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Support for minimally invasive mitral valve repair: Mini Mitral published
The trial, which was first presented earlier this year at the American College of Cardiology meeting, showed that minimally invasive mitral valve repair does not improve physical function at 12 weeks, compared with sternotomy, but outcomes at 1 year show minimally invasive repair is as safe and effective as sternotomy for degenerative mitral regurgitation.
The full results are now published online in JAMA.
The authors, led by Enoch Akowuah, MD, South Tees Hospitals NHS Foundation Trust, Middlesbrough, United Kingdom, explain that mitral valve repair surgery is the preferred treatment for patients with degenerative mitral regurgitation and is routinely performed via full sternotomy, enabling easy access to the heart, flexibility in myocardial protection strategies, and multiple ways of accessing the mitral valve and easing de-airing to prevent air emboli, which cause cerebrovascular accidents.
However, the invasiveness of sternotomy is associated with delayed return to presurgery physical function levels and an increase in postoperative complications.
An alternative new video-guided minimally invasive approach involving a 4- to 7-cm lateral thoracotomy, completely avoiding sternotomy, has been developed, with the hope that it should speed physical recovery function after surgery and reduce postoperative complications and costs by reducing hospital stay.
Dr. Akowuah et al. note that uptake of minithoracotomy is variable, with low rates in the United States and the United Kingdom but high rates in Germany. They say that this variation is attributable to the absence of high-quality evidence from randomized trials demonstrating equivalent or superior benefits, compared with sternotomy, and there are also concerns that the increased technical complexity of minithoracotomy may impair the ability to repair complex valve lesions or increase perioperative complications, particularly vascular injuries and stroke.
The U.K. Mini Mitral trial was therefore conducted to compare the effectiveness and safety of minithoracotomy versus sternotomy mitral valve repair.
For the trial, 330 patients with degenerative mitral regurgitation were randomized to receive either minithoracotomy or sternotomy mitral valve repair performed by an expert surgeon.
The primary outcome was physical functioning and associated return to usual activities measured by change from baseline in the 36-Item Short Form Health Survey (SF-36) physical functioning scale 12 weeks after the surgery.
This failed to show superiority of minithoracotomy, with a mean difference of 0.68 (95% confidence interval, −1.89 to 3.26) between the two groups.
Analysis of secondary outcomes demonstrated that time spent undertaking moderate to vigorous physical activity was higher among participants receiving minithoracotomy at 6 weeks, although the treatment effect was small at an average of 9 minutes and was not different at 12 weeks.
Postoperative length of hospital stay was reduced after minithoracotomy by 1 day, with a median of 5 days, compared with 6 days after sternotomy.
Although repair techniques were at the discretion of the surgeons and differed between the two procedures, high rates of valve repair and low rates of recurrent mitral regurgitation were observed in both groups. Cardiopulmonary bypass times were longer with minithoracotomy, but postoperative complications and adverse events were similar.
There was no difference between the two groups with respect to the prespecified safety outcome of death, repeat mitral valve surgery, or heart failure hospitalization up to 1 year, which occurred in 5.4% of patients undergoing minithoracotomy and 6.1% of those undergoing sternotomy.
“These findings can inform shared decision-making and treatment guidelines,” the authors conclude.
Approach ‘may appeal to patients’
In an editorial accompanying the publication of the study in JAMA, Maurice Enriquez-Sarano, MD, Minneapolis Heart Institute, Minnesota, says the results should be integrated into patient management.
“Mini-thoracotomy mitral repair carried low risk and was highly effective compared with sternotomy. It can thus be applied successfully by surgeons who achieve the necessary expertise,” he notes.
“Mini-thoracotomy may appeal to patients because the procedure is less disfiguring than sternotomy. The early (6-week) benefit, albeit small and transient, is important to patients,” he adds.
The study was funded by the United Kingdom’s National Institute for Health and Care Research. Dr. Akowuah reports no relevant financial relationships with industry. Dr. Enriquez-Sarano reports receiving consulting fees from Edwards Lifesciences, Artivion, ChemImage, HighLife, and Corcym.
A version of this article first appeared on Medscape.com.
The trial, which was first presented earlier this year at the American College of Cardiology meeting, showed that minimally invasive mitral valve repair does not improve physical function at 12 weeks, compared with sternotomy, but outcomes at 1 year show minimally invasive repair is as safe and effective as sternotomy for degenerative mitral regurgitation.
The full results are now published online in JAMA.
The authors, led by Enoch Akowuah, MD, South Tees Hospitals NHS Foundation Trust, Middlesbrough, United Kingdom, explain that mitral valve repair surgery is the preferred treatment for patients with degenerative mitral regurgitation and is routinely performed via full sternotomy, enabling easy access to the heart, flexibility in myocardial protection strategies, and multiple ways of accessing the mitral valve and easing de-airing to prevent air emboli, which cause cerebrovascular accidents.
However, the invasiveness of sternotomy is associated with delayed return to presurgery physical function levels and an increase in postoperative complications.
An alternative new video-guided minimally invasive approach involving a 4- to 7-cm lateral thoracotomy, completely avoiding sternotomy, has been developed, with the hope that it should speed physical recovery function after surgery and reduce postoperative complications and costs by reducing hospital stay.
Dr. Akowuah et al. note that uptake of minithoracotomy is variable, with low rates in the United States and the United Kingdom but high rates in Germany. They say that this variation is attributable to the absence of high-quality evidence from randomized trials demonstrating equivalent or superior benefits, compared with sternotomy, and there are also concerns that the increased technical complexity of minithoracotomy may impair the ability to repair complex valve lesions or increase perioperative complications, particularly vascular injuries and stroke.
The U.K. Mini Mitral trial was therefore conducted to compare the effectiveness and safety of minithoracotomy versus sternotomy mitral valve repair.
For the trial, 330 patients with degenerative mitral regurgitation were randomized to receive either minithoracotomy or sternotomy mitral valve repair performed by an expert surgeon.
The primary outcome was physical functioning and associated return to usual activities measured by change from baseline in the 36-Item Short Form Health Survey (SF-36) physical functioning scale 12 weeks after the surgery.
This failed to show superiority of minithoracotomy, with a mean difference of 0.68 (95% confidence interval, −1.89 to 3.26) between the two groups.
Analysis of secondary outcomes demonstrated that time spent undertaking moderate to vigorous physical activity was higher among participants receiving minithoracotomy at 6 weeks, although the treatment effect was small at an average of 9 minutes and was not different at 12 weeks.
Postoperative length of hospital stay was reduced after minithoracotomy by 1 day, with a median of 5 days, compared with 6 days after sternotomy.
Although repair techniques were at the discretion of the surgeons and differed between the two procedures, high rates of valve repair and low rates of recurrent mitral regurgitation were observed in both groups. Cardiopulmonary bypass times were longer with minithoracotomy, but postoperative complications and adverse events were similar.
There was no difference between the two groups with respect to the prespecified safety outcome of death, repeat mitral valve surgery, or heart failure hospitalization up to 1 year, which occurred in 5.4% of patients undergoing minithoracotomy and 6.1% of those undergoing sternotomy.
“These findings can inform shared decision-making and treatment guidelines,” the authors conclude.
Approach ‘may appeal to patients’
In an editorial accompanying the publication of the study in JAMA, Maurice Enriquez-Sarano, MD, Minneapolis Heart Institute, Minnesota, says the results should be integrated into patient management.
“Mini-thoracotomy mitral repair carried low risk and was highly effective compared with sternotomy. It can thus be applied successfully by surgeons who achieve the necessary expertise,” he notes.
“Mini-thoracotomy may appeal to patients because the procedure is less disfiguring than sternotomy. The early (6-week) benefit, albeit small and transient, is important to patients,” he adds.
The study was funded by the United Kingdom’s National Institute for Health and Care Research. Dr. Akowuah reports no relevant financial relationships with industry. Dr. Enriquez-Sarano reports receiving consulting fees from Edwards Lifesciences, Artivion, ChemImage, HighLife, and Corcym.
A version of this article first appeared on Medscape.com.
The trial, which was first presented earlier this year at the American College of Cardiology meeting, showed that minimally invasive mitral valve repair does not improve physical function at 12 weeks, compared with sternotomy, but outcomes at 1 year show minimally invasive repair is as safe and effective as sternotomy for degenerative mitral regurgitation.
The full results are now published online in JAMA.
The authors, led by Enoch Akowuah, MD, South Tees Hospitals NHS Foundation Trust, Middlesbrough, United Kingdom, explain that mitral valve repair surgery is the preferred treatment for patients with degenerative mitral regurgitation and is routinely performed via full sternotomy, enabling easy access to the heart, flexibility in myocardial protection strategies, and multiple ways of accessing the mitral valve and easing de-airing to prevent air emboli, which cause cerebrovascular accidents.
However, the invasiveness of sternotomy is associated with delayed return to presurgery physical function levels and an increase in postoperative complications.
An alternative new video-guided minimally invasive approach involving a 4- to 7-cm lateral thoracotomy, completely avoiding sternotomy, has been developed, with the hope that it should speed physical recovery function after surgery and reduce postoperative complications and costs by reducing hospital stay.
Dr. Akowuah et al. note that uptake of minithoracotomy is variable, with low rates in the United States and the United Kingdom but high rates in Germany. They say that this variation is attributable to the absence of high-quality evidence from randomized trials demonstrating equivalent or superior benefits, compared with sternotomy, and there are also concerns that the increased technical complexity of minithoracotomy may impair the ability to repair complex valve lesions or increase perioperative complications, particularly vascular injuries and stroke.
The U.K. Mini Mitral trial was therefore conducted to compare the effectiveness and safety of minithoracotomy versus sternotomy mitral valve repair.
For the trial, 330 patients with degenerative mitral regurgitation were randomized to receive either minithoracotomy or sternotomy mitral valve repair performed by an expert surgeon.
The primary outcome was physical functioning and associated return to usual activities measured by change from baseline in the 36-Item Short Form Health Survey (SF-36) physical functioning scale 12 weeks after the surgery.
This failed to show superiority of minithoracotomy, with a mean difference of 0.68 (95% confidence interval, −1.89 to 3.26) between the two groups.
Analysis of secondary outcomes demonstrated that time spent undertaking moderate to vigorous physical activity was higher among participants receiving minithoracotomy at 6 weeks, although the treatment effect was small at an average of 9 minutes and was not different at 12 weeks.
Postoperative length of hospital stay was reduced after minithoracotomy by 1 day, with a median of 5 days, compared with 6 days after sternotomy.
Although repair techniques were at the discretion of the surgeons and differed between the two procedures, high rates of valve repair and low rates of recurrent mitral regurgitation were observed in both groups. Cardiopulmonary bypass times were longer with minithoracotomy, but postoperative complications and adverse events were similar.
There was no difference between the two groups with respect to the prespecified safety outcome of death, repeat mitral valve surgery, or heart failure hospitalization up to 1 year, which occurred in 5.4% of patients undergoing minithoracotomy and 6.1% of those undergoing sternotomy.
“These findings can inform shared decision-making and treatment guidelines,” the authors conclude.
Approach ‘may appeal to patients’
In an editorial accompanying the publication of the study in JAMA, Maurice Enriquez-Sarano, MD, Minneapolis Heart Institute, Minnesota, says the results should be integrated into patient management.
“Mini-thoracotomy mitral repair carried low risk and was highly effective compared with sternotomy. It can thus be applied successfully by surgeons who achieve the necessary expertise,” he notes.
“Mini-thoracotomy may appeal to patients because the procedure is less disfiguring than sternotomy. The early (6-week) benefit, albeit small and transient, is important to patients,” he adds.
The study was funded by the United Kingdom’s National Institute for Health and Care Research. Dr. Akowuah reports no relevant financial relationships with industry. Dr. Enriquez-Sarano reports receiving consulting fees from Edwards Lifesciences, Artivion, ChemImage, HighLife, and Corcym.
A version of this article first appeared on Medscape.com.
AHA flags CV risk with lead, cadmium, and arsenic exposure
in a new scientific statement.
“In reality, identifying a new type of cardiovascular risk factor leads to more questions than answers,” Gervasio A. Lamas, MD, chair of the statement writing group, said in an interview.
“For the most part, as cardiologists, we are used to risk factors we can manage with antihypertensives, statins, weight loss, exercise, and avoidance of smoking. Unfortunately, the ubiquity of toxic metals and their multiple sources increases the complexity of potential treatment,” said Dr. Lamas, chairman of medicine and chief of the Columbia University division of cardiology at Mount Sinai Medical Center in Miami Beach, Fla.
The statement addressing contaminant metals as CV risk factors was published online in the Journal of the American Heart Association.
Involuntary exposure harms the heart
Exposure to contaminant metals most often happens involuntarily through air, water, soil, and food, and extensive industrial and public use, the writing group notes.
These contaminant metals interfere with critical intracellular reactions and functions, leading to oxidative stress and chronic inflammation; this in turn leads to endothelial dysfunction, hypertension, epigenetic dysregulation, dyslipidemia, and changes in myocardial excitation and contractile function, the authors point out.
Lead, cadmium, and arsenic have been linked to subclinical atherosclerosis, coronary artery stenosis and calcification, as well as to an increased risk for ischemic heart disease and stroke, left ventricular hypertrophy, and heart failure and peripheral artery disease.
Epidemiologic studies show that exposure to lead, cadmium, or arsenic is associated with cardiovascular death mostly attributable to ischemic heart disease. In the United States alone, one study suggested that more than 450,000 deaths annually could be attributed to lead exposure.
“This is a global issue in which lower-income communities are disproportionately exposed to toxic metals through contaminated air, water, and soil,” Ana Navas-Acien, MD, PhD, vice chair of the statement writing group, said in a news release.
“Addressing metal exposure in these populations may provide a strategy to reduce cardiovascular disease disparities and advance environmental justice,” adds Dr. Navas-Acien, professor of environmental health sciences at Columbia University, New York.
Dr. Lamas said in an interview that the writing group is “hopeful that there will be a multilevel response” to publication of the scientific statement.
“On the societal level, we believe more effort can be made to measure these pollutants and protect the public. On the physician level, knowledge of metal levels could become part of the routine risk evaluation of the cardiac patient. On the individual level, patients can try to avoid these pollutants, by knowing arsenic levels of well-water, lead and cadmium levels of drinking water, avoiding tobacco and vaping, and using filters when available or necessary,” Dr. Lamas said.
“On the scientific level, identifying ubiquitous pollutants should spur scientists and pharmaceutical companies to develop preventive and therapeutic approaches.”
Finally, clinical trials should be encouraged to assess existing drugs that can remove these atherogenic toxins from the body or treat their ill effects. One such trial is expected to be completed within a year, Dr. Lamas added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Cardiovascular and Stroke Nursing; the Council on Lifestyle and Cardiometabolic Health; the Council on Peripheral Vascular Disease; and the Council on the Kidney in Cardiovascular Disease.
A version of this article originally appeared on Medscape.com.
in a new scientific statement.
“In reality, identifying a new type of cardiovascular risk factor leads to more questions than answers,” Gervasio A. Lamas, MD, chair of the statement writing group, said in an interview.
“For the most part, as cardiologists, we are used to risk factors we can manage with antihypertensives, statins, weight loss, exercise, and avoidance of smoking. Unfortunately, the ubiquity of toxic metals and their multiple sources increases the complexity of potential treatment,” said Dr. Lamas, chairman of medicine and chief of the Columbia University division of cardiology at Mount Sinai Medical Center in Miami Beach, Fla.
The statement addressing contaminant metals as CV risk factors was published online in the Journal of the American Heart Association.
Involuntary exposure harms the heart
Exposure to contaminant metals most often happens involuntarily through air, water, soil, and food, and extensive industrial and public use, the writing group notes.
These contaminant metals interfere with critical intracellular reactions and functions, leading to oxidative stress and chronic inflammation; this in turn leads to endothelial dysfunction, hypertension, epigenetic dysregulation, dyslipidemia, and changes in myocardial excitation and contractile function, the authors point out.
Lead, cadmium, and arsenic have been linked to subclinical atherosclerosis, coronary artery stenosis and calcification, as well as to an increased risk for ischemic heart disease and stroke, left ventricular hypertrophy, and heart failure and peripheral artery disease.
Epidemiologic studies show that exposure to lead, cadmium, or arsenic is associated with cardiovascular death mostly attributable to ischemic heart disease. In the United States alone, one study suggested that more than 450,000 deaths annually could be attributed to lead exposure.
“This is a global issue in which lower-income communities are disproportionately exposed to toxic metals through contaminated air, water, and soil,” Ana Navas-Acien, MD, PhD, vice chair of the statement writing group, said in a news release.
“Addressing metal exposure in these populations may provide a strategy to reduce cardiovascular disease disparities and advance environmental justice,” adds Dr. Navas-Acien, professor of environmental health sciences at Columbia University, New York.
Dr. Lamas said in an interview that the writing group is “hopeful that there will be a multilevel response” to publication of the scientific statement.
“On the societal level, we believe more effort can be made to measure these pollutants and protect the public. On the physician level, knowledge of metal levels could become part of the routine risk evaluation of the cardiac patient. On the individual level, patients can try to avoid these pollutants, by knowing arsenic levels of well-water, lead and cadmium levels of drinking water, avoiding tobacco and vaping, and using filters when available or necessary,” Dr. Lamas said.
“On the scientific level, identifying ubiquitous pollutants should spur scientists and pharmaceutical companies to develop preventive and therapeutic approaches.”
Finally, clinical trials should be encouraged to assess existing drugs that can remove these atherogenic toxins from the body or treat their ill effects. One such trial is expected to be completed within a year, Dr. Lamas added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Cardiovascular and Stroke Nursing; the Council on Lifestyle and Cardiometabolic Health; the Council on Peripheral Vascular Disease; and the Council on the Kidney in Cardiovascular Disease.
A version of this article originally appeared on Medscape.com.
in a new scientific statement.
“In reality, identifying a new type of cardiovascular risk factor leads to more questions than answers,” Gervasio A. Lamas, MD, chair of the statement writing group, said in an interview.
“For the most part, as cardiologists, we are used to risk factors we can manage with antihypertensives, statins, weight loss, exercise, and avoidance of smoking. Unfortunately, the ubiquity of toxic metals and their multiple sources increases the complexity of potential treatment,” said Dr. Lamas, chairman of medicine and chief of the Columbia University division of cardiology at Mount Sinai Medical Center in Miami Beach, Fla.
The statement addressing contaminant metals as CV risk factors was published online in the Journal of the American Heart Association.
Involuntary exposure harms the heart
Exposure to contaminant metals most often happens involuntarily through air, water, soil, and food, and extensive industrial and public use, the writing group notes.
These contaminant metals interfere with critical intracellular reactions and functions, leading to oxidative stress and chronic inflammation; this in turn leads to endothelial dysfunction, hypertension, epigenetic dysregulation, dyslipidemia, and changes in myocardial excitation and contractile function, the authors point out.
Lead, cadmium, and arsenic have been linked to subclinical atherosclerosis, coronary artery stenosis and calcification, as well as to an increased risk for ischemic heart disease and stroke, left ventricular hypertrophy, and heart failure and peripheral artery disease.
Epidemiologic studies show that exposure to lead, cadmium, or arsenic is associated with cardiovascular death mostly attributable to ischemic heart disease. In the United States alone, one study suggested that more than 450,000 deaths annually could be attributed to lead exposure.
“This is a global issue in which lower-income communities are disproportionately exposed to toxic metals through contaminated air, water, and soil,” Ana Navas-Acien, MD, PhD, vice chair of the statement writing group, said in a news release.
“Addressing metal exposure in these populations may provide a strategy to reduce cardiovascular disease disparities and advance environmental justice,” adds Dr. Navas-Acien, professor of environmental health sciences at Columbia University, New York.
Dr. Lamas said in an interview that the writing group is “hopeful that there will be a multilevel response” to publication of the scientific statement.
“On the societal level, we believe more effort can be made to measure these pollutants and protect the public. On the physician level, knowledge of metal levels could become part of the routine risk evaluation of the cardiac patient. On the individual level, patients can try to avoid these pollutants, by knowing arsenic levels of well-water, lead and cadmium levels of drinking water, avoiding tobacco and vaping, and using filters when available or necessary,” Dr. Lamas said.
“On the scientific level, identifying ubiquitous pollutants should spur scientists and pharmaceutical companies to develop preventive and therapeutic approaches.”
Finally, clinical trials should be encouraged to assess existing drugs that can remove these atherogenic toxins from the body or treat their ill effects. One such trial is expected to be completed within a year, Dr. Lamas added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Epidemiology and Prevention; the Council on Cardiovascular and Stroke Nursing; the Council on Lifestyle and Cardiometabolic Health; the Council on Peripheral Vascular Disease; and the Council on the Kidney in Cardiovascular Disease.
A version of this article originally appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
New study backs up capecitabine dosing practice in metastatic BC
Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.
The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m2, but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.
The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m2 dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.
Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).
The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.
The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
Findings back up clinical practice
“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.
Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.
During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
Fixed dose versus body surface area
Dr. Kirshner also said his practice uses a dose of 1 g/m2 of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m2.”
Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”
Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”
Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.
Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.
Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.
The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m2, but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.
The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m2 dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.
Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).
The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.
The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
Findings back up clinical practice
“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.
Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.
During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
Fixed dose versus body surface area
Dr. Kirshner also said his practice uses a dose of 1 g/m2 of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m2.”
Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”
Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”
Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.
Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.
Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.
The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m2, but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.
The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m2 dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.
Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).
The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.
The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
Findings back up clinical practice
“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.
Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.
During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
Fixed dose versus body surface area
Dr. Kirshner also said his practice uses a dose of 1 g/m2 of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m2.”
Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”
Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”
Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.
Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.
FROM ASCO 2023
Ticagrelor may reduce brain lesions after carotid stenting
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
MUNICH – secondary endpoint results of the PRECISE-MRI trial suggest.
More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.
Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.
There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.
The research was presented at the annual European Stroke Organisation Conference .
Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”
Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.
Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”
Dr. Bonati cautioned, however, that the findings are preliminary.
‘Promising’ results
Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”
She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.
Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”
“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
Major complication
Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.
Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.
Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.
To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.
They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.
The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.
The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.
Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.
The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.
The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.
Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).
However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).
Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).
Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.
Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).
There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.
The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
FROM ESOC 2023
Alcohol may curb stress signaling in brain to protect heart
The study shows that light to moderate drinking was associated with lower major adverse cardiovascular events (MACE), and this was partly mediated by decreased stress signaling in the brain.
In addition, the benefit of light to moderate drinking with respect to MACE was most pronounced among people with a history of anxiety, a condition known to be associated with higher stress signaling in the brain.
However, the apparent CVD benefits of light to moderate drinking were counterbalanced by an increased risk of cancer.
“There is no safe level of alcohol consumption,” senior author and cardiologist Ahmed Tawakol, MD, codirector of the Cardiovascular Imaging Research Center at Massachusetts General Hospital, Boston, said in an interview.
“We see cancer risk even at the level that we see some protection from heart disease. And higher amounts of alcohol clearly increase heart disease risk,” Dr. Tawakol said.
The study was published online in the Journal of the American College of Cardiology.
Clear mechanistic link
Chronic stress is associated with MACE via stress-related neural network activity (SNA). Light to moderate alcohol consumption has been linked to lower MACE risk, but the mechanisms behind this connection remain unclear.
“We know that when the neural centers of stress are activated, they trigger downstream changes that result in heart disease. And we’ve long appreciated that alcohol in the short term reduces stress, so we hypothesized that maybe alcohol impacts those stress systems chronically and that might explain its cardiovascular effects,” Dr. Tawakol explained.
The study included roughly 53,000 adults (mean age, 60 years; 60% women) from the Mass General Brigham Biobank. The researchers first evaluated the relationship between light to moderate alcohol consumption and MACE after adjusting for a range of genetic, clinical, lifestyle, and socioeconomic factors.
During mean follow-up of 3.4 years, 1,914 individuals experienced MACE. Light to moderate alcohol consumption (compared to none/minimal) was associated with lower MACE risk (hazard ratio [HR], 0.786; 95% confidence interval [CI], 0.717-0.862; P < .0001) after adjustment for cardiovascular risk factors.
The researchers then studied a subset of 713 individuals who had undergone previous PET/CT brain imaging (primarily for cancer surveillance) to determine the effect of light to moderate alcohol consumption on resting SNA.
They found that light to moderate alcohol consumption correlated with decreased SNA (standardized beta, –0.192; 95% CI, –0.338 to 0.046; P = .01). Lower SNA partially mediated the beneficial effect of light to moderate alcohol intake on MACE risk (odds ratio [OR], –0.040; 95% CI, –0.097 to –0.003; P < .05).
Light to moderate alcohol consumption was associated with larger decreases in MACE risk among individuals with a history of anxiety (HR, 0.60; 95% CI, 0.50-0.72, vs. HR, 1.78; 95% CI, 0.73-0.80; P = .003).
The coauthors of an editorial say the discovery of a “new possible mechanism of action” for why light to moderate alcohol consumption might protect the heart “deserves closer attention in future investigations.”
However, Giovanni de Gaetano, MD, PhD, department of epidemiology and prevention, IRCCS NEUROMED, Pozzilli, Italy, one of the authors, emphasized that individuals who consume alcohol should not “exceed the recommended daily dose limits suggested in many countries and that no abstainer should start to drink, even in moderation, solely for the purpose of improving his/her health outcomes.”
Dr. Tawakol and colleagues said that, given alcohol’s adverse health effects, such as heightened cancer risk, new interventions that have positive effects on the neurobiology of stress but without the harmful effects of alcohol are needed.
To that end, they are studying the effect of exercise, stress-reduction interventions such as meditation, and pharmacologic therapies on stress-associated neural networks, and how they might induce CV benefits.
Dr. Tawakol said in an interview that one “additional important message is that anxiety and other related conditions like depression have really substantial health consequences, including increased MACE. Safer interventions that reduce anxiety may yet prove to reduce the risk of heart disease very nicely.”
The study was supported by the National Institutes of Health. Dr. Tawakol and Dr. de Gaetano have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The study shows that light to moderate drinking was associated with lower major adverse cardiovascular events (MACE), and this was partly mediated by decreased stress signaling in the brain.
In addition, the benefit of light to moderate drinking with respect to MACE was most pronounced among people with a history of anxiety, a condition known to be associated with higher stress signaling in the brain.
However, the apparent CVD benefits of light to moderate drinking were counterbalanced by an increased risk of cancer.
“There is no safe level of alcohol consumption,” senior author and cardiologist Ahmed Tawakol, MD, codirector of the Cardiovascular Imaging Research Center at Massachusetts General Hospital, Boston, said in an interview.
“We see cancer risk even at the level that we see some protection from heart disease. And higher amounts of alcohol clearly increase heart disease risk,” Dr. Tawakol said.
The study was published online in the Journal of the American College of Cardiology.
Clear mechanistic link
Chronic stress is associated with MACE via stress-related neural network activity (SNA). Light to moderate alcohol consumption has been linked to lower MACE risk, but the mechanisms behind this connection remain unclear.
“We know that when the neural centers of stress are activated, they trigger downstream changes that result in heart disease. And we’ve long appreciated that alcohol in the short term reduces stress, so we hypothesized that maybe alcohol impacts those stress systems chronically and that might explain its cardiovascular effects,” Dr. Tawakol explained.
The study included roughly 53,000 adults (mean age, 60 years; 60% women) from the Mass General Brigham Biobank. The researchers first evaluated the relationship between light to moderate alcohol consumption and MACE after adjusting for a range of genetic, clinical, lifestyle, and socioeconomic factors.
During mean follow-up of 3.4 years, 1,914 individuals experienced MACE. Light to moderate alcohol consumption (compared to none/minimal) was associated with lower MACE risk (hazard ratio [HR], 0.786; 95% confidence interval [CI], 0.717-0.862; P < .0001) after adjustment for cardiovascular risk factors.
The researchers then studied a subset of 713 individuals who had undergone previous PET/CT brain imaging (primarily for cancer surveillance) to determine the effect of light to moderate alcohol consumption on resting SNA.
They found that light to moderate alcohol consumption correlated with decreased SNA (standardized beta, –0.192; 95% CI, –0.338 to 0.046; P = .01). Lower SNA partially mediated the beneficial effect of light to moderate alcohol intake on MACE risk (odds ratio [OR], –0.040; 95% CI, –0.097 to –0.003; P < .05).
Light to moderate alcohol consumption was associated with larger decreases in MACE risk among individuals with a history of anxiety (HR, 0.60; 95% CI, 0.50-0.72, vs. HR, 1.78; 95% CI, 0.73-0.80; P = .003).
The coauthors of an editorial say the discovery of a “new possible mechanism of action” for why light to moderate alcohol consumption might protect the heart “deserves closer attention in future investigations.”
However, Giovanni de Gaetano, MD, PhD, department of epidemiology and prevention, IRCCS NEUROMED, Pozzilli, Italy, one of the authors, emphasized that individuals who consume alcohol should not “exceed the recommended daily dose limits suggested in many countries and that no abstainer should start to drink, even in moderation, solely for the purpose of improving his/her health outcomes.”
Dr. Tawakol and colleagues said that, given alcohol’s adverse health effects, such as heightened cancer risk, new interventions that have positive effects on the neurobiology of stress but without the harmful effects of alcohol are needed.
To that end, they are studying the effect of exercise, stress-reduction interventions such as meditation, and pharmacologic therapies on stress-associated neural networks, and how they might induce CV benefits.
Dr. Tawakol said in an interview that one “additional important message is that anxiety and other related conditions like depression have really substantial health consequences, including increased MACE. Safer interventions that reduce anxiety may yet prove to reduce the risk of heart disease very nicely.”
The study was supported by the National Institutes of Health. Dr. Tawakol and Dr. de Gaetano have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The study shows that light to moderate drinking was associated with lower major adverse cardiovascular events (MACE), and this was partly mediated by decreased stress signaling in the brain.
In addition, the benefit of light to moderate drinking with respect to MACE was most pronounced among people with a history of anxiety, a condition known to be associated with higher stress signaling in the brain.
However, the apparent CVD benefits of light to moderate drinking were counterbalanced by an increased risk of cancer.
“There is no safe level of alcohol consumption,” senior author and cardiologist Ahmed Tawakol, MD, codirector of the Cardiovascular Imaging Research Center at Massachusetts General Hospital, Boston, said in an interview.
“We see cancer risk even at the level that we see some protection from heart disease. And higher amounts of alcohol clearly increase heart disease risk,” Dr. Tawakol said.
The study was published online in the Journal of the American College of Cardiology.
Clear mechanistic link
Chronic stress is associated with MACE via stress-related neural network activity (SNA). Light to moderate alcohol consumption has been linked to lower MACE risk, but the mechanisms behind this connection remain unclear.
“We know that when the neural centers of stress are activated, they trigger downstream changes that result in heart disease. And we’ve long appreciated that alcohol in the short term reduces stress, so we hypothesized that maybe alcohol impacts those stress systems chronically and that might explain its cardiovascular effects,” Dr. Tawakol explained.
The study included roughly 53,000 adults (mean age, 60 years; 60% women) from the Mass General Brigham Biobank. The researchers first evaluated the relationship between light to moderate alcohol consumption and MACE after adjusting for a range of genetic, clinical, lifestyle, and socioeconomic factors.
During mean follow-up of 3.4 years, 1,914 individuals experienced MACE. Light to moderate alcohol consumption (compared to none/minimal) was associated with lower MACE risk (hazard ratio [HR], 0.786; 95% confidence interval [CI], 0.717-0.862; P < .0001) after adjustment for cardiovascular risk factors.
The researchers then studied a subset of 713 individuals who had undergone previous PET/CT brain imaging (primarily for cancer surveillance) to determine the effect of light to moderate alcohol consumption on resting SNA.
They found that light to moderate alcohol consumption correlated with decreased SNA (standardized beta, –0.192; 95% CI, –0.338 to 0.046; P = .01). Lower SNA partially mediated the beneficial effect of light to moderate alcohol intake on MACE risk (odds ratio [OR], –0.040; 95% CI, –0.097 to –0.003; P < .05).
Light to moderate alcohol consumption was associated with larger decreases in MACE risk among individuals with a history of anxiety (HR, 0.60; 95% CI, 0.50-0.72, vs. HR, 1.78; 95% CI, 0.73-0.80; P = .003).
The coauthors of an editorial say the discovery of a “new possible mechanism of action” for why light to moderate alcohol consumption might protect the heart “deserves closer attention in future investigations.”
However, Giovanni de Gaetano, MD, PhD, department of epidemiology and prevention, IRCCS NEUROMED, Pozzilli, Italy, one of the authors, emphasized that individuals who consume alcohol should not “exceed the recommended daily dose limits suggested in many countries and that no abstainer should start to drink, even in moderation, solely for the purpose of improving his/her health outcomes.”
Dr. Tawakol and colleagues said that, given alcohol’s adverse health effects, such as heightened cancer risk, new interventions that have positive effects on the neurobiology of stress but without the harmful effects of alcohol are needed.
To that end, they are studying the effect of exercise, stress-reduction interventions such as meditation, and pharmacologic therapies on stress-associated neural networks, and how they might induce CV benefits.
Dr. Tawakol said in an interview that one “additional important message is that anxiety and other related conditions like depression have really substantial health consequences, including increased MACE. Safer interventions that reduce anxiety may yet prove to reduce the risk of heart disease very nicely.”
The study was supported by the National Institutes of Health. Dr. Tawakol and Dr. de Gaetano have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
The cardiopulmonary effects of mask wearing
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
There was a time when I would have had to explain to you what an N95 mask is, how it is designed to filter out 95% of fine particles, defined as stuff in the air less than 2.5 microns in size.
But of course, you know that now. The N95 had its moment – a moment that seemed to be passing as the concentration of airborne coronavirus particles decreased.
But, as the poet said, all that is less than 2.5 microns in size is not coronavirus. Wildfire smoke is also chock full of fine particulate matter. And so, N95s are having something of a comeback.
That’s why an article that took a deep look at what happens to our cardiovascular system when we wear N95 masks caught my eye.
Mask wearing has been the subject of intense debate around the country. While the vast majority of evidence, as well as the personal experience of thousands of doctors, suggests that wearing a mask has no significant physiologic effects, it’s not hard to find those who suggest that mask wearing depletes oxygen levels, or leads to infection, or has other bizarre effects.
In a world of conflicting opinions, a controlled study is a wonderful thing, and that’s what appeared in JAMA Network Open.
This isn’t a huge study, but it’s big enough to make some important conclusions. Thirty individuals, all young and healthy, half female, were enrolled. Each participant spent 3 days in a metabolic chamber; this is essentially a giant, airtight room where all the inputs (oxygen levels and so on) and outputs (carbon dioxide levels and so on) can be precisely measured.
After a day of getting used to the environment, the participants spent a day either wearing an N95 mask or not for 16 waking hours. On the next day, they switched. Every other variable was controlled, from the calories in their diet to the temperature of the room itself.
They engaged in light exercise twice during the day – riding a stationary bike – and a host of physiologic parameters were measured. The question being, would the wearing of the mask for 16 hours straight change anything?
And the answer is yes, some things changed, but not by much.
Here’s a graph of the heart rate over time. You can see some separation, with higher heart rates during the mask-wearing day, particularly around 11 a.m. – when light exercise was scheduled.
Zooming in on the exercise period makes the difference more clear. The heart rate was about eight beats/min higher while masked and engaging in exercise. Systolic blood pressure was about 6 mm Hg higher. Oxygen saturation was lower by 0.7%.
So yes, exercising while wearing an N95 mask might be different from exercising without an N95 mask. But nothing here looks dangerous to me. The 0.7% decrease in oxygen saturation is smaller than the typical measurement error of a pulse oximeter. The authors write that venous pH decreased during the masked day, which is of more interest to me as a nephrologist, but they don’t show that data even in the supplement. I suspect it didn’t decrease much.
They also showed that respiratory rate during exercise decreased in the masked condition. That doesn’t really make sense when you think about it in the context of the other findings, which are all suggestive of increased metabolic rate and sympathetic drive. Does that call the whole procedure into question? No, but it’s worth noting.
These were young, healthy people. You could certainly argue that those with more vulnerable cardiopulmonary status might have had different effects from mask wearing, but without a specific study in those people, it’s just conjecture. Clearly, this study lets us conclude that mask wearing at rest has less of an effect than mask wearing during exercise.
But remember that, in reality, we are wearing masks for a reason. One could imagine a study where this metabolic chamber was filled with wildfire smoke at a concentration similar to what we saw in New York. In that situation, we might find that wearing an N95 is quite helpful. The thing is, studying masks in isolation is useful because you can control so many variables. But masks aren’t used in isolation. In fact, that’s sort of their defining characteristic.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
There was a time when I would have had to explain to you what an N95 mask is, how it is designed to filter out 95% of fine particles, defined as stuff in the air less than 2.5 microns in size.
But of course, you know that now. The N95 had its moment – a moment that seemed to be passing as the concentration of airborne coronavirus particles decreased.
But, as the poet said, all that is less than 2.5 microns in size is not coronavirus. Wildfire smoke is also chock full of fine particulate matter. And so, N95s are having something of a comeback.
That’s why an article that took a deep look at what happens to our cardiovascular system when we wear N95 masks caught my eye.
Mask wearing has been the subject of intense debate around the country. While the vast majority of evidence, as well as the personal experience of thousands of doctors, suggests that wearing a mask has no significant physiologic effects, it’s not hard to find those who suggest that mask wearing depletes oxygen levels, or leads to infection, or has other bizarre effects.
In a world of conflicting opinions, a controlled study is a wonderful thing, and that’s what appeared in JAMA Network Open.
This isn’t a huge study, but it’s big enough to make some important conclusions. Thirty individuals, all young and healthy, half female, were enrolled. Each participant spent 3 days in a metabolic chamber; this is essentially a giant, airtight room where all the inputs (oxygen levels and so on) and outputs (carbon dioxide levels and so on) can be precisely measured.
After a day of getting used to the environment, the participants spent a day either wearing an N95 mask or not for 16 waking hours. On the next day, they switched. Every other variable was controlled, from the calories in their diet to the temperature of the room itself.
They engaged in light exercise twice during the day – riding a stationary bike – and a host of physiologic parameters were measured. The question being, would the wearing of the mask for 16 hours straight change anything?
And the answer is yes, some things changed, but not by much.
Here’s a graph of the heart rate over time. You can see some separation, with higher heart rates during the mask-wearing day, particularly around 11 a.m. – when light exercise was scheduled.
Zooming in on the exercise period makes the difference more clear. The heart rate was about eight beats/min higher while masked and engaging in exercise. Systolic blood pressure was about 6 mm Hg higher. Oxygen saturation was lower by 0.7%.
So yes, exercising while wearing an N95 mask might be different from exercising without an N95 mask. But nothing here looks dangerous to me. The 0.7% decrease in oxygen saturation is smaller than the typical measurement error of a pulse oximeter. The authors write that venous pH decreased during the masked day, which is of more interest to me as a nephrologist, but they don’t show that data even in the supplement. I suspect it didn’t decrease much.
They also showed that respiratory rate during exercise decreased in the masked condition. That doesn’t really make sense when you think about it in the context of the other findings, which are all suggestive of increased metabolic rate and sympathetic drive. Does that call the whole procedure into question? No, but it’s worth noting.
These were young, healthy people. You could certainly argue that those with more vulnerable cardiopulmonary status might have had different effects from mask wearing, but without a specific study in those people, it’s just conjecture. Clearly, this study lets us conclude that mask wearing at rest has less of an effect than mask wearing during exercise.
But remember that, in reality, we are wearing masks for a reason. One could imagine a study where this metabolic chamber was filled with wildfire smoke at a concentration similar to what we saw in New York. In that situation, we might find that wearing an N95 is quite helpful. The thing is, studying masks in isolation is useful because you can control so many variables. But masks aren’t used in isolation. In fact, that’s sort of their defining characteristic.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.
There was a time when I would have had to explain to you what an N95 mask is, how it is designed to filter out 95% of fine particles, defined as stuff in the air less than 2.5 microns in size.
But of course, you know that now. The N95 had its moment – a moment that seemed to be passing as the concentration of airborne coronavirus particles decreased.
But, as the poet said, all that is less than 2.5 microns in size is not coronavirus. Wildfire smoke is also chock full of fine particulate matter. And so, N95s are having something of a comeback.
That’s why an article that took a deep look at what happens to our cardiovascular system when we wear N95 masks caught my eye.
Mask wearing has been the subject of intense debate around the country. While the vast majority of evidence, as well as the personal experience of thousands of doctors, suggests that wearing a mask has no significant physiologic effects, it’s not hard to find those who suggest that mask wearing depletes oxygen levels, or leads to infection, or has other bizarre effects.
In a world of conflicting opinions, a controlled study is a wonderful thing, and that’s what appeared in JAMA Network Open.
This isn’t a huge study, but it’s big enough to make some important conclusions. Thirty individuals, all young and healthy, half female, were enrolled. Each participant spent 3 days in a metabolic chamber; this is essentially a giant, airtight room where all the inputs (oxygen levels and so on) and outputs (carbon dioxide levels and so on) can be precisely measured.
After a day of getting used to the environment, the participants spent a day either wearing an N95 mask or not for 16 waking hours. On the next day, they switched. Every other variable was controlled, from the calories in their diet to the temperature of the room itself.
They engaged in light exercise twice during the day – riding a stationary bike – and a host of physiologic parameters were measured. The question being, would the wearing of the mask for 16 hours straight change anything?
And the answer is yes, some things changed, but not by much.
Here’s a graph of the heart rate over time. You can see some separation, with higher heart rates during the mask-wearing day, particularly around 11 a.m. – when light exercise was scheduled.
Zooming in on the exercise period makes the difference more clear. The heart rate was about eight beats/min higher while masked and engaging in exercise. Systolic blood pressure was about 6 mm Hg higher. Oxygen saturation was lower by 0.7%.
So yes, exercising while wearing an N95 mask might be different from exercising without an N95 mask. But nothing here looks dangerous to me. The 0.7% decrease in oxygen saturation is smaller than the typical measurement error of a pulse oximeter. The authors write that venous pH decreased during the masked day, which is of more interest to me as a nephrologist, but they don’t show that data even in the supplement. I suspect it didn’t decrease much.
They also showed that respiratory rate during exercise decreased in the masked condition. That doesn’t really make sense when you think about it in the context of the other findings, which are all suggestive of increased metabolic rate and sympathetic drive. Does that call the whole procedure into question? No, but it’s worth noting.
These were young, healthy people. You could certainly argue that those with more vulnerable cardiopulmonary status might have had different effects from mask wearing, but without a specific study in those people, it’s just conjecture. Clearly, this study lets us conclude that mask wearing at rest has less of an effect than mask wearing during exercise.
But remember that, in reality, we are wearing masks for a reason. One could imagine a study where this metabolic chamber was filled with wildfire smoke at a concentration similar to what we saw in New York. In that situation, we might find that wearing an N95 is quite helpful. The thing is, studying masks in isolation is useful because you can control so many variables. But masks aren’t used in isolation. In fact, that’s sort of their defining characteristic.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Insurers poised to crack down on off-label Ozempic prescriptions
The warning letters, first reported by The Washington Post, include threats such as the possibility of reporting “suspected inappropriate or fraudulent activity ... to the state licensure board, federal and/or state law enforcement.”
It’s the latest chapter in the story of the popular, highly effective, and very expensive drug intended for diabetes that results in quick weight loss. Off-label prescribing means a medicine has been prescribed for a reason other than the uses approved by the Food and Drug Administration. The practice is common and legal (the U.S. Agency for Healthcare Research and Quality says one in five prescriptions in the U.S. are off label).
But insurance companies are pushing back because many do not cover weight loss medications, while they do cover diabetes treatments. The insurance company letters suggest that prescribers are failing to document in a person’s medical record that the person actually has diabetes.
Ozempic, which is FDA approved for treatment of diabetes, is similar to the drug Wegovy, which is approved to be used for weight loss. Ozempic typically costs more than $900 per month. Both Wegovy and Ozempic contain semaglutide, which mimics a hormone that helps the brain regulate appetite and food intake. Clinical studies show that after taking semaglutide for more than 5 years, people lose on average 17% of their body weight. But once they stop taking it, most people regain much of the weight.
Demand for both Ozempic and Wegovy has been surging, leading to shortages and tactics to acquire the drugs outside of the United States, as well as warnings from public health officials about the dangers of knockoff versions of the drugs. The Centers for Disease Control and Prevention says 42% of people in the United States are obese.
“Obesity is a complex disease involving an excessive amount of body fat,” the Mayo Clinic explained. “Obesity isn’t just a cosmetic concern. It’s a medical problem that increases the risk of other diseases and health problems, such as heart disease, diabetes, high blood pressure, and certain cancers.”
A version of this article first appeared on WebMD.com.
The warning letters, first reported by The Washington Post, include threats such as the possibility of reporting “suspected inappropriate or fraudulent activity ... to the state licensure board, federal and/or state law enforcement.”
It’s the latest chapter in the story of the popular, highly effective, and very expensive drug intended for diabetes that results in quick weight loss. Off-label prescribing means a medicine has been prescribed for a reason other than the uses approved by the Food and Drug Administration. The practice is common and legal (the U.S. Agency for Healthcare Research and Quality says one in five prescriptions in the U.S. are off label).
But insurance companies are pushing back because many do not cover weight loss medications, while they do cover diabetes treatments. The insurance company letters suggest that prescribers are failing to document in a person’s medical record that the person actually has diabetes.
Ozempic, which is FDA approved for treatment of diabetes, is similar to the drug Wegovy, which is approved to be used for weight loss. Ozempic typically costs more than $900 per month. Both Wegovy and Ozempic contain semaglutide, which mimics a hormone that helps the brain regulate appetite and food intake. Clinical studies show that after taking semaglutide for more than 5 years, people lose on average 17% of their body weight. But once they stop taking it, most people regain much of the weight.
Demand for both Ozempic and Wegovy has been surging, leading to shortages and tactics to acquire the drugs outside of the United States, as well as warnings from public health officials about the dangers of knockoff versions of the drugs. The Centers for Disease Control and Prevention says 42% of people in the United States are obese.
“Obesity is a complex disease involving an excessive amount of body fat,” the Mayo Clinic explained. “Obesity isn’t just a cosmetic concern. It’s a medical problem that increases the risk of other diseases and health problems, such as heart disease, diabetes, high blood pressure, and certain cancers.”
A version of this article first appeared on WebMD.com.
The warning letters, first reported by The Washington Post, include threats such as the possibility of reporting “suspected inappropriate or fraudulent activity ... to the state licensure board, federal and/or state law enforcement.”
It’s the latest chapter in the story of the popular, highly effective, and very expensive drug intended for diabetes that results in quick weight loss. Off-label prescribing means a medicine has been prescribed for a reason other than the uses approved by the Food and Drug Administration. The practice is common and legal (the U.S. Agency for Healthcare Research and Quality says one in five prescriptions in the U.S. are off label).
But insurance companies are pushing back because many do not cover weight loss medications, while they do cover diabetes treatments. The insurance company letters suggest that prescribers are failing to document in a person’s medical record that the person actually has diabetes.
Ozempic, which is FDA approved for treatment of diabetes, is similar to the drug Wegovy, which is approved to be used for weight loss. Ozempic typically costs more than $900 per month. Both Wegovy and Ozempic contain semaglutide, which mimics a hormone that helps the brain regulate appetite and food intake. Clinical studies show that after taking semaglutide for more than 5 years, people lose on average 17% of their body weight. But once they stop taking it, most people regain much of the weight.
Demand for both Ozempic and Wegovy has been surging, leading to shortages and tactics to acquire the drugs outside of the United States, as well as warnings from public health officials about the dangers of knockoff versions of the drugs. The Centers for Disease Control and Prevention says 42% of people in the United States are obese.
“Obesity is a complex disease involving an excessive amount of body fat,” the Mayo Clinic explained. “Obesity isn’t just a cosmetic concern. It’s a medical problem that increases the risk of other diseases and health problems, such as heart disease, diabetes, high blood pressure, and certain cancers.”
A version of this article first appeared on WebMD.com.
Popular weight loss drugs can carry some unpleasant side effects
Johnna Mendenall had never been “the skinny friend,” she said, but the demands of motherhood – along with a sedentary desk job – made weight management even more difficult. Worried that family type 2 diabetes would catch up with her, she decided to start Wegovy shots for weight loss.
She was nervous about potential side effects. It took 5 days of staring at the Wegovy pen before she worked up the nerve for her first .25-milligram shot. And sure enough, the side effects came on strong.
“The nausea kicked in,” she said. “When I increased my dose to 1 milligram, I spent the entire night from 10 p.m. to 5 a.m. vomiting. I almost quit that day.”
While gastrointestinal (GI) symptoms seem to be the most common, a laundry list of others has been discussed in the news, on TikTok, and across online forums. Those include “Ozempic face,” or the gaunt look some get after taking the medication, along with hair loss, anxiety, depression, and debilitating fatigue.
Ms. Mendenall’s primary side effects have been vomiting, fatigue, and severe constipation, but she has also seen some positive changes: The “food noise,” or the urge to eat when she isn’t hungry, is gone. Since her first dose 12 weeks ago, she has gone from 236 pounds to 215.
Warning label
Wegovy’s active ingredient, semaglutide, mimics the role of a natural hormone called glucagonlike peptide–1 (GLP-1), which helps you feel well fed. Semaglutide is used at a lower dose under the brand name Ozempic, which is approved for type 2 diabetes and used off-label for weight loss.
Both Ozempic and Wegovy come with a warning label for potential side effects, the most common ones being nausea, diarrhea, stomach pain, and vomiting.
With the surging popularity of semaglutide, more people are getting prescriptions through telemedicine companies, forgoing more in-depth consultations, leading to more side effects, said Caroline Apovian, MD, professor of medicine at Harvard Medical School and codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, Boston.
Specialists say starting with low doses and gradually increasing over time helps avoid side effects, but insurance companies often require a faster timeline to continue covering the medication, Dr. Apovian said.
“Insurance companies are practicing medicine for us by demanding the patient go up in dosage [too quickly],” she explained.
Ms. Mendenall’s insurance has paid for her Wegovy shots, but without that coverage, she said it would cost her $1,200 per month.
There are similar medications on the market, such as liraglutide, sold under the name Saxenda. But it is a daily, rather than a weekly, shot and also comes with side effects and has been shown to be less effective. In one clinical trial, the people being studied saw their average body weight over 68 weeks drop by 15.8% with semaglutide, and by 6.4% with liraglutide.
Tirzepatide, branded Mounjaro – a type 2 diabetes drug made by Eli Lilly that may soon gain Food and Drug Administration approval for weight loss – could have fewer side effects. In clinical trials, 44% of those taking semaglutide had nausea and 31% reported diarrhea, compared with 33% and 23% of those taking tirzepatide, although no trial has directly compared the two agents.
Loss of bowel control
For now, Wegovy and Saxenda are the only GLP-1 agonist shots authorized for weight loss, and their maker, Danish drug company Novo Nordisk, is facing its second shortage of Wegovy amid growing demand.
Personal stories online about semaglutide range from overwhelmingly positive – just what some need to win a lifelong battle with obesity – to harsh scenarios with potentially long-term health consequences, and everything in between.
One private community on Reddit is dedicated to a particularly unpleasant side effect: loss of bowel control while sleeping. Others have reported uncontrollable vomiting.
Kimberly Carew of Clearwater, Fla., started on .5 milligrams of Ozempic last year after her rheumatologist and endocrinologist suggested it to treat her type 2 diabetes. She was told it came with the bonus of weight loss, which she was hoping would help with her joint and back pain.
But after she increased the dose to 1 milligram, her GI symptoms, which started out mild, became unbearable. She couldn’t keep food down, and when she vomited, the food would often come up whole, she said.
“One night I ate ramen before bed. And the next morning, it came out just as it went down,” said Ms. Carew, 42, a registered mental health counseling intern. “I was getting severe heartburn and could not take a couple bites of food without getting nauseous.”
She also had “sulfur burps,” a side effect discussed by some Ozempic users, causing her to taste rotten egg sometimes.
She was diagnosed with gastroparesis. Some types of gastroparesis can be resolved by discontinuing GLP-1 medications, as referenced in two case reports in the Journal of Investigative Medicine.
Gut hormone
GI symptoms are most common with semaglutide because the hormone it imitates, GLP-1, is secreted by cells in the stomach, small intestines, and pancreas, said Anne Peters, MD, director of the USC Clinical Diabetes Programs.
“This is the deal: The side effects are real because it’s a gut hormone. It’s increasing the level of something your body already has,” she said.
But, like Dr. Apovian, Dr. Peters said those side effects can likely be avoided if shots are started at the lowest doses and gradually adjusted up.
While the average starting dose is .25 milligrams, Dr. Peters said she often starts her patients on about an eighth of that – just “a whiff of a dose.”
“It’ll take them months to get up to the starting dose, but what’s the rush?”
Dr. Peters said she also avoids giving diabetes patients the maximum dose, which is 2 milligrams per week for Ozempic (and 2.4 milligrams for Wegovy for weight loss).
When asked about the drugs’ side effects, Novo Nordisk responded that “GLP-1 receptor agonists are a well-established class of medicines, which have demonstrated long-term safety in clinical trials. The most common adverse reactions, as with all GLP-1 [agonists], are gastrointestinal related.”
Is it the drug or the weight loss?
Still, non-gastrointestinal side effects such as hair loss, mood changes, and sunken facial features are reported among semaglutide users across the Internet. While these cases are often anecdotal, they can be very heartfelt.
Celina Horvath Myers, also known as CelinaSpookyBoo, a Canadian YouTuber who took Ozempic for type 2 diabetes, said she began having intense panic attacks and depression after starting the medication.
“Who I have been these last couple weeks, has probably been the scariest time of my life,” she said on her YouTube channel.
While severe depression and anxiety are not established side effects of the medication, some people get anhedonia, said W. Scott Butsch, MD, MSc, director of obesity medicine in the Bariatric and Metabolic Institute at Cleveland Clinic. But that could be a natural consequence of lower appetite, he said, given that food gives most people pleasure in the moment.
Many other reported changes come from the weight loss itself, not the medication, said Dr. Butsch.
“These are drugs that change the body’s weight regulatory system,” he said. “When someone loses weight, you get the shrinking of the fat cells, as well as the atrophy of the muscles. This rapid weight loss may give the appearance of one’s face changing.”
For some people, like Ms. Mendenall, the side effects are worth it. For others, like Ms. Carew, they’re intolerable.
Ms. Carew said she stopped the medication after about 7 months, and gradually worked up to eating solid foods again.
“It’s the American way, we’ve all got to be thin and beautiful,” she said. “But I feel like it’s very unsafe because we just don’t know how seriously our bodies will react to these things in the long term. People see it as a quick fix, but it comes with risks.”
A version of this article first appeared on WebMD.com.
Johnna Mendenall had never been “the skinny friend,” she said, but the demands of motherhood – along with a sedentary desk job – made weight management even more difficult. Worried that family type 2 diabetes would catch up with her, she decided to start Wegovy shots for weight loss.
She was nervous about potential side effects. It took 5 days of staring at the Wegovy pen before she worked up the nerve for her first .25-milligram shot. And sure enough, the side effects came on strong.
“The nausea kicked in,” she said. “When I increased my dose to 1 milligram, I spent the entire night from 10 p.m. to 5 a.m. vomiting. I almost quit that day.”
While gastrointestinal (GI) symptoms seem to be the most common, a laundry list of others has been discussed in the news, on TikTok, and across online forums. Those include “Ozempic face,” or the gaunt look some get after taking the medication, along with hair loss, anxiety, depression, and debilitating fatigue.
Ms. Mendenall’s primary side effects have been vomiting, fatigue, and severe constipation, but she has also seen some positive changes: The “food noise,” or the urge to eat when she isn’t hungry, is gone. Since her first dose 12 weeks ago, she has gone from 236 pounds to 215.
Warning label
Wegovy’s active ingredient, semaglutide, mimics the role of a natural hormone called glucagonlike peptide–1 (GLP-1), which helps you feel well fed. Semaglutide is used at a lower dose under the brand name Ozempic, which is approved for type 2 diabetes and used off-label for weight loss.
Both Ozempic and Wegovy come with a warning label for potential side effects, the most common ones being nausea, diarrhea, stomach pain, and vomiting.
With the surging popularity of semaglutide, more people are getting prescriptions through telemedicine companies, forgoing more in-depth consultations, leading to more side effects, said Caroline Apovian, MD, professor of medicine at Harvard Medical School and codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, Boston.
Specialists say starting with low doses and gradually increasing over time helps avoid side effects, but insurance companies often require a faster timeline to continue covering the medication, Dr. Apovian said.
“Insurance companies are practicing medicine for us by demanding the patient go up in dosage [too quickly],” she explained.
Ms. Mendenall’s insurance has paid for her Wegovy shots, but without that coverage, she said it would cost her $1,200 per month.
There are similar medications on the market, such as liraglutide, sold under the name Saxenda. But it is a daily, rather than a weekly, shot and also comes with side effects and has been shown to be less effective. In one clinical trial, the people being studied saw their average body weight over 68 weeks drop by 15.8% with semaglutide, and by 6.4% with liraglutide.
Tirzepatide, branded Mounjaro – a type 2 diabetes drug made by Eli Lilly that may soon gain Food and Drug Administration approval for weight loss – could have fewer side effects. In clinical trials, 44% of those taking semaglutide had nausea and 31% reported diarrhea, compared with 33% and 23% of those taking tirzepatide, although no trial has directly compared the two agents.
Loss of bowel control
For now, Wegovy and Saxenda are the only GLP-1 agonist shots authorized for weight loss, and their maker, Danish drug company Novo Nordisk, is facing its second shortage of Wegovy amid growing demand.
Personal stories online about semaglutide range from overwhelmingly positive – just what some need to win a lifelong battle with obesity – to harsh scenarios with potentially long-term health consequences, and everything in between.
One private community on Reddit is dedicated to a particularly unpleasant side effect: loss of bowel control while sleeping. Others have reported uncontrollable vomiting.
Kimberly Carew of Clearwater, Fla., started on .5 milligrams of Ozempic last year after her rheumatologist and endocrinologist suggested it to treat her type 2 diabetes. She was told it came with the bonus of weight loss, which she was hoping would help with her joint and back pain.
But after she increased the dose to 1 milligram, her GI symptoms, which started out mild, became unbearable. She couldn’t keep food down, and when she vomited, the food would often come up whole, she said.
“One night I ate ramen before bed. And the next morning, it came out just as it went down,” said Ms. Carew, 42, a registered mental health counseling intern. “I was getting severe heartburn and could not take a couple bites of food without getting nauseous.”
She also had “sulfur burps,” a side effect discussed by some Ozempic users, causing her to taste rotten egg sometimes.
She was diagnosed with gastroparesis. Some types of gastroparesis can be resolved by discontinuing GLP-1 medications, as referenced in two case reports in the Journal of Investigative Medicine.
Gut hormone
GI symptoms are most common with semaglutide because the hormone it imitates, GLP-1, is secreted by cells in the stomach, small intestines, and pancreas, said Anne Peters, MD, director of the USC Clinical Diabetes Programs.
“This is the deal: The side effects are real because it’s a gut hormone. It’s increasing the level of something your body already has,” she said.
But, like Dr. Apovian, Dr. Peters said those side effects can likely be avoided if shots are started at the lowest doses and gradually adjusted up.
While the average starting dose is .25 milligrams, Dr. Peters said she often starts her patients on about an eighth of that – just “a whiff of a dose.”
“It’ll take them months to get up to the starting dose, but what’s the rush?”
Dr. Peters said she also avoids giving diabetes patients the maximum dose, which is 2 milligrams per week for Ozempic (and 2.4 milligrams for Wegovy for weight loss).
When asked about the drugs’ side effects, Novo Nordisk responded that “GLP-1 receptor agonists are a well-established class of medicines, which have demonstrated long-term safety in clinical trials. The most common adverse reactions, as with all GLP-1 [agonists], are gastrointestinal related.”
Is it the drug or the weight loss?
Still, non-gastrointestinal side effects such as hair loss, mood changes, and sunken facial features are reported among semaglutide users across the Internet. While these cases are often anecdotal, they can be very heartfelt.
Celina Horvath Myers, also known as CelinaSpookyBoo, a Canadian YouTuber who took Ozempic for type 2 diabetes, said she began having intense panic attacks and depression after starting the medication.
“Who I have been these last couple weeks, has probably been the scariest time of my life,” she said on her YouTube channel.
While severe depression and anxiety are not established side effects of the medication, some people get anhedonia, said W. Scott Butsch, MD, MSc, director of obesity medicine in the Bariatric and Metabolic Institute at Cleveland Clinic. But that could be a natural consequence of lower appetite, he said, given that food gives most people pleasure in the moment.
Many other reported changes come from the weight loss itself, not the medication, said Dr. Butsch.
“These are drugs that change the body’s weight regulatory system,” he said. “When someone loses weight, you get the shrinking of the fat cells, as well as the atrophy of the muscles. This rapid weight loss may give the appearance of one’s face changing.”
For some people, like Ms. Mendenall, the side effects are worth it. For others, like Ms. Carew, they’re intolerable.
Ms. Carew said she stopped the medication after about 7 months, and gradually worked up to eating solid foods again.
“It’s the American way, we’ve all got to be thin and beautiful,” she said. “But I feel like it’s very unsafe because we just don’t know how seriously our bodies will react to these things in the long term. People see it as a quick fix, but it comes with risks.”
A version of this article first appeared on WebMD.com.
Johnna Mendenall had never been “the skinny friend,” she said, but the demands of motherhood – along with a sedentary desk job – made weight management even more difficult. Worried that family type 2 diabetes would catch up with her, she decided to start Wegovy shots for weight loss.
She was nervous about potential side effects. It took 5 days of staring at the Wegovy pen before she worked up the nerve for her first .25-milligram shot. And sure enough, the side effects came on strong.
“The nausea kicked in,” she said. “When I increased my dose to 1 milligram, I spent the entire night from 10 p.m. to 5 a.m. vomiting. I almost quit that day.”
While gastrointestinal (GI) symptoms seem to be the most common, a laundry list of others has been discussed in the news, on TikTok, and across online forums. Those include “Ozempic face,” or the gaunt look some get after taking the medication, along with hair loss, anxiety, depression, and debilitating fatigue.
Ms. Mendenall’s primary side effects have been vomiting, fatigue, and severe constipation, but she has also seen some positive changes: The “food noise,” or the urge to eat when she isn’t hungry, is gone. Since her first dose 12 weeks ago, she has gone from 236 pounds to 215.
Warning label
Wegovy’s active ingredient, semaglutide, mimics the role of a natural hormone called glucagonlike peptide–1 (GLP-1), which helps you feel well fed. Semaglutide is used at a lower dose under the brand name Ozempic, which is approved for type 2 diabetes and used off-label for weight loss.
Both Ozempic and Wegovy come with a warning label for potential side effects, the most common ones being nausea, diarrhea, stomach pain, and vomiting.
With the surging popularity of semaglutide, more people are getting prescriptions through telemedicine companies, forgoing more in-depth consultations, leading to more side effects, said Caroline Apovian, MD, professor of medicine at Harvard Medical School and codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, Boston.
Specialists say starting with low doses and gradually increasing over time helps avoid side effects, but insurance companies often require a faster timeline to continue covering the medication, Dr. Apovian said.
“Insurance companies are practicing medicine for us by demanding the patient go up in dosage [too quickly],” she explained.
Ms. Mendenall’s insurance has paid for her Wegovy shots, but without that coverage, she said it would cost her $1,200 per month.
There are similar medications on the market, such as liraglutide, sold under the name Saxenda. But it is a daily, rather than a weekly, shot and also comes with side effects and has been shown to be less effective. In one clinical trial, the people being studied saw their average body weight over 68 weeks drop by 15.8% with semaglutide, and by 6.4% with liraglutide.
Tirzepatide, branded Mounjaro – a type 2 diabetes drug made by Eli Lilly that may soon gain Food and Drug Administration approval for weight loss – could have fewer side effects. In clinical trials, 44% of those taking semaglutide had nausea and 31% reported diarrhea, compared with 33% and 23% of those taking tirzepatide, although no trial has directly compared the two agents.
Loss of bowel control
For now, Wegovy and Saxenda are the only GLP-1 agonist shots authorized for weight loss, and their maker, Danish drug company Novo Nordisk, is facing its second shortage of Wegovy amid growing demand.
Personal stories online about semaglutide range from overwhelmingly positive – just what some need to win a lifelong battle with obesity – to harsh scenarios with potentially long-term health consequences, and everything in between.
One private community on Reddit is dedicated to a particularly unpleasant side effect: loss of bowel control while sleeping. Others have reported uncontrollable vomiting.
Kimberly Carew of Clearwater, Fla., started on .5 milligrams of Ozempic last year after her rheumatologist and endocrinologist suggested it to treat her type 2 diabetes. She was told it came with the bonus of weight loss, which she was hoping would help with her joint and back pain.
But after she increased the dose to 1 milligram, her GI symptoms, which started out mild, became unbearable. She couldn’t keep food down, and when she vomited, the food would often come up whole, she said.
“One night I ate ramen before bed. And the next morning, it came out just as it went down,” said Ms. Carew, 42, a registered mental health counseling intern. “I was getting severe heartburn and could not take a couple bites of food without getting nauseous.”
She also had “sulfur burps,” a side effect discussed by some Ozempic users, causing her to taste rotten egg sometimes.
She was diagnosed with gastroparesis. Some types of gastroparesis can be resolved by discontinuing GLP-1 medications, as referenced in two case reports in the Journal of Investigative Medicine.
Gut hormone
GI symptoms are most common with semaglutide because the hormone it imitates, GLP-1, is secreted by cells in the stomach, small intestines, and pancreas, said Anne Peters, MD, director of the USC Clinical Diabetes Programs.
“This is the deal: The side effects are real because it’s a gut hormone. It’s increasing the level of something your body already has,” she said.
But, like Dr. Apovian, Dr. Peters said those side effects can likely be avoided if shots are started at the lowest doses and gradually adjusted up.
While the average starting dose is .25 milligrams, Dr. Peters said she often starts her patients on about an eighth of that – just “a whiff of a dose.”
“It’ll take them months to get up to the starting dose, but what’s the rush?”
Dr. Peters said she also avoids giving diabetes patients the maximum dose, which is 2 milligrams per week for Ozempic (and 2.4 milligrams for Wegovy for weight loss).
When asked about the drugs’ side effects, Novo Nordisk responded that “GLP-1 receptor agonists are a well-established class of medicines, which have demonstrated long-term safety in clinical trials. The most common adverse reactions, as with all GLP-1 [agonists], are gastrointestinal related.”
Is it the drug or the weight loss?
Still, non-gastrointestinal side effects such as hair loss, mood changes, and sunken facial features are reported among semaglutide users across the Internet. While these cases are often anecdotal, they can be very heartfelt.
Celina Horvath Myers, also known as CelinaSpookyBoo, a Canadian YouTuber who took Ozempic for type 2 diabetes, said she began having intense panic attacks and depression after starting the medication.
“Who I have been these last couple weeks, has probably been the scariest time of my life,” she said on her YouTube channel.
While severe depression and anxiety are not established side effects of the medication, some people get anhedonia, said W. Scott Butsch, MD, MSc, director of obesity medicine in the Bariatric and Metabolic Institute at Cleveland Clinic. But that could be a natural consequence of lower appetite, he said, given that food gives most people pleasure in the moment.
Many other reported changes come from the weight loss itself, not the medication, said Dr. Butsch.
“These are drugs that change the body’s weight regulatory system,” he said. “When someone loses weight, you get the shrinking of the fat cells, as well as the atrophy of the muscles. This rapid weight loss may give the appearance of one’s face changing.”
For some people, like Ms. Mendenall, the side effects are worth it. For others, like Ms. Carew, they’re intolerable.
Ms. Carew said she stopped the medication after about 7 months, and gradually worked up to eating solid foods again.
“It’s the American way, we’ve all got to be thin and beautiful,” she said. “But I feel like it’s very unsafe because we just don’t know how seriously our bodies will react to these things in the long term. People see it as a quick fix, but it comes with risks.”
A version of this article first appeared on WebMD.com.
PTSD: Children, adolescents, and all of us may be at risk
Not everyone will suffer an episode of posttraumatic stress disorder, even though everyday American life is characterized by a lot of uncertainty these days, particularly considering the proliferation of gun violence.
Also, everyone who does experience a traumatic event will not suffer an episode of PTSD – just as not everyone develops a heart attack or cancer, nor will everyone get every illness.
The data suggest that of those exposed to trauma, up to 25% of people will develop PTSD, according to Massachusetts General/McLean Hospital, Belmont, psychiatrist Kerry J. Ressler, MD, PhD, chief of the division of depression and anxiety disorders.
As I wrote in December 2022, our “kids” are not all right and psychiatry can help. I would say that many adolescents, and adults as well, may not be all right as we are terrorized not only by mass school shootings, but shootings happening almost anywhere and everywhere in our country: in supermarkets, hospitals, and shopping malls, at graduation parties, and on the streets.
According to a report published in Clinical Psychiatry News, a poll conducted by the American Psychiatric Association showed that most American adults [70%] reported that they were anxious or extremely anxious about keeping themselves or their families safe. APA President Rebecca W. Brendel, MD, JD, pointed out that there is “a lot of worry out there about economic uncertainty, about violence and how we are going to come out of this time period.”
Meanwhile, PTSD is still defined in the DSM-5 as exposure to actual or threatened death, serious injury, or sexual violence experienced directly, witnessing the traumatic event as it occurs to others, learning that a traumatic event occurred to a close family member or friend, or experiencing of traumatic events plus extreme exposure to aversive details of the event.
Examples of traumatic events can be numerous. They include natural disasters, man-made disasters, various types of assaults, war trauma, and severe illness with ICU experiences. I would add encounters with racism and bigotry – including homophobia when one fears for their very life or physical injury. This list includes only a few triggers that may invoke this disorder.
Interestingly, the DSM-5 excludes aversive exposure through electronic media, television, movies, or pictures. Including these aspects of trauma exposure would indeed increase PTSD diagnoses, and I believe this type of exposure needs to be included, especially considering how different people process information. Some viewers of media remain “outside” the events depicted on television, movies, or electronic media while others fit directly “into” the film or TV show. Even, for example, a news program, as evidenced by those people suffering from PTSD after viewing the Sept. 11, 2001, disaster on TV.
I have interviewed numerous people who witnessed Sept. 11 tragedies on TV, some during and some after the event, and they genuinely had experienced key factors of PTSD, including nightmares and intrusive recollections of the event. It’s important to include the ways in which people process information and events in order to make a correct diagnosis, in that “one [diagnostic] size does not fit all.”
PTSD at school
In my December column, I noted the fear of death that my generation and beyond experienced with the endless threat of nuclear war, which by its very nature meant death, and if not, the saying went “the living would envy the dead” – that is, in post–nuclear war.
As I pointed out in the column, that war never came and hopefully never will, yet the intensity of those many decades of threatened terror with regular school exercises of “hide under the desk” and “don’t look at the flash” left some with intrusive fearful thoughts, nightmares, and even visualization of atomic destruction, as well as the many scenes of destruction portrayed in news casts and films of nuclear explosions.
Clearly, most U.S. school children who participate in school lockdown drills will not suffer from PTSD episodes, but some will. If that “some” approaches 20% or even 10% or less, that will amount to a lot of kids.
I decided to interview two of my grandchildren, each living in different communities and attending different school systems, but both experiencing “lockdown drills.”
Jack, who is 13 and going into eighth grade, was quite clear regarding the drills and reported that in his age group, both he and the kids in his class felt scared while in lockdown. He told me some kids looked nervous. He mentioned that they were taught in school that if the “real thing” happened, the message was “hide, run, and fight.” I was curious and asked why not run first. He was quick to answer and said if you run, you might run into danger, so it’s better to hide and wait for help to arrive. I said to myself, if not PTSD, then being scared or nervous may also lead to anxiety or even to an anxiety disorder.
Next, I interviewed almost 11-year-old Charley, who is going into sixth grade. She was very clear about not at all being fearful or nervous during these drills and was confident that her classmates felt the same way. Then she explained that the school did a great job with a security officer and had locked doors all around that only opened from the inside. She was proud of the school and not fearful or worried at all.
The diverse views of these two young people surprised me but confirm that PTSD is not at all a given based on what is occurring in society. However, it should always be considered by clinicians if a child or adolescent begins to show signs consistent with PTSD.
These two interviews were quite short, but after I finished talking with Charley, she reported spontaneously that while she and her classmates were neither worried nor scared, some of their teachers did look nervous and seemed scared.
I was quite impressed with her sharpness and nuanced observation, and as noted, adults as well may be adversely affected by the entire concept of school lockdowns, as the awareness of their purpose rests in the forefront of their minds.
The way forward
So how do we prepare kids and adolescents for potential emotional problems like PTSD arising from lockdowns, even though most children or adults will not suffer any of these PTSD issues?
First, I believe that Second, it is important that school children be aware that if they feel bad in any way emotionally, they should speak to their parents, guardians, teachers, or school nurses.
Clearly, communicating simple problems without embarrassment or shame can lead to solutions, often quickly. Larger, more complicated issues may need professional intervention. Equally important, many mental health interventions need not be long in duration but client-centered, focused, and short term.
But what needs to be emphasized is that speaking and addressing what’s going on, if your thoughts and emotions are troubling, are in themselves therapeutic. Talk therapy works – especially if you get a new perspective on the old set of problems.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
Not everyone will suffer an episode of posttraumatic stress disorder, even though everyday American life is characterized by a lot of uncertainty these days, particularly considering the proliferation of gun violence.
Also, everyone who does experience a traumatic event will not suffer an episode of PTSD – just as not everyone develops a heart attack or cancer, nor will everyone get every illness.
The data suggest that of those exposed to trauma, up to 25% of people will develop PTSD, according to Massachusetts General/McLean Hospital, Belmont, psychiatrist Kerry J. Ressler, MD, PhD, chief of the division of depression and anxiety disorders.
As I wrote in December 2022, our “kids” are not all right and psychiatry can help. I would say that many adolescents, and adults as well, may not be all right as we are terrorized not only by mass school shootings, but shootings happening almost anywhere and everywhere in our country: in supermarkets, hospitals, and shopping malls, at graduation parties, and on the streets.
According to a report published in Clinical Psychiatry News, a poll conducted by the American Psychiatric Association showed that most American adults [70%] reported that they were anxious or extremely anxious about keeping themselves or their families safe. APA President Rebecca W. Brendel, MD, JD, pointed out that there is “a lot of worry out there about economic uncertainty, about violence and how we are going to come out of this time period.”
Meanwhile, PTSD is still defined in the DSM-5 as exposure to actual or threatened death, serious injury, or sexual violence experienced directly, witnessing the traumatic event as it occurs to others, learning that a traumatic event occurred to a close family member or friend, or experiencing of traumatic events plus extreme exposure to aversive details of the event.
Examples of traumatic events can be numerous. They include natural disasters, man-made disasters, various types of assaults, war trauma, and severe illness with ICU experiences. I would add encounters with racism and bigotry – including homophobia when one fears for their very life or physical injury. This list includes only a few triggers that may invoke this disorder.
Interestingly, the DSM-5 excludes aversive exposure through electronic media, television, movies, or pictures. Including these aspects of trauma exposure would indeed increase PTSD diagnoses, and I believe this type of exposure needs to be included, especially considering how different people process information. Some viewers of media remain “outside” the events depicted on television, movies, or electronic media while others fit directly “into” the film or TV show. Even, for example, a news program, as evidenced by those people suffering from PTSD after viewing the Sept. 11, 2001, disaster on TV.
I have interviewed numerous people who witnessed Sept. 11 tragedies on TV, some during and some after the event, and they genuinely had experienced key factors of PTSD, including nightmares and intrusive recollections of the event. It’s important to include the ways in which people process information and events in order to make a correct diagnosis, in that “one [diagnostic] size does not fit all.”
PTSD at school
In my December column, I noted the fear of death that my generation and beyond experienced with the endless threat of nuclear war, which by its very nature meant death, and if not, the saying went “the living would envy the dead” – that is, in post–nuclear war.
As I pointed out in the column, that war never came and hopefully never will, yet the intensity of those many decades of threatened terror with regular school exercises of “hide under the desk” and “don’t look at the flash” left some with intrusive fearful thoughts, nightmares, and even visualization of atomic destruction, as well as the many scenes of destruction portrayed in news casts and films of nuclear explosions.
Clearly, most U.S. school children who participate in school lockdown drills will not suffer from PTSD episodes, but some will. If that “some” approaches 20% or even 10% or less, that will amount to a lot of kids.
I decided to interview two of my grandchildren, each living in different communities and attending different school systems, but both experiencing “lockdown drills.”
Jack, who is 13 and going into eighth grade, was quite clear regarding the drills and reported that in his age group, both he and the kids in his class felt scared while in lockdown. He told me some kids looked nervous. He mentioned that they were taught in school that if the “real thing” happened, the message was “hide, run, and fight.” I was curious and asked why not run first. He was quick to answer and said if you run, you might run into danger, so it’s better to hide and wait for help to arrive. I said to myself, if not PTSD, then being scared or nervous may also lead to anxiety or even to an anxiety disorder.
Next, I interviewed almost 11-year-old Charley, who is going into sixth grade. She was very clear about not at all being fearful or nervous during these drills and was confident that her classmates felt the same way. Then she explained that the school did a great job with a security officer and had locked doors all around that only opened from the inside. She was proud of the school and not fearful or worried at all.
The diverse views of these two young people surprised me but confirm that PTSD is not at all a given based on what is occurring in society. However, it should always be considered by clinicians if a child or adolescent begins to show signs consistent with PTSD.
These two interviews were quite short, but after I finished talking with Charley, she reported spontaneously that while she and her classmates were neither worried nor scared, some of their teachers did look nervous and seemed scared.
I was quite impressed with her sharpness and nuanced observation, and as noted, adults as well may be adversely affected by the entire concept of school lockdowns, as the awareness of their purpose rests in the forefront of their minds.
The way forward
So how do we prepare kids and adolescents for potential emotional problems like PTSD arising from lockdowns, even though most children or adults will not suffer any of these PTSD issues?
First, I believe that Second, it is important that school children be aware that if they feel bad in any way emotionally, they should speak to their parents, guardians, teachers, or school nurses.
Clearly, communicating simple problems without embarrassment or shame can lead to solutions, often quickly. Larger, more complicated issues may need professional intervention. Equally important, many mental health interventions need not be long in duration but client-centered, focused, and short term.
But what needs to be emphasized is that speaking and addressing what’s going on, if your thoughts and emotions are troubling, are in themselves therapeutic. Talk therapy works – especially if you get a new perspective on the old set of problems.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
Not everyone will suffer an episode of posttraumatic stress disorder, even though everyday American life is characterized by a lot of uncertainty these days, particularly considering the proliferation of gun violence.
Also, everyone who does experience a traumatic event will not suffer an episode of PTSD – just as not everyone develops a heart attack or cancer, nor will everyone get every illness.
The data suggest that of those exposed to trauma, up to 25% of people will develop PTSD, according to Massachusetts General/McLean Hospital, Belmont, psychiatrist Kerry J. Ressler, MD, PhD, chief of the division of depression and anxiety disorders.
As I wrote in December 2022, our “kids” are not all right and psychiatry can help. I would say that many adolescents, and adults as well, may not be all right as we are terrorized not only by mass school shootings, but shootings happening almost anywhere and everywhere in our country: in supermarkets, hospitals, and shopping malls, at graduation parties, and on the streets.
According to a report published in Clinical Psychiatry News, a poll conducted by the American Psychiatric Association showed that most American adults [70%] reported that they were anxious or extremely anxious about keeping themselves or their families safe. APA President Rebecca W. Brendel, MD, JD, pointed out that there is “a lot of worry out there about economic uncertainty, about violence and how we are going to come out of this time period.”
Meanwhile, PTSD is still defined in the DSM-5 as exposure to actual or threatened death, serious injury, or sexual violence experienced directly, witnessing the traumatic event as it occurs to others, learning that a traumatic event occurred to a close family member or friend, or experiencing of traumatic events plus extreme exposure to aversive details of the event.
Examples of traumatic events can be numerous. They include natural disasters, man-made disasters, various types of assaults, war trauma, and severe illness with ICU experiences. I would add encounters with racism and bigotry – including homophobia when one fears for their very life or physical injury. This list includes only a few triggers that may invoke this disorder.
Interestingly, the DSM-5 excludes aversive exposure through electronic media, television, movies, or pictures. Including these aspects of trauma exposure would indeed increase PTSD diagnoses, and I believe this type of exposure needs to be included, especially considering how different people process information. Some viewers of media remain “outside” the events depicted on television, movies, or electronic media while others fit directly “into” the film or TV show. Even, for example, a news program, as evidenced by those people suffering from PTSD after viewing the Sept. 11, 2001, disaster on TV.
I have interviewed numerous people who witnessed Sept. 11 tragedies on TV, some during and some after the event, and they genuinely had experienced key factors of PTSD, including nightmares and intrusive recollections of the event. It’s important to include the ways in which people process information and events in order to make a correct diagnosis, in that “one [diagnostic] size does not fit all.”
PTSD at school
In my December column, I noted the fear of death that my generation and beyond experienced with the endless threat of nuclear war, which by its very nature meant death, and if not, the saying went “the living would envy the dead” – that is, in post–nuclear war.
As I pointed out in the column, that war never came and hopefully never will, yet the intensity of those many decades of threatened terror with regular school exercises of “hide under the desk” and “don’t look at the flash” left some with intrusive fearful thoughts, nightmares, and even visualization of atomic destruction, as well as the many scenes of destruction portrayed in news casts and films of nuclear explosions.
Clearly, most U.S. school children who participate in school lockdown drills will not suffer from PTSD episodes, but some will. If that “some” approaches 20% or even 10% or less, that will amount to a lot of kids.
I decided to interview two of my grandchildren, each living in different communities and attending different school systems, but both experiencing “lockdown drills.”
Jack, who is 13 and going into eighth grade, was quite clear regarding the drills and reported that in his age group, both he and the kids in his class felt scared while in lockdown. He told me some kids looked nervous. He mentioned that they were taught in school that if the “real thing” happened, the message was “hide, run, and fight.” I was curious and asked why not run first. He was quick to answer and said if you run, you might run into danger, so it’s better to hide and wait for help to arrive. I said to myself, if not PTSD, then being scared or nervous may also lead to anxiety or even to an anxiety disorder.
Next, I interviewed almost 11-year-old Charley, who is going into sixth grade. She was very clear about not at all being fearful or nervous during these drills and was confident that her classmates felt the same way. Then she explained that the school did a great job with a security officer and had locked doors all around that only opened from the inside. She was proud of the school and not fearful or worried at all.
The diverse views of these two young people surprised me but confirm that PTSD is not at all a given based on what is occurring in society. However, it should always be considered by clinicians if a child or adolescent begins to show signs consistent with PTSD.
These two interviews were quite short, but after I finished talking with Charley, she reported spontaneously that while she and her classmates were neither worried nor scared, some of their teachers did look nervous and seemed scared.
I was quite impressed with her sharpness and nuanced observation, and as noted, adults as well may be adversely affected by the entire concept of school lockdowns, as the awareness of their purpose rests in the forefront of their minds.
The way forward
So how do we prepare kids and adolescents for potential emotional problems like PTSD arising from lockdowns, even though most children or adults will not suffer any of these PTSD issues?
First, I believe that Second, it is important that school children be aware that if they feel bad in any way emotionally, they should speak to their parents, guardians, teachers, or school nurses.
Clearly, communicating simple problems without embarrassment or shame can lead to solutions, often quickly. Larger, more complicated issues may need professional intervention. Equally important, many mental health interventions need not be long in duration but client-centered, focused, and short term.
But what needs to be emphasized is that speaking and addressing what’s going on, if your thoughts and emotions are troubling, are in themselves therapeutic. Talk therapy works – especially if you get a new perspective on the old set of problems.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
Good COP, bad COP. Is this cardiorespiratory measure the best predictor of early death?
according to clinicians who champion the assessment. The COP is easier to obtain than cardiorespiratory measures that require people to exercise to their limit, advocates say; rather than running full speed, someone can walk or lightly jog on a treadmill, with a COP value obtained easily.
But other clinicians argue that maximal exercise tests have many prognostic benefits, and that physicians should do everything in their power to push patients to exercise as hard as possible. In particular, the VO2 max test captures the maximum amount of oxygen someone uses when exercising at their capacity and is the preferred method for measuring cardiovascular endurance.
The COP is a measure of the minimum number of liters of air during breathing required to move one liter of oxygen through the bloodstream. The lower the COP the better, because this means that someone is working less strenuously than someone else to transport the same amount of oxygen, denoting a more efficient interaction between their heart and lungs.
The COP for a fit person might be 15, about 20-25 for a healthy person, and 35 for someone with heart failure, according to Claudio Gil Araújo, MD, PhD, director of research and education at CLINIMEX, an exercise medicine clinic in Rio de Janeiro.
“Max VO2 is very important, that’s indisputable. But when do you use max VO2 in your daily life? Never,” Dr. Araújo said. But almost anyone can generate a COP.
Emerging uses for the COP
“I can put someone on the treadmill or bike, and after 3 or 4 minutes I have the COP. It’s like a walking pace,” Dr. Araújo said. Yet the values are obtained with roughly half the effort as VO2 max. Other clinicians argue exercising to the limits of endurance offers unique clinical insights.
“We should do everything in our power to exercise our patients to maximum. How long a patient is able to go is really important,” said Anu Lala, MD, a cardiologist who specializes in heart failure treatment at Mount Sinai Hospital in New York. A full-capacity exercise test gives useful insights into someone’s heart rate, heart rate recovery, blood pressure, and ECG response to vigorous exercise, Dr. Lala added, all of which are important clues to someone’s overall health.
In 2012 Dr. Araújo coauthored a study that first defined the COP, which is calculated by measuring expired gasses people produce while gently exercising, perhaps to the point where they begin to perspire, and then dividing their breathing capacity by their oxygen uptake every minute. The lowest value obtained during any exercise session is the COP.
Various studies show that higher COP values are associated with more severe heart lesions in patients with congenital heart disease; higher levels of mortality in seemingly healthy male adults; and with worse prognoses in patients with heart failure. These studies all appeared within the last 7 months.
The mortality study, which Dr. Araújo coauthored, compared COP in more than 3,000 U.S. men and women who completed an exercise test from 1973 to 2018 and were tracked for an average of 23 years. Although COP was introduced as an assessment in 2012, calculating the value from tests prior to that date was possible because those tests had captured the relevant breathing rate and oxygen uptake. In males aged 18-85 years, a worse COP was significantly associated with an increased risk for earlier death. This finding did not hold for females, however; Dr. Araújo noted that more research is needed to understand the discrepancy in COP’s predictive power by sex.
In the heart failure study, everyone enrolled had heart failure and completed a COP test. People with the worse COPs also had the worst symptoms of heart failure, but completing an exercise rehabilitation program improved COP values when researchers measured them again. Dr. Araújo was also part of this study, based in the Netherlands.
“I think the COP could become a novel parameter in clinical care,” for most people, said Thijs Eijsvogels, PhD, an exercise physiologist at Radboud University in Nijmegen, the Netherlands, and the senior author of the heart failure study. That said, Dr. Eijsvogels said elite athletes will always be more interested in measuring VO2 max.
Dr. Lala agreed that tests such as the COP have some value. Her own work has shown that measuring the efficiency of someone’s breathing patterns for exhaling carbon dioxide, which can also be done without making people exercise full strength, has prognostic value for patients with advanced heart failure. Even so, she said she would like to see maximal effort tests used as much as possible.
“I worry about saying we’re going to settle for a parameter that can be achieved at 50% of peak VO2 and then we don’t exercise our patients,” Dr. Lala said.
Dr. Araújo said he plans to continue to measure VO2 max but he believes COP has utility – even for elite athletes. One of his patients is a frequent Ironman competitor who competes well despite having a solid but not amazing VO2 max level. But her COP is quite low, Dr. Araújo said, which to him suggests an especially efficient interaction between her respiratory and cardiovascular systems.
“We have a new player in the game,” Dr. Araújo said.
The sources in this study report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to clinicians who champion the assessment. The COP is easier to obtain than cardiorespiratory measures that require people to exercise to their limit, advocates say; rather than running full speed, someone can walk or lightly jog on a treadmill, with a COP value obtained easily.
But other clinicians argue that maximal exercise tests have many prognostic benefits, and that physicians should do everything in their power to push patients to exercise as hard as possible. In particular, the VO2 max test captures the maximum amount of oxygen someone uses when exercising at their capacity and is the preferred method for measuring cardiovascular endurance.
The COP is a measure of the minimum number of liters of air during breathing required to move one liter of oxygen through the bloodstream. The lower the COP the better, because this means that someone is working less strenuously than someone else to transport the same amount of oxygen, denoting a more efficient interaction between their heart and lungs.
The COP for a fit person might be 15, about 20-25 for a healthy person, and 35 for someone with heart failure, according to Claudio Gil Araújo, MD, PhD, director of research and education at CLINIMEX, an exercise medicine clinic in Rio de Janeiro.
“Max VO2 is very important, that’s indisputable. But when do you use max VO2 in your daily life? Never,” Dr. Araújo said. But almost anyone can generate a COP.
Emerging uses for the COP
“I can put someone on the treadmill or bike, and after 3 or 4 minutes I have the COP. It’s like a walking pace,” Dr. Araújo said. Yet the values are obtained with roughly half the effort as VO2 max. Other clinicians argue exercising to the limits of endurance offers unique clinical insights.
“We should do everything in our power to exercise our patients to maximum. How long a patient is able to go is really important,” said Anu Lala, MD, a cardiologist who specializes in heart failure treatment at Mount Sinai Hospital in New York. A full-capacity exercise test gives useful insights into someone’s heart rate, heart rate recovery, blood pressure, and ECG response to vigorous exercise, Dr. Lala added, all of which are important clues to someone’s overall health.
In 2012 Dr. Araújo coauthored a study that first defined the COP, which is calculated by measuring expired gasses people produce while gently exercising, perhaps to the point where they begin to perspire, and then dividing their breathing capacity by their oxygen uptake every minute. The lowest value obtained during any exercise session is the COP.
Various studies show that higher COP values are associated with more severe heart lesions in patients with congenital heart disease; higher levels of mortality in seemingly healthy male adults; and with worse prognoses in patients with heart failure. These studies all appeared within the last 7 months.
The mortality study, which Dr. Araújo coauthored, compared COP in more than 3,000 U.S. men and women who completed an exercise test from 1973 to 2018 and were tracked for an average of 23 years. Although COP was introduced as an assessment in 2012, calculating the value from tests prior to that date was possible because those tests had captured the relevant breathing rate and oxygen uptake. In males aged 18-85 years, a worse COP was significantly associated with an increased risk for earlier death. This finding did not hold for females, however; Dr. Araújo noted that more research is needed to understand the discrepancy in COP’s predictive power by sex.
In the heart failure study, everyone enrolled had heart failure and completed a COP test. People with the worse COPs also had the worst symptoms of heart failure, but completing an exercise rehabilitation program improved COP values when researchers measured them again. Dr. Araújo was also part of this study, based in the Netherlands.
“I think the COP could become a novel parameter in clinical care,” for most people, said Thijs Eijsvogels, PhD, an exercise physiologist at Radboud University in Nijmegen, the Netherlands, and the senior author of the heart failure study. That said, Dr. Eijsvogels said elite athletes will always be more interested in measuring VO2 max.
Dr. Lala agreed that tests such as the COP have some value. Her own work has shown that measuring the efficiency of someone’s breathing patterns for exhaling carbon dioxide, which can also be done without making people exercise full strength, has prognostic value for patients with advanced heart failure. Even so, she said she would like to see maximal effort tests used as much as possible.
“I worry about saying we’re going to settle for a parameter that can be achieved at 50% of peak VO2 and then we don’t exercise our patients,” Dr. Lala said.
Dr. Araújo said he plans to continue to measure VO2 max but he believes COP has utility – even for elite athletes. One of his patients is a frequent Ironman competitor who competes well despite having a solid but not amazing VO2 max level. But her COP is quite low, Dr. Araújo said, which to him suggests an especially efficient interaction between her respiratory and cardiovascular systems.
“We have a new player in the game,” Dr. Araújo said.
The sources in this study report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to clinicians who champion the assessment. The COP is easier to obtain than cardiorespiratory measures that require people to exercise to their limit, advocates say; rather than running full speed, someone can walk or lightly jog on a treadmill, with a COP value obtained easily.
But other clinicians argue that maximal exercise tests have many prognostic benefits, and that physicians should do everything in their power to push patients to exercise as hard as possible. In particular, the VO2 max test captures the maximum amount of oxygen someone uses when exercising at their capacity and is the preferred method for measuring cardiovascular endurance.
The COP is a measure of the minimum number of liters of air during breathing required to move one liter of oxygen through the bloodstream. The lower the COP the better, because this means that someone is working less strenuously than someone else to transport the same amount of oxygen, denoting a more efficient interaction between their heart and lungs.
The COP for a fit person might be 15, about 20-25 for a healthy person, and 35 for someone with heart failure, according to Claudio Gil Araújo, MD, PhD, director of research and education at CLINIMEX, an exercise medicine clinic in Rio de Janeiro.
“Max VO2 is very important, that’s indisputable. But when do you use max VO2 in your daily life? Never,” Dr. Araújo said. But almost anyone can generate a COP.
Emerging uses for the COP
“I can put someone on the treadmill or bike, and after 3 or 4 minutes I have the COP. It’s like a walking pace,” Dr. Araújo said. Yet the values are obtained with roughly half the effort as VO2 max. Other clinicians argue exercising to the limits of endurance offers unique clinical insights.
“We should do everything in our power to exercise our patients to maximum. How long a patient is able to go is really important,” said Anu Lala, MD, a cardiologist who specializes in heart failure treatment at Mount Sinai Hospital in New York. A full-capacity exercise test gives useful insights into someone’s heart rate, heart rate recovery, blood pressure, and ECG response to vigorous exercise, Dr. Lala added, all of which are important clues to someone’s overall health.
In 2012 Dr. Araújo coauthored a study that first defined the COP, which is calculated by measuring expired gasses people produce while gently exercising, perhaps to the point where they begin to perspire, and then dividing their breathing capacity by their oxygen uptake every minute. The lowest value obtained during any exercise session is the COP.
Various studies show that higher COP values are associated with more severe heart lesions in patients with congenital heart disease; higher levels of mortality in seemingly healthy male adults; and with worse prognoses in patients with heart failure. These studies all appeared within the last 7 months.
The mortality study, which Dr. Araújo coauthored, compared COP in more than 3,000 U.S. men and women who completed an exercise test from 1973 to 2018 and were tracked for an average of 23 years. Although COP was introduced as an assessment in 2012, calculating the value from tests prior to that date was possible because those tests had captured the relevant breathing rate and oxygen uptake. In males aged 18-85 years, a worse COP was significantly associated with an increased risk for earlier death. This finding did not hold for females, however; Dr. Araújo noted that more research is needed to understand the discrepancy in COP’s predictive power by sex.
In the heart failure study, everyone enrolled had heart failure and completed a COP test. People with the worse COPs also had the worst symptoms of heart failure, but completing an exercise rehabilitation program improved COP values when researchers measured them again. Dr. Araújo was also part of this study, based in the Netherlands.
“I think the COP could become a novel parameter in clinical care,” for most people, said Thijs Eijsvogels, PhD, an exercise physiologist at Radboud University in Nijmegen, the Netherlands, and the senior author of the heart failure study. That said, Dr. Eijsvogels said elite athletes will always be more interested in measuring VO2 max.
Dr. Lala agreed that tests such as the COP have some value. Her own work has shown that measuring the efficiency of someone’s breathing patterns for exhaling carbon dioxide, which can also be done without making people exercise full strength, has prognostic value for patients with advanced heart failure. Even so, she said she would like to see maximal effort tests used as much as possible.
“I worry about saying we’re going to settle for a parameter that can be achieved at 50% of peak VO2 and then we don’t exercise our patients,” Dr. Lala said.
Dr. Araújo said he plans to continue to measure VO2 max but he believes COP has utility – even for elite athletes. One of his patients is a frequent Ironman competitor who competes well despite having a solid but not amazing VO2 max level. But her COP is quite low, Dr. Araújo said, which to him suggests an especially efficient interaction between her respiratory and cardiovascular systems.
“We have a new player in the game,” Dr. Araújo said.
The sources in this study report no relevant financial relationships.
A version of this article first appeared on Medscape.com.