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Heart attack care not equal for women and people of color
Radiating chest pain, shortness of breath, nausea, lightheadedness. Everyone knows the telltale signs of a myocardial infarction. Yet a new study shows that despite this widespread recognition, heart attacks aren’t attended to quickly across the board. Historically, the study says, women and people of color wait longer to access emergency care for a heart attack.
Researchers from the University of California, San Francisco published these findings in the Annals of Emergency Medicine. The study used the Office of Statewide Health Planning and Development dataset to gather information on 453,136 cases of heart attack in California between 2005 and 2015. They found that over time, differences in timely treatment between the demographics narrowed, but the gap still existed.
The study defined timely treatment as receiving care for a heart attack within 3 days of admission to a hospital. Women and people of color were found to wait 3 days or more to receive care than their White male counterparts. A disparity of this sort can cause ripples of health effects across society, ripples that doctors should be aware of, says lead author Juan Carlos Montoy, MD. Dr. Montoy was “sadly surprised by our findings that disparities for women and for Black patients only decreased slightly or not at all over time.”
In the study, the team separated the dataset between the two primary types of heart attack: ST-segment elevation myocardial infarction (STEMI), caused by blood vessel blockage, and non–ST-segment elevation myocardial infarction (NSTEMI), caused by a narrowing or temporary blockage of the artery.
Regardless of the type of heart attack, the standard first step in treatment is a coronary angiogram. After finding out where blood flow is disrupted using the angiogram, a physician can proceed with treatment.
But when looking back, the team found that it took a while for many patients to receive this first step in treatment. In 2005, 50% of men and 35.7% of women with STEMI and 45% of men and 33.1% of women with NSTEMI had a timely angiography. In the same year, 46% of White patients and 31.2% of Black patients with STEMI underwent timely angiography.
By 2015, timely treatment increased across the board, but there were still discrepancies, with 76.7% of men and 66.8% of women with STEMI undergoing timely angiography and 56.3% of men and 45.9% of women with NSTEMI undergoing timely angiography. Also in 2015, 75.2% of White patients and 69.2% of Black patients underwent timely angiography for STEMI.
Although differences in care decreased between the demographics, the gap still exists. Whereas this dataset only extends to 2015, this trend may still persist today, says Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, who was not involved in the study. Therefore, physicians need to consider this bias when treating patients. “The bottom line is that we continue to have much work to do to achieve equality in managing not only medical conditions but treating people who have them equally,” Dr. Glatter said.
“Raising awareness of ongoing inequality in care related to gender and ethnic disparities is critical to drive change in our institutions,” he emphasized. “We simply cannot accept the status quo.”
The study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Glatter and the authors declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Radiating chest pain, shortness of breath, nausea, lightheadedness. Everyone knows the telltale signs of a myocardial infarction. Yet a new study shows that despite this widespread recognition, heart attacks aren’t attended to quickly across the board. Historically, the study says, women and people of color wait longer to access emergency care for a heart attack.
Researchers from the University of California, San Francisco published these findings in the Annals of Emergency Medicine. The study used the Office of Statewide Health Planning and Development dataset to gather information on 453,136 cases of heart attack in California between 2005 and 2015. They found that over time, differences in timely treatment between the demographics narrowed, but the gap still existed.
The study defined timely treatment as receiving care for a heart attack within 3 days of admission to a hospital. Women and people of color were found to wait 3 days or more to receive care than their White male counterparts. A disparity of this sort can cause ripples of health effects across society, ripples that doctors should be aware of, says lead author Juan Carlos Montoy, MD. Dr. Montoy was “sadly surprised by our findings that disparities for women and for Black patients only decreased slightly or not at all over time.”
In the study, the team separated the dataset between the two primary types of heart attack: ST-segment elevation myocardial infarction (STEMI), caused by blood vessel blockage, and non–ST-segment elevation myocardial infarction (NSTEMI), caused by a narrowing or temporary blockage of the artery.
Regardless of the type of heart attack, the standard first step in treatment is a coronary angiogram. After finding out where blood flow is disrupted using the angiogram, a physician can proceed with treatment.
But when looking back, the team found that it took a while for many patients to receive this first step in treatment. In 2005, 50% of men and 35.7% of women with STEMI and 45% of men and 33.1% of women with NSTEMI had a timely angiography. In the same year, 46% of White patients and 31.2% of Black patients with STEMI underwent timely angiography.
By 2015, timely treatment increased across the board, but there were still discrepancies, with 76.7% of men and 66.8% of women with STEMI undergoing timely angiography and 56.3% of men and 45.9% of women with NSTEMI undergoing timely angiography. Also in 2015, 75.2% of White patients and 69.2% of Black patients underwent timely angiography for STEMI.
Although differences in care decreased between the demographics, the gap still exists. Whereas this dataset only extends to 2015, this trend may still persist today, says Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, who was not involved in the study. Therefore, physicians need to consider this bias when treating patients. “The bottom line is that we continue to have much work to do to achieve equality in managing not only medical conditions but treating people who have them equally,” Dr. Glatter said.
“Raising awareness of ongoing inequality in care related to gender and ethnic disparities is critical to drive change in our institutions,” he emphasized. “We simply cannot accept the status quo.”
The study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Glatter and the authors declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Radiating chest pain, shortness of breath, nausea, lightheadedness. Everyone knows the telltale signs of a myocardial infarction. Yet a new study shows that despite this widespread recognition, heart attacks aren’t attended to quickly across the board. Historically, the study says, women and people of color wait longer to access emergency care for a heart attack.
Researchers from the University of California, San Francisco published these findings in the Annals of Emergency Medicine. The study used the Office of Statewide Health Planning and Development dataset to gather information on 453,136 cases of heart attack in California between 2005 and 2015. They found that over time, differences in timely treatment between the demographics narrowed, but the gap still existed.
The study defined timely treatment as receiving care for a heart attack within 3 days of admission to a hospital. Women and people of color were found to wait 3 days or more to receive care than their White male counterparts. A disparity of this sort can cause ripples of health effects across society, ripples that doctors should be aware of, says lead author Juan Carlos Montoy, MD. Dr. Montoy was “sadly surprised by our findings that disparities for women and for Black patients only decreased slightly or not at all over time.”
In the study, the team separated the dataset between the two primary types of heart attack: ST-segment elevation myocardial infarction (STEMI), caused by blood vessel blockage, and non–ST-segment elevation myocardial infarction (NSTEMI), caused by a narrowing or temporary blockage of the artery.
Regardless of the type of heart attack, the standard first step in treatment is a coronary angiogram. After finding out where blood flow is disrupted using the angiogram, a physician can proceed with treatment.
But when looking back, the team found that it took a while for many patients to receive this first step in treatment. In 2005, 50% of men and 35.7% of women with STEMI and 45% of men and 33.1% of women with NSTEMI had a timely angiography. In the same year, 46% of White patients and 31.2% of Black patients with STEMI underwent timely angiography.
By 2015, timely treatment increased across the board, but there were still discrepancies, with 76.7% of men and 66.8% of women with STEMI undergoing timely angiography and 56.3% of men and 45.9% of women with NSTEMI undergoing timely angiography. Also in 2015, 75.2% of White patients and 69.2% of Black patients underwent timely angiography for STEMI.
Although differences in care decreased between the demographics, the gap still exists. Whereas this dataset only extends to 2015, this trend may still persist today, says Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, who was not involved in the study. Therefore, physicians need to consider this bias when treating patients. “The bottom line is that we continue to have much work to do to achieve equality in managing not only medical conditions but treating people who have them equally,” Dr. Glatter said.
“Raising awareness of ongoing inequality in care related to gender and ethnic disparities is critical to drive change in our institutions,” he emphasized. “We simply cannot accept the status quo.”
The study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Glatter and the authors declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF EMERGENCY MEDICINE
New biomarker data add to concerns over REDUCE-IT trial
A new analysis of the REDUCE-IT study has reignited concerns that the benefit shown by the high-dose fish oil product in the study, icosapent ethyl (Vascepa, Amarin), may have been related to harms caused by the placebo mineral oil.
Results show that allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels of these biomarkers increased among those allocated to mineral oil.
At 12 months, the median percent increases from baseline in the mineral oil group were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density-lipoprotein (LDL) cholesterol, 16.2% for interleukin (IL)-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein (hsCRP), and 28.9% for IL-1β. The changes were similar at 24 months. However, in the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months.
The study was published online in Circulation.
The authors, led by Paul Ridker, MD, Brigham & Women’s Hospital, Boston, do not voice much opinion on what the results mean, concluding that “the effect of these findings on the interpretation of the REDUCE-IT trial results remains unclear and will require further investigation.”
They also say that a second icosapent ethyl trial using a nonmineral oil comparator “would help resolve ongoing controversy.”
However, the authors are a mixed group; Dr. Ridker and some of his coauthors were not part of the original REDUCE-IT trial, whereas other coauthors were members of the REDUCE-IT steering committee, and one was an employee of Amarin.
Lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, also from Brigham & Women’s Hospital, who is the senior author of the current study, played down the new findings, saying they did not offer much new incremental information on mechanistic insight.
“These are small degrees of biomarker increases on an absolute level we are seeing with the placebo that would not be expected to produce harm,” Dr. Bhatt told this news organization. He also said the Circulation peer-review process had removed some of the discussion, which could lead to some “misinterpretation” of the authors’ views.
Dr. Ridker was unavailable for further comment.
The publication of this study has inevitably poured fuel on the fire regarding the controversy that has long dogged the REDUCE-IT trial, with questions about the large reduction in event rates seen with icosapent ethyl without an obvious mechanistic explanation.
‘Smoking gun’
One of the loudest critics of the study, Steve Nissen, MD, Cleveland Clinic, described the new findings as “the closest thing I’ve seen to a smoking gun in medicine for a long, long time.”
“The result of this new analysis shows that mineral oil increases virtually every inflammatory and lipid marker that they measured,” he commented.
“There are a lot of theories, but the bottom line is that something really bad happened in the mineral-oil group, which makes icosapent ethyl look efficacious. In my view, this needs to be reviewed by the FDA for consideration of removing the label claim for cardiovascular benefit.”
Other experts in the field not directly involved in the study voiced concern about these new findings, adding to calls for another trial.
In a Twitter thread on the issue, Harlan Krumholz, MD, describes the Circulation publication as “an exceptionally important article,” adding that it is “time to rethink this drug.”
“My point is ... once you know you have non-neutral comparator and the effect on risk biomarkers is far from trivial ... then you have introduced substantial uncertainty about the trial result, as conveyed by the authors ... and no one can say what would happen with a neutral comparator,” Dr. Krumholz writes.
In an accompanying editorial in Circulation, Robert Harrington, MD, professor of medicine at Stanford (Calif.) University, concludes that “the hard reality is that we are left with uncertainties and the questions raised by use of the mineral oil as placebo can only be answered by another randomized controlled trial.”
“My main points are that the chosen placebo was not inert (an essential characteristic for an active control–placebo comparison), that the biomarker data show elevations in multiple markers involved with inflammatory pathways associated with atherosclerosis, and that these data create enough uncertainty in the trial interpretation that the best recourse to answer the criticisms is to do another trial with a truly inert placebo,” Dr. Harrington said in an interview.
He added that Dr. Bhatt’s point that the changes in biomarkers are too small to really matter clinically may be right. “But for me, the uncertainties mean that I have less confidence in the true magnitude of the treatment effect than I would have if there were no changes in the inflammatory markers.”
In Circulation, the authors say it is unclear why multiple biomarkers increased over time among REDUCE-IT participants allocated to mineral oil. They note that no substantive changes in these biomarkers were observed in the placebo groups over periods of 3-5 years in other trials, including JUPITER, CIRT, CANTOS, SPIRE, and the STRENGTH trials, which evaluated a different high-dose omega-3 oil product but used corn oil as the placebo.
“The core design of REDUCE-IT does not make it possible to resolve convincingly whether any adverse effects associated with mineral oil use as a comparator may have affected clinical outcomes,” they write.
They point out that regulatory agencies evaluating REDUCE-IT estimated that approximately 3% of the net clinical benefit observed with icosapent ethyl might have been a consequence of adverse biomarker effects on LDL cholesterol and hsCRP attributable to mineral oil. But in the context of an overall 25% relative risk reduction in first events and a 30% reduction in total ischemic events observed, a potential bias of this magnitude, even if doubled in size, would be unlikely to fully attenuate the overall benefit of icosapent ethyl observed.
They add that they are not aware of a method to assess what the potential magnitude might be of a combination of the multiple effects.
New data do not change the debate
“We did a large, well-powered randomized trial, and this paper shouldn’t change anything in how that trial should be interpreted,” Dr. Bhatt said in an interview.
He claims the new biomarkers evaluated in the study are correlated with LDL and CRP, data which have already been reported and analyzed so have limited relevance.
“It’s not really independent biomarker information; this is what we would expect to see when we see small increases in LDL and CRP. So, I don’t think this new information fundamentally changes the debate,” he said.
Dr. Bhatt also pointed out that the study highlights relative increases rather than absolute increases in the biomarkers, making it seem more alarming than is actually the case.
“The paper makes it seem like that there are large increases in these other biomarkers, but the values reported are relative increases and the absolute increases were actually rather small. In many cases, the changes reported are less than the lower limit of quantification of the assay used,” he noted.
He added: “Even if one is unable to get around the placebo issue in the REDUCE-IT trial, there will always be the JELIS trial – a randomized trial with no placebo showing a 19% relative risk reduction. While the biomarker data may be interesting, what really matters in the end is clinical events. And significant reductions in two independent trials should be enough.”
Dr. Bhatt says the REDUCE-IT steering committee does not believe another trial is needed. “Maybe a different population would be good – such as primary prevention, patients without elevated triglycerides – but just repeating REDUCE- IT with a different placebo would be a waste of resources,” he commented.
But Dr. Nissen refuted Dr. Bhatt’s claims.
“These biomarkers are not in the same pathways as LDL and CRP, and these are not small increases. In the CANTOS trial, a monoclonal antibody against interleukin-1β beta showed a significant benefit. The increase in interleukin-1β now reported in REDUCE-IT is exactly the opposite of CANTOS,” he pointed out.
“The FDA did not know about these additional biomarkers when it reviewed the data on LDL and CRP. Now we have new information. It needs to be looked at again,” Dr. Nissen added.
Funding for the study was provided by Amarin Pharma. Dr. Bhatt was the lead investigator of the REDUCE-IT trial. Dr. Nissen was the lead investigator the STRENGTH trial. Further disclosures of the authors can be found in Circulation.
A version of this article first appeared on Medscape.com.
A new analysis of the REDUCE-IT study has reignited concerns that the benefit shown by the high-dose fish oil product in the study, icosapent ethyl (Vascepa, Amarin), may have been related to harms caused by the placebo mineral oil.
Results show that allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels of these biomarkers increased among those allocated to mineral oil.
At 12 months, the median percent increases from baseline in the mineral oil group were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density-lipoprotein (LDL) cholesterol, 16.2% for interleukin (IL)-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein (hsCRP), and 28.9% for IL-1β. The changes were similar at 24 months. However, in the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months.
The study was published online in Circulation.
The authors, led by Paul Ridker, MD, Brigham & Women’s Hospital, Boston, do not voice much opinion on what the results mean, concluding that “the effect of these findings on the interpretation of the REDUCE-IT trial results remains unclear and will require further investigation.”
They also say that a second icosapent ethyl trial using a nonmineral oil comparator “would help resolve ongoing controversy.”
However, the authors are a mixed group; Dr. Ridker and some of his coauthors were not part of the original REDUCE-IT trial, whereas other coauthors were members of the REDUCE-IT steering committee, and one was an employee of Amarin.
Lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, also from Brigham & Women’s Hospital, who is the senior author of the current study, played down the new findings, saying they did not offer much new incremental information on mechanistic insight.
“These are small degrees of biomarker increases on an absolute level we are seeing with the placebo that would not be expected to produce harm,” Dr. Bhatt told this news organization. He also said the Circulation peer-review process had removed some of the discussion, which could lead to some “misinterpretation” of the authors’ views.
Dr. Ridker was unavailable for further comment.
The publication of this study has inevitably poured fuel on the fire regarding the controversy that has long dogged the REDUCE-IT trial, with questions about the large reduction in event rates seen with icosapent ethyl without an obvious mechanistic explanation.
‘Smoking gun’
One of the loudest critics of the study, Steve Nissen, MD, Cleveland Clinic, described the new findings as “the closest thing I’ve seen to a smoking gun in medicine for a long, long time.”
“The result of this new analysis shows that mineral oil increases virtually every inflammatory and lipid marker that they measured,” he commented.
“There are a lot of theories, but the bottom line is that something really bad happened in the mineral-oil group, which makes icosapent ethyl look efficacious. In my view, this needs to be reviewed by the FDA for consideration of removing the label claim for cardiovascular benefit.”
Other experts in the field not directly involved in the study voiced concern about these new findings, adding to calls for another trial.
In a Twitter thread on the issue, Harlan Krumholz, MD, describes the Circulation publication as “an exceptionally important article,” adding that it is “time to rethink this drug.”
“My point is ... once you know you have non-neutral comparator and the effect on risk biomarkers is far from trivial ... then you have introduced substantial uncertainty about the trial result, as conveyed by the authors ... and no one can say what would happen with a neutral comparator,” Dr. Krumholz writes.
In an accompanying editorial in Circulation, Robert Harrington, MD, professor of medicine at Stanford (Calif.) University, concludes that “the hard reality is that we are left with uncertainties and the questions raised by use of the mineral oil as placebo can only be answered by another randomized controlled trial.”
“My main points are that the chosen placebo was not inert (an essential characteristic for an active control–placebo comparison), that the biomarker data show elevations in multiple markers involved with inflammatory pathways associated with atherosclerosis, and that these data create enough uncertainty in the trial interpretation that the best recourse to answer the criticisms is to do another trial with a truly inert placebo,” Dr. Harrington said in an interview.
He added that Dr. Bhatt’s point that the changes in biomarkers are too small to really matter clinically may be right. “But for me, the uncertainties mean that I have less confidence in the true magnitude of the treatment effect than I would have if there were no changes in the inflammatory markers.”
In Circulation, the authors say it is unclear why multiple biomarkers increased over time among REDUCE-IT participants allocated to mineral oil. They note that no substantive changes in these biomarkers were observed in the placebo groups over periods of 3-5 years in other trials, including JUPITER, CIRT, CANTOS, SPIRE, and the STRENGTH trials, which evaluated a different high-dose omega-3 oil product but used corn oil as the placebo.
“The core design of REDUCE-IT does not make it possible to resolve convincingly whether any adverse effects associated with mineral oil use as a comparator may have affected clinical outcomes,” they write.
They point out that regulatory agencies evaluating REDUCE-IT estimated that approximately 3% of the net clinical benefit observed with icosapent ethyl might have been a consequence of adverse biomarker effects on LDL cholesterol and hsCRP attributable to mineral oil. But in the context of an overall 25% relative risk reduction in first events and a 30% reduction in total ischemic events observed, a potential bias of this magnitude, even if doubled in size, would be unlikely to fully attenuate the overall benefit of icosapent ethyl observed.
They add that they are not aware of a method to assess what the potential magnitude might be of a combination of the multiple effects.
New data do not change the debate
“We did a large, well-powered randomized trial, and this paper shouldn’t change anything in how that trial should be interpreted,” Dr. Bhatt said in an interview.
He claims the new biomarkers evaluated in the study are correlated with LDL and CRP, data which have already been reported and analyzed so have limited relevance.
“It’s not really independent biomarker information; this is what we would expect to see when we see small increases in LDL and CRP. So, I don’t think this new information fundamentally changes the debate,” he said.
Dr. Bhatt also pointed out that the study highlights relative increases rather than absolute increases in the biomarkers, making it seem more alarming than is actually the case.
“The paper makes it seem like that there are large increases in these other biomarkers, but the values reported are relative increases and the absolute increases were actually rather small. In many cases, the changes reported are less than the lower limit of quantification of the assay used,” he noted.
He added: “Even if one is unable to get around the placebo issue in the REDUCE-IT trial, there will always be the JELIS trial – a randomized trial with no placebo showing a 19% relative risk reduction. While the biomarker data may be interesting, what really matters in the end is clinical events. And significant reductions in two independent trials should be enough.”
Dr. Bhatt says the REDUCE-IT steering committee does not believe another trial is needed. “Maybe a different population would be good – such as primary prevention, patients without elevated triglycerides – but just repeating REDUCE- IT with a different placebo would be a waste of resources,” he commented.
But Dr. Nissen refuted Dr. Bhatt’s claims.
“These biomarkers are not in the same pathways as LDL and CRP, and these are not small increases. In the CANTOS trial, a monoclonal antibody against interleukin-1β beta showed a significant benefit. The increase in interleukin-1β now reported in REDUCE-IT is exactly the opposite of CANTOS,” he pointed out.
“The FDA did not know about these additional biomarkers when it reviewed the data on LDL and CRP. Now we have new information. It needs to be looked at again,” Dr. Nissen added.
Funding for the study was provided by Amarin Pharma. Dr. Bhatt was the lead investigator of the REDUCE-IT trial. Dr. Nissen was the lead investigator the STRENGTH trial. Further disclosures of the authors can be found in Circulation.
A version of this article first appeared on Medscape.com.
A new analysis of the REDUCE-IT study has reignited concerns that the benefit shown by the high-dose fish oil product in the study, icosapent ethyl (Vascepa, Amarin), may have been related to harms caused by the placebo mineral oil.
Results show that allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels of these biomarkers increased among those allocated to mineral oil.
At 12 months, the median percent increases from baseline in the mineral oil group were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density-lipoprotein (LDL) cholesterol, 16.2% for interleukin (IL)-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein (hsCRP), and 28.9% for IL-1β. The changes were similar at 24 months. However, in the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months.
The study was published online in Circulation.
The authors, led by Paul Ridker, MD, Brigham & Women’s Hospital, Boston, do not voice much opinion on what the results mean, concluding that “the effect of these findings on the interpretation of the REDUCE-IT trial results remains unclear and will require further investigation.”
They also say that a second icosapent ethyl trial using a nonmineral oil comparator “would help resolve ongoing controversy.”
However, the authors are a mixed group; Dr. Ridker and some of his coauthors were not part of the original REDUCE-IT trial, whereas other coauthors were members of the REDUCE-IT steering committee, and one was an employee of Amarin.
Lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, also from Brigham & Women’s Hospital, who is the senior author of the current study, played down the new findings, saying they did not offer much new incremental information on mechanistic insight.
“These are small degrees of biomarker increases on an absolute level we are seeing with the placebo that would not be expected to produce harm,” Dr. Bhatt told this news organization. He also said the Circulation peer-review process had removed some of the discussion, which could lead to some “misinterpretation” of the authors’ views.
Dr. Ridker was unavailable for further comment.
The publication of this study has inevitably poured fuel on the fire regarding the controversy that has long dogged the REDUCE-IT trial, with questions about the large reduction in event rates seen with icosapent ethyl without an obvious mechanistic explanation.
‘Smoking gun’
One of the loudest critics of the study, Steve Nissen, MD, Cleveland Clinic, described the new findings as “the closest thing I’ve seen to a smoking gun in medicine for a long, long time.”
“The result of this new analysis shows that mineral oil increases virtually every inflammatory and lipid marker that they measured,” he commented.
“There are a lot of theories, but the bottom line is that something really bad happened in the mineral-oil group, which makes icosapent ethyl look efficacious. In my view, this needs to be reviewed by the FDA for consideration of removing the label claim for cardiovascular benefit.”
Other experts in the field not directly involved in the study voiced concern about these new findings, adding to calls for another trial.
In a Twitter thread on the issue, Harlan Krumholz, MD, describes the Circulation publication as “an exceptionally important article,” adding that it is “time to rethink this drug.”
“My point is ... once you know you have non-neutral comparator and the effect on risk biomarkers is far from trivial ... then you have introduced substantial uncertainty about the trial result, as conveyed by the authors ... and no one can say what would happen with a neutral comparator,” Dr. Krumholz writes.
In an accompanying editorial in Circulation, Robert Harrington, MD, professor of medicine at Stanford (Calif.) University, concludes that “the hard reality is that we are left with uncertainties and the questions raised by use of the mineral oil as placebo can only be answered by another randomized controlled trial.”
“My main points are that the chosen placebo was not inert (an essential characteristic for an active control–placebo comparison), that the biomarker data show elevations in multiple markers involved with inflammatory pathways associated with atherosclerosis, and that these data create enough uncertainty in the trial interpretation that the best recourse to answer the criticisms is to do another trial with a truly inert placebo,” Dr. Harrington said in an interview.
He added that Dr. Bhatt’s point that the changes in biomarkers are too small to really matter clinically may be right. “But for me, the uncertainties mean that I have less confidence in the true magnitude of the treatment effect than I would have if there were no changes in the inflammatory markers.”
In Circulation, the authors say it is unclear why multiple biomarkers increased over time among REDUCE-IT participants allocated to mineral oil. They note that no substantive changes in these biomarkers were observed in the placebo groups over periods of 3-5 years in other trials, including JUPITER, CIRT, CANTOS, SPIRE, and the STRENGTH trials, which evaluated a different high-dose omega-3 oil product but used corn oil as the placebo.
“The core design of REDUCE-IT does not make it possible to resolve convincingly whether any adverse effects associated with mineral oil use as a comparator may have affected clinical outcomes,” they write.
They point out that regulatory agencies evaluating REDUCE-IT estimated that approximately 3% of the net clinical benefit observed with icosapent ethyl might have been a consequence of adverse biomarker effects on LDL cholesterol and hsCRP attributable to mineral oil. But in the context of an overall 25% relative risk reduction in first events and a 30% reduction in total ischemic events observed, a potential bias of this magnitude, even if doubled in size, would be unlikely to fully attenuate the overall benefit of icosapent ethyl observed.
They add that they are not aware of a method to assess what the potential magnitude might be of a combination of the multiple effects.
New data do not change the debate
“We did a large, well-powered randomized trial, and this paper shouldn’t change anything in how that trial should be interpreted,” Dr. Bhatt said in an interview.
He claims the new biomarkers evaluated in the study are correlated with LDL and CRP, data which have already been reported and analyzed so have limited relevance.
“It’s not really independent biomarker information; this is what we would expect to see when we see small increases in LDL and CRP. So, I don’t think this new information fundamentally changes the debate,” he said.
Dr. Bhatt also pointed out that the study highlights relative increases rather than absolute increases in the biomarkers, making it seem more alarming than is actually the case.
“The paper makes it seem like that there are large increases in these other biomarkers, but the values reported are relative increases and the absolute increases were actually rather small. In many cases, the changes reported are less than the lower limit of quantification of the assay used,” he noted.
He added: “Even if one is unable to get around the placebo issue in the REDUCE-IT trial, there will always be the JELIS trial – a randomized trial with no placebo showing a 19% relative risk reduction. While the biomarker data may be interesting, what really matters in the end is clinical events. And significant reductions in two independent trials should be enough.”
Dr. Bhatt says the REDUCE-IT steering committee does not believe another trial is needed. “Maybe a different population would be good – such as primary prevention, patients without elevated triglycerides – but just repeating REDUCE- IT with a different placebo would be a waste of resources,” he commented.
But Dr. Nissen refuted Dr. Bhatt’s claims.
“These biomarkers are not in the same pathways as LDL and CRP, and these are not small increases. In the CANTOS trial, a monoclonal antibody against interleukin-1β beta showed a significant benefit. The increase in interleukin-1β now reported in REDUCE-IT is exactly the opposite of CANTOS,” he pointed out.
“The FDA did not know about these additional biomarkers when it reviewed the data on LDL and CRP. Now we have new information. It needs to be looked at again,” Dr. Nissen added.
Funding for the study was provided by Amarin Pharma. Dr. Bhatt was the lead investigator of the REDUCE-IT trial. Dr. Nissen was the lead investigator the STRENGTH trial. Further disclosures of the authors can be found in Circulation.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Nordic walking bests other workouts on functional outcome in CVD
Nordic walking was significantly better at improving functional capacity than were moderate- to vigorous-intensity continuous training and high-intensity interval training (HIIT) in a single-center randomized controlled trial.
Participants who did Nordic walking saw better improvements in functional capacity, measured via the 6-minute walk test distances, than did individuals doing either of the other exercise strategies (interaction effect, P = .010).
From baseline to 26 weeks, the average changes in 6-minute walk test distance were 55.6 m and 59.9 m for moderate- to vigorous-intensity continuous training and HIIT, respectively, but 94.2 m in the Nordic walking group, reported Tasuku Terada, PhD, University of Ottawa Heart Institute, Ontario, and colleagues.
Previous research looked at these results at the end of a 12-week supervised exercise intervention and showed that although all three strategies were safe and had positive effects on physical and mental health in these patients, Nordic walking had a better effect in raising the 6-minute walk test scores than did moderate- to vigorous-intensity continuous training and HIIT, the researchers noted.
“This study is a follow-up on the previous study to show that Nordic walking had greater sustained effects even after the observation phase,” from 12 to 26 weeks, Dr. Terada said in an interview.
“Exercise is a medicine to improve the health of patients, but unfortunately, sometimes it is not as often utilized,” Dr. Terada told this news organization.
Giving patients additional exercise modalities is beneficial because not everyone likes HIIT workouts or long continuous walking, Dr. Terada said. “So, if that’s the case, we can recommend Nordic walking as another type of exercise and expect a similar or good impact in functional capacity.”
The results were published online in the Canadian Journal of Cardiology.
“I think it honestly supports the idea that, as many other studies show, physical activity and exercise improve functional capacity no matter how you measure it and have beneficial effects on mental health and quality of life and particularly depression as well,” Carl “Chip” Lavie, MD, University of Queensland, New Orleans, who coauthored an editorial accompanying the publication, said in an interview.
“Clinicians need to get patients to do the type of exercise that they are going to do. A lot of people ask what’s the best exercise, and the best exercise is one that the person is going to do,” Dr. Lavie said.
Nordic walking is an enhanced form of walking that engages the upper and lower body musculatures, noted Dr. Lavie.
“With regard to Nordic walking, I think that now adds an additional option that many people wouldn’t have thought about. For many of the patients that have issues that are musculoskeletal, issues with posture, gait, or balance, using the poles can be a way to allow them to walk much better and increase their speed, and as they do that, they become fitter,” Dr. Lavie continued.
Moreover, these findings support the use of Nordic walking in cardiac rehabilitation programs, the editorialists noted.
Cardiac rehabilitation
The study examined patients with coronary artery disease who underwent cardiac revascularization. They were then referred by their physicians to cardiac rehabilitation.
Participants were randomly assigned to one of the following intervention groups: Nordic walking (n = 30), moderate- to vigorous-intensity continuous training (n = 27), and HIIT (n = 29) for a 12-week period. There was then an additional 14-week observation period after the exercise program. Mean age was 60 years across the intervention groups.
The research team analyzed the extent of participants’ depression with Beck Depression Inventory–II, quality of life with Short Form–36 and HeartQoL, and functional capacity with a 6-minute walk test. They assessed functional capacity, depression, and quality of life at baseline, 12 weeks, and 26 weeks.
Using linear mixed models with extended measures, the study authors evaluated sustained effects, which were between week 12 and week 26, and prolonged effects, which were between baseline and week 26.
From baseline to 26 weeks, participants saw significantly better outcomes in quality of life, depression symptoms, and 6-minute walk test (P < .05).
Physical quality of life and 6-minute walk test distance rose significantly between weeks 12 and 26 (P < .05).
Notably, at week 26, all training groups achieved the minimal clinical threshold difference of 54 m, although participants in the Nordic walking cohort demonstrated significantly greater improvement in outcomes.
Other data indicated the following:
- From baseline to week 12, physical activity levels rose significantly, and this improvement was sustained through the observation period.
- During the observation period, mental component summary significantly declined while physical component summary outcomes improved.
- After completion of cardiac rehabilitation, functional capacity continued to increase significantly.
- Moderate- to vigorous-intensity continuous training, HIIT, and Nordic walking had positive and significant prolonged effects on depression symptoms and general and disease-specific quality of life, with no differences in the extent of improvements between exercise types.
Some limitations of the study include the fact that women comprised a small portion of the study group, which limits the generalizability of these data, the cohort was recruited from a single medical facility, and there was a short follow-up time, the researchers noted.
“Further research is warranted to investigate the efficacy and integration of Nordic walking into home-based exercise after supervised cardiac rehabilitation for maintenance of physical and mental health,” the editorialists concluded.
Dr. Terada, Dr. Lavie, and Dr. Taylor reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nordic walking was significantly better at improving functional capacity than were moderate- to vigorous-intensity continuous training and high-intensity interval training (HIIT) in a single-center randomized controlled trial.
Participants who did Nordic walking saw better improvements in functional capacity, measured via the 6-minute walk test distances, than did individuals doing either of the other exercise strategies (interaction effect, P = .010).
From baseline to 26 weeks, the average changes in 6-minute walk test distance were 55.6 m and 59.9 m for moderate- to vigorous-intensity continuous training and HIIT, respectively, but 94.2 m in the Nordic walking group, reported Tasuku Terada, PhD, University of Ottawa Heart Institute, Ontario, and colleagues.
Previous research looked at these results at the end of a 12-week supervised exercise intervention and showed that although all three strategies were safe and had positive effects on physical and mental health in these patients, Nordic walking had a better effect in raising the 6-minute walk test scores than did moderate- to vigorous-intensity continuous training and HIIT, the researchers noted.
“This study is a follow-up on the previous study to show that Nordic walking had greater sustained effects even after the observation phase,” from 12 to 26 weeks, Dr. Terada said in an interview.
“Exercise is a medicine to improve the health of patients, but unfortunately, sometimes it is not as often utilized,” Dr. Terada told this news organization.
Giving patients additional exercise modalities is beneficial because not everyone likes HIIT workouts or long continuous walking, Dr. Terada said. “So, if that’s the case, we can recommend Nordic walking as another type of exercise and expect a similar or good impact in functional capacity.”
The results were published online in the Canadian Journal of Cardiology.
“I think it honestly supports the idea that, as many other studies show, physical activity and exercise improve functional capacity no matter how you measure it and have beneficial effects on mental health and quality of life and particularly depression as well,” Carl “Chip” Lavie, MD, University of Queensland, New Orleans, who coauthored an editorial accompanying the publication, said in an interview.
“Clinicians need to get patients to do the type of exercise that they are going to do. A lot of people ask what’s the best exercise, and the best exercise is one that the person is going to do,” Dr. Lavie said.
Nordic walking is an enhanced form of walking that engages the upper and lower body musculatures, noted Dr. Lavie.
“With regard to Nordic walking, I think that now adds an additional option that many people wouldn’t have thought about. For many of the patients that have issues that are musculoskeletal, issues with posture, gait, or balance, using the poles can be a way to allow them to walk much better and increase their speed, and as they do that, they become fitter,” Dr. Lavie continued.
Moreover, these findings support the use of Nordic walking in cardiac rehabilitation programs, the editorialists noted.
Cardiac rehabilitation
The study examined patients with coronary artery disease who underwent cardiac revascularization. They were then referred by their physicians to cardiac rehabilitation.
Participants were randomly assigned to one of the following intervention groups: Nordic walking (n = 30), moderate- to vigorous-intensity continuous training (n = 27), and HIIT (n = 29) for a 12-week period. There was then an additional 14-week observation period after the exercise program. Mean age was 60 years across the intervention groups.
The research team analyzed the extent of participants’ depression with Beck Depression Inventory–II, quality of life with Short Form–36 and HeartQoL, and functional capacity with a 6-minute walk test. They assessed functional capacity, depression, and quality of life at baseline, 12 weeks, and 26 weeks.
Using linear mixed models with extended measures, the study authors evaluated sustained effects, which were between week 12 and week 26, and prolonged effects, which were between baseline and week 26.
From baseline to 26 weeks, participants saw significantly better outcomes in quality of life, depression symptoms, and 6-minute walk test (P < .05).
Physical quality of life and 6-minute walk test distance rose significantly between weeks 12 and 26 (P < .05).
Notably, at week 26, all training groups achieved the minimal clinical threshold difference of 54 m, although participants in the Nordic walking cohort demonstrated significantly greater improvement in outcomes.
Other data indicated the following:
- From baseline to week 12, physical activity levels rose significantly, and this improvement was sustained through the observation period.
- During the observation period, mental component summary significantly declined while physical component summary outcomes improved.
- After completion of cardiac rehabilitation, functional capacity continued to increase significantly.
- Moderate- to vigorous-intensity continuous training, HIIT, and Nordic walking had positive and significant prolonged effects on depression symptoms and general and disease-specific quality of life, with no differences in the extent of improvements between exercise types.
Some limitations of the study include the fact that women comprised a small portion of the study group, which limits the generalizability of these data, the cohort was recruited from a single medical facility, and there was a short follow-up time, the researchers noted.
“Further research is warranted to investigate the efficacy and integration of Nordic walking into home-based exercise after supervised cardiac rehabilitation for maintenance of physical and mental health,” the editorialists concluded.
Dr. Terada, Dr. Lavie, and Dr. Taylor reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nordic walking was significantly better at improving functional capacity than were moderate- to vigorous-intensity continuous training and high-intensity interval training (HIIT) in a single-center randomized controlled trial.
Participants who did Nordic walking saw better improvements in functional capacity, measured via the 6-minute walk test distances, than did individuals doing either of the other exercise strategies (interaction effect, P = .010).
From baseline to 26 weeks, the average changes in 6-minute walk test distance were 55.6 m and 59.9 m for moderate- to vigorous-intensity continuous training and HIIT, respectively, but 94.2 m in the Nordic walking group, reported Tasuku Terada, PhD, University of Ottawa Heart Institute, Ontario, and colleagues.
Previous research looked at these results at the end of a 12-week supervised exercise intervention and showed that although all three strategies were safe and had positive effects on physical and mental health in these patients, Nordic walking had a better effect in raising the 6-minute walk test scores than did moderate- to vigorous-intensity continuous training and HIIT, the researchers noted.
“This study is a follow-up on the previous study to show that Nordic walking had greater sustained effects even after the observation phase,” from 12 to 26 weeks, Dr. Terada said in an interview.
“Exercise is a medicine to improve the health of patients, but unfortunately, sometimes it is not as often utilized,” Dr. Terada told this news organization.
Giving patients additional exercise modalities is beneficial because not everyone likes HIIT workouts or long continuous walking, Dr. Terada said. “So, if that’s the case, we can recommend Nordic walking as another type of exercise and expect a similar or good impact in functional capacity.”
The results were published online in the Canadian Journal of Cardiology.
“I think it honestly supports the idea that, as many other studies show, physical activity and exercise improve functional capacity no matter how you measure it and have beneficial effects on mental health and quality of life and particularly depression as well,” Carl “Chip” Lavie, MD, University of Queensland, New Orleans, who coauthored an editorial accompanying the publication, said in an interview.
“Clinicians need to get patients to do the type of exercise that they are going to do. A lot of people ask what’s the best exercise, and the best exercise is one that the person is going to do,” Dr. Lavie said.
Nordic walking is an enhanced form of walking that engages the upper and lower body musculatures, noted Dr. Lavie.
“With regard to Nordic walking, I think that now adds an additional option that many people wouldn’t have thought about. For many of the patients that have issues that are musculoskeletal, issues with posture, gait, or balance, using the poles can be a way to allow them to walk much better and increase their speed, and as they do that, they become fitter,” Dr. Lavie continued.
Moreover, these findings support the use of Nordic walking in cardiac rehabilitation programs, the editorialists noted.
Cardiac rehabilitation
The study examined patients with coronary artery disease who underwent cardiac revascularization. They were then referred by their physicians to cardiac rehabilitation.
Participants were randomly assigned to one of the following intervention groups: Nordic walking (n = 30), moderate- to vigorous-intensity continuous training (n = 27), and HIIT (n = 29) for a 12-week period. There was then an additional 14-week observation period after the exercise program. Mean age was 60 years across the intervention groups.
The research team analyzed the extent of participants’ depression with Beck Depression Inventory–II, quality of life with Short Form–36 and HeartQoL, and functional capacity with a 6-minute walk test. They assessed functional capacity, depression, and quality of life at baseline, 12 weeks, and 26 weeks.
Using linear mixed models with extended measures, the study authors evaluated sustained effects, which were between week 12 and week 26, and prolonged effects, which were between baseline and week 26.
From baseline to 26 weeks, participants saw significantly better outcomes in quality of life, depression symptoms, and 6-minute walk test (P < .05).
Physical quality of life and 6-minute walk test distance rose significantly between weeks 12 and 26 (P < .05).
Notably, at week 26, all training groups achieved the minimal clinical threshold difference of 54 m, although participants in the Nordic walking cohort demonstrated significantly greater improvement in outcomes.
Other data indicated the following:
- From baseline to week 12, physical activity levels rose significantly, and this improvement was sustained through the observation period.
- During the observation period, mental component summary significantly declined while physical component summary outcomes improved.
- After completion of cardiac rehabilitation, functional capacity continued to increase significantly.
- Moderate- to vigorous-intensity continuous training, HIIT, and Nordic walking had positive and significant prolonged effects on depression symptoms and general and disease-specific quality of life, with no differences in the extent of improvements between exercise types.
Some limitations of the study include the fact that women comprised a small portion of the study group, which limits the generalizability of these data, the cohort was recruited from a single medical facility, and there was a short follow-up time, the researchers noted.
“Further research is warranted to investigate the efficacy and integration of Nordic walking into home-based exercise after supervised cardiac rehabilitation for maintenance of physical and mental health,” the editorialists concluded.
Dr. Terada, Dr. Lavie, and Dr. Taylor reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE CANADIAN JOURNAL OF CARDIOLOGY
Early cardiac rehab as effective as later start after sternotomy
Cardiac rehabilitation (CR) started 2 weeks after sternotomy for a cardiac procedure was noninferior to usual care, in which CR starts 6 weeks after the procedure, with a greater improvement in 6-minute walk test outcomes, a randomized study suggests.
There was no difference in adverse events between groups, although the researchers pointed out that the study was not powered specifically for safety outcomes.
“Cardiac surgical techniques have evolved significantly over the last 60 years, leading to improved survival and shorter hospital stays,” Gordon McGregor, PhD, University of Warwick, Coventry, England, told this news organization. “However, sternal precautions and rehabilitation guidelines have not changed accordingly. There has never been a guideline based on empirical evidence to support rehabilitation professionals working with cardiac surgery patients after median sternotomy.”
“By adopting a progressive individualized approach,” he added, “cardiac surgery sternotomy patients can start cardiac rehabilitation up to 4 weeks earlier than current guidance, and thus potentially complete their recovery sooner.”
Results of the Early Initiation of Poststernotomy Cardiac Rehabilitation Exercise Training study were published online in JAMA Cardiology.
In the study, Dr. McGregor and colleagues randomly assigned 158 patients (mean age, 63 years; 84% men) to 8 weeks of 1-hour, twice-weekly supervised CR exercise training starting 2 weeks (early) or 6 weeks (usual care) after sternotomy.
The primary outcome was change in the 6-minute walk test distance from baseline to 10 or 14 weeks after sternotomy, respectively, and 12 months after randomization.
For usual care, training followed British standards: a warm-up with light cardiovascular and mobility exercises; continuous moderate-intensity cardiovascular exercise; a cooldown; functional exercises using resistance machines and free weights; and upper-body exercises designed to prevent sternal and leg wound pain and complications.
There are no specific outpatient CR exercise guidelines for early CR, so study participants followed an individualized exercise program for the first 2-3 weeks after surgery, starting with light mobility and moderate-intensity cardiovascular training when they could do those exercises with minimal discomfort. They then progressed to current British standards, as per usual care.
Forty patients were lost to follow-up, largely because of the pandemic; about half the participants in each group were included in the primary analysis.
Early CR was not inferior to usual care, the authors wrote. The mean change in 6-minute walk distance from baseline to completion of CR was 28 meters greater in the early group than in the usual-care group, and was achieved 4 weeks earlier in the recovery timeline.
Secondary outcomes (functional fitness and quality of life) improved in both groups and between-group differences were not statistically significant, indicating the noninferiority of early CR, the authors noted.
Safety not proven
There were more adverse events in the early group than in the usual-care group (58 vs. 46) and more serious adverse events (18 vs. 14), but fewer deaths (1 vs. 2).
Although there was no between-group difference in the likelihood of having an adverse or serious adverse event, Dr. McGregor acknowledged that the study was “not powered specifically for safety outcomes.” He added that “there is the potential to run a very large multination definitive superiority [randomized, controlled trial] with safety as the primary outcome; however, a very large sample would be required.”
Meanwhile, he said, “we can say with some degree of certainty that early CR was likely as safe as usual-care CR. In the United Kingdom, we work closely with the British Association for Cardiovascular Prevention and Rehabilitation and the Association of Chartered Physiotherapists in Cardiovascular Rehabilitation, who will incorporate our findings in their guidelines and training courses.”
Questions remain
Asked to comment on the study, John Larry, MD, medical director of cardiology and cardiac rehabilitation at the Ohio State University Wexner Medical Center East Hospital, Columbus, said: “For those under time pressure to return to work, [early CR] could be an advantage to allow more rehab time and improved stamina prior to their return-to-work date.”
That said, he noted, “we typically delay any significant upper-body training activities for 8-10 weeks to avoid impact on healing of the sternum. Thus ... starting sooner would limit the amount of time a patient would have to engage in any upper-body resistance training. Many lose upper body strength after surgery, so this is an important part of the recovery/rehab process.”
Matthew Tomey, MD, director of the cardiac intensive care unit, Mount Sinai Morningside, New York, advised “caution” when interpreting the findings, stating that “there was no evident difference in the primary outcome measure of functional capacity by 14 weeks, and the trial was not designed to directly assess impact on either social functioning or economic productivity.”
“I would be interested to [see] more comprehensive data on safety in a larger, more diverse sample of postoperative patients,” he said, “as well as evidence to indicate clear advantage of an earlier start for patient-centered outcomes specifically after cardiac surgery.
“Perhaps the greatest challenges to full realization of the benefits of CR in practice have been gaps in referral and gaps in enrollment,” he added. “It is incumbent upon us as clinicians to counsel our patients and to provide appropriate referrals.”
The study was supported by the Medical and Life Sciences Research Fund and the Jeremy Pilcher Memorial Fund. No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
Cardiac rehabilitation (CR) started 2 weeks after sternotomy for a cardiac procedure was noninferior to usual care, in which CR starts 6 weeks after the procedure, with a greater improvement in 6-minute walk test outcomes, a randomized study suggests.
There was no difference in adverse events between groups, although the researchers pointed out that the study was not powered specifically for safety outcomes.
“Cardiac surgical techniques have evolved significantly over the last 60 years, leading to improved survival and shorter hospital stays,” Gordon McGregor, PhD, University of Warwick, Coventry, England, told this news organization. “However, sternal precautions and rehabilitation guidelines have not changed accordingly. There has never been a guideline based on empirical evidence to support rehabilitation professionals working with cardiac surgery patients after median sternotomy.”
“By adopting a progressive individualized approach,” he added, “cardiac surgery sternotomy patients can start cardiac rehabilitation up to 4 weeks earlier than current guidance, and thus potentially complete their recovery sooner.”
Results of the Early Initiation of Poststernotomy Cardiac Rehabilitation Exercise Training study were published online in JAMA Cardiology.
In the study, Dr. McGregor and colleagues randomly assigned 158 patients (mean age, 63 years; 84% men) to 8 weeks of 1-hour, twice-weekly supervised CR exercise training starting 2 weeks (early) or 6 weeks (usual care) after sternotomy.
The primary outcome was change in the 6-minute walk test distance from baseline to 10 or 14 weeks after sternotomy, respectively, and 12 months after randomization.
For usual care, training followed British standards: a warm-up with light cardiovascular and mobility exercises; continuous moderate-intensity cardiovascular exercise; a cooldown; functional exercises using resistance machines and free weights; and upper-body exercises designed to prevent sternal and leg wound pain and complications.
There are no specific outpatient CR exercise guidelines for early CR, so study participants followed an individualized exercise program for the first 2-3 weeks after surgery, starting with light mobility and moderate-intensity cardiovascular training when they could do those exercises with minimal discomfort. They then progressed to current British standards, as per usual care.
Forty patients were lost to follow-up, largely because of the pandemic; about half the participants in each group were included in the primary analysis.
Early CR was not inferior to usual care, the authors wrote. The mean change in 6-minute walk distance from baseline to completion of CR was 28 meters greater in the early group than in the usual-care group, and was achieved 4 weeks earlier in the recovery timeline.
Secondary outcomes (functional fitness and quality of life) improved in both groups and between-group differences were not statistically significant, indicating the noninferiority of early CR, the authors noted.
Safety not proven
There were more adverse events in the early group than in the usual-care group (58 vs. 46) and more serious adverse events (18 vs. 14), but fewer deaths (1 vs. 2).
Although there was no between-group difference in the likelihood of having an adverse or serious adverse event, Dr. McGregor acknowledged that the study was “not powered specifically for safety outcomes.” He added that “there is the potential to run a very large multination definitive superiority [randomized, controlled trial] with safety as the primary outcome; however, a very large sample would be required.”
Meanwhile, he said, “we can say with some degree of certainty that early CR was likely as safe as usual-care CR. In the United Kingdom, we work closely with the British Association for Cardiovascular Prevention and Rehabilitation and the Association of Chartered Physiotherapists in Cardiovascular Rehabilitation, who will incorporate our findings in their guidelines and training courses.”
Questions remain
Asked to comment on the study, John Larry, MD, medical director of cardiology and cardiac rehabilitation at the Ohio State University Wexner Medical Center East Hospital, Columbus, said: “For those under time pressure to return to work, [early CR] could be an advantage to allow more rehab time and improved stamina prior to their return-to-work date.”
That said, he noted, “we typically delay any significant upper-body training activities for 8-10 weeks to avoid impact on healing of the sternum. Thus ... starting sooner would limit the amount of time a patient would have to engage in any upper-body resistance training. Many lose upper body strength after surgery, so this is an important part of the recovery/rehab process.”
Matthew Tomey, MD, director of the cardiac intensive care unit, Mount Sinai Morningside, New York, advised “caution” when interpreting the findings, stating that “there was no evident difference in the primary outcome measure of functional capacity by 14 weeks, and the trial was not designed to directly assess impact on either social functioning or economic productivity.”
“I would be interested to [see] more comprehensive data on safety in a larger, more diverse sample of postoperative patients,” he said, “as well as evidence to indicate clear advantage of an earlier start for patient-centered outcomes specifically after cardiac surgery.
“Perhaps the greatest challenges to full realization of the benefits of CR in practice have been gaps in referral and gaps in enrollment,” he added. “It is incumbent upon us as clinicians to counsel our patients and to provide appropriate referrals.”
The study was supported by the Medical and Life Sciences Research Fund and the Jeremy Pilcher Memorial Fund. No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
Cardiac rehabilitation (CR) started 2 weeks after sternotomy for a cardiac procedure was noninferior to usual care, in which CR starts 6 weeks after the procedure, with a greater improvement in 6-minute walk test outcomes, a randomized study suggests.
There was no difference in adverse events between groups, although the researchers pointed out that the study was not powered specifically for safety outcomes.
“Cardiac surgical techniques have evolved significantly over the last 60 years, leading to improved survival and shorter hospital stays,” Gordon McGregor, PhD, University of Warwick, Coventry, England, told this news organization. “However, sternal precautions and rehabilitation guidelines have not changed accordingly. There has never been a guideline based on empirical evidence to support rehabilitation professionals working with cardiac surgery patients after median sternotomy.”
“By adopting a progressive individualized approach,” he added, “cardiac surgery sternotomy patients can start cardiac rehabilitation up to 4 weeks earlier than current guidance, and thus potentially complete their recovery sooner.”
Results of the Early Initiation of Poststernotomy Cardiac Rehabilitation Exercise Training study were published online in JAMA Cardiology.
In the study, Dr. McGregor and colleagues randomly assigned 158 patients (mean age, 63 years; 84% men) to 8 weeks of 1-hour, twice-weekly supervised CR exercise training starting 2 weeks (early) or 6 weeks (usual care) after sternotomy.
The primary outcome was change in the 6-minute walk test distance from baseline to 10 or 14 weeks after sternotomy, respectively, and 12 months after randomization.
For usual care, training followed British standards: a warm-up with light cardiovascular and mobility exercises; continuous moderate-intensity cardiovascular exercise; a cooldown; functional exercises using resistance machines and free weights; and upper-body exercises designed to prevent sternal and leg wound pain and complications.
There are no specific outpatient CR exercise guidelines for early CR, so study participants followed an individualized exercise program for the first 2-3 weeks after surgery, starting with light mobility and moderate-intensity cardiovascular training when they could do those exercises with minimal discomfort. They then progressed to current British standards, as per usual care.
Forty patients were lost to follow-up, largely because of the pandemic; about half the participants in each group were included in the primary analysis.
Early CR was not inferior to usual care, the authors wrote. The mean change in 6-minute walk distance from baseline to completion of CR was 28 meters greater in the early group than in the usual-care group, and was achieved 4 weeks earlier in the recovery timeline.
Secondary outcomes (functional fitness and quality of life) improved in both groups and between-group differences were not statistically significant, indicating the noninferiority of early CR, the authors noted.
Safety not proven
There were more adverse events in the early group than in the usual-care group (58 vs. 46) and more serious adverse events (18 vs. 14), but fewer deaths (1 vs. 2).
Although there was no between-group difference in the likelihood of having an adverse or serious adverse event, Dr. McGregor acknowledged that the study was “not powered specifically for safety outcomes.” He added that “there is the potential to run a very large multination definitive superiority [randomized, controlled trial] with safety as the primary outcome; however, a very large sample would be required.”
Meanwhile, he said, “we can say with some degree of certainty that early CR was likely as safe as usual-care CR. In the United Kingdom, we work closely with the British Association for Cardiovascular Prevention and Rehabilitation and the Association of Chartered Physiotherapists in Cardiovascular Rehabilitation, who will incorporate our findings in their guidelines and training courses.”
Questions remain
Asked to comment on the study, John Larry, MD, medical director of cardiology and cardiac rehabilitation at the Ohio State University Wexner Medical Center East Hospital, Columbus, said: “For those under time pressure to return to work, [early CR] could be an advantage to allow more rehab time and improved stamina prior to their return-to-work date.”
That said, he noted, “we typically delay any significant upper-body training activities for 8-10 weeks to avoid impact on healing of the sternum. Thus ... starting sooner would limit the amount of time a patient would have to engage in any upper-body resistance training. Many lose upper body strength after surgery, so this is an important part of the recovery/rehab process.”
Matthew Tomey, MD, director of the cardiac intensive care unit, Mount Sinai Morningside, New York, advised “caution” when interpreting the findings, stating that “there was no evident difference in the primary outcome measure of functional capacity by 14 weeks, and the trial was not designed to directly assess impact on either social functioning or economic productivity.”
“I would be interested to [see] more comprehensive data on safety in a larger, more diverse sample of postoperative patients,” he said, “as well as evidence to indicate clear advantage of an earlier start for patient-centered outcomes specifically after cardiac surgery.
“Perhaps the greatest challenges to full realization of the benefits of CR in practice have been gaps in referral and gaps in enrollment,” he added. “It is incumbent upon us as clinicians to counsel our patients and to provide appropriate referrals.”
The study was supported by the Medical and Life Sciences Research Fund and the Jeremy Pilcher Memorial Fund. No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
FROM JAMA CARDIOLOGY
Cardiologists concerned for patient safety after abortion ruling
Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.
That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.
“We know that the rising maternal mortality rate is predominantly driven by cardiovascular disease, women having children at older ages, and ... risk factors like hypertension, diabetes, and obesity,” Jennifer H. Haythe, MD, told this news organization.
So the high court’s decision in Dobbs v. Jackson Women’s Health Organization, which overturned Roe v. Wade and leaves the legality of abortion up to the 50 separate state legislatures, “is very relevant to cardiologists specifically,” said Dr. Haythe, who is director of cardiology in the cardio-obstetrics program at New York-Presbyterian/Columbia University Irving Medical Center, New York.
The ruling “is going to have a huge effect on women who may not be able to tolerate pregnancy,” she said. Whether to terminate a pregnancy “is a relatively common discussion I have with women with bad heart failure about their risk of further decompensation, death, or needing a heart transplant or heart pump after delivery, or the risk of death in women with pulmonary hypertension.”
The high court’s decision “is a direct attack on the practice of medicine and really the sanctity of the patient-clinician relationship,” Rachel M. Bond, MD, director of Women’s Heart Health Systems Dignity Health of Arizona, told this news organization.
Physicians take an oath “that we should do no harm to our patients, and once the law or governance impacts that, it places us in a very vulnerable situation,” Dr. Bond said. “As a cardiologist who focuses a lot on high-risk pregnancies, I am worried and hesitant to give guidance to many of these patients in the states that may not have access to something that is a medical right, which at times is an abortion.”
She has colleagues in obstetrics in states where abortion is newly illegal who “don’t know what to do,” Dr. Bond said. Many have sought guidance from their legal teams, she said, “and many of them are now trying to figure out what is the best path.”
Pregnancy is “a very significant cardiovascular stress test, and women who may tolerate certain conditions reasonably well outside of the setting of pregnancy may have severe issues, not just for the mother, but for the baby as well,” Ki Park, MD, University of Florida Health, Gainesville, said in an interview.
“As clinicians, none of us like recommending a medically indicated abortion. But it is health care, just like any other medication or treatment that we advise to our patients in cases where the risk of the mother is excessively high and mortality risk is elevated,” said Dr. Park, who is cochair of the American College of Cardiology Cardio-Obstetrics Work Group.
Some conditions, such as pulmonary hypertension and severe aortic valve stenosis, during pregnancy are well recognized as very high risk, and there are various scoring systems to help clinicians with risk stratification, she observed. “But there are also a lot of gray areas where patients don’t necessarily fit into these risk scores that we use.”
So physician-patient discussions in high-risk pregnancies “are already complicated,” Dr. Park said. “Patients want to have options, and they look to us as physicians for guidance with regard to their risks. And if abortion is not available as an option, then part of our toolbox is no longer available to help us care for the mother.”
In the new legal climate, clinicians in states where abortion is illegal may well want to put more emphasis on preconception counseling, so more of their patients with high-risk conditions are aware of the new barriers to pregnancy termination.
“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”
Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.
“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”
Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”
Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”
A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”
Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.
“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”
The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”
The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”
The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”
Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”
A version of this article first appeared on Medscape.com.
Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.
That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.
“We know that the rising maternal mortality rate is predominantly driven by cardiovascular disease, women having children at older ages, and ... risk factors like hypertension, diabetes, and obesity,” Jennifer H. Haythe, MD, told this news organization.
So the high court’s decision in Dobbs v. Jackson Women’s Health Organization, which overturned Roe v. Wade and leaves the legality of abortion up to the 50 separate state legislatures, “is very relevant to cardiologists specifically,” said Dr. Haythe, who is director of cardiology in the cardio-obstetrics program at New York-Presbyterian/Columbia University Irving Medical Center, New York.
The ruling “is going to have a huge effect on women who may not be able to tolerate pregnancy,” she said. Whether to terminate a pregnancy “is a relatively common discussion I have with women with bad heart failure about their risk of further decompensation, death, or needing a heart transplant or heart pump after delivery, or the risk of death in women with pulmonary hypertension.”
The high court’s decision “is a direct attack on the practice of medicine and really the sanctity of the patient-clinician relationship,” Rachel M. Bond, MD, director of Women’s Heart Health Systems Dignity Health of Arizona, told this news organization.
Physicians take an oath “that we should do no harm to our patients, and once the law or governance impacts that, it places us in a very vulnerable situation,” Dr. Bond said. “As a cardiologist who focuses a lot on high-risk pregnancies, I am worried and hesitant to give guidance to many of these patients in the states that may not have access to something that is a medical right, which at times is an abortion.”
She has colleagues in obstetrics in states where abortion is newly illegal who “don’t know what to do,” Dr. Bond said. Many have sought guidance from their legal teams, she said, “and many of them are now trying to figure out what is the best path.”
Pregnancy is “a very significant cardiovascular stress test, and women who may tolerate certain conditions reasonably well outside of the setting of pregnancy may have severe issues, not just for the mother, but for the baby as well,” Ki Park, MD, University of Florida Health, Gainesville, said in an interview.
“As clinicians, none of us like recommending a medically indicated abortion. But it is health care, just like any other medication or treatment that we advise to our patients in cases where the risk of the mother is excessively high and mortality risk is elevated,” said Dr. Park, who is cochair of the American College of Cardiology Cardio-Obstetrics Work Group.
Some conditions, such as pulmonary hypertension and severe aortic valve stenosis, during pregnancy are well recognized as very high risk, and there are various scoring systems to help clinicians with risk stratification, she observed. “But there are also a lot of gray areas where patients don’t necessarily fit into these risk scores that we use.”
So physician-patient discussions in high-risk pregnancies “are already complicated,” Dr. Park said. “Patients want to have options, and they look to us as physicians for guidance with regard to their risks. And if abortion is not available as an option, then part of our toolbox is no longer available to help us care for the mother.”
In the new legal climate, clinicians in states where abortion is illegal may well want to put more emphasis on preconception counseling, so more of their patients with high-risk conditions are aware of the new barriers to pregnancy termination.
“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”
Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.
“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”
Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”
Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”
A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”
Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.
“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”
The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”
The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”
The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”
Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”
A version of this article first appeared on Medscape.com.
Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.
That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.
“We know that the rising maternal mortality rate is predominantly driven by cardiovascular disease, women having children at older ages, and ... risk factors like hypertension, diabetes, and obesity,” Jennifer H. Haythe, MD, told this news organization.
So the high court’s decision in Dobbs v. Jackson Women’s Health Organization, which overturned Roe v. Wade and leaves the legality of abortion up to the 50 separate state legislatures, “is very relevant to cardiologists specifically,” said Dr. Haythe, who is director of cardiology in the cardio-obstetrics program at New York-Presbyterian/Columbia University Irving Medical Center, New York.
The ruling “is going to have a huge effect on women who may not be able to tolerate pregnancy,” she said. Whether to terminate a pregnancy “is a relatively common discussion I have with women with bad heart failure about their risk of further decompensation, death, or needing a heart transplant or heart pump after delivery, or the risk of death in women with pulmonary hypertension.”
The high court’s decision “is a direct attack on the practice of medicine and really the sanctity of the patient-clinician relationship,” Rachel M. Bond, MD, director of Women’s Heart Health Systems Dignity Health of Arizona, told this news organization.
Physicians take an oath “that we should do no harm to our patients, and once the law or governance impacts that, it places us in a very vulnerable situation,” Dr. Bond said. “As a cardiologist who focuses a lot on high-risk pregnancies, I am worried and hesitant to give guidance to many of these patients in the states that may not have access to something that is a medical right, which at times is an abortion.”
She has colleagues in obstetrics in states where abortion is newly illegal who “don’t know what to do,” Dr. Bond said. Many have sought guidance from their legal teams, she said, “and many of them are now trying to figure out what is the best path.”
Pregnancy is “a very significant cardiovascular stress test, and women who may tolerate certain conditions reasonably well outside of the setting of pregnancy may have severe issues, not just for the mother, but for the baby as well,” Ki Park, MD, University of Florida Health, Gainesville, said in an interview.
“As clinicians, none of us like recommending a medically indicated abortion. But it is health care, just like any other medication or treatment that we advise to our patients in cases where the risk of the mother is excessively high and mortality risk is elevated,” said Dr. Park, who is cochair of the American College of Cardiology Cardio-Obstetrics Work Group.
Some conditions, such as pulmonary hypertension and severe aortic valve stenosis, during pregnancy are well recognized as very high risk, and there are various scoring systems to help clinicians with risk stratification, she observed. “But there are also a lot of gray areas where patients don’t necessarily fit into these risk scores that we use.”
So physician-patient discussions in high-risk pregnancies “are already complicated,” Dr. Park said. “Patients want to have options, and they look to us as physicians for guidance with regard to their risks. And if abortion is not available as an option, then part of our toolbox is no longer available to help us care for the mother.”
In the new legal climate, clinicians in states where abortion is illegal may well want to put more emphasis on preconception counseling, so more of their patients with high-risk conditions are aware of the new barriers to pregnancy termination.
“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”
Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.
“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”
Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”
Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”
A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”
Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.
“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”
The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”
The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”
The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”
Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”
A version of this article first appeared on Medscape.com.
Women benefit but lag behind in intracoronary imaging in PCI
A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.
Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).
After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.
“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”
Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:
- Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
- Stent thrombosis: 30.9% vs. 34.9% (P < .01).
- Long lesions: 13.1% vs. 16.3% (P < .01).
- Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
- Left main stem PCI: 55.1% vs. 57.5% (P < .01).
- In-stent restenosis: 28.0% vs. 30.7%.
- Calcified lesions: 36.6% vs. 40.1% (P < .01).
- Renal disease: 17.4% vs. 19.5% (P < .01).
As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.
“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”
Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.
“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.
“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
Getting worse, not better
Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.
To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.
Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.
One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.
“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.
Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.
“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”
Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.
“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”
Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.
“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”
Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.
“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.
A version of this article first appeared on Medscape.com.
A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.
Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).
After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.
“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”
Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:
- Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
- Stent thrombosis: 30.9% vs. 34.9% (P < .01).
- Long lesions: 13.1% vs. 16.3% (P < .01).
- Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
- Left main stem PCI: 55.1% vs. 57.5% (P < .01).
- In-stent restenosis: 28.0% vs. 30.7%.
- Calcified lesions: 36.6% vs. 40.1% (P < .01).
- Renal disease: 17.4% vs. 19.5% (P < .01).
As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.
“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”
Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.
“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.
“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
Getting worse, not better
Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.
To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.
Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.
One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.
“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.
Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.
“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”
Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.
“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”
Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.
“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”
Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.
“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.
A version of this article first appeared on Medscape.com.
A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.
Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).
After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.
“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”
Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:
- Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
- Stent thrombosis: 30.9% vs. 34.9% (P < .01).
- Long lesions: 13.1% vs. 16.3% (P < .01).
- Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
- Left main stem PCI: 55.1% vs. 57.5% (P < .01).
- In-stent restenosis: 28.0% vs. 30.7%.
- Calcified lesions: 36.6% vs. 40.1% (P < .01).
- Renal disease: 17.4% vs. 19.5% (P < .01).
As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.
“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”
Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.
“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.
“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
Getting worse, not better
Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.
To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.
Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.
One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.
“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.
Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.
“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”
Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.
“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”
Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.
“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”
Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.
“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.
A version of this article first appeared on Medscape.com.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
Evidence still lacking that vitamins prevent CVD, cancer: USPSTF
There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.
However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.
These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.
“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.
“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.
“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.
Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.
“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.
The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.
“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.
On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.
However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.
“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.
But he noted that the task force did not find any significant harms from taking multivitamins.
“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.
Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.
“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
‘Any benefit likely to be small’
In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.
The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.
They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).
“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.
The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.
However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.
The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
Possible benefit for older adults?
Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.
“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”
However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.
She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.
“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.
“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”
A version of this article first appeared on Medscape.com.
There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.
However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.
These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.
“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.
“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.
“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.
Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.
“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.
The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.
“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.
On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.
However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.
“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.
But he noted that the task force did not find any significant harms from taking multivitamins.
“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.
Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.
“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
‘Any benefit likely to be small’
In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.
The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.
They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).
“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.
The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.
However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.
The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
Possible benefit for older adults?
Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.
“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”
However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.
She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.
“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.
“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”
A version of this article first appeared on Medscape.com.
There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.
However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.
These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.
“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.
“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.
“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.
Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.
“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.
The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.
“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.
On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.
However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.
“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.
But he noted that the task force did not find any significant harms from taking multivitamins.
“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.
Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.
“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
‘Any benefit likely to be small’
In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.
The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.
They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).
“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.
The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.
However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.
The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
Possible benefit for older adults?
Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.
“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”
However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.
She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.
“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.
“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”
A version of this article first appeared on Medscape.com.
FROM JAMA
Add AFib to noncardiac surgery risk evaluation: New support
Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.
But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.
Indeed, AFib emerged as a significant, independent risk factor for a number of bad postoperative outcomes. Mortality within a month of the procedure climbed about 30% for patients with AFib before the noncardiac surgery. Their 30-day risks for stroke and for heart failure hospitalization went up similarly.
The addition of AFib to the RCRI significantly improved its ability to discriminate 30-day postoperative risk levels regardless of age, sex, and type of noncardiac surgery, Amgad Mentias, MD, Cleveland Clinic, told this news organization. And “it was able to correctly up-classify patients to high risk, if AFib was there, and it was able to down-classify some patients to lower risk if it wasn’t there.”
“I think [the findings] are convincing evidence that atrial fib should at least be part of the thought process for the surgical team and the medical team taking care of the patient,” said Dr. Mentias, who is senior author on the study published in the Journal of the American College of Cardiology, with lead author Sameer Prasada, MD, also of the Cleveland Clinic.
The results “call for incorporating AFib as a risk factor in perioperative risk scores for cardiovascular morbidity and mortality,” the published report states.
Supraventricular arrhythmias had been part of the Goldman Risk Index once widely used preoperatively to assess cardiac risk before practice adopted the RCRI in the past decade, observe Anne B. Curtis, MD, and Sai Krishna C. Korada, MD, University at Buffalo, New York, in an accompanying editorial.
The current findings “demonstrate improved prediction of adverse postsurgical outcomes” from supplementing the RCRI with AFib, they write. Given associations between preexisting AFib and serious cardiac events, “it is time to ‘re-revise’ the RCRI and acknowledge the importance of AFib in predicting adverse outcomes” after noncardiac surgery.
The new findings, however, aren’t all straightforward. In one result that remains a bit of a head-scratcher, postoperative risk of myocardial infarction (MI) in patients with preexisting AFib went in the opposite direction of risk for death and other CV outcomes, falling by almost 20%.
That is “hard to explain with the available data,” the report states, but “the use of anticoagulation, whether oral or parenteral (as a bridge therapy in the perioperative period), is a plausible explanation” given the frequent role of thrombosis in triggering MIs.
Consistent with such a mechanism, the group argues, the MI risk reduction was seen primarily among patients with AFib and a CHA2DS2-VASc score of 2 or higher – that is, those at highest risk for stroke and therefore most likely to be on oral anticoagulation. The MI risk reduction wasn’t seen in such patients with a CHA2DS2-VASc score of 0 or 1.
“I think that’s part of the explanation, that anticoagulation can reduce risk of MI. But it’s not the whole explanation,” Dr. Mentias said in an interview. If it were the sole mechanism, he said, then the same oral anticoagulation that protected against MI should have also cut the postoperative stroke risk. Yet that risk climbed 40% among patients with preexisting AFib.
The analysis started with 8.6 million Medicare patients with planned noncardiac surgery, seen from 2015 to 2019, of whom 16.4% had preexisting AFib. Propensity matching for demographics, urgency and type of surgery, CHA2DS2-VASc score, and RCRI index created two cohorts for comparison: 1.13 million patients with and 1.92 million without preexisting AFib.
Preexisting AFib was associated with a higher 30-day risk for death from any cause, the primary endpoint being 8.3% versus 5.8% for those without such AFib (P < .001), for an odds ratio of 1.31 (95% confidence interval, 1.30-1.32).
Corresponding 30-day ORs for other events, all significant at P < .001, were:
- 1.31 (95% CI, 1.30-1.33) for heart failure
- 1.40 (95% CI, 1.37-1.43) for stroke
- 1.59 (95% CI, 1.43-1.75) for systemic embolism
- 1.14 (95% CI, 1.13-1.16) for major bleeding
- 0.81 (95% CI, 0.79-0.82) for MI
Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).
The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.
For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.
“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”
Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.
But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.
Indeed, AFib emerged as a significant, independent risk factor for a number of bad postoperative outcomes. Mortality within a month of the procedure climbed about 30% for patients with AFib before the noncardiac surgery. Their 30-day risks for stroke and for heart failure hospitalization went up similarly.
The addition of AFib to the RCRI significantly improved its ability to discriminate 30-day postoperative risk levels regardless of age, sex, and type of noncardiac surgery, Amgad Mentias, MD, Cleveland Clinic, told this news organization. And “it was able to correctly up-classify patients to high risk, if AFib was there, and it was able to down-classify some patients to lower risk if it wasn’t there.”
“I think [the findings] are convincing evidence that atrial fib should at least be part of the thought process for the surgical team and the medical team taking care of the patient,” said Dr. Mentias, who is senior author on the study published in the Journal of the American College of Cardiology, with lead author Sameer Prasada, MD, also of the Cleveland Clinic.
The results “call for incorporating AFib as a risk factor in perioperative risk scores for cardiovascular morbidity and mortality,” the published report states.
Supraventricular arrhythmias had been part of the Goldman Risk Index once widely used preoperatively to assess cardiac risk before practice adopted the RCRI in the past decade, observe Anne B. Curtis, MD, and Sai Krishna C. Korada, MD, University at Buffalo, New York, in an accompanying editorial.
The current findings “demonstrate improved prediction of adverse postsurgical outcomes” from supplementing the RCRI with AFib, they write. Given associations between preexisting AFib and serious cardiac events, “it is time to ‘re-revise’ the RCRI and acknowledge the importance of AFib in predicting adverse outcomes” after noncardiac surgery.
The new findings, however, aren’t all straightforward. In one result that remains a bit of a head-scratcher, postoperative risk of myocardial infarction (MI) in patients with preexisting AFib went in the opposite direction of risk for death and other CV outcomes, falling by almost 20%.
That is “hard to explain with the available data,” the report states, but “the use of anticoagulation, whether oral or parenteral (as a bridge therapy in the perioperative period), is a plausible explanation” given the frequent role of thrombosis in triggering MIs.
Consistent with such a mechanism, the group argues, the MI risk reduction was seen primarily among patients with AFib and a CHA2DS2-VASc score of 2 or higher – that is, those at highest risk for stroke and therefore most likely to be on oral anticoagulation. The MI risk reduction wasn’t seen in such patients with a CHA2DS2-VASc score of 0 or 1.
“I think that’s part of the explanation, that anticoagulation can reduce risk of MI. But it’s not the whole explanation,” Dr. Mentias said in an interview. If it were the sole mechanism, he said, then the same oral anticoagulation that protected against MI should have also cut the postoperative stroke risk. Yet that risk climbed 40% among patients with preexisting AFib.
The analysis started with 8.6 million Medicare patients with planned noncardiac surgery, seen from 2015 to 2019, of whom 16.4% had preexisting AFib. Propensity matching for demographics, urgency and type of surgery, CHA2DS2-VASc score, and RCRI index created two cohorts for comparison: 1.13 million patients with and 1.92 million without preexisting AFib.
Preexisting AFib was associated with a higher 30-day risk for death from any cause, the primary endpoint being 8.3% versus 5.8% for those without such AFib (P < .001), for an odds ratio of 1.31 (95% confidence interval, 1.30-1.32).
Corresponding 30-day ORs for other events, all significant at P < .001, were:
- 1.31 (95% CI, 1.30-1.33) for heart failure
- 1.40 (95% CI, 1.37-1.43) for stroke
- 1.59 (95% CI, 1.43-1.75) for systemic embolism
- 1.14 (95% CI, 1.13-1.16) for major bleeding
- 0.81 (95% CI, 0.79-0.82) for MI
Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).
The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.
For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.
“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”
Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.
But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.
Indeed, AFib emerged as a significant, independent risk factor for a number of bad postoperative outcomes. Mortality within a month of the procedure climbed about 30% for patients with AFib before the noncardiac surgery. Their 30-day risks for stroke and for heart failure hospitalization went up similarly.
The addition of AFib to the RCRI significantly improved its ability to discriminate 30-day postoperative risk levels regardless of age, sex, and type of noncardiac surgery, Amgad Mentias, MD, Cleveland Clinic, told this news organization. And “it was able to correctly up-classify patients to high risk, if AFib was there, and it was able to down-classify some patients to lower risk if it wasn’t there.”
“I think [the findings] are convincing evidence that atrial fib should at least be part of the thought process for the surgical team and the medical team taking care of the patient,” said Dr. Mentias, who is senior author on the study published in the Journal of the American College of Cardiology, with lead author Sameer Prasada, MD, also of the Cleveland Clinic.
The results “call for incorporating AFib as a risk factor in perioperative risk scores for cardiovascular morbidity and mortality,” the published report states.
Supraventricular arrhythmias had been part of the Goldman Risk Index once widely used preoperatively to assess cardiac risk before practice adopted the RCRI in the past decade, observe Anne B. Curtis, MD, and Sai Krishna C. Korada, MD, University at Buffalo, New York, in an accompanying editorial.
The current findings “demonstrate improved prediction of adverse postsurgical outcomes” from supplementing the RCRI with AFib, they write. Given associations between preexisting AFib and serious cardiac events, “it is time to ‘re-revise’ the RCRI and acknowledge the importance of AFib in predicting adverse outcomes” after noncardiac surgery.
The new findings, however, aren’t all straightforward. In one result that remains a bit of a head-scratcher, postoperative risk of myocardial infarction (MI) in patients with preexisting AFib went in the opposite direction of risk for death and other CV outcomes, falling by almost 20%.
That is “hard to explain with the available data,” the report states, but “the use of anticoagulation, whether oral or parenteral (as a bridge therapy in the perioperative period), is a plausible explanation” given the frequent role of thrombosis in triggering MIs.
Consistent with such a mechanism, the group argues, the MI risk reduction was seen primarily among patients with AFib and a CHA2DS2-VASc score of 2 or higher – that is, those at highest risk for stroke and therefore most likely to be on oral anticoagulation. The MI risk reduction wasn’t seen in such patients with a CHA2DS2-VASc score of 0 or 1.
“I think that’s part of the explanation, that anticoagulation can reduce risk of MI. But it’s not the whole explanation,” Dr. Mentias said in an interview. If it were the sole mechanism, he said, then the same oral anticoagulation that protected against MI should have also cut the postoperative stroke risk. Yet that risk climbed 40% among patients with preexisting AFib.
The analysis started with 8.6 million Medicare patients with planned noncardiac surgery, seen from 2015 to 2019, of whom 16.4% had preexisting AFib. Propensity matching for demographics, urgency and type of surgery, CHA2DS2-VASc score, and RCRI index created two cohorts for comparison: 1.13 million patients with and 1.92 million without preexisting AFib.
Preexisting AFib was associated with a higher 30-day risk for death from any cause, the primary endpoint being 8.3% versus 5.8% for those without such AFib (P < .001), for an odds ratio of 1.31 (95% confidence interval, 1.30-1.32).
Corresponding 30-day ORs for other events, all significant at P < .001, were:
- 1.31 (95% CI, 1.30-1.33) for heart failure
- 1.40 (95% CI, 1.37-1.43) for stroke
- 1.59 (95% CI, 1.43-1.75) for systemic embolism
- 1.14 (95% CI, 1.13-1.16) for major bleeding
- 0.81 (95% CI, 0.79-0.82) for MI
Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).
The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.
For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.
“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”
Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Remnant cholesterol improves CV risk prediction
, a new study suggests.
The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.
“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.
They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.
They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.
However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.
“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.
The study was published online in the Journal of the American College of Cardiology.
The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.
“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.
They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.
They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.
The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.
For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.
During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).
Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.
Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.
Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.
When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.
In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.
The editorialists note that both fasting and nonfasting lipid values provide useful information for atherosclerotic cardiovascular disease (ASCVD) risk estimation, and elevated nonfasting remnant cholesterol appears to help identify persons at greater risk for an initial cardiovascular ischemic event.
They add that very elevated levels (above the 75th percentile) of nonfasting remnant cholesterol deserve further evaluation as a potentially valuable “modifier of ASCVD risk,” and replication of the results could move these findings forward to potentially improve prognostication and care for patients at risk for ischemic heart disease events.
An indirect measure of triglycerides
Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.
“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”
He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.
“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.
While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.
“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.
This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.
A version of this article first appeared on Medscape.com.
, a new study suggests.
The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.
“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.
They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.
They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.
However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.
“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.
The study was published online in the Journal of the American College of Cardiology.
The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.
“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.
They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.
They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.
The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.
For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.
During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).
Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.
Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.
Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.
When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.
In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.
The editorialists note that both fasting and nonfasting lipid values provide useful information for atherosclerotic cardiovascular disease (ASCVD) risk estimation, and elevated nonfasting remnant cholesterol appears to help identify persons at greater risk for an initial cardiovascular ischemic event.
They add that very elevated levels (above the 75th percentile) of nonfasting remnant cholesterol deserve further evaluation as a potentially valuable “modifier of ASCVD risk,” and replication of the results could move these findings forward to potentially improve prognostication and care for patients at risk for ischemic heart disease events.
An indirect measure of triglycerides
Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.
“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”
He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.
“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.
While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.
“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.
This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.
A version of this article first appeared on Medscape.com.
, a new study suggests.
The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.
“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.
They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.
They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.
However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.
“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.
The study was published online in the Journal of the American College of Cardiology.
The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.
“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.
They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.
They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.
The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.
For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.
During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).
Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.
Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.
Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.
When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.
In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.
The editorialists note that both fasting and nonfasting lipid values provide useful information for atherosclerotic cardiovascular disease (ASCVD) risk estimation, and elevated nonfasting remnant cholesterol appears to help identify persons at greater risk for an initial cardiovascular ischemic event.
They add that very elevated levels (above the 75th percentile) of nonfasting remnant cholesterol deserve further evaluation as a potentially valuable “modifier of ASCVD risk,” and replication of the results could move these findings forward to potentially improve prognostication and care for patients at risk for ischemic heart disease events.
An indirect measure of triglycerides
Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.
“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”
He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.
“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.
While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.
“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.
This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.
A version of this article first appeared on Medscape.com.
Meta-analysis points to safety of acetylcholine coronary testing
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.