 21%-47%, abdominal pain requiring narcotics in 29%-73%, nausea in 20%-65%, vomiting in 10%-44%, diarrhea in 3%-29%, chills or fever in 7%-44%, headache in 27%-32%, dizziness in 12%-38%, and passage of the pregnancy before misoprostol in 4%, she said.

When asked to comment on the comparison of regimens, Dr. Eve Espey said that fewer side effects are seen with buccal or vaginal administration of misoprostol compared with taking the drug orally, and that the lower dose of mifepristone in the alternative regimen also may reduce side effects.

The comparison of regimens "is useful to clinicians who may be confused about the legal challenges to the ‘alternative’ or ‘evidence-based’ medical abortion regimen. Dr. Steinauer highlights the superiority of the alternative regimen: it uses less medication, making it less expensive with fewer side effects, and offers a more convenient schedule with fewer total visits for the patient," said Dr. Espey, an ob.gyn. at the University of New Mexico, Albuquerque. "Legal restrictions on the alternative medical abortion regimen are non–evidence based and are harmful to women."

When asked why the alternative regimen has not been reviewed by the FDA, an FDA spokeswoman responded in an e-mail, “The Agency reviews applications for changes to approved applications that are submitted by drug manufacturers.” The FDA cannot comment on whether or not it has received an application, added Andrea Fischer of the FDA’s Office of Media Affairs.

When asked to comment on moves by some politicians to restrict medical abortions to the FDA-approved regimen, she wrote, “FDA works to ensure that approved products are appropriately labeled based on data submitted in applications for the drugs’ approvals; this provides health care practitioners with accurate information about the safety and effectiveness data supporting each approval.”*

Dr. Steinauer and Dr. Espey reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

* This story was updated 1/27/2014

SAN FRANCISCO – The medical abortion regimen approved by the Food and Drug Administration is less effective and less convenient than an alternative evidence-based regimen, yet in some areas women are being denied access to the more effective regimen, Dr. Jody Steinauer said.

Some U.S. states are mandating that only the FDA-approved regimen be offered to women. "That is going to have a real impact on women’s care," she said at a conference on women’s health sponsored by the University of California, San Francisco.

The FDA-approved regimen is 92%-96% effective in causing abortions in pregnancies of less than 49 days, and in 50% of cases the abortion will be complete within 4 hours. The alternative regimen is 96%-99% effective for gestations of less than 63 days, with complete abortions in less than 4 hours in 93% of cases, said Dr. Steinauer of the university.

Sherry Boschert/Frontline Medical News

Two states – Arizona and Ohio – require that the FDA-approved regimen be used when prescribing the progesterone antagonist mifepristone for abortion, according to the Guttmacher Institute, which seeks to advance reproductive rights. Two other states – North Dakota and Oklahoma – passed similar laws that have been stayed by the courts.

Under the FDA-approved regimen, the woman is given 600 mg of mifepristone orally (three tablets of Mifeprex) in the clinic. That’s a higher dose than the 200 mg (one tablet) of mifepristone that has been shown to be effective and is also is taken in the clinic under the alternative regimen, Dr. Steinauer said. In both scenarios, the woman then goes home with pain medications to use as needed.

Two days later, according to the FDA-approved regimen, the woman is given 400 mcg of the prostaglandin misoprostol orally in the clinic to induce bleeding over the next 4-24 hours or more. "In the FDA-approved regimen as modeled by France, women have to pass the pregnancy in the clinic, so you would have to have a place for her to be bleeding," Dr. Steinauer said.

Under the alternative regimen, the woman places 800 mcg of misoprostol pills in the vagina or buccally to induce bleeding, but she can decide to take it anywhere from 6 hours to 3 days after taking the mifepristone and she can take the misoprostol at home. "There’s a lot of flexibility in when women take `miso,’ so they can decide when they will have bleeding," which can happen at home, she said.

The vaginal or buccal administration of misoprostol in the alternative regimen is "much more effective" than oral administration, she added.

The FDA regimen calls for follow-up on day 14. The alternative regimen again is more flexible, allowing follow-up in the range of days 3-14. The FDA says that the approved regimen can be used for gestations up to 7 weeks, while the gestational limit for the alternative regimen is 9 weeks.

Dr. Steinauer’s institution follows the alternative regimen. Patients may return for follow-up as soon as 3 days after taking the misoprostol, and they are instructed to call earlier if they experience unexpected symptoms.

Both the FDA regimen and the alternative regimen are safe, "and, given the higher efficacy of the evidence-based regimen," it might be safer than the FDA-approved one, she said.

On average, the alternative regimen is 97% effective, with incomplete abortion in 2% and continuing pregnancy in 1%, Dr. Steinauer said.

Studies on side effects from medical abortions show bleeding longer than 30 days in 9% of cases, bleeding before misoprostol (after mifepristone) in 21%-47%, abdominal pain requiring narcotics in 29%-73%, nausea in 20%-65%, vomiting in 10%-44%, diarrhea in 3%-29%, chills or fever in 7%-44%, headache in 27%-32%, dizziness in 12%-38%, and passage of the pregnancy before misoprostol in 4%, she said.

When asked to comment on the comparison of regimens, Dr. Eve Espey said that fewer side effects are seen with buccal or vaginal administration of misoprostol compared with taking the drug orally, and that the lower dose of mifepristone in the alternative regimen also may reduce side effects.

The comparison of regimens "is useful to clinicians who may be confused about the legal challenges to the ‘alternative’ or ‘evidence-based’ medical abortion regimen. Dr. Steinauer highlights the superiority of the alternative regimen: it uses less medication, making it less expensive with fewer side effects, and offers a more convenient schedule with fewer total visits for the patient," said Dr. Espey, an ob.gyn. at the University of New Mexico, Albuquerque. "Legal restrictions on the alternative medical abortion regimen are non–evidence based and are harmful to women."

When asked why the alternative regimen has not been reviewed by the FDA, an FDA spokeswoman responded in an e-mail, “The Agency reviews applications for changes to approved applications that are submitted by drug manufacturers.” The FDA cannot comment on whether or not it has received an application, added Andrea Fischer of the FDA’s Office of Media Affairs.

When asked to comment on moves by some politicians to restrict medical abortions to the FDA-approved regimen, she wrote, “FDA works to ensure that approved products are appropriately labeled based on data submitted in applications for the drugs’ approvals; this provides health care practitioners with accurate information about the safety and effectiveness data supporting each approval.”*

Dr. Steinauer and Dr. Espey reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

* This story was updated 1/27/2014

SAN FRANCISCO – Two separate randomized studies of treating coronary bifurcation lesions with a two-stent strategy rather than provisional stenting produced varying results that were reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The 450-patient BIF IV (Nordic-Baltic Bifurcation Study IV) found statistically comparable 6-month rates of major adverse cardiac events in the two-stent and provisional stenting groups for the treatment of bifurcation lesions involving a large side branch. The two-stent strategy failed to meet a noninferiority endpoint at 9 months, however, in the separate 704-patient TRYTON (Tryton Bifurcation) trial compared with provisional stenting, which is the conventional strategy of stenting the main vessel and only stenting the side branch if it is compromised.

In BIF IV, at the 6-month follow-up, 1.8% of 229 patients in the two-stent group and 4.6% of 221 patients in the provisional stenting group developed one of the major adverse cardiac events (MACEs) in the primary composite endpoint: cardiac death; non–index-procedure-related myocardial infarction (MI); target-lesion revascularization; or definite stent thrombosis. The difference was not statistically significant, Dr. Indulis Kumsars and his associates reported.

Rates for individual secondary outcomes also were similar between groups, including rates for the separate MACE components and for target-vessel revascularization or for angina.

The study randomized patients at 16 European centers who had angina or non-ST elevation MI with stenosis involving the main vessel (at least 3 mm) and a true bifurcation lesion (at least 2.75 mm) in a large side branch. Average side branch lesions were significantly longer in the two-stent group (8 mm) than in the provisional stenting group (7.4 mm). Compared with the provisional stenting procedures, the two-stent procedures were significantly longer (93 vs. 74 minutes), and required more contrast volume (238 vs. 187 mL) and fluoroscopy time (23 vs. 14 minutes).

Provisional stenting has been accepted for treating most bifurcation lesions, but it had not been known whether it would work equally well in true bifurcation lesions involving a large side branch, said Dr. Kumsars of Pauls Stradins Clinical University Hospital, Riga, Latvia. The investigators had expected the two-stent technique to produce superior results.

"Longer and more complex procedures in the two-stent group did not translate into more procedural MIs," he said. Perhaps longer follow-up will identify the optimal strategy for treating true bifurcation lesions, he added.

The TRYTON trial included patients at 58 international sites with symptoms or evidence of ischemia from true bifurcation lesions involving a main coronary artery (2.5-4.0 mm) and a side branch (2.5-3.5 mm). Patients were randomized to receive a drug-eluting stent in the main vessel and provisional stenting in the side branch or the Tryton bare-metal dedicated bifurcation stent in the side branch and a drug-eluting stent in the main vessel. The Tryton stent is approved in Europe but is investigational in the United States.

At 9 months of follow-up, 12.8% in the provisional stenting group and 17.4% in the two-stent group showed target vessel failure, defined as cardiac death, target vessel MI, or target vessel revascularization. The 4.6% difference in failure rates had an upper limit of a 10.3% difference in the confidence interval, and so did not fall within the prespecified 5.5% difference to show noninferiority of one technique over the other, Dr. Martin B. Leon and his associates reported at the meeting, which was cosponsored by the American College of Cardiology.

The failure to reach clinical noninferiority was due mainly to relatively higher frequencies of small periprocedural creatinine kinase MB (CK-MB) elevations in the Tryton group, said Dr. Leon, professor of medicine at Columbia University, N.Y., and director of the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center. One of the components of the primary outcome of target vessel failure – target vessel MI – was defined as periprocedural CK-MB elevations greater than three times normal levels.

Definite or probable stent thrombosis rates were low at 9 months: 0.3% in the provisional stenting group and 0.6% in the Tryton group. Target vessel revascularization was needed in 3.6% of the provisional group and 4.7% of the Tryton group. The percent diameter stenosis in the side branch at 9 months was significantly lower in the Tryton group (31.6%) than in the control group (38.6%), a positive outcome in the main secondary outcome measure.

Eight percent of patients in the provisional stenting arm crossed over to treatment with a second stent, a relatively low proportion. "It means the site investigators adhered to rigorous crossover criteria," Dr. Leon said.

Post hoc subset analyses suggested that the 41% of patients with larger side branches (more than 2.25 mm) showed greater benefit from the two-stent approach than did other patients.

Bifurcation lesions account for 15%-20% of all coronary lesions treated by percutaneous coronary intervention, Dr. Kumsars said.

Dr. Kumsars reported having no financial disclosures. Dr. Leon reported financial associations with Abbott, Boston Scientific, and Medtronic. Tryton Medical sponsored the TRYTON study.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Two separate randomized studies of treating coronary bifurcation lesions with a two-stent strategy rather than provisional stenting produced varying results that were reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The 450-patient BIF IV (Nordic-Baltic Bifurcation Study IV) found statistically comparable 6-month rates of major adverse cardiac events in the two-stent and provisional stenting groups for the treatment of bifurcation lesions involving a large side branch. The two-stent strategy failed to meet a noninferiority endpoint at 9 months, however, in the separate 704-patient TRYTON (Tryton Bifurcation) trial compared with provisional stenting, which is the conventional strategy of stenting the main vessel and only stenting the side branch if it is compromised.

In BIF IV, at the 6-month follow-up, 1.8% of 229 patients in the two-stent group and 4.6% of 221 patients in the provisional stenting group developed one of the major adverse cardiac events (MACEs) in the primary composite endpoint: cardiac death; non–index-procedure-related myocardial infarction (MI); target-lesion revascularization; or definite stent thrombosis. The difference was not statistically significant, Dr. Indulis Kumsars and his associates reported.

Rates for individual secondary outcomes also were similar between groups, including rates for the separate MACE components and for target-vessel revascularization or for angina.

The study randomized patients at 16 European centers who had angina or non-ST elevation MI with stenosis involving the main vessel (at least 3 mm) and a true bifurcation lesion (at least 2.75 mm) in a large side branch. Average side branch lesions were significantly longer in the two-stent group (8 mm) than in the provisional stenting group (7.4 mm). Compared with the provisional stenting procedures, the two-stent procedures were significantly longer (93 vs. 74 minutes), and required more contrast volume (238 vs. 187 mL) and fluoroscopy time (23 vs. 14 minutes).

Provisional stenting has been accepted for treating most bifurcation lesions, but it had not been known whether it would work equally well in true bifurcation lesions involving a large side branch, said Dr. Kumsars of Pauls Stradins Clinical University Hospital, Riga, Latvia. The investigators had expected the two-stent technique to produce superior results.

"Longer and more complex procedures in the two-stent group did not translate into more procedural MIs," he said. Perhaps longer follow-up will identify the optimal strategy for treating true bifurcation lesions, he added.

The TRYTON trial included patients at 58 international sites with symptoms or evidence of ischemia from true bifurcation lesions involving a main coronary artery (2.5-4.0 mm) and a side branch (2.5-3.5 mm). Patients were randomized to receive a drug-eluting stent in the main vessel and provisional stenting in the side branch or the Tryton bare-metal dedicated bifurcation stent in the side branch and a drug-eluting stent in the main vessel. The Tryton stent is approved in Europe but is investigational in the United States.

At 9 months of follow-up, 12.8% in the provisional stenting group and 17.4% in the two-stent group showed target vessel failure, defined as cardiac death, target vessel MI, or target vessel revascularization. The 4.6% difference in failure rates had an upper limit of a 10.3% difference in the confidence interval, and so did not fall within the prespecified 5.5% difference to show noninferiority of one technique over the other, Dr. Martin B. Leon and his associates reported at the meeting, which was cosponsored by the American College of Cardiology.

The failure to reach clinical noninferiority was due mainly to relatively higher frequencies of small periprocedural creatinine kinase MB (CK-MB) elevations in the Tryton group, said Dr. Leon, professor of medicine at Columbia University, N.Y., and director of the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center. One of the components of the primary outcome of target vessel failure – target vessel MI – was defined as periprocedural CK-MB elevations greater than three times normal levels.

Definite or probable stent thrombosis rates were low at 9 months: 0.3% in the provisional stenting group and 0.6% in the Tryton group. Target vessel revascularization was needed in 3.6% of the provisional group and 4.7% of the Tryton group. The percent diameter stenosis in the side branch at 9 months was significantly lower in the Tryton group (31.6%) than in the control group (38.6%), a positive outcome in the main secondary outcome measure.

Eight percent of patients in the provisional stenting arm crossed over to treatment with a second stent, a relatively low proportion. "It means the site investigators adhered to rigorous crossover criteria," Dr. Leon said.

Post hoc subset analyses suggested that the 41% of patients with larger side branches (more than 2.25 mm) showed greater benefit from the two-stent approach than did other patients.

Bifurcation lesions account for 15%-20% of all coronary lesions treated by percutaneous coronary intervention, Dr. Kumsars said.

Dr. Kumsars reported having no financial disclosures. Dr. Leon reported financial associations with Abbott, Boston Scientific, and Medtronic. Tryton Medical sponsored the TRYTON study.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Two separate randomized studies of treating coronary bifurcation lesions with a two-stent strategy rather than provisional stenting produced varying results that were reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

The 450-patient BIF IV (Nordic-Baltic Bifurcation Study IV) found statistically comparable 6-month rates of major adverse cardiac events in the two-stent and provisional stenting groups for the treatment of bifurcation lesions involving a large side branch. The two-stent strategy failed to meet a noninferiority endpoint at 9 months, however, in the separate 704-patient TRYTON (Tryton Bifurcation) trial compared with provisional stenting, which is the conventional strategy of stenting the main vessel and only stenting the side branch if it is compromised.

In BIF IV, at the 6-month follow-up, 1.8% of 229 patients in the two-stent group and 4.6% of 221 patients in the provisional stenting group developed one of the major adverse cardiac events (MACEs) in the primary composite endpoint: cardiac death; non–index-procedure-related myocardial infarction (MI); target-lesion revascularization; or definite stent thrombosis. The difference was not statistically significant, Dr. Indulis Kumsars and his associates reported.

Rates for individual secondary outcomes also were similar between groups, including rates for the separate MACE components and for target-vessel revascularization or for angina.

The study randomized patients at 16 European centers who had angina or non-ST elevation MI with stenosis involving the main vessel (at least 3 mm) and a true bifurcation lesion (at least 2.75 mm) in a large side branch. Average side branch lesions were significantly longer in the two-stent group (8 mm) than in the provisional stenting group (7.4 mm). Compared with the provisional stenting procedures, the two-stent procedures were significantly longer (93 vs. 74 minutes), and required more contrast volume (238 vs. 187 mL) and fluoroscopy time (23 vs. 14 minutes).

Provisional stenting has been accepted for treating most bifurcation lesions, but it had not been known whether it would work equally well in true bifurcation lesions involving a large side branch, said Dr. Kumsars of Pauls Stradins Clinical University Hospital, Riga, Latvia. The investigators had expected the two-stent technique to produce superior results.

"Longer and more complex procedures in the two-stent group did not translate into more procedural MIs," he said. Perhaps longer follow-up will identify the optimal strategy for treating true bifurcation lesions, he added.

The TRYTON trial included patients at 58 international sites with symptoms or evidence of ischemia from true bifurcation lesions involving a main coronary artery (2.5-4.0 mm) and a side branch (2.5-3.5 mm). Patients were randomized to receive a drug-eluting stent in the main vessel and provisional stenting in the side branch or the Tryton bare-metal dedicated bifurcation stent in the side branch and a drug-eluting stent in the main vessel. The Tryton stent is approved in Europe but is investigational in the United States.

At 9 months of follow-up, 12.8% in the provisional stenting group and 17.4% in the two-stent group showed target vessel failure, defined as cardiac death, target vessel MI, or target vessel revascularization. The 4.6% difference in failure rates had an upper limit of a 10.3% difference in the confidence interval, and so did not fall within the prespecified 5.5% difference to show noninferiority of one technique over the other, Dr. Martin B. Leon and his associates reported at the meeting, which was cosponsored by the American College of Cardiology.

The failure to reach clinical noninferiority was due mainly to relatively higher frequencies of small periprocedural creatinine kinase MB (CK-MB) elevations in the Tryton group, said Dr. Leon, professor of medicine at Columbia University, N.Y., and director of the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center. One of the components of the primary outcome of target vessel failure – target vessel MI – was defined as periprocedural CK-MB elevations greater than three times normal levels.

Definite or probable stent thrombosis rates were low at 9 months: 0.3% in the provisional stenting group and 0.6% in the Tryton group. Target vessel revascularization was needed in 3.6% of the provisional group and 4.7% of the Tryton group. The percent diameter stenosis in the side branch at 9 months was significantly lower in the Tryton group (31.6%) than in the control group (38.6%), a positive outcome in the main secondary outcome measure.

Eight percent of patients in the provisional stenting arm crossed over to treatment with a second stent, a relatively low proportion. "It means the site investigators adhered to rigorous crossover criteria," Dr. Leon said.

Post hoc subset analyses suggested that the 41% of patients with larger side branches (more than 2.25 mm) showed greater benefit from the two-stent approach than did other patients.

Bifurcation lesions account for 15%-20% of all coronary lesions treated by percutaneous coronary intervention, Dr. Kumsars said.

Dr. Kumsars reported having no financial disclosures. Dr. Leon reported financial associations with Abbott, Boston Scientific, and Medtronic. Tryton Medical sponsored the TRYTON study.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Insulin use did not influence the higher risk for cardiovascular events after percutaneous coronary intervention compared with coronary artery bypass grafting in patients with diabetes and multivessel coronary disease, according to a secondary analysis of data from a 1,900-patient randomized trial.

The differences in clinical outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with a drug-eluting stent were maintained regardless of the presence or absence of insulin treatment, Dr. George D. Dangas and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

In the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial, rates for the primary outcomes (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke) were significantly higher in patients treated with PCI than in those treated with CABG – 27% vs. 19% (N. Engl. J. Med. 2012;367:2375-84).

The current analysis of data for the 1,850 patients who underwent revascularization compared the 32% who were on insulin at baseline with the 68% who were not on insulin treatment. Five-year rates for the primary endpoint were 29% in the insulin-treated group and 19% in the non–insulin-treated group, said Dr. Dangas, professor of medicine and surgery at the Icahn School of Medicine at Mount Sinai, New York.

Within both the insulin and noninsulin treatment subgroups, outcomes were worse with PCI than with CABG. In the insulin-treated subgroup, 5-year rates for the primary outcome were 32% after PCI and 24% after CABG. In the non–insulin-treated subgroup, 5-year rates for the primary outcome were 25% after PCI and 16% after CABG.

As in the main study, stroke rates were higher after CABG than with PCI in both the insulin and noninsulin groups, but rates of death, myocardial infarction, or major adverse cardiac and cerebrovascular events were higher after PCI compared with CABG. The fact that these trends appeared in both insulin and noninsulin subgroups is "something we really haven’t seen before so clearly," coinvestigator Dr. Michael E. Farkouh said at a separate press briefing

Baseline variables were very different in the insulin-treated and non–insulin-treated subgroups. "They were a sicker group of patients," said Dr. Farkouh, a cardiologist at the Icahn School of Medicine at Mount Sinai.

Patients on insulin were significantly more likely to be female and to have a higher body mass index; a longer history of diabetes; a higher hemoglobin A_1c level; higher glucose level on the day of the procedure; higher blood urea nitrogen level; and a history of hypertension, peripheral neuropathy, congestive heart failure, and acute coronary syndrome. Insulin-treated patients were less likely to be New York Heart Association class 1.

The secondary analysis was limited because the study did not randomize patients based on insulin treatment, Dr. Dangas said at the meeting, which was cosponsored by the American College of Cardiology. The differences in outcomes between the insulin and noninsulin subgroups could be due to residual confounding, insulin resistance, or side effects of insulin treatment.

Not all patients in the FREEDOM trial have reached 5 years of follow-up. "We believe that there is no interaction" between insulin and outcomes "based on our statistical analysis, but we believe longer-term follow-up will help us to define this better," Dr. Farkouh said.

Approximately 26% of U.S. diabetes patients are treated with insulin.

FREEDOM was sponsored by the National Heart, Lung, and Blood Institute. Dr. Dangas reported having no financial disclosures. Dr. Farkouh reported financial associations with Eli Lilly, Sanofi, and other companies.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Insulin use did not influence the higher risk for cardiovascular events after percutaneous coronary intervention compared with coronary artery bypass grafting in patients with diabetes and multivessel coronary disease, according to a secondary analysis of data from a 1,900-patient randomized trial.

The differences in clinical outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with a drug-eluting stent were maintained regardless of the presence or absence of insulin treatment, Dr. George D. Dangas and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

In the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial, rates for the primary outcomes (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke) were significantly higher in patients treated with PCI than in those treated with CABG – 27% vs. 19% (N. Engl. J. Med. 2012;367:2375-84).

The current analysis of data for the 1,850 patients who underwent revascularization compared the 32% who were on insulin at baseline with the 68% who were not on insulin treatment. Five-year rates for the primary endpoint were 29% in the insulin-treated group and 19% in the non–insulin-treated group, said Dr. Dangas, professor of medicine and surgery at the Icahn School of Medicine at Mount Sinai, New York.

Within both the insulin and noninsulin treatment subgroups, outcomes were worse with PCI than with CABG. In the insulin-treated subgroup, 5-year rates for the primary outcome were 32% after PCI and 24% after CABG. In the non–insulin-treated subgroup, 5-year rates for the primary outcome were 25% after PCI and 16% after CABG.

As in the main study, stroke rates were higher after CABG than with PCI in both the insulin and noninsulin groups, but rates of death, myocardial infarction, or major adverse cardiac and cerebrovascular events were higher after PCI compared with CABG. The fact that these trends appeared in both insulin and noninsulin subgroups is "something we really haven’t seen before so clearly," coinvestigator Dr. Michael E. Farkouh said at a separate press briefing

Baseline variables were very different in the insulin-treated and non–insulin-treated subgroups. "They were a sicker group of patients," said Dr. Farkouh, a cardiologist at the Icahn School of Medicine at Mount Sinai.

Patients on insulin were significantly more likely to be female and to have a higher body mass index; a longer history of diabetes; a higher hemoglobin A_1c level; higher glucose level on the day of the procedure; higher blood urea nitrogen level; and a history of hypertension, peripheral neuropathy, congestive heart failure, and acute coronary syndrome. Insulin-treated patients were less likely to be New York Heart Association class 1.

The secondary analysis was limited because the study did not randomize patients based on insulin treatment, Dr. Dangas said at the meeting, which was cosponsored by the American College of Cardiology. The differences in outcomes between the insulin and noninsulin subgroups could be due to residual confounding, insulin resistance, or side effects of insulin treatment.

Not all patients in the FREEDOM trial have reached 5 years of follow-up. "We believe that there is no interaction" between insulin and outcomes "based on our statistical analysis, but we believe longer-term follow-up will help us to define this better," Dr. Farkouh said.

Approximately 26% of U.S. diabetes patients are treated with insulin.

FREEDOM was sponsored by the National Heart, Lung, and Blood Institute. Dr. Dangas reported having no financial disclosures. Dr. Farkouh reported financial associations with Eli Lilly, Sanofi, and other companies.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Insulin use did not influence the higher risk for cardiovascular events after percutaneous coronary intervention compared with coronary artery bypass grafting in patients with diabetes and multivessel coronary disease, according to a secondary analysis of data from a 1,900-patient randomized trial.

The differences in clinical outcomes between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with a drug-eluting stent were maintained regardless of the presence or absence of insulin treatment, Dr. George D. Dangas and his associates reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

In the FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease) trial, rates for the primary outcomes (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke) were significantly higher in patients treated with PCI than in those treated with CABG – 27% vs. 19% (N. Engl. J. Med. 2012;367:2375-84).

The current analysis of data for the 1,850 patients who underwent revascularization compared the 32% who were on insulin at baseline with the 68% who were not on insulin treatment. Five-year rates for the primary endpoint were 29% in the insulin-treated group and 19% in the non–insulin-treated group, said Dr. Dangas, professor of medicine and surgery at the Icahn School of Medicine at Mount Sinai, New York.

Within both the insulin and noninsulin treatment subgroups, outcomes were worse with PCI than with CABG. In the insulin-treated subgroup, 5-year rates for the primary outcome were 32% after PCI and 24% after CABG. In the non–insulin-treated subgroup, 5-year rates for the primary outcome were 25% after PCI and 16% after CABG.

As in the main study, stroke rates were higher after CABG than with PCI in both the insulin and noninsulin groups, but rates of death, myocardial infarction, or major adverse cardiac and cerebrovascular events were higher after PCI compared with CABG. The fact that these trends appeared in both insulin and noninsulin subgroups is "something we really haven’t seen before so clearly," coinvestigator Dr. Michael E. Farkouh said at a separate press briefing

Baseline variables were very different in the insulin-treated and non–insulin-treated subgroups. "They were a sicker group of patients," said Dr. Farkouh, a cardiologist at the Icahn School of Medicine at Mount Sinai.

Patients on insulin were significantly more likely to be female and to have a higher body mass index; a longer history of diabetes; a higher hemoglobin A_1c level; higher glucose level on the day of the procedure; higher blood urea nitrogen level; and a history of hypertension, peripheral neuropathy, congestive heart failure, and acute coronary syndrome. Insulin-treated patients were less likely to be New York Heart Association class 1.

The secondary analysis was limited because the study did not randomize patients based on insulin treatment, Dr. Dangas said at the meeting, which was cosponsored by the American College of Cardiology. The differences in outcomes between the insulin and noninsulin subgroups could be due to residual confounding, insulin resistance, or side effects of insulin treatment.

Not all patients in the FREEDOM trial have reached 5 years of follow-up. "We believe that there is no interaction" between insulin and outcomes "based on our statistical analysis, but we believe longer-term follow-up will help us to define this better," Dr. Farkouh said.

Approximately 26% of U.S. diabetes patients are treated with insulin.

FREEDOM was sponsored by the National Heart, Lung, and Blood Institute. Dr. Dangas reported having no financial disclosures. Dr. Farkouh reported financial associations with Eli Lilly, Sanofi, and other companies.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Preoperative light transmission aggregometry assessments of platelet aggregation may help identify which patients on dual antiplatelet therapy are at greater risk of sustained bleeding from noncardiac surgery, a prospective study of 147 consecutive patients suggests.

The light transmission aggregometry (LTA) assessments of blood drawn immediately before noncardiac surgery were significantly lower in the 32% of patients with sustained bleeding than in the other patients.

All patients were on dual antiplatelet therapy, 95% of them on maintenance therapy with aspirin plus clopidogrel. Timing of the surgery was at the discretion of the surgeons. Treating physicians were blinded to LTA results. The mean preoperative washout period for dual antiplatelet therapy was 1.5 days. Patients had vascular (76%), orthopedic (10%), abdominal (7%), or other (7%) surgery.

The ongoing study might help define a "bleeding cutoff" measure by LTA to better individualize the timing of surgery, Dr. Wolfgang Toller and his colleagues said in a poster session at the annual meeting of the American Society of Anesthesiologists.

In general, approximately 5% of patients in their first year of dual antiplatelet therapy undergo noncardiac surgery, which creates a conundrum for management. Discontinuing dual antiplatelet therapy before noncardiac surgery has been associated with a 20% risk of major adverse cardiac events, but there’s a 20%-40% risk of moderate to severe bleeding if dual antiplatelet therapy is continued during noncardiac surgery, said Dr. Toller of the Medical University of Graz, Austria.

The 147 patients in the study underwent vascular surgery (76%), orthopedic surgery (10%), abdominal surgery (7%), or other surgical procedures (7%). All had been on P2Y12 receptor inhibitors within 7 days before surgery.

Investigators used the Chronolog 700 Lumi-Aggregometer to assess platelet aggregation in preoperative blood, using 5 mcm of adenosine diphosphate as the specific inductor for platelet aggregation.

Overall, they found an average 40% maximum change in light transmission from baseline after adding the adenosine diphosphate to blood samples. In patients with increased bleeding, however, the mean maximum change in light transmission was approximately 30% (suggesting less platelet aggregation), compared with a more than 40% change in patients who bled less from the surgery.

Dr. Toller reported having no financial disclosures.

Surgery adds risk of perioperative bleeding

Dr. Lary Robinson, FCCP, comments: The vast majority of patients on dual platelet therapy (aspirin plus another agent such as clopidogrel) have had implantation of a drug-eluting coronary stent, who need to remain on this regimen for 1 year, after which it may be safely reduced to aspirin alone in most cases. In this first year, urgent surgery, such as that needed for cancer, as well as vascular surgery for ischemia or trauma, comes with the added risk of significant perioperative bleeding.

Anesthesiologists Wolfgang Toller and associates describe using the in vitro platelet function test, called light transmission aggregometry, in 147 patients. When used just prior to surgery, the test was somewhat predictive of which patients were at elevated bleeding risk. They propose that this test may better define and individualize the timing of surgery. However, the differences in test results are small and recommendations are not yet definite. Nevertheless, refinements in testing may lead to more specific recommendations about which patients should have surgery postponed due to a much greater bleeding risk.

[email protected]

SAN FRANCISCO – Preoperative light transmission aggregometry assessments of platelet aggregation may help identify which patients on dual antiplatelet therapy are at greater risk of sustained bleeding from noncardiac surgery, a prospective study of 147 consecutive patients suggests.

The light transmission aggregometry (LTA) assessments of blood drawn immediately before noncardiac surgery were significantly lower in the 32% of patients with sustained bleeding than in the other patients.

All patients were on dual antiplatelet therapy, 95% of them on maintenance therapy with aspirin plus clopidogrel. Timing of the surgery was at the discretion of the surgeons. Treating physicians were blinded to LTA results. The mean preoperative washout period for dual antiplatelet therapy was 1.5 days. Patients had vascular (76%), orthopedic (10%), abdominal (7%), or other (7%) surgery.

The ongoing study might help define a "bleeding cutoff" measure by LTA to better individualize the timing of surgery, Dr. Wolfgang Toller and his colleagues said in a poster session at the annual meeting of the American Society of Anesthesiologists.

In general, approximately 5% of patients in their first year of dual antiplatelet therapy undergo noncardiac surgery, which creates a conundrum for management. Discontinuing dual antiplatelet therapy before noncardiac surgery has been associated with a 20% risk of major adverse cardiac events, but there’s a 20%-40% risk of moderate to severe bleeding if dual antiplatelet therapy is continued during noncardiac surgery, said Dr. Toller of the Medical University of Graz, Austria.

The 147 patients in the study underwent vascular surgery (76%), orthopedic surgery (10%), abdominal surgery (7%), or other surgical procedures (7%). All had been on P2Y12 receptor inhibitors within 7 days before surgery.

Investigators used the Chronolog 700 Lumi-Aggregometer to assess platelet aggregation in preoperative blood, using 5 mcm of adenosine diphosphate as the specific inductor for platelet aggregation.

Overall, they found an average 40% maximum change in light transmission from baseline after adding the adenosine diphosphate to blood samples. In patients with increased bleeding, however, the mean maximum change in light transmission was approximately 30% (suggesting less platelet aggregation), compared with a more than 40% change in patients who bled less from the surgery.

Dr. Toller reported having no financial disclosures.

Surgery adds risk of perioperative bleeding

Dr. Lary Robinson, FCCP, comments: The vast majority of patients on dual platelet therapy (aspirin plus another agent such as clopidogrel) have had implantation of a drug-eluting coronary stent, who need to remain on this regimen for 1 year, after which it may be safely reduced to aspirin alone in most cases. In this first year, urgent surgery, such as that needed for cancer, as well as vascular surgery for ischemia or trauma, comes with the added risk of significant perioperative bleeding.

Anesthesiologists Wolfgang Toller and associates describe using the in vitro platelet function test, called light transmission aggregometry, in 147 patients. When used just prior to surgery, the test was somewhat predictive of which patients were at elevated bleeding risk. They propose that this test may better define and individualize the timing of surgery. However, the differences in test results are small and recommendations are not yet definite. Nevertheless, refinements in testing may lead to more specific recommendations about which patients should have surgery postponed due to a much greater bleeding risk.

[email protected]

SAN FRANCISCO – Preoperative light transmission aggregometry assessments of platelet aggregation may help identify which patients on dual antiplatelet therapy are at greater risk of sustained bleeding from noncardiac surgery, a prospective study of 147 consecutive patients suggests.

The light transmission aggregometry (LTA) assessments of blood drawn immediately before noncardiac surgery were significantly lower in the 32% of patients with sustained bleeding than in the other patients.

All patients were on dual antiplatelet therapy, 95% of them on maintenance therapy with aspirin plus clopidogrel. Timing of the surgery was at the discretion of the surgeons. Treating physicians were blinded to LTA results. The mean preoperative washout period for dual antiplatelet therapy was 1.5 days. Patients had vascular (76%), orthopedic (10%), abdominal (7%), or other (7%) surgery.

The ongoing study might help define a "bleeding cutoff" measure by LTA to better individualize the timing of surgery, Dr. Wolfgang Toller and his colleagues said in a poster session at the annual meeting of the American Society of Anesthesiologists.

In general, approximately 5% of patients in their first year of dual antiplatelet therapy undergo noncardiac surgery, which creates a conundrum for management. Discontinuing dual antiplatelet therapy before noncardiac surgery has been associated with a 20% risk of major adverse cardiac events, but there’s a 20%-40% risk of moderate to severe bleeding if dual antiplatelet therapy is continued during noncardiac surgery, said Dr. Toller of the Medical University of Graz, Austria.

The 147 patients in the study underwent vascular surgery (76%), orthopedic surgery (10%), abdominal surgery (7%), or other surgical procedures (7%). All had been on P2Y12 receptor inhibitors within 7 days before surgery.

Investigators used the Chronolog 700 Lumi-Aggregometer to assess platelet aggregation in preoperative blood, using 5 mcm of adenosine diphosphate as the specific inductor for platelet aggregation.

Overall, they found an average 40% maximum change in light transmission from baseline after adding the adenosine diphosphate to blood samples. In patients with increased bleeding, however, the mean maximum change in light transmission was approximately 30% (suggesting less platelet aggregation), compared with a more than 40% change in patients who bled less from the surgery.

Dr. Toller reported having no financial disclosures.

Surgery adds risk of perioperative bleeding

Dr. Lary Robinson, FCCP, comments: The vast majority of patients on dual platelet therapy (aspirin plus another agent such as clopidogrel) have had implantation of a drug-eluting coronary stent, who need to remain on this regimen for 1 year, after which it may be safely reduced to aspirin alone in most cases. In this first year, urgent surgery, such as that needed for cancer, as well as vascular surgery for ischemia or trauma, comes with the added risk of significant perioperative bleeding.

Anesthesiologists Wolfgang Toller and associates describe using the in vitro platelet function test, called light transmission aggregometry, in 147 patients. When used just prior to surgery, the test was somewhat predictive of which patients were at elevated bleeding risk. They propose that this test may better define and individualize the timing of surgery. However, the differences in test results are small and recommendations are not yet definite. Nevertheless, refinements in testing may lead to more specific recommendations about which patients should have surgery postponed due to a much greater bleeding risk.

[email protected]