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New TAVI Platform Adds More Valve Sizes to Choose From
PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.
In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval® by Merril Life Sciences and compared them with the balloon-expandable Sapien® from Edwards Lifesciences and the self-expanding Evolut® valve from Medtronic.
The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.
at the Congress of the European Association of Percutaneous Coronary Interventions 2024.
The LANDMARK Trial
The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.
Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.
The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.
Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.
For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.
When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms.
Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.
Precise Matching
The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.
The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.
Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.
However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.
Longer Follow-Up to Come
Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.
Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”
And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.
A version of this article appeared on Medscape.com.
PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.
In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval® by Merril Life Sciences and compared them with the balloon-expandable Sapien® from Edwards Lifesciences and the self-expanding Evolut® valve from Medtronic.
The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.
at the Congress of the European Association of Percutaneous Coronary Interventions 2024.
The LANDMARK Trial
The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.
Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.
The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.
Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.
For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.
When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms.
Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.
Precise Matching
The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.
The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.
Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.
However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.
Longer Follow-Up to Come
Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.
Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”
And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.
A version of this article appeared on Medscape.com.
PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.
In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval® by Merril Life Sciences and compared them with the balloon-expandable Sapien® from Edwards Lifesciences and the self-expanding Evolut® valve from Medtronic.
The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.
at the Congress of the European Association of Percutaneous Coronary Interventions 2024.
The LANDMARK Trial
The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.
Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.
The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.
Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.
For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.
When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms.
Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.
Precise Matching
The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.
The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.
Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.
However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.
Longer Follow-Up to Come
Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.
Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”
And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.
A version of this article appeared on Medscape.com.
FROM EUROPCR 2024
Is Red Meat Healthy? Multiverse Analysis Has Lessons Beyond Meat
Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise.
Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.
My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.
But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.
A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
Multiple Ways to Slice the Data
Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality.
Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies.
You might wonder how there could be thousands of ways to analyze a dataset. I surely did.
The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.
Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.
For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association.
Is Red Meat Good or Bad?
Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality.
Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review.
They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals.
Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology.
Specification Curve Analyses Results
Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.
- The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
- The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
- Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
- As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
- Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
- Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.
Paradigm Changing
As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have.
Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method.
Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result.
Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null.
What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible.
The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data.
I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices?
Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.
Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise.
Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.
My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.
But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.
A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
Multiple Ways to Slice the Data
Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality.
Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies.
You might wonder how there could be thousands of ways to analyze a dataset. I surely did.
The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.
Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.
For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association.
Is Red Meat Good or Bad?
Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality.
Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review.
They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals.
Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology.
Specification Curve Analyses Results
Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.
- The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
- The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
- Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
- As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
- Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
- Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.
Paradigm Changing
As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have.
Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method.
Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result.
Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null.
What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible.
The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data.
I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices?
Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.
Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise.
Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.
My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.
But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.
A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
Multiple Ways to Slice the Data
Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality.
Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies.
You might wonder how there could be thousands of ways to analyze a dataset. I surely did.
The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.
Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.
For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association.
Is Red Meat Good or Bad?
Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality.
Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review.
They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals.
Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology.
Specification Curve Analyses Results
Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.
- The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
- The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
- Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
- As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
- Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
- Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.
Paradigm Changing
As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have.
Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method.
Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result.
Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null.
What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible.
The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data.
I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices?
Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.
Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Neutrophils Take Center Stage in Growing Understanding of Colchicine’s Role in Treating Atherosclerotic Cardiovascular Disease
NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.
In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.
“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.
The Inflammatory Pathway
Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.
“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation.
Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.
“This is where colchicine can potentially play a role,” she said.
Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.
The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted.
Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.
Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.
What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.
“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.
“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
Slow to Embrace Colchicine
Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.
“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.
Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.
Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.
Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com .
NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.
In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.
“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.
The Inflammatory Pathway
Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.
“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation.
Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.
“This is where colchicine can potentially play a role,” she said.
Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.
The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted.
Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.
Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.
What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.
“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.
“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
Slow to Embrace Colchicine
Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.
“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.
Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.
Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.
Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com .
NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.
In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.
“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.
The Inflammatory Pathway
Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.
“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation.
Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.
“This is where colchicine can potentially play a role,” she said.
Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.
The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted.
Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.
Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.
What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.
“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.
“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
Slow to Embrace Colchicine
Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.
“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.
Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.
Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.
Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com .
The History of Aspirin in Heart Disease Prevention
As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.
A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.
Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.
But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).
The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.
According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.
who haven’t had a heart attack or stroke.”
Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.
But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.
“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.
However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
Benefits Persist for Some Patients
The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.
The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.
Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”
With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.
“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.
For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.
Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.
Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.
“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.
Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.
“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”
Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.
Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.
“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.
His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.
Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”
Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.
A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.
Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.
But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).
The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.
According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.
who haven’t had a heart attack or stroke.”
Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.
But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.
“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.
However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
Benefits Persist for Some Patients
The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.
The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.
Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”
With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.
“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.
For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.
Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.
Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.
“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.
Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.
“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”
Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.
Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.
“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.
His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.
Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”
Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.
A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.
Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.
But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).
The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.
According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.
who haven’t had a heart attack or stroke.”
Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.
But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.
“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.
However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
Benefits Persist for Some Patients
The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.
The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.
Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”
With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.
“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.
For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.
Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.
Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.
“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.
Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.
“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”
Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.
Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.
“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.
His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.
Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”
Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Evening May Be the Best Time for Exercise
TOPLINE:
Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).
METHODOLOGY:
- Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
- Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
- Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
- Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
- The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.
TAKEAWAY:
- Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
- The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
- Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.
IN PRACTICE:
The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”
SOURCE:
The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.
LIMITATIONS:
Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.
DISCLOSURES:
The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).
METHODOLOGY:
- Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
- Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
- Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
- Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
- The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.
TAKEAWAY:
- Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
- The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
- Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.
IN PRACTICE:
The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”
SOURCE:
The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.
LIMITATIONS:
Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.
DISCLOSURES:
The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).
METHODOLOGY:
- Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
- Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
- Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
- Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
- The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.
TAKEAWAY:
- Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
- The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
- Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.
IN PRACTICE:
The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”
SOURCE:
The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.
LIMITATIONS:
Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.
DISCLOSURES:
The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Are E-Cigarettes Bad for the Heart?
E-cigarettes entered the market as consumer products without comprehensive toxicological testing,based on the assessment that they were 95% less harmful than traditional cigarettes. Further, consumer dvertising suggests that e-cigarettes are a good alternative to conventional combustible cigarettes and can serve as a gateway to quitting smoking.
However, hen considering damage to the endothelium and toxicity, e-cigarettes have a negative impact like that of conventional cigarettes. Moreover, switching to e-cigarettes often leads to dual use, said Stefan Andreas, MD, director of the Lungenfachklinik in Immenhausen, Germany, at the Congress of the German Respiratory Society and Intensive Care Medicine.
Subclinical Atherosclerosis
Because e-cigarettes have emerged relatively recently, long-term studies on their cardiac consequences are not yet available. Dr. Andreas explained that the impact on endothelial function is relevant for risk assessment. Endothelial function is a biomarker for early, subclinical atherosclerosis. “If endothelial function is impaired, the risk for heart attack and stroke is significantly increased 5-10 years later,” said Dr. Andreas.
The results of a crossover study showed reduced vascular elasticity after consuming both tobacco cigarettes and e-cigarettes. The study included 20 smokers, and endothelial function was measured using flow-mediated vasodilation.
Significant effects on the vessels were also found in a study of 31 participants who had never smoked. The study participants inhaled a nicotine-free aerosol from e-cigarettes. Before and after, parameters of endothelial function were examined using a 3.0-T MRI. After aerosol inhalation, the resistance index was 2.3% higher (P < .05), and flow-mediated vascular dilation was reduced by 34% (P < .001).
A recent review involving 372 participants from China showed that e-cigarettes lead to an increase in pulse wave velocity, with a difference of 3.08 (P < .001). “Pulse wave velocity is also a marker of endothelial function: The stiffer the vessels, the higher the pulse wave velocity,” said Dr. Andreas. The authors of the review concluded that “e-cigarettes should not be promoted as a healthier alternative to tobacco smoking.”
No Harmless Alternative
A recent review compared the effects of tobacco smoking and e-cigarettes. Although the toxic mixture in smoke is more complex, both e-cigarettes and tobacco cigarettes “impaired endothelial function to a similar extent,” they wrote. The authors attributed this finding to oxidative stress as the central mechanism.
“There is increasing evidence that e-cigarettes are not a harmless alternative to tobacco cigarettes,” wrote Thomas Münzel, MD, professor of cardiology at the University of Mainz and his team in their 2020 review, which examined studies in humans and animals. They provided an overview of the effects of tobacco/hookah smoking and e-cigarette vaping on endothelial function. They also pointed to emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and circadian clock.
Finally, a toxicological review of e-cigarettes also found alarmingly high levels of carcinogens and toxins that could have long-term effects on other organs, including the development of neurological symptoms, lung cancer, cardiovascular diseases, and cavities.
Dr. Andreas observed that even small amounts, such as those obtained through secondhand smoking, can be harmful. In 2007, Dr. Andreas and his colleagues showed that even low exposure to tobacco smoke can lead to a significant increase in cardiovascular events.
Conflicts of Interest
Dr. Andreas recommended closely examining the studies that suggest that e-cigarettes are less risky. “It is noticeable that there is a significant difference depending on whether publications were supported by the tobacco industry or not,” he emphasized.
Danish scientists found that a conflict of interest (COI) has a strong influence on study results. “In studies without a COI, e-cigarettes are found to cause damage 95% of the time. In contrast, when there is a strong conflict of interest, the result is often ‘no harm,’” said Dr. Andreas.
This effect is quite relevant for the discussion of e-cigarettes. “If scientists make a critical statement in a position paper, there will always be someone who says, ‘No, it’s different, there are these and those publications.’ The true nature of interest-driven publications on e-cigarettes is not always easy to discern,” said Dr. Andreas.
No Gateway to Quitting
E-cigarettes are used in clinical studies for tobacco cessation. The results of a randomized study showed that significantly more smokers who were switched to e-cigarettes quit smoking, compared with controls. But there was no significant difference in complete smoking cessation between groups. Moreover, 45% of smokers who switched to e-cigarettes became dual users, compared with 11% of controls.
“Translating these results means that for one person who quits smoking by using e-cigarettes, they gain five people who use both traditional cigarettes and e-cigarettes,” explained Dr. Andreas.
In their recent review, Münzel and colleagues pointed out that the assessment that e-cigarettes could help with quitting might be wrong. Rather, it seems that “e-cigarettes have the opposite effect.” They also note that the age of initiation for e-cigarettes is generally lower than for tobacco cigarettes: Consumption often starts at age 13 or 14 years. And the consumption of e-cigarettes among children and adolescents increased by 7% from 2016 to 2023.
A meta-analysis published at the end of February also shows that e-cigarettes are about as dangerous as tobacco cigarettes. They are more dangerous than not smoking, and dual use is more dangerous than tobacco cigarettes alone. “There is a need to reassess the assumption that e-cigarette use provides substantial harm reduction across all cigarette-caused diseases, particularly accounting for dual use,” wrote the authors.
“One must always consider that e-cigarettes have only been available for a relatively short time. We can only see the cumulative toxicity in 10, 20 years when we have patients who have smoked e-cigarettes only for 20 years,” said Dr. Andreas. Ultimately, however, e-cigarettes promote dual use and, consequently, additive toxicity.
Nicotine Replacement Therapies
Quitting smoking reduces the risk of cardiovascular events and premature death by 40%, even among patients with cardiovascular disease, according to a Cochrane meta-analysis. Smoking cessation reduces the risk for cardiovascular death by 39%, the risk for major adverse cardiovascular events by 43%, the risk for heart attack by 36%, the risk for stroke by 30%, and overall mortality by 40%.
Quitting smoking is the most effective measure for risk reduction, as a meta-analysis of 20 studies in patients with coronary heart disease found. Smoking cessation was associated with a 36% risk reduction compared with 29% risk reduction for statin therapy, 23% risk reduction with beta-blockers and ACE inhibitors and 15% risk reduction with aspirin.
Dr. Andreas emphasized that nicotine replacement therapies are well-researched and safe even in cardiovascular disease, as shown by a US study that included patients who had sustained a heart attack. A group of the participants was treated with nicotine patches for 10 weeks, while the other group received a placebo. After 14 weeks, 21% of the nicotine patch group achieved abstinence vs 9% of the placebo group (P = .001). Transdermal nicotine application does not lead to a significant increase in cardiovascular events in high-risk patients.
The German “Nonsmoker Heroes” app has proven to be an effective means of behavioral therapeutic coaching. A recent study of it included 17 study centers with 661 participants. About 21% of the subjects had chronic obstructive pulmonary disease, 19% had asthma. Smoking onset occurred at age 16 years. The subjects were highly dependent: > 72% had at least moderate dependence, > 58% had high to very high dependence, and the population had an average of 3.6 quit attempts. The odds ratio for self-reported abstinence was 2.2 after 6 months. “The app is not only effective, but also can be prescribed on an extrabudgetary basis,” said Dr. Andreas.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
E-cigarettes entered the market as consumer products without comprehensive toxicological testing,based on the assessment that they were 95% less harmful than traditional cigarettes. Further, consumer dvertising suggests that e-cigarettes are a good alternative to conventional combustible cigarettes and can serve as a gateway to quitting smoking.
However, hen considering damage to the endothelium and toxicity, e-cigarettes have a negative impact like that of conventional cigarettes. Moreover, switching to e-cigarettes often leads to dual use, said Stefan Andreas, MD, director of the Lungenfachklinik in Immenhausen, Germany, at the Congress of the German Respiratory Society and Intensive Care Medicine.
Subclinical Atherosclerosis
Because e-cigarettes have emerged relatively recently, long-term studies on their cardiac consequences are not yet available. Dr. Andreas explained that the impact on endothelial function is relevant for risk assessment. Endothelial function is a biomarker for early, subclinical atherosclerosis. “If endothelial function is impaired, the risk for heart attack and stroke is significantly increased 5-10 years later,” said Dr. Andreas.
The results of a crossover study showed reduced vascular elasticity after consuming both tobacco cigarettes and e-cigarettes. The study included 20 smokers, and endothelial function was measured using flow-mediated vasodilation.
Significant effects on the vessels were also found in a study of 31 participants who had never smoked. The study participants inhaled a nicotine-free aerosol from e-cigarettes. Before and after, parameters of endothelial function were examined using a 3.0-T MRI. After aerosol inhalation, the resistance index was 2.3% higher (P < .05), and flow-mediated vascular dilation was reduced by 34% (P < .001).
A recent review involving 372 participants from China showed that e-cigarettes lead to an increase in pulse wave velocity, with a difference of 3.08 (P < .001). “Pulse wave velocity is also a marker of endothelial function: The stiffer the vessels, the higher the pulse wave velocity,” said Dr. Andreas. The authors of the review concluded that “e-cigarettes should not be promoted as a healthier alternative to tobacco smoking.”
No Harmless Alternative
A recent review compared the effects of tobacco smoking and e-cigarettes. Although the toxic mixture in smoke is more complex, both e-cigarettes and tobacco cigarettes “impaired endothelial function to a similar extent,” they wrote. The authors attributed this finding to oxidative stress as the central mechanism.
“There is increasing evidence that e-cigarettes are not a harmless alternative to tobacco cigarettes,” wrote Thomas Münzel, MD, professor of cardiology at the University of Mainz and his team in their 2020 review, which examined studies in humans and animals. They provided an overview of the effects of tobacco/hookah smoking and e-cigarette vaping on endothelial function. They also pointed to emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and circadian clock.
Finally, a toxicological review of e-cigarettes also found alarmingly high levels of carcinogens and toxins that could have long-term effects on other organs, including the development of neurological symptoms, lung cancer, cardiovascular diseases, and cavities.
Dr. Andreas observed that even small amounts, such as those obtained through secondhand smoking, can be harmful. In 2007, Dr. Andreas and his colleagues showed that even low exposure to tobacco smoke can lead to a significant increase in cardiovascular events.
Conflicts of Interest
Dr. Andreas recommended closely examining the studies that suggest that e-cigarettes are less risky. “It is noticeable that there is a significant difference depending on whether publications were supported by the tobacco industry or not,” he emphasized.
Danish scientists found that a conflict of interest (COI) has a strong influence on study results. “In studies without a COI, e-cigarettes are found to cause damage 95% of the time. In contrast, when there is a strong conflict of interest, the result is often ‘no harm,’” said Dr. Andreas.
This effect is quite relevant for the discussion of e-cigarettes. “If scientists make a critical statement in a position paper, there will always be someone who says, ‘No, it’s different, there are these and those publications.’ The true nature of interest-driven publications on e-cigarettes is not always easy to discern,” said Dr. Andreas.
No Gateway to Quitting
E-cigarettes are used in clinical studies for tobacco cessation. The results of a randomized study showed that significantly more smokers who were switched to e-cigarettes quit smoking, compared with controls. But there was no significant difference in complete smoking cessation between groups. Moreover, 45% of smokers who switched to e-cigarettes became dual users, compared with 11% of controls.
“Translating these results means that for one person who quits smoking by using e-cigarettes, they gain five people who use both traditional cigarettes and e-cigarettes,” explained Dr. Andreas.
In their recent review, Münzel and colleagues pointed out that the assessment that e-cigarettes could help with quitting might be wrong. Rather, it seems that “e-cigarettes have the opposite effect.” They also note that the age of initiation for e-cigarettes is generally lower than for tobacco cigarettes: Consumption often starts at age 13 or 14 years. And the consumption of e-cigarettes among children and adolescents increased by 7% from 2016 to 2023.
A meta-analysis published at the end of February also shows that e-cigarettes are about as dangerous as tobacco cigarettes. They are more dangerous than not smoking, and dual use is more dangerous than tobacco cigarettes alone. “There is a need to reassess the assumption that e-cigarette use provides substantial harm reduction across all cigarette-caused diseases, particularly accounting for dual use,” wrote the authors.
“One must always consider that e-cigarettes have only been available for a relatively short time. We can only see the cumulative toxicity in 10, 20 years when we have patients who have smoked e-cigarettes only for 20 years,” said Dr. Andreas. Ultimately, however, e-cigarettes promote dual use and, consequently, additive toxicity.
Nicotine Replacement Therapies
Quitting smoking reduces the risk of cardiovascular events and premature death by 40%, even among patients with cardiovascular disease, according to a Cochrane meta-analysis. Smoking cessation reduces the risk for cardiovascular death by 39%, the risk for major adverse cardiovascular events by 43%, the risk for heart attack by 36%, the risk for stroke by 30%, and overall mortality by 40%.
Quitting smoking is the most effective measure for risk reduction, as a meta-analysis of 20 studies in patients with coronary heart disease found. Smoking cessation was associated with a 36% risk reduction compared with 29% risk reduction for statin therapy, 23% risk reduction with beta-blockers and ACE inhibitors and 15% risk reduction with aspirin.
Dr. Andreas emphasized that nicotine replacement therapies are well-researched and safe even in cardiovascular disease, as shown by a US study that included patients who had sustained a heart attack. A group of the participants was treated with nicotine patches for 10 weeks, while the other group received a placebo. After 14 weeks, 21% of the nicotine patch group achieved abstinence vs 9% of the placebo group (P = .001). Transdermal nicotine application does not lead to a significant increase in cardiovascular events in high-risk patients.
The German “Nonsmoker Heroes” app has proven to be an effective means of behavioral therapeutic coaching. A recent study of it included 17 study centers with 661 participants. About 21% of the subjects had chronic obstructive pulmonary disease, 19% had asthma. Smoking onset occurred at age 16 years. The subjects were highly dependent: > 72% had at least moderate dependence, > 58% had high to very high dependence, and the population had an average of 3.6 quit attempts. The odds ratio for self-reported abstinence was 2.2 after 6 months. “The app is not only effective, but also can be prescribed on an extrabudgetary basis,” said Dr. Andreas.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
E-cigarettes entered the market as consumer products without comprehensive toxicological testing,based on the assessment that they were 95% less harmful than traditional cigarettes. Further, consumer dvertising suggests that e-cigarettes are a good alternative to conventional combustible cigarettes and can serve as a gateway to quitting smoking.
However, hen considering damage to the endothelium and toxicity, e-cigarettes have a negative impact like that of conventional cigarettes. Moreover, switching to e-cigarettes often leads to dual use, said Stefan Andreas, MD, director of the Lungenfachklinik in Immenhausen, Germany, at the Congress of the German Respiratory Society and Intensive Care Medicine.
Subclinical Atherosclerosis
Because e-cigarettes have emerged relatively recently, long-term studies on their cardiac consequences are not yet available. Dr. Andreas explained that the impact on endothelial function is relevant for risk assessment. Endothelial function is a biomarker for early, subclinical atherosclerosis. “If endothelial function is impaired, the risk for heart attack and stroke is significantly increased 5-10 years later,” said Dr. Andreas.
The results of a crossover study showed reduced vascular elasticity after consuming both tobacco cigarettes and e-cigarettes. The study included 20 smokers, and endothelial function was measured using flow-mediated vasodilation.
Significant effects on the vessels were also found in a study of 31 participants who had never smoked. The study participants inhaled a nicotine-free aerosol from e-cigarettes. Before and after, parameters of endothelial function were examined using a 3.0-T MRI. After aerosol inhalation, the resistance index was 2.3% higher (P < .05), and flow-mediated vascular dilation was reduced by 34% (P < .001).
A recent review involving 372 participants from China showed that e-cigarettes lead to an increase in pulse wave velocity, with a difference of 3.08 (P < .001). “Pulse wave velocity is also a marker of endothelial function: The stiffer the vessels, the higher the pulse wave velocity,” said Dr. Andreas. The authors of the review concluded that “e-cigarettes should not be promoted as a healthier alternative to tobacco smoking.”
No Harmless Alternative
A recent review compared the effects of tobacco smoking and e-cigarettes. Although the toxic mixture in smoke is more complex, both e-cigarettes and tobacco cigarettes “impaired endothelial function to a similar extent,” they wrote. The authors attributed this finding to oxidative stress as the central mechanism.
“There is increasing evidence that e-cigarettes are not a harmless alternative to tobacco cigarettes,” wrote Thomas Münzel, MD, professor of cardiology at the University of Mainz and his team in their 2020 review, which examined studies in humans and animals. They provided an overview of the effects of tobacco/hookah smoking and e-cigarette vaping on endothelial function. They also pointed to emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and circadian clock.
Finally, a toxicological review of e-cigarettes also found alarmingly high levels of carcinogens and toxins that could have long-term effects on other organs, including the development of neurological symptoms, lung cancer, cardiovascular diseases, and cavities.
Dr. Andreas observed that even small amounts, such as those obtained through secondhand smoking, can be harmful. In 2007, Dr. Andreas and his colleagues showed that even low exposure to tobacco smoke can lead to a significant increase in cardiovascular events.
Conflicts of Interest
Dr. Andreas recommended closely examining the studies that suggest that e-cigarettes are less risky. “It is noticeable that there is a significant difference depending on whether publications were supported by the tobacco industry or not,” he emphasized.
Danish scientists found that a conflict of interest (COI) has a strong influence on study results. “In studies without a COI, e-cigarettes are found to cause damage 95% of the time. In contrast, when there is a strong conflict of interest, the result is often ‘no harm,’” said Dr. Andreas.
This effect is quite relevant for the discussion of e-cigarettes. “If scientists make a critical statement in a position paper, there will always be someone who says, ‘No, it’s different, there are these and those publications.’ The true nature of interest-driven publications on e-cigarettes is not always easy to discern,” said Dr. Andreas.
No Gateway to Quitting
E-cigarettes are used in clinical studies for tobacco cessation. The results of a randomized study showed that significantly more smokers who were switched to e-cigarettes quit smoking, compared with controls. But there was no significant difference in complete smoking cessation between groups. Moreover, 45% of smokers who switched to e-cigarettes became dual users, compared with 11% of controls.
“Translating these results means that for one person who quits smoking by using e-cigarettes, they gain five people who use both traditional cigarettes and e-cigarettes,” explained Dr. Andreas.
In their recent review, Münzel and colleagues pointed out that the assessment that e-cigarettes could help with quitting might be wrong. Rather, it seems that “e-cigarettes have the opposite effect.” They also note that the age of initiation for e-cigarettes is generally lower than for tobacco cigarettes: Consumption often starts at age 13 or 14 years. And the consumption of e-cigarettes among children and adolescents increased by 7% from 2016 to 2023.
A meta-analysis published at the end of February also shows that e-cigarettes are about as dangerous as tobacco cigarettes. They are more dangerous than not smoking, and dual use is more dangerous than tobacco cigarettes alone. “There is a need to reassess the assumption that e-cigarette use provides substantial harm reduction across all cigarette-caused diseases, particularly accounting for dual use,” wrote the authors.
“One must always consider that e-cigarettes have only been available for a relatively short time. We can only see the cumulative toxicity in 10, 20 years when we have patients who have smoked e-cigarettes only for 20 years,” said Dr. Andreas. Ultimately, however, e-cigarettes promote dual use and, consequently, additive toxicity.
Nicotine Replacement Therapies
Quitting smoking reduces the risk of cardiovascular events and premature death by 40%, even among patients with cardiovascular disease, according to a Cochrane meta-analysis. Smoking cessation reduces the risk for cardiovascular death by 39%, the risk for major adverse cardiovascular events by 43%, the risk for heart attack by 36%, the risk for stroke by 30%, and overall mortality by 40%.
Quitting smoking is the most effective measure for risk reduction, as a meta-analysis of 20 studies in patients with coronary heart disease found. Smoking cessation was associated with a 36% risk reduction compared with 29% risk reduction for statin therapy, 23% risk reduction with beta-blockers and ACE inhibitors and 15% risk reduction with aspirin.
Dr. Andreas emphasized that nicotine replacement therapies are well-researched and safe even in cardiovascular disease, as shown by a US study that included patients who had sustained a heart attack. A group of the participants was treated with nicotine patches for 10 weeks, while the other group received a placebo. After 14 weeks, 21% of the nicotine patch group achieved abstinence vs 9% of the placebo group (P = .001). Transdermal nicotine application does not lead to a significant increase in cardiovascular events in high-risk patients.
The German “Nonsmoker Heroes” app has proven to be an effective means of behavioral therapeutic coaching. A recent study of it included 17 study centers with 661 participants. About 21% of the subjects had chronic obstructive pulmonary disease, 19% had asthma. Smoking onset occurred at age 16 years. The subjects were highly dependent: > 72% had at least moderate dependence, > 58% had high to very high dependence, and the population had an average of 3.6 quit attempts. The odds ratio for self-reported abstinence was 2.2 after 6 months. “The app is not only effective, but also can be prescribed on an extrabudgetary basis,” said Dr. Andreas.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Telemedicine Reduces Rehospitalization, Revascularization in Post-PCI ACS Patients
ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.
The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.
“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.”
The study findings were published online simultaneously in the Journal of the American College of Cardiology.
Telemedicine Protocol
The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter.
Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years.
If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.
Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.
Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).
MACE rates were similar between the two groups.
At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.
The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).
Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
Human Element Key
In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.
However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”
Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology.
“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”
While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”
The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.
A version of this article first appeared on Medscape.com.
ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.
The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.
“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.”
The study findings were published online simultaneously in the Journal of the American College of Cardiology.
Telemedicine Protocol
The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter.
Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years.
If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.
Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.
Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).
MACE rates were similar between the two groups.
At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.
The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).
Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
Human Element Key
In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.
However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”
Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology.
“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”
While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”
The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.
A version of this article first appeared on Medscape.com.
ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.
The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.
“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.”
The study findings were published online simultaneously in the Journal of the American College of Cardiology.
Telemedicine Protocol
The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter.
Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years.
If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.
Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.
Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).
MACE rates were similar between the two groups.
At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.
The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).
Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
Human Element Key
In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.
However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”
Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology.
“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”
While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”
The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Heat Exposure Tied to Acute Immune Changes
In this study, blood work from volunteers was examined for immune biomarkers, and the findings mapped against environmental data.
“With rising global temperatures, the association between heat exposure and a temporarily weakened response from the immune system is a concern because temperature and humidity are known to be important environmental drivers of infectious, airborne disease transmission,” lead author Daniel W. Riggs, PhD, with the Christina Lee Brown Envirome Institute, University of Louisville in Louisville, Kentucky, said in a news release.
“In this study, even exposure to relatively modest increases in temperature were associated with acute changes in immune system functioning indexed by low-grade inflammation known to be linked to cardiovascular disorders, as well as potential secondary effects on the ability to optimally protect against infection,” said Rosalind J. Wright, MD, MPH, who wasn’t involved in the study.
“Further elucidation of the effects of both acute and more prolonged heat exposures (heat waves) on immune signaling will be important given potential broad health implications beyond the heart,” said Dr. Wright, dean of public health and professor and chair, Department of Public Health, Mount Sinai Health System.
The study was presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
High Temps Hard on Multiple Organs
Extreme-heat events have been shown to increase mortality, and excessive deaths due to heat waves are overwhelmingly cardiovascular in origin. Many prior studies only considered ambient temperature, which fails to capture the actual heat stress experienced by individuals, Dr. Riggs and colleagues wrote.
They designed their study to gauge how short-term heat exposures are related to markers of inflammation and the immune response.
They recruited 624 adults (mean age 49 years, 59% women) from a neighborhood in Louisville during the summer months, when median temperatures over 24 hours were 24.5 °C (76 °F).
They obtained blood samples to measure circulating cytokines and immune cells during clinic visits. Heat metrics, collected on the same day as blood draws, included 24-hour averages of temperature, net effective temperature, and the Universal Thermal Climate Index (UTCI), a metric that incorporates temperature, humidity, wind speed, and ultraviolet radiation, to determine the physiological comfort of the human body under specific weather conditions.
The results were adjusted for multiple factors, including sex, age, race, education, body mass index, smoking status, anti-inflammatory medication use, and daily air pollution (PM 2.5).
In adjusted analyses, for every five-degree increase in UTCI, there was an increase in levels of several inflammatory markers, including monocytes (4.2%), eosinophils (9.5%), natural killer T cells (9.9%), and tumor necrosis factor-alpha (7.0%) and a decrease in infection-fighting B cells (−6.8%).
Study Raises Important Questions
“We’re finding that heat is associated with health effects across a wide range of organ systems and outcomes, but this study helps start to get at the ‘how,’” said Perry E. Sheffield, MD, MPH, with the Departments of Pediatrics and Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York City, who wasn’t involved in the study.
Dr. Sheffield said the study raises “important questions like, Does the timing of heat exposure matter (going in and out of air-conditioned spaces for example)? and Could some people be more vulnerable than others based on things like what they eat, whether they exercise, or their genetics?”
The study comes on the heels of a report released earlier this month from the World Meteorological Organization noting that climate change indicators reached record levels in 2023.
“The most critical challenges facing medicine are occurring at the intersection of climate and health, underscoring the urgent need to understand how climate-related factors, such as exposure to more extreme temperatures, shift key regulatory systems in our bodies to contribute to disease,” Dr. Wright told this news organization.
The study was supported by grants from the National Institute of Environmental Health Sciences. Dr. Riggs, Dr. Wright, and Sheffield had no relevant disclosures.
A version of this article appeared on Medscape.com.
In this study, blood work from volunteers was examined for immune biomarkers, and the findings mapped against environmental data.
“With rising global temperatures, the association between heat exposure and a temporarily weakened response from the immune system is a concern because temperature and humidity are known to be important environmental drivers of infectious, airborne disease transmission,” lead author Daniel W. Riggs, PhD, with the Christina Lee Brown Envirome Institute, University of Louisville in Louisville, Kentucky, said in a news release.
“In this study, even exposure to relatively modest increases in temperature were associated with acute changes in immune system functioning indexed by low-grade inflammation known to be linked to cardiovascular disorders, as well as potential secondary effects on the ability to optimally protect against infection,” said Rosalind J. Wright, MD, MPH, who wasn’t involved in the study.
“Further elucidation of the effects of both acute and more prolonged heat exposures (heat waves) on immune signaling will be important given potential broad health implications beyond the heart,” said Dr. Wright, dean of public health and professor and chair, Department of Public Health, Mount Sinai Health System.
The study was presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
High Temps Hard on Multiple Organs
Extreme-heat events have been shown to increase mortality, and excessive deaths due to heat waves are overwhelmingly cardiovascular in origin. Many prior studies only considered ambient temperature, which fails to capture the actual heat stress experienced by individuals, Dr. Riggs and colleagues wrote.
They designed their study to gauge how short-term heat exposures are related to markers of inflammation and the immune response.
They recruited 624 adults (mean age 49 years, 59% women) from a neighborhood in Louisville during the summer months, when median temperatures over 24 hours were 24.5 °C (76 °F).
They obtained blood samples to measure circulating cytokines and immune cells during clinic visits. Heat metrics, collected on the same day as blood draws, included 24-hour averages of temperature, net effective temperature, and the Universal Thermal Climate Index (UTCI), a metric that incorporates temperature, humidity, wind speed, and ultraviolet radiation, to determine the physiological comfort of the human body under specific weather conditions.
The results were adjusted for multiple factors, including sex, age, race, education, body mass index, smoking status, anti-inflammatory medication use, and daily air pollution (PM 2.5).
In adjusted analyses, for every five-degree increase in UTCI, there was an increase in levels of several inflammatory markers, including monocytes (4.2%), eosinophils (9.5%), natural killer T cells (9.9%), and tumor necrosis factor-alpha (7.0%) and a decrease in infection-fighting B cells (−6.8%).
Study Raises Important Questions
“We’re finding that heat is associated with health effects across a wide range of organ systems and outcomes, but this study helps start to get at the ‘how,’” said Perry E. Sheffield, MD, MPH, with the Departments of Pediatrics and Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York City, who wasn’t involved in the study.
Dr. Sheffield said the study raises “important questions like, Does the timing of heat exposure matter (going in and out of air-conditioned spaces for example)? and Could some people be more vulnerable than others based on things like what they eat, whether they exercise, or their genetics?”
The study comes on the heels of a report released earlier this month from the World Meteorological Organization noting that climate change indicators reached record levels in 2023.
“The most critical challenges facing medicine are occurring at the intersection of climate and health, underscoring the urgent need to understand how climate-related factors, such as exposure to more extreme temperatures, shift key regulatory systems in our bodies to contribute to disease,” Dr. Wright told this news organization.
The study was supported by grants from the National Institute of Environmental Health Sciences. Dr. Riggs, Dr. Wright, and Sheffield had no relevant disclosures.
A version of this article appeared on Medscape.com.
In this study, blood work from volunteers was examined for immune biomarkers, and the findings mapped against environmental data.
“With rising global temperatures, the association between heat exposure and a temporarily weakened response from the immune system is a concern because temperature and humidity are known to be important environmental drivers of infectious, airborne disease transmission,” lead author Daniel W. Riggs, PhD, with the Christina Lee Brown Envirome Institute, University of Louisville in Louisville, Kentucky, said in a news release.
“In this study, even exposure to relatively modest increases in temperature were associated with acute changes in immune system functioning indexed by low-grade inflammation known to be linked to cardiovascular disorders, as well as potential secondary effects on the ability to optimally protect against infection,” said Rosalind J. Wright, MD, MPH, who wasn’t involved in the study.
“Further elucidation of the effects of both acute and more prolonged heat exposures (heat waves) on immune signaling will be important given potential broad health implications beyond the heart,” said Dr. Wright, dean of public health and professor and chair, Department of Public Health, Mount Sinai Health System.
The study was presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
High Temps Hard on Multiple Organs
Extreme-heat events have been shown to increase mortality, and excessive deaths due to heat waves are overwhelmingly cardiovascular in origin. Many prior studies only considered ambient temperature, which fails to capture the actual heat stress experienced by individuals, Dr. Riggs and colleagues wrote.
They designed their study to gauge how short-term heat exposures are related to markers of inflammation and the immune response.
They recruited 624 adults (mean age 49 years, 59% women) from a neighborhood in Louisville during the summer months, when median temperatures over 24 hours were 24.5 °C (76 °F).
They obtained blood samples to measure circulating cytokines and immune cells during clinic visits. Heat metrics, collected on the same day as blood draws, included 24-hour averages of temperature, net effective temperature, and the Universal Thermal Climate Index (UTCI), a metric that incorporates temperature, humidity, wind speed, and ultraviolet radiation, to determine the physiological comfort of the human body under specific weather conditions.
The results were adjusted for multiple factors, including sex, age, race, education, body mass index, smoking status, anti-inflammatory medication use, and daily air pollution (PM 2.5).
In adjusted analyses, for every five-degree increase in UTCI, there was an increase in levels of several inflammatory markers, including monocytes (4.2%), eosinophils (9.5%), natural killer T cells (9.9%), and tumor necrosis factor-alpha (7.0%) and a decrease in infection-fighting B cells (−6.8%).
Study Raises Important Questions
“We’re finding that heat is associated with health effects across a wide range of organ systems and outcomes, but this study helps start to get at the ‘how,’” said Perry E. Sheffield, MD, MPH, with the Departments of Pediatrics and Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai in New York City, who wasn’t involved in the study.
Dr. Sheffield said the study raises “important questions like, Does the timing of heat exposure matter (going in and out of air-conditioned spaces for example)? and Could some people be more vulnerable than others based on things like what they eat, whether they exercise, or their genetics?”
The study comes on the heels of a report released earlier this month from the World Meteorological Organization noting that climate change indicators reached record levels in 2023.
“The most critical challenges facing medicine are occurring at the intersection of climate and health, underscoring the urgent need to understand how climate-related factors, such as exposure to more extreme temperatures, shift key regulatory systems in our bodies to contribute to disease,” Dr. Wright told this news organization.
The study was supported by grants from the National Institute of Environmental Health Sciences. Dr. Riggs, Dr. Wright, and Sheffield had no relevant disclosures.
A version of this article appeared on Medscape.com.
Magnesium Spray for Better Sleep? Experts Weigh In
As your patient’s scheduled bedtime is approaching, they begin to worry another restless night is looming. Could magnesium oil spray actually help them sleep? Some — even doctors — are sharing testimonials about how this simple tactic transformed their sleep quality. Experts suggest some sleep improvement is possible, though it does not negate the need for treatment, and should not be used in patients with cardiovascular disease.
Take Daniel Barrett, MD, a board-certified plastic surgeon and owner of Barrett Plastic Surgery in Beverly Hills, as an example. He decided to test whether magnesium oil could indeed give him a sleepy sensation and shared his experience. Dr. Barrett sprayed magnesium oil on his feet — until they felt “slippery and wet,” he said — and put his socks back on. (He said magnesium is absorbed more easily through the skin. Putting it on the skin helps this mineral get into the lymphatics and circulatory system, offering a way to get a higher concentration of magnesium in the bloodstream. The pores on the feet are also said to be the largest on the body, making them an ideal place for absorption.)
“My central nervous system had calmed down a bit — it’s similar to what I feel when I take oral magnesium as well. It took about 15 minutes to feel the effect,” Dr. Barrett said.
Research shows that magnesium blocks N-methyl-D-aspartate (a receptor that can hinder sleep) and stimulates gamma-aminobutyric acid (a receptor that can promote good sleep), said Dennis Auckley, MD, director of MetroHealth’s Center for Sleep Medicine. And studies looking at the effects of oral magnesium have shown that taking it may be linked to better self-reported sleep quality and less daytime sleepiness, he said. But traditional magnesium supplements taken orally can sometimes come with side effects in your gut, so putting magnesium on the skin could help to avoid this.
Magnesium oil on the feet could also help with certain sleep disturbances, such as nocturnal leg cramps and restless legs syndrome, said Sam Kashani, MD, a sleep medicine specialist and assistant clinical professor at UCLA Medical School. (Nocturnal leg cramps – one of the most common secondary factors of insomnia and sleep disturbances in older adults – includes sudden, painful contractions in the lower leg muscles while sleeping. Restless legs syndrome, on the other hand, is like nocturnal leg cramps, but minus the painful contractions, said Dr. Kashani.)
“Magnesium is a mineral that does have some benefit with regard to reducing the muscle tightness and promoting a little bit more of relaxation of the muscles,” Dr. Kashani said. “This [magnesium oil on your soles] could be beneficial for these types of sleep problems.”
Still, sleep medicine experts stressed that putting magnesium oil on your feet should not be viewed a cure-all for sleep troubles.
“High-quality scientific evidence supporting magnesium as a sleep remedy is severely limited,” said Emerson Wickwire, PhD, an American Academy of Sleep Medicine spokesperson and section head of sleep medicine at the University of Maryland Medical School. “Certainly, magnesium is not supported as a treatment for sleep disorders.”
If your patients plan to use magnesium oil on their feet to help them sleep, make sure they carefully follow the directions to make sure they are taking the proper dosage. Most importantly, patients with a history of cardiovascular complications, or issues with the heart and blood vessels should consult their doctor.
“Magnesium is an electrolyte that has multiple roles and functions in the body, including within our cardiovascular system,” Dr. Kashani said. “So, if you are somebody who has heart troubles, you definitely want to talk to your primary doctor about any kind of supplements that you are taking, including magnesium.”
A version of this article appeared on WebMD.com.
As your patient’s scheduled bedtime is approaching, they begin to worry another restless night is looming. Could magnesium oil spray actually help them sleep? Some — even doctors — are sharing testimonials about how this simple tactic transformed their sleep quality. Experts suggest some sleep improvement is possible, though it does not negate the need for treatment, and should not be used in patients with cardiovascular disease.
Take Daniel Barrett, MD, a board-certified plastic surgeon and owner of Barrett Plastic Surgery in Beverly Hills, as an example. He decided to test whether magnesium oil could indeed give him a sleepy sensation and shared his experience. Dr. Barrett sprayed magnesium oil on his feet — until they felt “slippery and wet,” he said — and put his socks back on. (He said magnesium is absorbed more easily through the skin. Putting it on the skin helps this mineral get into the lymphatics and circulatory system, offering a way to get a higher concentration of magnesium in the bloodstream. The pores on the feet are also said to be the largest on the body, making them an ideal place for absorption.)
“My central nervous system had calmed down a bit — it’s similar to what I feel when I take oral magnesium as well. It took about 15 minutes to feel the effect,” Dr. Barrett said.
Research shows that magnesium blocks N-methyl-D-aspartate (a receptor that can hinder sleep) and stimulates gamma-aminobutyric acid (a receptor that can promote good sleep), said Dennis Auckley, MD, director of MetroHealth’s Center for Sleep Medicine. And studies looking at the effects of oral magnesium have shown that taking it may be linked to better self-reported sleep quality and less daytime sleepiness, he said. But traditional magnesium supplements taken orally can sometimes come with side effects in your gut, so putting magnesium on the skin could help to avoid this.
Magnesium oil on the feet could also help with certain sleep disturbances, such as nocturnal leg cramps and restless legs syndrome, said Sam Kashani, MD, a sleep medicine specialist and assistant clinical professor at UCLA Medical School. (Nocturnal leg cramps – one of the most common secondary factors of insomnia and sleep disturbances in older adults – includes sudden, painful contractions in the lower leg muscles while sleeping. Restless legs syndrome, on the other hand, is like nocturnal leg cramps, but minus the painful contractions, said Dr. Kashani.)
“Magnesium is a mineral that does have some benefit with regard to reducing the muscle tightness and promoting a little bit more of relaxation of the muscles,” Dr. Kashani said. “This [magnesium oil on your soles] could be beneficial for these types of sleep problems.”
Still, sleep medicine experts stressed that putting magnesium oil on your feet should not be viewed a cure-all for sleep troubles.
“High-quality scientific evidence supporting magnesium as a sleep remedy is severely limited,” said Emerson Wickwire, PhD, an American Academy of Sleep Medicine spokesperson and section head of sleep medicine at the University of Maryland Medical School. “Certainly, magnesium is not supported as a treatment for sleep disorders.”
If your patients plan to use magnesium oil on their feet to help them sleep, make sure they carefully follow the directions to make sure they are taking the proper dosage. Most importantly, patients with a history of cardiovascular complications, or issues with the heart and blood vessels should consult their doctor.
“Magnesium is an electrolyte that has multiple roles and functions in the body, including within our cardiovascular system,” Dr. Kashani said. “So, if you are somebody who has heart troubles, you definitely want to talk to your primary doctor about any kind of supplements that you are taking, including magnesium.”
A version of this article appeared on WebMD.com.
As your patient’s scheduled bedtime is approaching, they begin to worry another restless night is looming. Could magnesium oil spray actually help them sleep? Some — even doctors — are sharing testimonials about how this simple tactic transformed their sleep quality. Experts suggest some sleep improvement is possible, though it does not negate the need for treatment, and should not be used in patients with cardiovascular disease.
Take Daniel Barrett, MD, a board-certified plastic surgeon and owner of Barrett Plastic Surgery in Beverly Hills, as an example. He decided to test whether magnesium oil could indeed give him a sleepy sensation and shared his experience. Dr. Barrett sprayed magnesium oil on his feet — until they felt “slippery and wet,” he said — and put his socks back on. (He said magnesium is absorbed more easily through the skin. Putting it on the skin helps this mineral get into the lymphatics and circulatory system, offering a way to get a higher concentration of magnesium in the bloodstream. The pores on the feet are also said to be the largest on the body, making them an ideal place for absorption.)
“My central nervous system had calmed down a bit — it’s similar to what I feel when I take oral magnesium as well. It took about 15 minutes to feel the effect,” Dr. Barrett said.
Research shows that magnesium blocks N-methyl-D-aspartate (a receptor that can hinder sleep) and stimulates gamma-aminobutyric acid (a receptor that can promote good sleep), said Dennis Auckley, MD, director of MetroHealth’s Center for Sleep Medicine. And studies looking at the effects of oral magnesium have shown that taking it may be linked to better self-reported sleep quality and less daytime sleepiness, he said. But traditional magnesium supplements taken orally can sometimes come with side effects in your gut, so putting magnesium on the skin could help to avoid this.
Magnesium oil on the feet could also help with certain sleep disturbances, such as nocturnal leg cramps and restless legs syndrome, said Sam Kashani, MD, a sleep medicine specialist and assistant clinical professor at UCLA Medical School. (Nocturnal leg cramps – one of the most common secondary factors of insomnia and sleep disturbances in older adults – includes sudden, painful contractions in the lower leg muscles while sleeping. Restless legs syndrome, on the other hand, is like nocturnal leg cramps, but minus the painful contractions, said Dr. Kashani.)
“Magnesium is a mineral that does have some benefit with regard to reducing the muscle tightness and promoting a little bit more of relaxation of the muscles,” Dr. Kashani said. “This [magnesium oil on your soles] could be beneficial for these types of sleep problems.”
Still, sleep medicine experts stressed that putting magnesium oil on your feet should not be viewed a cure-all for sleep troubles.
“High-quality scientific evidence supporting magnesium as a sleep remedy is severely limited,” said Emerson Wickwire, PhD, an American Academy of Sleep Medicine spokesperson and section head of sleep medicine at the University of Maryland Medical School. “Certainly, magnesium is not supported as a treatment for sleep disorders.”
If your patients plan to use magnesium oil on their feet to help them sleep, make sure they carefully follow the directions to make sure they are taking the proper dosage. Most importantly, patients with a history of cardiovascular complications, or issues with the heart and blood vessels should consult their doctor.
“Magnesium is an electrolyte that has multiple roles and functions in the body, including within our cardiovascular system,” Dr. Kashani said. “So, if you are somebody who has heart troubles, you definitely want to talk to your primary doctor about any kind of supplements that you are taking, including magnesium.”
A version of this article appeared on WebMD.com.
Gaps Found in Appropriate SGLT2, GLP-1 Prescribing
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.
First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.
The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.
“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
Low Prescription Rates
In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.
Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.
The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).
Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.
Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).
“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.
“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.
Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.
The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.
In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.
Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.
“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.
“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
‘Concerning’ Data Raise Key Questions
The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.
“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.
“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.
Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.
Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.
Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.
SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.
“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.
“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.
In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”
“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.
None of the studies had commercial funding. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.
First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.
The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.
“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
Low Prescription Rates
In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.
Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.
The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).
Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.
Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).
“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.
“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.
Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.
The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.
In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.
Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.
“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.
“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
‘Concerning’ Data Raise Key Questions
The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.
“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.
“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.
Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.
Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.
Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.
SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.
“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.
“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.
In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”
“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.
None of the studies had commercial funding. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.
First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.
The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.
The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.
“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
Low Prescription Rates
In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.
Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.
The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).
Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.
Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).
“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.
“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.
Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.
The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.
In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.
Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.
“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.
“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
‘Concerning’ Data Raise Key Questions
The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.
“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.
“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.
Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.
Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.
Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.
SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.
“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.
“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.
In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”
“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.
None of the studies had commercial funding. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.