News & Analysis
Myocardial Infarction Risks Remain for Patients Undergoing Noncardiac Elective Surgery Mike Mitka, MSJ
Leeds Teaching Hosptial NHS Trust/www.sciencesource.com
W
ashington, DC—Recent efforts to reduce the not uncommon risk of myocardial infarction in patients undergoing noncardiac surgery have turned up empty. Researchers presenting findings at the Scientific Sessions of the American College of Cardiology (ACC) in March from 2 studies using aspirin or clonidine found no reduction in the rate of composite death or nonfatal myocardial infarction among patients undergoing surgery for problems not related to cardiac problems. The findings were from the Perioperative Ischemic Evaluation (POISE-2) studies, a blinded and randomized trial with a 2-by-2 factorial design allowing for comparisons of low-dose aspirin vs placebo or low-dose clonidine vs placebo in 10 010 patients treated at 135 centers in 23 countries. Many of these researchers were also involved in the original POISE trial, which found use of a β-blocker (extended-release metoprolol succinate) in patients undergoing noncardiac surgery did reduce risk of cardiac death, nonfatal myocardial infarction, or cardiac arrest, but it did so at the expense of increased risk of total mortality and stroke (Devereaux PJ et al. Lancet. 2008; 371[9627]:1839-1847). Because noncardiac surgery is associated with platelet activation that can result in thrombus formation, the POISE-2 researchers hypothesized that platelet activation might be the mechanism underlying perioperative myocardial infarction and that aspirin, which inhibits platelet aggregation, might stop this cascade of events. The selection of clonidine as a potential intervention targeted a different potential mechanism. During and after noncardiac surgery, the sympathetic nervous system is markedly activated, which can lead to a mismatch between the supply and demand for myocardial oxygen and subsequent myocardial infarction. The researchers hypothesized that use of an α2-adrenergic agonist (clonidine), which blunts the sympathetic nervous system activation, might prevent perioperative myocardial infarction.
In the aspirin study, 5628 patients were randomly assigned to receive either aspirin (200 mg just before surgery followed by 100 mg of aspirin daily for 30 days postsurgery) or placebo. Another 4998 patients who were already taking aspirin were randomly assigned to continue aspirin therapy or to take a placebo instead. At 30 days, 351 of 4998 patients (7.0%) in the aspirin group and 2355 of 5012 patients (7.1%) in the placebo group died or had a nonfatal myocardial infarction, a nonsignificant difference of the primary end point. However, major bleeding was more common in the aspirin group (230 patients [4.6%]) compared with placebo group (188 patients [3.8%]), suggesting a 23% increased risk with aspirin therapy (Devereaux PJ et al. N Engl J Med. doi:10.1056/NEJMoa1401105 [published online March 31, 2014]). For the clonidine study, 10 010 patients were randomly assigned to receive clonidine (0.2 mg just before surgery and then daily for 7 days postsurgery) or placebo. At 30 days, 367 patients taking clonidine and 339 patients who received placebo died or had a nonfatal myocardial infarction, a nonsignificant difference of the primary end point. However, 2385 patients
taking clonidine (47.6%) had clinically important hypotension compared with 1854 patients (37.1%) receiving placebo, suggesting a 32% increased risk with clonidine. Cardiac arrest occurred in 16 patients (0.3%) in the clonidine group compared with 5 patients (0.1%) in the placebo group (Devereaux PJ et al. N Engl J Med. doi:10.1056 /NEJMoa1401106 [published online March 31, 2014]). P. J. Devereaux, MD, lead author of all 3 POISE studies and an associate professor in the department of Clinical Epidemiology and Biostatistics at McMaster University in Hamilton, Ontario, Canada, said his research team is not ready to give up on the search for treatment to reduce myocardial infarction risk for patients undergoing noncardiac surgery. “I think there’s something to do with the sympathetic nervous system that is worthwhile to keep exploring,” Devereaux said. “βblockers do work in that they prevent myocardial infarction and we should not ignore that signal. While we got less hypotension with clonidine relative to the β-blockers, we didn’t get the heart rate control we got with the β-blockers.” β-blockers decrease the effects of increased catecholamine levels, which can
Efforts to reduce the risk of myocardial infarction in patients during noncardiac surgery remain unsuccessful.
jama.com
JAMA May 21, 2014 Volume 311, Number 19
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of St. Andrews Library User on 05/15/2015
1955
News & Analysis
Kim A. Eagle, MD, who cowrote an editorial accompanying the POISE-2 studies, acknowledged the dynamics at play during surgery. “The idea that we can systematically alter the blood pressure response and heart rate response in a way that reliably reduces heart events without harm appears very difficult to achieve,” said Eagle, director of the Cardiovascular Center at the University of Michigan Health System in Ann Arbor. Eagle said it’s important to get back to basics when preparing a patient for elective noncardiac surgery. “We need to go back to bedside medicine and taking careful histories,” Eagle said. “What we want to do is identify unsuspected or undertreated heart disease and make sure we’re giving patients the best medical treatment we can based on whatever knowledge we have.”
FDA Warns Against Procedure Used in Removing Fibroids Joan Stephenson, PhD
T
he US Food and Drug Administration (FDA) is discouraging the use of a surgical technique often used during minimally invasive surgery to treat uterine fibroids because it poses a risk of inadvertently spreading cancer cells from an undetected uterine tumor. “Health care providers and patients should carefully consider available alternative treatment options for symptomatic uterine fibroids,” the FDA said. The focus of the agency’s concern is the use of electric or power morcellators during laparoscopic surgery to cut uterine tissue or fibroids into fragments that can be removed through the small incisions used in minimally invasive surgery. In a safety communication released on April 17, the FDA said that based on its analysis of currently available data, 1 in 350 women who are treated for fibroids with a hysterectomy or myomectomy is found to have an unsuspected uterine sarcoma, such as a leiomyosarcoma.
1956
“If power morcellation is performed in women with unsuspected uterine sarcoma, there is a risk that the procedure will spread the cancerous tissue within the abdomen and pelvis, significantly worsening the patient’s likelihood of long-term survival,”theFDAsaid.“Forthisreason,andbecause there is no reliable method for predicting whether a woman with fibroids may have a uterine sarcoma, the FDA discourages the use of laparoscopic power morcellation during hysterectomy or myomectomy for uterine fibroids.” In recent months, some critics of the procedure have said that use of the technique may be too risky, whereas others said that more research on risks was needed before banning it outright (Hampton T. JAMA. 2014;311[9]:891-893). Some prominent US medical centers, including Brigham and Women’s Hospital, Massachusetts General Hospital, and the Cleveland Clinic, issued statements stressing the importance of counseling patients about the procedure and potential risks.
news@JAMA FROM JAMA’S DAILY NEWS SITE
Stimulant Use and Obesity in Children With ADHD Long-term use of stimulants to treat children with attention-deficit/hyperactivity disorder (ADHD) may contribute to higher rates of obesity later in youth, according to new research. Children with unmedicated ADHD tended to have higher body mass index (BMI) than those without a diagnosis. In contrast, children who were treated with stimulant medications had lower-than-average BMIs, but their BMIs rebounded later in childhood, with longer duration of treatment associated with a steep increase. Those with the diagnosis but no medication leveled off after age 15 years. “Our findings should motivate greater attention to the possibility that longer-term stimulant use plays a role in the development of obesity in children,” the authors stated. http://jama.md/1lCp79A Preventing Falls Among Older Adults A simple, inexpensive program at senior community centers can help prevent falls among older adults. Pennsylvania’s Department of Aging has offered a free program to all adults aged 50 years or older throughout the state since 2007. Participants receive assessments of their balance and mobility and a referral for physician care or a home safety evaluation if their scores are below the norms for their age and sex. The program also includes a class with information about household hazards and exercises designed to improve balance and mobility. After a year of follow-up, the incidence of falls was 17% lower. http://jama.md/QvBHJP New Insights Into Genes and Obesity Researchers have found that potentially modifiable chemical tagging of a particular gene is associated with obesity in humans, a finding that underscores the complex roots of obesity involving interactions among lifestyle, genetics, and the environment. The new work reveals that tagging by DNA methylation of a specific gene involved in oxygen metabolism and energy expenditure appears to be highly linked to body mass index in a large population of Europeans. Understanding the role such changes play could “identify novel therapeutic targets” for this widespread condition, the authors said. http://jama.md/1rfVH06
For more on these stories and other medical news, visit http://newsatjama.jama.com.
JAMA May 21, 2014 Volume 311, Number 19
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of St. Andrews Library User on 05/15/2015
jama.com
©iStock.com/ Edward Samuel Cornwall
increase heart rate, blood pressure, and free fatty acids released during sympathetic nervous system agitation. Devereaux’s team is launching POISE-3 to study whether ivabradine or tranexamic acid will decrease myocardial infarction risk in patients undergoing noncardiac surgery. “I remain optimistic that we will crack this case.” Offering a surgeon’s perspective, Mary T. Hawn, MD, a professor of surgery at the University of Alabama at Birmingham, said she was especially interested in the aspirin results, as many of her patients are already taking aspirin. “I still think there’s a major question for many of us about patients on aspirin,” Hawn said. “So really, it’s back to just good clinical judgment. If bleeding risk is low and a chance for a cardiac event high, then maybe continue antiplatelet therapy, but if it’s the reverse, there may be harm in continuing antiplatelet therapy.”
Myocardial Infarction Risks Remain for Patients Undergoing Noncardiac Elective Surgery Mike Mitka, MSJ
Leeds Teaching Hosptial NHS Trust/www.sciencesource.com
W
ashington, DC—Recent efforts to reduce the not uncommon risk of myocardial infarction in patients undergoing noncardiac surgery have turned up empty. Researchers presenting findings at the Scientific Sessions of the American College of Cardiology (ACC) in March from 2 studies using aspirin or clonidine found no reduction in the rate of composite death or nonfatal myocardial infarction among patients undergoing surgery for problems not related to cardiac problems. The findings were from the Perioperative Ischemic Evaluation (POISE-2) studies, a blinded and randomized trial with a 2-by-2 factorial design allowing for comparisons of low-dose aspirin vs placebo or low-dose clonidine vs placebo in 10 010 patients treated at 135 centers in 23 countries. Many of these researchers were also involved in the original POISE trial, which found use of a β-blocker (extended-release metoprolol succinate) in patients undergoing noncardiac surgery did reduce risk of cardiac death, nonfatal myocardial infarction, or cardiac arrest, but it did so at the expense of increased risk of total mortality and stroke (Devereaux PJ et al. Lancet. 2008; 371[9627]:1839-1847). Because noncardiac surgery is associated with platelet activation that can result in thrombus formation, the POISE-2 researchers hypothesized that platelet activation might be the mechanism underlying perioperative myocardial infarction and that aspirin, which inhibits platelet aggregation, might stop this cascade of events. The selection of clonidine as a potential intervention targeted a different potential mechanism. During and after noncardiac surgery, the sympathetic nervous system is markedly activated, which can lead to a mismatch between the supply and demand for myocardial oxygen and subsequent myocardial infarction. The researchers hypothesized that use of an α2-adrenergic agonist (clonidine), which blunts the sympathetic nervous system activation, might prevent perioperative myocardial infarction.
In the aspirin study, 5628 patients were randomly assigned to receive either aspirin (200 mg just before surgery followed by 100 mg of aspirin daily for 30 days postsurgery) or placebo. Another 4998 patients who were already taking aspirin were randomly assigned to continue aspirin therapy or to take a placebo instead. At 30 days, 351 of 4998 patients (7.0%) in the aspirin group and 2355 of 5012 patients (7.1%) in the placebo group died or had a nonfatal myocardial infarction, a nonsignificant difference of the primary end point. However, major bleeding was more common in the aspirin group (230 patients [4.6%]) compared with placebo group (188 patients [3.8%]), suggesting a 23% increased risk with aspirin therapy (Devereaux PJ et al. N Engl J Med. doi:10.1056/NEJMoa1401105 [published online March 31, 2014]). For the clonidine study, 10 010 patients were randomly assigned to receive clonidine (0.2 mg just before surgery and then daily for 7 days postsurgery) or placebo. At 30 days, 367 patients taking clonidine and 339 patients who received placebo died or had a nonfatal myocardial infarction, a nonsignificant difference of the primary end point. However, 2385 patients
taking clonidine (47.6%) had clinically important hypotension compared with 1854 patients (37.1%) receiving placebo, suggesting a 32% increased risk with clonidine. Cardiac arrest occurred in 16 patients (0.3%) in the clonidine group compared with 5 patients (0.1%) in the placebo group (Devereaux PJ et al. N Engl J Med. doi:10.1056 /NEJMoa1401106 [published online March 31, 2014]). P. J. Devereaux, MD, lead author of all 3 POISE studies and an associate professor in the department of Clinical Epidemiology and Biostatistics at McMaster University in Hamilton, Ontario, Canada, said his research team is not ready to give up on the search for treatment to reduce myocardial infarction risk for patients undergoing noncardiac surgery. “I think there’s something to do with the sympathetic nervous system that is worthwhile to keep exploring,” Devereaux said. “βblockers do work in that they prevent myocardial infarction and we should not ignore that signal. While we got less hypotension with clonidine relative to the β-blockers, we didn’t get the heart rate control we got with the β-blockers.” β-blockers decrease the effects of increased catecholamine levels, which can
Efforts to reduce the risk of myocardial infarction in patients during noncardiac surgery remain unsuccessful.
jama.com
JAMA May 21, 2014 Volume 311, Number 19
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of St. Andrews Library User on 05/15/2015
1955
News & Analysis
Kim A. Eagle, MD, who cowrote an editorial accompanying the POISE-2 studies, acknowledged the dynamics at play during surgery. “The idea that we can systematically alter the blood pressure response and heart rate response in a way that reliably reduces heart events without harm appears very difficult to achieve,” said Eagle, director of the Cardiovascular Center at the University of Michigan Health System in Ann Arbor. Eagle said it’s important to get back to basics when preparing a patient for elective noncardiac surgery. “We need to go back to bedside medicine and taking careful histories,” Eagle said. “What we want to do is identify unsuspected or undertreated heart disease and make sure we’re giving patients the best medical treatment we can based on whatever knowledge we have.”
FDA Warns Against Procedure Used in Removing Fibroids Joan Stephenson, PhD
T
he US Food and Drug Administration (FDA) is discouraging the use of a surgical technique often used during minimally invasive surgery to treat uterine fibroids because it poses a risk of inadvertently spreading cancer cells from an undetected uterine tumor. “Health care providers and patients should carefully consider available alternative treatment options for symptomatic uterine fibroids,” the FDA said. The focus of the agency’s concern is the use of electric or power morcellators during laparoscopic surgery to cut uterine tissue or fibroids into fragments that can be removed through the small incisions used in minimally invasive surgery. In a safety communication released on April 17, the FDA said that based on its analysis of currently available data, 1 in 350 women who are treated for fibroids with a hysterectomy or myomectomy is found to have an unsuspected uterine sarcoma, such as a leiomyosarcoma.
1956
“If power morcellation is performed in women with unsuspected uterine sarcoma, there is a risk that the procedure will spread the cancerous tissue within the abdomen and pelvis, significantly worsening the patient’s likelihood of long-term survival,”theFDAsaid.“Forthisreason,andbecause there is no reliable method for predicting whether a woman with fibroids may have a uterine sarcoma, the FDA discourages the use of laparoscopic power morcellation during hysterectomy or myomectomy for uterine fibroids.” In recent months, some critics of the procedure have said that use of the technique may be too risky, whereas others said that more research on risks was needed before banning it outright (Hampton T. JAMA. 2014;311[9]:891-893). Some prominent US medical centers, including Brigham and Women’s Hospital, Massachusetts General Hospital, and the Cleveland Clinic, issued statements stressing the importance of counseling patients about the procedure and potential risks.
news@JAMA FROM JAMA’S DAILY NEWS SITE
Stimulant Use and Obesity in Children With ADHD Long-term use of stimulants to treat children with attention-deficit/hyperactivity disorder (ADHD) may contribute to higher rates of obesity later in youth, according to new research. Children with unmedicated ADHD tended to have higher body mass index (BMI) than those without a diagnosis. In contrast, children who were treated with stimulant medications had lower-than-average BMIs, but their BMIs rebounded later in childhood, with longer duration of treatment associated with a steep increase. Those with the diagnosis but no medication leveled off after age 15 years. “Our findings should motivate greater attention to the possibility that longer-term stimulant use plays a role in the development of obesity in children,” the authors stated. http://jama.md/1lCp79A Preventing Falls Among Older Adults A simple, inexpensive program at senior community centers can help prevent falls among older adults. Pennsylvania’s Department of Aging has offered a free program to all adults aged 50 years or older throughout the state since 2007. Participants receive assessments of their balance and mobility and a referral for physician care or a home safety evaluation if their scores are below the norms for their age and sex. The program also includes a class with information about household hazards and exercises designed to improve balance and mobility. After a year of follow-up, the incidence of falls was 17% lower. http://jama.md/QvBHJP New Insights Into Genes and Obesity Researchers have found that potentially modifiable chemical tagging of a particular gene is associated with obesity in humans, a finding that underscores the complex roots of obesity involving interactions among lifestyle, genetics, and the environment. The new work reveals that tagging by DNA methylation of a specific gene involved in oxygen metabolism and energy expenditure appears to be highly linked to body mass index in a large population of Europeans. Understanding the role such changes play could “identify novel therapeutic targets” for this widespread condition, the authors said. http://jama.md/1rfVH06
For more on these stories and other medical news, visit http://newsatjama.jama.com.
JAMA May 21, 2014 Volume 311, Number 19
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a University of St. Andrews Library User on 05/15/2015
jama.com
©iStock.com/ Edward Samuel Cornwall
increase heart rate, blood pressure, and free fatty acids released during sympathetic nervous system agitation. Devereaux’s team is launching POISE-3 to study whether ivabradine or tranexamic acid will decrease myocardial infarction risk in patients undergoing noncardiac surgery. “I remain optimistic that we will crack this case.” Offering a surgeon’s perspective, Mary T. Hawn, MD, a professor of surgery at the University of Alabama at Birmingham, said she was especially interested in the aspirin results, as many of her patients are already taking aspirin. “I still think there’s a major question for many of us about patients on aspirin,” Hawn said. “So really, it’s back to just good clinical judgment. If bleeding risk is low and a chance for a cardiac event high, then maybe continue antiplatelet therapy, but if it’s the reverse, there may be harm in continuing antiplatelet therapy.”
