Cardiology

DENVER — Unlike traditional antidiabetic therapies, which have never been associated with a significant reduction in stroke in a major trial, some of the newer drugs are showing that benefit, but the protection is not linked to tighter glycemic control.

In patients with type 2 diabetes mellitus (T2DM), the evidence is strong that “they are not working through glycemic control per se,” according to Larry B. Goldstein, MD, chair of neurology, University of Kentucky School of Medicine, Louisville. “But it is not yet clear what the mechanism of benefit is.”

Ted Bosworth/MDedge News

Stroke Prevention With Antidiabetic Drugs

“What has changed is that we have new ways of glycemic control, and some of these do show protection against stroke,” Dr. Goldstein said. Yet, the newer drugs do not do a better job at sustained reductions of HbA1c or other measures of reaching lower blood glucose reductions when adherence is similar.

“The level of glucose control with the newer agents is really about the same,” Dr. Goldstein said at the annual meeting of the American Academy of Neurology, where he led a symposium called Controversies in Stroke Treatment and Prevention.

The newer agents, such as sodium glucose co-transport-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have been associated with significant and clinically meaningful reductions in cardiovascular events. However, it is not clear that even these two medications perform similarly for stroke prevention specifically.

Of these two drug classes, Dr. Goldstein said the evidence most strongly supports GLP-1 receptor agonists. He cited one meta-analysis of eight randomized studies that calculated a risk reduction of about 15% whether calculated for fatal or nonfatal strokes. For each the protection was highly statistically significant (P = .0002 and P < .001, respectively).

In contrast, the effect of SGLT-2 inhibitors is weaker. In a study that distilled data from large cardiovascular trials with GLP-1RA, SGLT2i, dipeptidyl peptidase-4 inhibitors (DPP4i), and pioglitazone, a thiazolidinedione, only GLP-1RA drugs were associated with a highly significant (P < .001) reduction in risk of stroke. The risk reduction for pioglitazone reached significance (P = .025), but there was no signal of risk reduction for SGLT2i (P = .88) or for DPP4i (P = .5).
 

Weight Loss Is Potential Mechanism

Looking to explain the protection from stroke associated with some of the newer antidiabetic therapies, Gordon Kelley, MD, who leads the stroke program for AdventHealth Medical Group, Shawnee Mission, Kansas, suggested that weight loss is probably important.

“In our group, we work as a team to manage stroke risk in patients with diabetes, so I am not much involved in the choice of antidiabetic therapies, but it does seem that SGLT2 inhibitors and the GLP-1 receptor agonists share weight loss as an effect beyond glucose control,” he said.

Dr. Goldstein agreed that weight loss is a potential contributor to the cardiovascular benefits of GLP-1RA and SGLT2i, but he indicated that it might not help explain the reduction in stroke, an effect demonstrated repeatedly with GLP-1RA but inconsistently with SGLT2i.

The argument against weight loss as the critical mechanism of stroke prevention from newer antidiabetic drugs is strengthened by studies that suggest weight loss with SGLT2i appears to be even better than on GLP-1RA. In a study published in a pharmacy journal, weight loss was about twice as great among T2DM patients after 6 months of treatment managed with SGLT2i relative to those on a GLP-1RA (-2.8 vs 1.15 kg; P = .014).
 

Newer Antidiabetic Agents Guideline Recommended

In the 2019 American College of Cardiology/American Heart Association guidelines on the Primary Prevention of Cardiovascular Disease, stroke reduction is not discussed as an isolated risk, but these guidelines do recommend GLP-1RA or SGLT2i after metformin for glycemic control in T2DM patients with atherosclerotic cardiovascular disease (ASCVD) risk factors. This is based on evidence that drugs of both classes reduce risk for ASCVD events. The risk reduction has been particularly strong for heart failure.

For the risk of stroke specifically in patients with T2DM, Dr. Goldstein recommended calculating the ASCVD risk with the simple but well validated ACC risk calculator that is available online and is quickly completed when values for patient risk factors are readily available. For those with greater than 10% risk of an event in the next 10 years, he thinks GLP-1RA are a reasonable choice for prevention of stroke and other ASCVD events.

“GLP-1RA is mentioned in the guidelines, so this is supported,” said Dr. Goldstein, although adding that his choice of this class over SGLT2i is a personal if informed recommendation. He believes that the data favor GLP-1RA even if the exact mechanism of this protection is yet to be identified.

Dr. Goldstein and Dr. Kelley report no potential conflicts of interest.

DENVER — Unlike traditional antidiabetic therapies, which have never been associated with a significant reduction in stroke in a major trial, some of the newer drugs are showing that benefit, but the protection is not linked to tighter glycemic control.

In patients with type 2 diabetes mellitus (T2DM), the evidence is strong that “they are not working through glycemic control per se,” according to Larry B. Goldstein, MD, chair of neurology, University of Kentucky School of Medicine, Louisville. “But it is not yet clear what the mechanism of benefit is.”

Ted Bosworth/MDedge News

Stroke Prevention With Antidiabetic Drugs

“What has changed is that we have new ways of glycemic control, and some of these do show protection against stroke,” Dr. Goldstein said. Yet, the newer drugs do not do a better job at sustained reductions of HbA1c or other measures of reaching lower blood glucose reductions when adherence is similar.

“The level of glucose control with the newer agents is really about the same,” Dr. Goldstein said at the annual meeting of the American Academy of Neurology, where he led a symposium called Controversies in Stroke Treatment and Prevention.

The newer agents, such as sodium glucose co-transport-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have been associated with significant and clinically meaningful reductions in cardiovascular events. However, it is not clear that even these two medications perform similarly for stroke prevention specifically.

Of these two drug classes, Dr. Goldstein said the evidence most strongly supports GLP-1 receptor agonists. He cited one meta-analysis of eight randomized studies that calculated a risk reduction of about 15% whether calculated for fatal or nonfatal strokes. For each the protection was highly statistically significant (P = .0002 and P < .001, respectively).

In contrast, the effect of SGLT-2 inhibitors is weaker. In a study that distilled data from large cardiovascular trials with GLP-1RA, SGLT2i, dipeptidyl peptidase-4 inhibitors (DPP4i), and pioglitazone, a thiazolidinedione, only GLP-1RA drugs were associated with a highly significant (P < .001) reduction in risk of stroke. The risk reduction for pioglitazone reached significance (P = .025), but there was no signal of risk reduction for SGLT2i (P = .88) or for DPP4i (P = .5).
 

Weight Loss Is Potential Mechanism

Looking to explain the protection from stroke associated with some of the newer antidiabetic therapies, Gordon Kelley, MD, who leads the stroke program for AdventHealth Medical Group, Shawnee Mission, Kansas, suggested that weight loss is probably important.

“In our group, we work as a team to manage stroke risk in patients with diabetes, so I am not much involved in the choice of antidiabetic therapies, but it does seem that SGLT2 inhibitors and the GLP-1 receptor agonists share weight loss as an effect beyond glucose control,” he said.

Dr. Goldstein agreed that weight loss is a potential contributor to the cardiovascular benefits of GLP-1RA and SGLT2i, but he indicated that it might not help explain the reduction in stroke, an effect demonstrated repeatedly with GLP-1RA but inconsistently with SGLT2i.

The argument against weight loss as the critical mechanism of stroke prevention from newer antidiabetic drugs is strengthened by studies that suggest weight loss with SGLT2i appears to be even better than on GLP-1RA. In a study published in a pharmacy journal, weight loss was about twice as great among T2DM patients after 6 months of treatment managed with SGLT2i relative to those on a GLP-1RA (-2.8 vs 1.15 kg; P = .014).
 

Newer Antidiabetic Agents Guideline Recommended

In the 2019 American College of Cardiology/American Heart Association guidelines on the Primary Prevention of Cardiovascular Disease, stroke reduction is not discussed as an isolated risk, but these guidelines do recommend GLP-1RA or SGLT2i after metformin for glycemic control in T2DM patients with atherosclerotic cardiovascular disease (ASCVD) risk factors. This is based on evidence that drugs of both classes reduce risk for ASCVD events. The risk reduction has been particularly strong for heart failure.

For the risk of stroke specifically in patients with T2DM, Dr. Goldstein recommended calculating the ASCVD risk with the simple but well validated ACC risk calculator that is available online and is quickly completed when values for patient risk factors are readily available. For those with greater than 10% risk of an event in the next 10 years, he thinks GLP-1RA are a reasonable choice for prevention of stroke and other ASCVD events.

“GLP-1RA is mentioned in the guidelines, so this is supported,” said Dr. Goldstein, although adding that his choice of this class over SGLT2i is a personal if informed recommendation. He believes that the data favor GLP-1RA even if the exact mechanism of this protection is yet to be identified.

Dr. Goldstein and Dr. Kelley report no potential conflicts of interest.

DENVER — Unlike traditional antidiabetic therapies, which have never been associated with a significant reduction in stroke in a major trial, some of the newer drugs are showing that benefit, but the protection is not linked to tighter glycemic control.

In patients with type 2 diabetes mellitus (T2DM), the evidence is strong that “they are not working through glycemic control per se,” according to Larry B. Goldstein, MD, chair of neurology, University of Kentucky School of Medicine, Louisville. “But it is not yet clear what the mechanism of benefit is.”

Ted Bosworth/MDedge News

Stroke Prevention With Antidiabetic Drugs

“What has changed is that we have new ways of glycemic control, and some of these do show protection against stroke,” Dr. Goldstein said. Yet, the newer drugs do not do a better job at sustained reductions of HbA1c or other measures of reaching lower blood glucose reductions when adherence is similar.

“The level of glucose control with the newer agents is really about the same,” Dr. Goldstein said at the annual meeting of the American Academy of Neurology, where he led a symposium called Controversies in Stroke Treatment and Prevention.

The newer agents, such as sodium glucose co-transport-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have been associated with significant and clinically meaningful reductions in cardiovascular events. However, it is not clear that even these two medications perform similarly for stroke prevention specifically.

Of these two drug classes, Dr. Goldstein said the evidence most strongly supports GLP-1 receptor agonists. He cited one meta-analysis of eight randomized studies that calculated a risk reduction of about 15% whether calculated for fatal or nonfatal strokes. For each the protection was highly statistically significant (P = .0002 and P < .001, respectively).

In contrast, the effect of SGLT-2 inhibitors is weaker. In a study that distilled data from large cardiovascular trials with GLP-1RA, SGLT2i, dipeptidyl peptidase-4 inhibitors (DPP4i), and pioglitazone, a thiazolidinedione, only GLP-1RA drugs were associated with a highly significant (P < .001) reduction in risk of stroke. The risk reduction for pioglitazone reached significance (P = .025), but there was no signal of risk reduction for SGLT2i (P = .88) or for DPP4i (P = .5).
 

Weight Loss Is Potential Mechanism

Looking to explain the protection from stroke associated with some of the newer antidiabetic therapies, Gordon Kelley, MD, who leads the stroke program for AdventHealth Medical Group, Shawnee Mission, Kansas, suggested that weight loss is probably important.

“In our group, we work as a team to manage stroke risk in patients with diabetes, so I am not much involved in the choice of antidiabetic therapies, but it does seem that SGLT2 inhibitors and the GLP-1 receptor agonists share weight loss as an effect beyond glucose control,” he said.

Dr. Goldstein agreed that weight loss is a potential contributor to the cardiovascular benefits of GLP-1RA and SGLT2i, but he indicated that it might not help explain the reduction in stroke, an effect demonstrated repeatedly with GLP-1RA but inconsistently with SGLT2i.

The argument against weight loss as the critical mechanism of stroke prevention from newer antidiabetic drugs is strengthened by studies that suggest weight loss with SGLT2i appears to be even better than on GLP-1RA. In a study published in a pharmacy journal, weight loss was about twice as great among T2DM patients after 6 months of treatment managed with SGLT2i relative to those on a GLP-1RA (-2.8 vs 1.15 kg; P = .014).
 

Newer Antidiabetic Agents Guideline Recommended

In the 2019 American College of Cardiology/American Heart Association guidelines on the Primary Prevention of Cardiovascular Disease, stroke reduction is not discussed as an isolated risk, but these guidelines do recommend GLP-1RA or SGLT2i after metformin for glycemic control in T2DM patients with atherosclerotic cardiovascular disease (ASCVD) risk factors. This is based on evidence that drugs of both classes reduce risk for ASCVD events. The risk reduction has been particularly strong for heart failure.

For the risk of stroke specifically in patients with T2DM, Dr. Goldstein recommended calculating the ASCVD risk with the simple but well validated ACC risk calculator that is available online and is quickly completed when values for patient risk factors are readily available. For those with greater than 10% risk of an event in the next 10 years, he thinks GLP-1RA are a reasonable choice for prevention of stroke and other ASCVD events.

“GLP-1RA is mentioned in the guidelines, so this is supported,” said Dr. Goldstein, although adding that his choice of this class over SGLT2i is a personal if informed recommendation. He believes that the data favor GLP-1RA even if the exact mechanism of this protection is yet to be identified.

Dr. Goldstein and Dr. Kelley report no potential conflicts of interest.

Use of a mandibular advancement device (MAD) proved non-inferior to guideline-recommended continuous positive airway pressure (CPAP) to reduce blood pressure in patients with hypertension and obstructive sleep apnea (OSA), in a randomized trial.

The investigator-initiated CRESCENT trial showed that at 6 months, the MAD group had a reduction of 2.5 mm Hg in 24-hour mean arterial blood pressure vs no change in the CPAP group, for a nonsignificant between-group difference of 1.6 mm Hg. 

“These findings suggest that MAD could be considered an alternative to CPAP for optimizing blood pressure control in OSA patients with hypertension and high cardiovascular risk,” the researchers conclude. 

“Looking at the totality of evidence available in the literature, it is still reasonable to say that CPAP is the first-line treatment until we have more data on the MAD,” said Ronald Lee Chi-Hang, MD, professor of medicine at Yong Loo Lin School of Medicine, National University of Singapore, who presented the results.

“However, for patients who truly cannot tolerate or accept using a CPAP, we should be more open-minded in looking for an alternative therapy such as a MAD, which based on our study, numerically had a better blood pressure reduction in patients compared with a CPAP,” said Dr. Chi-Hang, who is also a senior consultant in the Department of Cardiology at Singapore’s National University Heart Centre. 

The results were presented April 6 at the American College of Cardiology Scientific Sessions 2024 and published online simultaneously in the Journal of the American College of Cardiology
 

Oral Appliance

OSA is increasingly recognized as “an underdiagnosed and modifiable cause of hypertension,” the researchers note in their report. “Patients with OSA develop recurrent collapse of the upper airway during sleep, resulting in hypoxemia, sympathetic hyperactivity, and BP surges.” 

Current guidelines recommend screening and treatment of OSA in patients with hypertension, and CPAP is considered first-line therapy, they note. 

“Despite being effective, unfortunately, many patients decline to use a CPAP or find it challenging to stick to the therapy,” Dr. Chi-Hang said, particularly those without daytime sleepiness. 

MADs are oral appliances that work by advancing the mandible about 5 to 10 mm during sleep, he said. They provide an alternative to OSA patients and have been shown to improve daytime sleepiness and quality of life, “and in general, is better accepted and tolerated than CPAP.” 

However, early studies are small, with short follow up, included patients with and without hypertension, and didn’t specify BP reduction as the primary outcome. 

The CRESCENT trial was an investigator-initiated, randomized, non-inferiority trial that aimed to compare the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure in patients with moderate-to-severe OSA, hypertension and high cardiovascular risk. The prespecified margin for non-inferiority was 1.5 mm Hg. 

A total of 321 participants were recruited at three public hospitals for polysomnography. All were older than age 40 years, had hypertension, and were at increased cardiovascular risk. Of these, 220 with moderate-to-severe OSA, defined as an apnea–hypopnea index (AHI) of ≥ 15 events/hour, were randomly assigned to either MAD or CPAP treatment. 

The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. The median age was 61 years, most patients (85.5%) were male, and all were Chinese. All had essential hypertension and were on one or more antihypertensive medications. Hypertension was relatively well controlled at baseline.

At 6 months, 24-hour mean arterial BP decreased by 2.5 mm Hg in the MAD group (P = .003) compared to no change from baseline in the CPAP group (P = .374). 

The between-group difference was -1.6 mm Hg (95% CI, -3.51 to 0.24, non-inferiority P < .001). 

There was a larger between-group reduction in all secondary ambulatory BP parameters in the MAD versus the CPAP group, with the most pronounced effects seen in the asleep BP parameters. 

Both the MAD and CPAP significantly improved daytime sleepiness, with no between-group differences (P =.384). There were no between-group differences in cardiovascular biomarkers. 

During the presentation, panel discussant Julie B. Damp, MD, associate professor of medicine at Vanderbilt Health in Nashville, Tennessee, called CRESCENT “a really interesting study, and I think it has a lot of information to add [regarding] what we know about this comparison in the literature, because this is a big study and it also followed these patients for longer than we’ve seen in some of the previous studies.”

Dr. Damp asked, however, about how these results might be extrapolated to other populations, since the vast majority of participants were male. 

Dr. Chi-Hang pointed out that most OSA studies include mostly male patients, but noted that particularly in Asian culture, female patients may be more conservative in seeking treatment for problems with snoring, poor quality of sleep, or extensive daytime sleepiness. “Therefore, lots of times, even in clinical practice, we see that over 80 or 90% of patients are male patients,” he said. 

Dr. Damp followed up by asking about the differential effectiveness of CPAP vs MAD. “Just in thinking about these two therapies, there is some evidence that the mandibular devices are potentially less effective on some of the sleep apnea-specific measures, so how much of this do you think is an issue of a better vs a not better treatment as opposed to an issue truly of compliance and what patients are able to tolerate?”

Dr. Chi-Hang agreed that in terms of reducing the AHI, CPAP is more effective than MAD. “In fact, in our data, the residual AHI was 10 for the MAD group and 2 for the CPAP group. Clearly, CPAP is more effective,” he said. “But the problem we are facing in this area is the value of AHI as an index is being questioned.” 

AHI considers only the number of events, without taking into account the duration or the depth of the apnea, he said. “AHI is simply not an ideal index to document the disease severity,” or the impact on cardiovascular outcomes. 
 

A Tailored Approach

In an editorial accompanying the JACC publication, Michele Emdin, MD, PhD, Francesco Gentile, MD, and Alberto Giannoni, MD, PhD, all from the Health Science Interdisciplinary Center, Scuola Superiore Sant’ Anna, and Fondazione Toscana Gabriele Monasterio, in Pisa, Italy, commend the researchers for designing and conducting “such a pragmatic and informative trial, which confirms and extends previous findings.” 

They also discuss the compliance vs effectiveness issue, pointing out that although CPAP appeared to be more effective in reducing apnea burden, there was higher adherence to MAD — with 57% using the device 6 or more hours per night, vs 23% for CPAP — which might have offset the greater reduction in apnea burden and resulted in the reduction in blood pressure seen in the trial. 

“Addressing poor adherence to OSA treatments seems therefore necessary, particularly in the case of less symptomatic patients, who often have a lower perception of the related risks,” they write. 

“Currently, a tailored approach seems reasonable, based on updated evidence, considering: a) the differential effects of CPAP or MAD on OSA, blood pressure; b) the treatment feasibility; c) the individual baseline demographic and clinical characteristics, including the presence of resistant hypertension; and d) compliance with the therapeutic tool and patient’s preferences,” the editorialists conclude. 

The study was funded by the Singapore Ministry of Health. The authors and editorialists report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Use of a mandibular advancement device (MAD) proved non-inferior to guideline-recommended continuous positive airway pressure (CPAP) to reduce blood pressure in patients with hypertension and obstructive sleep apnea (OSA), in a randomized trial.

The investigator-initiated CRESCENT trial showed that at 6 months, the MAD group had a reduction of 2.5 mm Hg in 24-hour mean arterial blood pressure vs no change in the CPAP group, for a nonsignificant between-group difference of 1.6 mm Hg. 

“These findings suggest that MAD could be considered an alternative to CPAP for optimizing blood pressure control in OSA patients with hypertension and high cardiovascular risk,” the researchers conclude. 

“Looking at the totality of evidence available in the literature, it is still reasonable to say that CPAP is the first-line treatment until we have more data on the MAD,” said Ronald Lee Chi-Hang, MD, professor of medicine at Yong Loo Lin School of Medicine, National University of Singapore, who presented the results.

“However, for patients who truly cannot tolerate or accept using a CPAP, we should be more open-minded in looking for an alternative therapy such as a MAD, which based on our study, numerically had a better blood pressure reduction in patients compared with a CPAP,” said Dr. Chi-Hang, who is also a senior consultant in the Department of Cardiology at Singapore’s National University Heart Centre. 

The results were presented April 6 at the American College of Cardiology Scientific Sessions 2024 and published online simultaneously in the Journal of the American College of Cardiology
 

Oral Appliance

OSA is increasingly recognized as “an underdiagnosed and modifiable cause of hypertension,” the researchers note in their report. “Patients with OSA develop recurrent collapse of the upper airway during sleep, resulting in hypoxemia, sympathetic hyperactivity, and BP surges.” 

Current guidelines recommend screening and treatment of OSA in patients with hypertension, and CPAP is considered first-line therapy, they note. 

“Despite being effective, unfortunately, many patients decline to use a CPAP or find it challenging to stick to the therapy,” Dr. Chi-Hang said, particularly those without daytime sleepiness. 

MADs are oral appliances that work by advancing the mandible about 5 to 10 mm during sleep, he said. They provide an alternative to OSA patients and have been shown to improve daytime sleepiness and quality of life, “and in general, is better accepted and tolerated than CPAP.” 

However, early studies are small, with short follow up, included patients with and without hypertension, and didn’t specify BP reduction as the primary outcome. 

The CRESCENT trial was an investigator-initiated, randomized, non-inferiority trial that aimed to compare the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure in patients with moderate-to-severe OSA, hypertension and high cardiovascular risk. The prespecified margin for non-inferiority was 1.5 mm Hg. 

A total of 321 participants were recruited at three public hospitals for polysomnography. All were older than age 40 years, had hypertension, and were at increased cardiovascular risk. Of these, 220 with moderate-to-severe OSA, defined as an apnea–hypopnea index (AHI) of ≥ 15 events/hour, were randomly assigned to either MAD or CPAP treatment. 

The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. The median age was 61 years, most patients (85.5%) were male, and all were Chinese. All had essential hypertension and were on one or more antihypertensive medications. Hypertension was relatively well controlled at baseline.

At 6 months, 24-hour mean arterial BP decreased by 2.5 mm Hg in the MAD group (P = .003) compared to no change from baseline in the CPAP group (P = .374). 

The between-group difference was -1.6 mm Hg (95% CI, -3.51 to 0.24, non-inferiority P < .001). 

There was a larger between-group reduction in all secondary ambulatory BP parameters in the MAD versus the CPAP group, with the most pronounced effects seen in the asleep BP parameters. 

Both the MAD and CPAP significantly improved daytime sleepiness, with no between-group differences (P =.384). There were no between-group differences in cardiovascular biomarkers. 

During the presentation, panel discussant Julie B. Damp, MD, associate professor of medicine at Vanderbilt Health in Nashville, Tennessee, called CRESCENT “a really interesting study, and I think it has a lot of information to add [regarding] what we know about this comparison in the literature, because this is a big study and it also followed these patients for longer than we’ve seen in some of the previous studies.”

Dr. Damp asked, however, about how these results might be extrapolated to other populations, since the vast majority of participants were male. 

Dr. Chi-Hang pointed out that most OSA studies include mostly male patients, but noted that particularly in Asian culture, female patients may be more conservative in seeking treatment for problems with snoring, poor quality of sleep, or extensive daytime sleepiness. “Therefore, lots of times, even in clinical practice, we see that over 80 or 90% of patients are male patients,” he said. 

Dr. Damp followed up by asking about the differential effectiveness of CPAP vs MAD. “Just in thinking about these two therapies, there is some evidence that the mandibular devices are potentially less effective on some of the sleep apnea-specific measures, so how much of this do you think is an issue of a better vs a not better treatment as opposed to an issue truly of compliance and what patients are able to tolerate?”

Dr. Chi-Hang agreed that in terms of reducing the AHI, CPAP is more effective than MAD. “In fact, in our data, the residual AHI was 10 for the MAD group and 2 for the CPAP group. Clearly, CPAP is more effective,” he said. “But the problem we are facing in this area is the value of AHI as an index is being questioned.” 

AHI considers only the number of events, without taking into account the duration or the depth of the apnea, he said. “AHI is simply not an ideal index to document the disease severity,” or the impact on cardiovascular outcomes. 
 

A Tailored Approach

In an editorial accompanying the JACC publication, Michele Emdin, MD, PhD, Francesco Gentile, MD, and Alberto Giannoni, MD, PhD, all from the Health Science Interdisciplinary Center, Scuola Superiore Sant’ Anna, and Fondazione Toscana Gabriele Monasterio, in Pisa, Italy, commend the researchers for designing and conducting “such a pragmatic and informative trial, which confirms and extends previous findings.” 

They also discuss the compliance vs effectiveness issue, pointing out that although CPAP appeared to be more effective in reducing apnea burden, there was higher adherence to MAD — with 57% using the device 6 or more hours per night, vs 23% for CPAP — which might have offset the greater reduction in apnea burden and resulted in the reduction in blood pressure seen in the trial. 

“Addressing poor adherence to OSA treatments seems therefore necessary, particularly in the case of less symptomatic patients, who often have a lower perception of the related risks,” they write. 

“Currently, a tailored approach seems reasonable, based on updated evidence, considering: a) the differential effects of CPAP or MAD on OSA, blood pressure; b) the treatment feasibility; c) the individual baseline demographic and clinical characteristics, including the presence of resistant hypertension; and d) compliance with the therapeutic tool and patient’s preferences,” the editorialists conclude. 

The study was funded by the Singapore Ministry of Health. The authors and editorialists report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Use of a mandibular advancement device (MAD) proved non-inferior to guideline-recommended continuous positive airway pressure (CPAP) to reduce blood pressure in patients with hypertension and obstructive sleep apnea (OSA), in a randomized trial.

The investigator-initiated CRESCENT trial showed that at 6 months, the MAD group had a reduction of 2.5 mm Hg in 24-hour mean arterial blood pressure vs no change in the CPAP group, for a nonsignificant between-group difference of 1.6 mm Hg. 

“These findings suggest that MAD could be considered an alternative to CPAP for optimizing blood pressure control in OSA patients with hypertension and high cardiovascular risk,” the researchers conclude. 

“Looking at the totality of evidence available in the literature, it is still reasonable to say that CPAP is the first-line treatment until we have more data on the MAD,” said Ronald Lee Chi-Hang, MD, professor of medicine at Yong Loo Lin School of Medicine, National University of Singapore, who presented the results.

“However, for patients who truly cannot tolerate or accept using a CPAP, we should be more open-minded in looking for an alternative therapy such as a MAD, which based on our study, numerically had a better blood pressure reduction in patients compared with a CPAP,” said Dr. Chi-Hang, who is also a senior consultant in the Department of Cardiology at Singapore’s National University Heart Centre. 

The results were presented April 6 at the American College of Cardiology Scientific Sessions 2024 and published online simultaneously in the Journal of the American College of Cardiology
 

Oral Appliance

OSA is increasingly recognized as “an underdiagnosed and modifiable cause of hypertension,” the researchers note in their report. “Patients with OSA develop recurrent collapse of the upper airway during sleep, resulting in hypoxemia, sympathetic hyperactivity, and BP surges.” 

Current guidelines recommend screening and treatment of OSA in patients with hypertension, and CPAP is considered first-line therapy, they note. 

“Despite being effective, unfortunately, many patients decline to use a CPAP or find it challenging to stick to the therapy,” Dr. Chi-Hang said, particularly those without daytime sleepiness. 

MADs are oral appliances that work by advancing the mandible about 5 to 10 mm during sleep, he said. They provide an alternative to OSA patients and have been shown to improve daytime sleepiness and quality of life, “and in general, is better accepted and tolerated than CPAP.” 

However, early studies are small, with short follow up, included patients with and without hypertension, and didn’t specify BP reduction as the primary outcome. 

The CRESCENT trial was an investigator-initiated, randomized, non-inferiority trial that aimed to compare the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure in patients with moderate-to-severe OSA, hypertension and high cardiovascular risk. The prespecified margin for non-inferiority was 1.5 mm Hg. 

A total of 321 participants were recruited at three public hospitals for polysomnography. All were older than age 40 years, had hypertension, and were at increased cardiovascular risk. Of these, 220 with moderate-to-severe OSA, defined as an apnea–hypopnea index (AHI) of ≥ 15 events/hour, were randomly assigned to either MAD or CPAP treatment. 

The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. The median age was 61 years, most patients (85.5%) were male, and all were Chinese. All had essential hypertension and were on one or more antihypertensive medications. Hypertension was relatively well controlled at baseline.

At 6 months, 24-hour mean arterial BP decreased by 2.5 mm Hg in the MAD group (P = .003) compared to no change from baseline in the CPAP group (P = .374). 

The between-group difference was -1.6 mm Hg (95% CI, -3.51 to 0.24, non-inferiority P < .001). 

There was a larger between-group reduction in all secondary ambulatory BP parameters in the MAD versus the CPAP group, with the most pronounced effects seen in the asleep BP parameters. 

Both the MAD and CPAP significantly improved daytime sleepiness, with no between-group differences (P =.384). There were no between-group differences in cardiovascular biomarkers. 

During the presentation, panel discussant Julie B. Damp, MD, associate professor of medicine at Vanderbilt Health in Nashville, Tennessee, called CRESCENT “a really interesting study, and I think it has a lot of information to add [regarding] what we know about this comparison in the literature, because this is a big study and it also followed these patients for longer than we’ve seen in some of the previous studies.”

Dr. Damp asked, however, about how these results might be extrapolated to other populations, since the vast majority of participants were male. 

Dr. Chi-Hang pointed out that most OSA studies include mostly male patients, but noted that particularly in Asian culture, female patients may be more conservative in seeking treatment for problems with snoring, poor quality of sleep, or extensive daytime sleepiness. “Therefore, lots of times, even in clinical practice, we see that over 80 or 90% of patients are male patients,” he said. 

Dr. Damp followed up by asking about the differential effectiveness of CPAP vs MAD. “Just in thinking about these two therapies, there is some evidence that the mandibular devices are potentially less effective on some of the sleep apnea-specific measures, so how much of this do you think is an issue of a better vs a not better treatment as opposed to an issue truly of compliance and what patients are able to tolerate?”

Dr. Chi-Hang agreed that in terms of reducing the AHI, CPAP is more effective than MAD. “In fact, in our data, the residual AHI was 10 for the MAD group and 2 for the CPAP group. Clearly, CPAP is more effective,” he said. “But the problem we are facing in this area is the value of AHI as an index is being questioned.” 

AHI considers only the number of events, without taking into account the duration or the depth of the apnea, he said. “AHI is simply not an ideal index to document the disease severity,” or the impact on cardiovascular outcomes. 
 

A Tailored Approach

In an editorial accompanying the JACC publication, Michele Emdin, MD, PhD, Francesco Gentile, MD, and Alberto Giannoni, MD, PhD, all from the Health Science Interdisciplinary Center, Scuola Superiore Sant’ Anna, and Fondazione Toscana Gabriele Monasterio, in Pisa, Italy, commend the researchers for designing and conducting “such a pragmatic and informative trial, which confirms and extends previous findings.” 

They also discuss the compliance vs effectiveness issue, pointing out that although CPAP appeared to be more effective in reducing apnea burden, there was higher adherence to MAD — with 57% using the device 6 or more hours per night, vs 23% for CPAP — which might have offset the greater reduction in apnea burden and resulted in the reduction in blood pressure seen in the trial. 

“Addressing poor adherence to OSA treatments seems therefore necessary, particularly in the case of less symptomatic patients, who often have a lower perception of the related risks,” they write. 

“Currently, a tailored approach seems reasonable, based on updated evidence, considering: a) the differential effects of CPAP or MAD on OSA, blood pressure; b) the treatment feasibility; c) the individual baseline demographic and clinical characteristics, including the presence of resistant hypertension; and d) compliance with the therapeutic tool and patient’s preferences,” the editorialists conclude. 

The study was funded by the Singapore Ministry of Health. The authors and editorialists report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Bond University

University of Georgia

University of Sydney

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Bond University

University of Georgia

University of Sydney

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Bond University

University of Georgia

University of Sydney

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. The results showed that vaping e-cigarettes causes oxidative stress, inflammation, endothelial dysfunction, and related cardiovascular consequences. The authors attributed the findings to overlapping toxic compounds in vapor and tobacco smoke and similar pathomechanical features of vaping and smoking. 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. The results showed that vaping e-cigarettes causes oxidative stress, inflammation, endothelial dysfunction, and related cardiovascular consequences. The authors attributed the findings to overlapping toxic compounds in vapor and tobacco smoke and similar pathomechanical features of vaping and smoking. 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. The results showed that vaping e-cigarettes causes oxidative stress, inflammation, endothelial dysfunction, and related cardiovascular consequences. The authors attributed the findings to overlapping toxic compounds in vapor and tobacco smoke and similar pathomechanical features of vaping and smoking. 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.

Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series by this news organization that tells these stories.

It was my first night off after 12 days. It was a Friday night, and I went to a bar in Naples to get a beer with some friends. As it turned out, it wasn’t a night off after all.

As soon as we got inside, we heard over the speaker that they needed medical personnel and to please go to the left side of the bar. I thought it would be syncope or something like that.

I went over there and saw a woman holding up a man. He was basically leaning all over her. The light was low, and the music was pounding. I started to assess him and tried to get him to answer me. No response. I checked for pulses — nothing.

Now, I’m in a bar, right? It’s a cardiac arrest. The first thing you think is overdose or alcohol. I asked the woman if the man was doing any drugs. She said she didn’t know. Turns out they were both employees. He was a bouncer and a DJ.

The woman helped me lower him to the floor. I checked again for a pulse. Still nothing. I said, “Call 911,” and started compressions.

The difficult part was the place was completely dark. I knew where his body was on the floor. I could see his chest. But I couldn’t see his face at all.

It was also extremely loud with the music thumping. After a while, they finally shut it off.

Pretty soon, the security personnel from the bar brought me an automated external defibrillator, and it showed the man was having V-fib arrest. I shocked him. Still no pulse. I continued with cardiopulmonary resuscitation (CPR).

I hadn’t noticed, but lots of people were crowding around us. Somebody came up and said, “He’s my friend. He has a 9-year-old daughter. He can’t die. Let me help with the compressions.” I was like, “Go for it.”

The guy started kind of pushing on the man’s abdomen. He had no idea how to do compressions. I said, “Okay, let me take over again.”

Out of the crowd, nobody else volunteered to help. No one asked me, “Hey, what can I do?” Meanwhile, I found out later that someone was filming the whole thing on their phone.

But what the guy said about the man’s young daughter stayed in my brain. I thought, we need to keep going.

I did more compressions and shocked him again. Still no pulse. At that point, the police and emergency medical services showed up. They checked, nothing had changed, so they got him into the ambulance.

I asked one of the paramedics, “Where are you taking him? I can call ahead.”

But he said, “That’s HIPAA. We can’t tell you.” They also wouldn’t let me go with him in the ambulance.

“I have an active Florida license, and I work in the ICU [intensive care unit],” I said.

“No, we need to follow our protocol,” he replied.

I understood that, but I just wanted to help.

It was around 10:30 PM by then, and I was drenched in sweat. I had to go home. The first thing I did after taking a shower was open the computer and check my system. I needed to find out what happened to the guy.

I was looking for admissions, and I didn’t see him. I called the main hospital downtown and the one in North Naples. I couldn’t find him anywhere. I stayed up until almost 1:00 AM checking for his name. At that point I thought, okay, maybe he died.

The next night, Saturday, I was home and got a call from one of my colleagues. “Hey, were you in a bar yesterday? Did you do CPR on somebody?”

“How did you know?” I said.

He said the paramedics had described me — “a tall doctor with glasses who was a nice guy.” It was funny that he knew that was me.

He told me, “The guy’s alive. He’s sick and needs to be put on dialysis, but he’s alive.”

Apparently, the guy had gone to the emergency department at North Naples, and the doctors in the emergency room (ER) worked on him for over an hour. They did continuous CPR and shocked him for close to 40 minutes. They finally got his pulse back, and after that, he was transferred to the main hospital ICU. They didn’t admit him at the ER, which was why I couldn’t find his name.

On Sunday, I was checking my patients’ charts for the ICU that coming week. And there he was. I saw his name and the documentation by the ED that CPR was provided by a critical care doctor in the field. He was still alive. That gave me so much joy.

So, the man I had helped became my patient. When I saw him on Monday, he was intubated and needed dialysis. I finally saw his face and thought, Oh, so that’s what you look like. I hadn’t realized he was only 39 years old.

When he was awake, I explained to him I was the doctor that provided CPR at the bar. He was very grateful, but of course, he didn’t remember anything.

Eventually, I met his daughter, and she just said, “Thank you for allowing me to have my dad.”

The funny part is that he broke his leg. Well, that’s not funny, but no one had any idea how it happened. That was his only complaint. He was asking me, “Doctor, how did you break my leg?”

“Hey, I have no idea how you broke your leg,” I replied. “I was trying to save your life.”

He was in the hospital for almost a month but made a full recovery. The amazing part: After all the evaluations, he has no neurological deficits. He’s back to a normal life now.

They never found a cause for the cardiac arrest. I mean, he had an ejection fraction of 10%. All my money was on something drug related, but that wasn’t the case. They’d done a cardiac cut, and there was no obstruction. They couldn’t find a reason.

We’ve become friends. He still works as a DJ at the bar. He changed his name to “DJ the Survivor” or something like that.

Sometimes, he’ll text me: “Doctor, what are you doing? You want to come down to the bar?”

I’m like, “No. I don’t.”

It’s been more than a year, but I remember every detail. When you go into medicine, you dream that one day you’ll be able to say, “I saved somebody.”

He texted me a year later and told me he’s celebrating two birthdays now. He said, “I’m turning 1 year old today!”

I think about the value of life. How we can take it for granted. We think, I’m young, nothing is going to happen to me. But this guy was 39. He went to work and died that night.

I was able to help bring him back. That makes me thankful for every day.

Jose Valle Giler, MD, is a pulmonary, critical care, and sleep medicine physician at NCH Healthcare System in Naples, Florida.

A version of this article appeared on Medscape.com .

Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series by this news organization that tells these stories.

It was my first night off after 12 days. It was a Friday night, and I went to a bar in Naples to get a beer with some friends. As it turned out, it wasn’t a night off after all.

As soon as we got inside, we heard over the speaker that they needed medical personnel and to please go to the left side of the bar. I thought it would be syncope or something like that.

I went over there and saw a woman holding up a man. He was basically leaning all over her. The light was low, and the music was pounding. I started to assess him and tried to get him to answer me. No response. I checked for pulses — nothing.

Now, I’m in a bar, right? It’s a cardiac arrest. The first thing you think is overdose or alcohol. I asked the woman if the man was doing any drugs. She said she didn’t know. Turns out they were both employees. He was a bouncer and a DJ.

The woman helped me lower him to the floor. I checked again for a pulse. Still nothing. I said, “Call 911,” and started compressions.

The difficult part was the place was completely dark. I knew where his body was on the floor. I could see his chest. But I couldn’t see his face at all.

It was also extremely loud with the music thumping. After a while, they finally shut it off.

Pretty soon, the security personnel from the bar brought me an automated external defibrillator, and it showed the man was having V-fib arrest. I shocked him. Still no pulse. I continued with cardiopulmonary resuscitation (CPR).

I hadn’t noticed, but lots of people were crowding around us. Somebody came up and said, “He’s my friend. He has a 9-year-old daughter. He can’t die. Let me help with the compressions.” I was like, “Go for it.”

The guy started kind of pushing on the man’s abdomen. He had no idea how to do compressions. I said, “Okay, let me take over again.”

Out of the crowd, nobody else volunteered to help. No one asked me, “Hey, what can I do?” Meanwhile, I found out later that someone was filming the whole thing on their phone.

But what the guy said about the man’s young daughter stayed in my brain. I thought, we need to keep going.

I did more compressions and shocked him again. Still no pulse. At that point, the police and emergency medical services showed up. They checked, nothing had changed, so they got him into the ambulance.

I asked one of the paramedics, “Where are you taking him? I can call ahead.”

But he said, “That’s HIPAA. We can’t tell you.” They also wouldn’t let me go with him in the ambulance.

“I have an active Florida license, and I work in the ICU [intensive care unit],” I said.

“No, we need to follow our protocol,” he replied.

I understood that, but I just wanted to help.

It was around 10:30 PM by then, and I was drenched in sweat. I had to go home. The first thing I did after taking a shower was open the computer and check my system. I needed to find out what happened to the guy.

I was looking for admissions, and I didn’t see him. I called the main hospital downtown and the one in North Naples. I couldn’t find him anywhere. I stayed up until almost 1:00 AM checking for his name. At that point I thought, okay, maybe he died.

The next night, Saturday, I was home and got a call from one of my colleagues. “Hey, were you in a bar yesterday? Did you do CPR on somebody?”

“How did you know?” I said.

He said the paramedics had described me — “a tall doctor with glasses who was a nice guy.” It was funny that he knew that was me.

He told me, “The guy’s alive. He’s sick and needs to be put on dialysis, but he’s alive.”

Apparently, the guy had gone to the emergency department at North Naples, and the doctors in the emergency room (ER) worked on him for over an hour. They did continuous CPR and shocked him for close to 40 minutes. They finally got his pulse back, and after that, he was transferred to the main hospital ICU. They didn’t admit him at the ER, which was why I couldn’t find his name.

On Sunday, I was checking my patients’ charts for the ICU that coming week. And there he was. I saw his name and the documentation by the ED that CPR was provided by a critical care doctor in the field. He was still alive. That gave me so much joy.

So, the man I had helped became my patient. When I saw him on Monday, he was intubated and needed dialysis. I finally saw his face and thought, Oh, so that’s what you look like. I hadn’t realized he was only 39 years old.

When he was awake, I explained to him I was the doctor that provided CPR at the bar. He was very grateful, but of course, he didn’t remember anything.

Eventually, I met his daughter, and she just said, “Thank you for allowing me to have my dad.”

The funny part is that he broke his leg. Well, that’s not funny, but no one had any idea how it happened. That was his only complaint. He was asking me, “Doctor, how did you break my leg?”

“Hey, I have no idea how you broke your leg,” I replied. “I was trying to save your life.”

He was in the hospital for almost a month but made a full recovery. The amazing part: After all the evaluations, he has no neurological deficits. He’s back to a normal life now.

They never found a cause for the cardiac arrest. I mean, he had an ejection fraction of 10%. All my money was on something drug related, but that wasn’t the case. They’d done a cardiac cut, and there was no obstruction. They couldn’t find a reason.

We’ve become friends. He still works as a DJ at the bar. He changed his name to “DJ the Survivor” or something like that.

Sometimes, he’ll text me: “Doctor, what are you doing? You want to come down to the bar?”

I’m like, “No. I don’t.”

It’s been more than a year, but I remember every detail. When you go into medicine, you dream that one day you’ll be able to say, “I saved somebody.”

He texted me a year later and told me he’s celebrating two birthdays now. He said, “I’m turning 1 year old today!”

I think about the value of life. How we can take it for granted. We think, I’m young, nothing is going to happen to me. But this guy was 39. He went to work and died that night.

I was able to help bring him back. That makes me thankful for every day.

Jose Valle Giler, MD, is a pulmonary, critical care, and sleep medicine physician at NCH Healthcare System in Naples, Florida.

A version of this article appeared on Medscape.com .

Emergencies happen anywhere, anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series by this news organization that tells these stories.

It was my first night off after 12 days. It was a Friday night, and I went to a bar in Naples to get a beer with some friends. As it turned out, it wasn’t a night off after all.

As soon as we got inside, we heard over the speaker that they needed medical personnel and to please go to the left side of the bar. I thought it would be syncope or something like that.

I went over there and saw a woman holding up a man. He was basically leaning all over her. The light was low, and the music was pounding. I started to assess him and tried to get him to answer me. No response. I checked for pulses — nothing.

Now, I’m in a bar, right? It’s a cardiac arrest. The first thing you think is overdose or alcohol. I asked the woman if the man was doing any drugs. She said she didn’t know. Turns out they were both employees. He was a bouncer and a DJ.

The woman helped me lower him to the floor. I checked again for a pulse. Still nothing. I said, “Call 911,” and started compressions.

The difficult part was the place was completely dark. I knew where his body was on the floor. I could see his chest. But I couldn’t see his face at all.

It was also extremely loud with the music thumping. After a while, they finally shut it off.

Pretty soon, the security personnel from the bar brought me an automated external defibrillator, and it showed the man was having V-fib arrest. I shocked him. Still no pulse. I continued with cardiopulmonary resuscitation (CPR).

I hadn’t noticed, but lots of people were crowding around us. Somebody came up and said, “He’s my friend. He has a 9-year-old daughter. He can’t die. Let me help with the compressions.” I was like, “Go for it.”

The guy started kind of pushing on the man’s abdomen. He had no idea how to do compressions. I said, “Okay, let me take over again.”

Out of the crowd, nobody else volunteered to help. No one asked me, “Hey, what can I do?” Meanwhile, I found out later that someone was filming the whole thing on their phone.

But what the guy said about the man’s young daughter stayed in my brain. I thought, we need to keep going.

I did more compressions and shocked him again. Still no pulse. At that point, the police and emergency medical services showed up. They checked, nothing had changed, so they got him into the ambulance.

I asked one of the paramedics, “Where are you taking him? I can call ahead.”

But he said, “That’s HIPAA. We can’t tell you.” They also wouldn’t let me go with him in the ambulance.

“I have an active Florida license, and I work in the ICU [intensive care unit],” I said.

“No, we need to follow our protocol,” he replied.

I understood that, but I just wanted to help.

It was around 10:30 PM by then, and I was drenched in sweat. I had to go home. The first thing I did after taking a shower was open the computer and check my system. I needed to find out what happened to the guy.

I was looking for admissions, and I didn’t see him. I called the main hospital downtown and the one in North Naples. I couldn’t find him anywhere. I stayed up until almost 1:00 AM checking for his name. At that point I thought, okay, maybe he died.

The next night, Saturday, I was home and got a call from one of my colleagues. “Hey, were you in a bar yesterday? Did you do CPR on somebody?”

“How did you know?” I said.

He said the paramedics had described me — “a tall doctor with glasses who was a nice guy.” It was funny that he knew that was me.

He told me, “The guy’s alive. He’s sick and needs to be put on dialysis, but he’s alive.”

Apparently, the guy had gone to the emergency department at North Naples, and the doctors in the emergency room (ER) worked on him for over an hour. They did continuous CPR and shocked him for close to 40 minutes. They finally got his pulse back, and after that, he was transferred to the main hospital ICU. They didn’t admit him at the ER, which was why I couldn’t find his name.

On Sunday, I was checking my patients’ charts for the ICU that coming week. And there he was. I saw his name and the documentation by the ED that CPR was provided by a critical care doctor in the field. He was still alive. That gave me so much joy.

So, the man I had helped became my patient. When I saw him on Monday, he was intubated and needed dialysis. I finally saw his face and thought, Oh, so that’s what you look like. I hadn’t realized he was only 39 years old.

When he was awake, I explained to him I was the doctor that provided CPR at the bar. He was very grateful, but of course, he didn’t remember anything.

Eventually, I met his daughter, and she just said, “Thank you for allowing me to have my dad.”

The funny part is that he broke his leg. Well, that’s not funny, but no one had any idea how it happened. That was his only complaint. He was asking me, “Doctor, how did you break my leg?”

“Hey, I have no idea how you broke your leg,” I replied. “I was trying to save your life.”

He was in the hospital for almost a month but made a full recovery. The amazing part: After all the evaluations, he has no neurological deficits. He’s back to a normal life now.

They never found a cause for the cardiac arrest. I mean, he had an ejection fraction of 10%. All my money was on something drug related, but that wasn’t the case. They’d done a cardiac cut, and there was no obstruction. They couldn’t find a reason.

We’ve become friends. He still works as a DJ at the bar. He changed his name to “DJ the Survivor” or something like that.

Sometimes, he’ll text me: “Doctor, what are you doing? You want to come down to the bar?”

I’m like, “No. I don’t.”

It’s been more than a year, but I remember every detail. When you go into medicine, you dream that one day you’ll be able to say, “I saved somebody.”

He texted me a year later and told me he’s celebrating two birthdays now. He said, “I’m turning 1 year old today!”

I think about the value of life. How we can take it for granted. We think, I’m young, nothing is going to happen to me. But this guy was 39. He went to work and died that night.

I was able to help bring him back. That makes me thankful for every day.

Jose Valle Giler, MD, is a pulmonary, critical care, and sleep medicine physician at NCH Healthcare System in Naples, Florida.

A version of this article appeared on Medscape.com .

Statins raise the risks for increased glucose levels and the development of type 2 diabetes among people who don’t have it at baseline, but those risks are outweighed by the cardiovascular benefit, new data suggested.

The findings come from an analysis of individual participant data from a total of 23 randomized trials of statin therapy involving 154,664 individuals. In people without diabetes at baseline, statin therapy produces a dose-dependent increase in the risk for diabetes diagnosis, particularly among those whose glycemia marker levels are already at the diagnostic threshold.

Statins also tend to raise glucose levels in people who already have diabetes, but “the diabetes-related risks arising from the small changes in glycemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration,” wrote the authors of the Cholesterol Treatment Trialists’ (CTT) Collaboration in their paper, published online in The Lancet Diabetes & Endocrinology.

Moreover, they say, “since the effect of statin therapy on measures of glycemia within an individual is small, there is likely to be little clinical benefit in measuring glucose concentrations and A1c values routinely after starting statin therapy with the aim of making comparisons to values taken before the initiation of a statin. However, people should continue to be screened for diabetes and associated risk factors and have their glycemic control monitored in accordance with current clinical guidelines.”

The CTT is co-led by Christina Reith, MBChB, PhD, and David Preiss, PhD, FRCPath, MRCP, both of the Nuffield Department of Population Health, University of Oxford, England.

In an accompanying editorial, Hertzel C. Gerstein, MD, and Marie Pigeyre, MD, PhD, both of McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada, noted that the decreased absolute annual incidence of life-threatening cardiovascular outcomes with statins in people at high risk for type 2 diabetes “clearly exceeds the 0.1%-1.3% per year increased absolute incidence of type 2 diabetes.”

Dr. Gerstein and Dr. Pigeyre also said “these findings emphasize the importance of holistic care. As people at risk for cardiovascular outcomes are also at risk for type 2 diabetes, any prescription of a statin should be accompanied by promoting proven strategies to prevent or delay diabetes, such as modest weight reduction and increased physical activity. Finally, these findings emphasize the importance of always being alert for harmful adverse effects, even with the most beneficial and successful preventive therapies.”
 

Statins Raise Diabetes Risk, Glucose Levels Slightly

The meta-analysis of trials in the CTT Collaboration included individual participant data from 19 double-blind randomized, controlled trials with a median follow-up of 4.3 years comparing statins with placebo in a total of 123,940 participants, including 18% who had known type 2 diabetes at randomization. Also analyzed were another four double-blind trials of lower- vs higher-intensity statins involving a total of 30,724 participants followed for a median of 4.9 years, with 15% having diabetes at baseline.

In the 19 trials of low- or moderate-intensity statins vs placebo, statins resulted in a significant 10% increase in new-onset diabetes compared with placebo (rate ratio, 1.10), while high-intensity statins raised the risk by an also significant 36% (1.36). This translated to a mean absolute excess of 0.12% per year of treatment.

Compared with less intensive statin therapy, more intensive statin therapy resulted in a significant 10% proportional increase in new-onset diabetes (1.10), giving an absolute annual excess of 0.22%.

In the statin vs placebo trials, differences in A1c values from placebo were 0.06 percentage points higher for low- or moderate-intensity statins and 0.08 points greater for high-intensity statins.

Nearly two thirds (62%) of the excess cases of new-onset diabetes occurred among participants in the highest quarter of the baseline glycemia distribution for both low-intensity or moderate-intensity and high-intensity statin therapy.

And among participants who already had diabetes at baseline, there was a significant 10% relative increase in worsening glycemia (defined by adverse glycemic event, A1c increase of ≥ 0.5 percentage points, or medication escalation) with low- or moderate-intensity statins compared with placebo and a 24% relative increase in the high-intensity trials.

The Nuffield Department of Population Health has an explicit policy of not accepting any personal honoraria payments directly or indirectly from the pharmaceutical and food industries. It seeks reimbursement to the University of Oxford for the costs of travel and accommodation to participate in scientific meetings. Dr. Reith reported receiving funding to the University of Oxford from the UK National Institute for Health and Care Research Health Technology Assessment Programme and holding unpaid roles on the Clinical Data Interchange Standards Consortium as a board member and WHO as a scientific advisor. Dr. Preiss reported receiving funding to his research institution (but no personal funding) from Novartis for the ORION 4 trial of inclisiran, Novo Nordisk for the ASCEND PLUS trial of semaglutide, and Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial and being a committee member for a National Institute for Health and Care Excellence guideline.

Dr. Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reported research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing medical education grants to McMaster University from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig Pharma, Sanofi, and Jiangsu Hanson; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Pfizer, Carbon Brand, Sanofi, Kowa, and Hanmi. Pigeyre had no disclosures.
 

A version of this article appeared on Medscape.com.

Statins raise the risks for increased glucose levels and the development of type 2 diabetes among people who don’t have it at baseline, but those risks are outweighed by the cardiovascular benefit, new data suggested.

The findings come from an analysis of individual participant data from a total of 23 randomized trials of statin therapy involving 154,664 individuals. In people without diabetes at baseline, statin therapy produces a dose-dependent increase in the risk for diabetes diagnosis, particularly among those whose glycemia marker levels are already at the diagnostic threshold.

Statins also tend to raise glucose levels in people who already have diabetes, but “the diabetes-related risks arising from the small changes in glycemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration,” wrote the authors of the Cholesterol Treatment Trialists’ (CTT) Collaboration in their paper, published online in The Lancet Diabetes & Endocrinology.

Moreover, they say, “since the effect of statin therapy on measures of glycemia within an individual is small, there is likely to be little clinical benefit in measuring glucose concentrations and A1c values routinely after starting statin therapy with the aim of making comparisons to values taken before the initiation of a statin. However, people should continue to be screened for diabetes and associated risk factors and have their glycemic control monitored in accordance with current clinical guidelines.”

The CTT is co-led by Christina Reith, MBChB, PhD, and David Preiss, PhD, FRCPath, MRCP, both of the Nuffield Department of Population Health, University of Oxford, England.

In an accompanying editorial, Hertzel C. Gerstein, MD, and Marie Pigeyre, MD, PhD, both of McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada, noted that the decreased absolute annual incidence of life-threatening cardiovascular outcomes with statins in people at high risk for type 2 diabetes “clearly exceeds the 0.1%-1.3% per year increased absolute incidence of type 2 diabetes.”

Dr. Gerstein and Dr. Pigeyre also said “these findings emphasize the importance of holistic care. As people at risk for cardiovascular outcomes are also at risk for type 2 diabetes, any prescription of a statin should be accompanied by promoting proven strategies to prevent or delay diabetes, such as modest weight reduction and increased physical activity. Finally, these findings emphasize the importance of always being alert for harmful adverse effects, even with the most beneficial and successful preventive therapies.”
 

Statins Raise Diabetes Risk, Glucose Levels Slightly

The meta-analysis of trials in the CTT Collaboration included individual participant data from 19 double-blind randomized, controlled trials with a median follow-up of 4.3 years comparing statins with placebo in a total of 123,940 participants, including 18% who had known type 2 diabetes at randomization. Also analyzed were another four double-blind trials of lower- vs higher-intensity statins involving a total of 30,724 participants followed for a median of 4.9 years, with 15% having diabetes at baseline.

In the 19 trials of low- or moderate-intensity statins vs placebo, statins resulted in a significant 10% increase in new-onset diabetes compared with placebo (rate ratio, 1.10), while high-intensity statins raised the risk by an also significant 36% (1.36). This translated to a mean absolute excess of 0.12% per year of treatment.

Compared with less intensive statin therapy, more intensive statin therapy resulted in a significant 10% proportional increase in new-onset diabetes (1.10), giving an absolute annual excess of 0.22%.

In the statin vs placebo trials, differences in A1c values from placebo were 0.06 percentage points higher for low- or moderate-intensity statins and 0.08 points greater for high-intensity statins.

Nearly two thirds (62%) of the excess cases of new-onset diabetes occurred among participants in the highest quarter of the baseline glycemia distribution for both low-intensity or moderate-intensity and high-intensity statin therapy.

And among participants who already had diabetes at baseline, there was a significant 10% relative increase in worsening glycemia (defined by adverse glycemic event, A1c increase of ≥ 0.5 percentage points, or medication escalation) with low- or moderate-intensity statins compared with placebo and a 24% relative increase in the high-intensity trials.

The Nuffield Department of Population Health has an explicit policy of not accepting any personal honoraria payments directly or indirectly from the pharmaceutical and food industries. It seeks reimbursement to the University of Oxford for the costs of travel and accommodation to participate in scientific meetings. Dr. Reith reported receiving funding to the University of Oxford from the UK National Institute for Health and Care Research Health Technology Assessment Programme and holding unpaid roles on the Clinical Data Interchange Standards Consortium as a board member and WHO as a scientific advisor. Dr. Preiss reported receiving funding to his research institution (but no personal funding) from Novartis for the ORION 4 trial of inclisiran, Novo Nordisk for the ASCEND PLUS trial of semaglutide, and Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial and being a committee member for a National Institute for Health and Care Excellence guideline.

Dr. Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reported research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing medical education grants to McMaster University from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig Pharma, Sanofi, and Jiangsu Hanson; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Pfizer, Carbon Brand, Sanofi, Kowa, and Hanmi. Pigeyre had no disclosures.
 

A version of this article appeared on Medscape.com.

Statins raise the risks for increased glucose levels and the development of type 2 diabetes among people who don’t have it at baseline, but those risks are outweighed by the cardiovascular benefit, new data suggested.

The findings come from an analysis of individual participant data from a total of 23 randomized trials of statin therapy involving 154,664 individuals. In people without diabetes at baseline, statin therapy produces a dose-dependent increase in the risk for diabetes diagnosis, particularly among those whose glycemia marker levels are already at the diagnostic threshold.

Statins also tend to raise glucose levels in people who already have diabetes, but “the diabetes-related risks arising from the small changes in glycemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration,” wrote the authors of the Cholesterol Treatment Trialists’ (CTT) Collaboration in their paper, published online in The Lancet Diabetes & Endocrinology.

Moreover, they say, “since the effect of statin therapy on measures of glycemia within an individual is small, there is likely to be little clinical benefit in measuring glucose concentrations and A1c values routinely after starting statin therapy with the aim of making comparisons to values taken before the initiation of a statin. However, people should continue to be screened for diabetes and associated risk factors and have their glycemic control monitored in accordance with current clinical guidelines.”

The CTT is co-led by Christina Reith, MBChB, PhD, and David Preiss, PhD, FRCPath, MRCP, both of the Nuffield Department of Population Health, University of Oxford, England.

In an accompanying editorial, Hertzel C. Gerstein, MD, and Marie Pigeyre, MD, PhD, both of McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada, noted that the decreased absolute annual incidence of life-threatening cardiovascular outcomes with statins in people at high risk for type 2 diabetes “clearly exceeds the 0.1%-1.3% per year increased absolute incidence of type 2 diabetes.”

Dr. Gerstein and Dr. Pigeyre also said “these findings emphasize the importance of holistic care. As people at risk for cardiovascular outcomes are also at risk for type 2 diabetes, any prescription of a statin should be accompanied by promoting proven strategies to prevent or delay diabetes, such as modest weight reduction and increased physical activity. Finally, these findings emphasize the importance of always being alert for harmful adverse effects, even with the most beneficial and successful preventive therapies.”
 

Statins Raise Diabetes Risk, Glucose Levels Slightly

The meta-analysis of trials in the CTT Collaboration included individual participant data from 19 double-blind randomized, controlled trials with a median follow-up of 4.3 years comparing statins with placebo in a total of 123,940 participants, including 18% who had known type 2 diabetes at randomization. Also analyzed were another four double-blind trials of lower- vs higher-intensity statins involving a total of 30,724 participants followed for a median of 4.9 years, with 15% having diabetes at baseline.

In the 19 trials of low- or moderate-intensity statins vs placebo, statins resulted in a significant 10% increase in new-onset diabetes compared with placebo (rate ratio, 1.10), while high-intensity statins raised the risk by an also significant 36% (1.36). This translated to a mean absolute excess of 0.12% per year of treatment.

Compared with less intensive statin therapy, more intensive statin therapy resulted in a significant 10% proportional increase in new-onset diabetes (1.10), giving an absolute annual excess of 0.22%.

In the statin vs placebo trials, differences in A1c values from placebo were 0.06 percentage points higher for low- or moderate-intensity statins and 0.08 points greater for high-intensity statins.

Nearly two thirds (62%) of the excess cases of new-onset diabetes occurred among participants in the highest quarter of the baseline glycemia distribution for both low-intensity or moderate-intensity and high-intensity statin therapy.

And among participants who already had diabetes at baseline, there was a significant 10% relative increase in worsening glycemia (defined by adverse glycemic event, A1c increase of ≥ 0.5 percentage points, or medication escalation) with low- or moderate-intensity statins compared with placebo and a 24% relative increase in the high-intensity trials.

The Nuffield Department of Population Health has an explicit policy of not accepting any personal honoraria payments directly or indirectly from the pharmaceutical and food industries. It seeks reimbursement to the University of Oxford for the costs of travel and accommodation to participate in scientific meetings. Dr. Reith reported receiving funding to the University of Oxford from the UK National Institute for Health and Care Research Health Technology Assessment Programme and holding unpaid roles on the Clinical Data Interchange Standards Consortium as a board member and WHO as a scientific advisor. Dr. Preiss reported receiving funding to his research institution (but no personal funding) from Novartis for the ORION 4 trial of inclisiran, Novo Nordisk for the ASCEND PLUS trial of semaglutide, and Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial and being a committee member for a National Institute for Health and Care Excellence guideline.

Dr. Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reported research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing medical education grants to McMaster University from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig Pharma, Sanofi, and Jiangsu Hanson; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Pfizer, Carbon Brand, Sanofi, Kowa, and Hanmi. Pigeyre had no disclosures.
 

A version of this article appeared on Medscape.com.

ATLANTA — A novel antisense therapy called olezarsen reduced triglycerides (TGs) by approximately 50% with either of the two study doses relative to placebo and did so with a low relative risk for adverse events, new data from a phase 2b trial showed.

“The reduction in triglycerides was greater than that currently possible with any available therapy,” reported Brian A. Bergmark, MD, an interventional cardiologist at Brigham and Women’s Hospital, Boston.

The drug also produced meaningful improvements in multiple other lipid subfractions associated with increased cardiovascular (CV) risk, including ApoC-III, very low–density lipoprotein (VLDL) cholesterol, ApoB, and non-LDL cholesterol. High-density lipoprotein (HDL) cholesterol levels were significantly raised.

The results were presented on April 7 as a late breaker at the American College of Cardiology (ACC) Scientific Session 2024 and published online simultaneously in The New England Journal of Medicine.
 

No Major Subgroup Failed to Respond

The effect was seen across all the key subgroups evaluated, including women and patients with diabetes, obesity, and severe as well as moderate elevations in TGs at baseline, Dr. Bergmark reported.

Olezarsen is a N-acetylgalactosamine–conjugated antisense oligonucleotide targeting APOC3 RNA. The results of this randomized trial, called BRIDGE-TIMI 73a, are consistent with other evidence that inhibiting expression of ApoC-III lowers the levels of TGs and other lipid subfractions to a degree that would predict clinical benefit.

In this study, 154 patients at 24 sites in North America were randomized in a 1:1 ratio to 50 or 80 mg olezarsen. Those in each of these cohorts were then randomized in a 3:1 ratio to active therapy or placebo. All therapies were administered by subcutaneous injection once per month.

Patients were eligible for the trial if they had moderate hypertriglyceridemia, defined as a level of 150-499 mg/dL, and elevated CV risk or if they had severe hypertriglyceridemia (≥ 500 mg/dL) with or without other evidence of elevated CV risk. The primary endpoint was a change in TGs at 6 months. Complete follow-up was available in about 97% of patients regardless of treatment assignment.

With a slight numerical advantage for the higher dose, the TG reductions were 49.1% for the 50-mg dose and 53.1% for the 80-mg dose relative to no significant change in the placebo group (P < .001 for both olezarsen doses). The reductions in ApoC-III, an upstream driver of TG production and a CV risk factor, were 64.2% and 73.2% relative to placebo (both P < .001), respectively, Dr. Bergmark reported.

In those with moderate hypertriglyceridemia, normal TG levels, defined as < 150 mg/dL, were reached at 6 months in 85.7% and 93.3% in the 40-mg and 80-mg dose groups, respectively. Relative to these reductions, normalization was seen in only 11.8% of placebo patients (P < .001).
 

TG Lowering Might Not Be Best Endpoint

The primary endpoint in this trial was a change in TGs, but this target was questioned by an invited ACC discussant, Daniel Soffer, MD, who is both an adjunct professor assistant professor of medicine at Penn Medicine, Philadelphia, and current president of the National Lipid Association.

Dr. Soffer noted that highly elevated TGs are a major risk factor for acute pancreatitis, so this predicts a clinical benefit for this purpose, but he thought the other lipid subfractions are far more important for the goal of reducing atherosclerotic cardiovascular disease (ASCVD).

Indeed, he said categorically that it is not TGs that drive ASCVD risk and therefore not what is the real importance of these data. Rather, “it is the non-HDL cholesterol and ApoB lowering” that will drive the likely benefits from this therapy in CV disease.

In addition to the TG reductions, olezarsen did, in fact, produce significant reductions in many of the lipid subfractions associated with increased CV risk. While slightly more favorable in most cases with the higher dose of olezarsen, even the lower dose reduced Apo C-III from baseline by 64.2% (P < .001), VLDL by 46.2% (P < .001), remnant cholesterol by 46.6% (P < .001), ApoB by 18.2% (P < .001), and non-HDL cholesterol by 25.4% (P < .001). HDL cholesterol was increased by 39.6% (P < .001).

These favorable effects on TG and other lipid subfractions were achieved with a safety profile that was reassuring, Dr. Bergmark said. Serious adverse events leading to discontinuation occurred in 0%, 1.7%, and 1.8% of the placebo, lower-dose, and higher-dose arms, respectively. These rates did not differ significantly.
 

Increased Liver Enzymes Is Common

Liver enzymes were significantly elevated (P < .001) for both doses of olezarsen vs placebo, but liver enzymes > 3× the upper limit of normal did not reach significance on either dose of olezarsen relative to placebo. Low platelet counts and reductions in kidney function were observed in a minority of patients but were generally manageable, according to Dr. Bergmark. There was no impact on hemoglobin A1c levels.

Further evaluation of change in hepatic function is planned in the ongoing extension studies.

Characterizing these results as “exciting,” Neha J. Pagidipati, MD, a member of the Duke Clinical Research Institute and an assistant professor at the Duke School of Medicine, Durham, North Carolina, said that identifying a drug effective for hypertriglyceridemia is likely to be a major advance. While elevated TGs are “one of the toughest” lipid abnormalities to manage, “there is not much out there to offer for treatment.”

She, like Dr. Soffer, was encouraged by the favorable effects on multiple lipid abnormalities associated with increased CV risk, but she said the ultimate clinical utility of this or other agents that lower TGs for ASCVD requires a study showing a change in CV events.

Dr. Bergmark reported financial relationships with 15 pharmaceutical companies, including Ionis, which provided funding for the BRIDGE-TIMI 73a trial. Soffer had financial relationships with Akcea, Amgen, Amryt, AstraZeneca, Ionis, Novartis, Regeneron, and Verve. Dr. Pagidipati had financial relationships with more than 10 pharmaceutical companies but was not involved in the design of management of the BRIDGE-TIMI 73a trial.

A version of this article first appeared on Medscape.com.

ATLANTA — A novel antisense therapy called olezarsen reduced triglycerides (TGs) by approximately 50% with either of the two study doses relative to placebo and did so with a low relative risk for adverse events, new data from a phase 2b trial showed.

“The reduction in triglycerides was greater than that currently possible with any available therapy,” reported Brian A. Bergmark, MD, an interventional cardiologist at Brigham and Women’s Hospital, Boston.

The drug also produced meaningful improvements in multiple other lipid subfractions associated with increased cardiovascular (CV) risk, including ApoC-III, very low–density lipoprotein (VLDL) cholesterol, ApoB, and non-LDL cholesterol. High-density lipoprotein (HDL) cholesterol levels were significantly raised.

The results were presented on April 7 as a late breaker at the American College of Cardiology (ACC) Scientific Session 2024 and published online simultaneously in The New England Journal of Medicine.
 

No Major Subgroup Failed to Respond

The effect was seen across all the key subgroups evaluated, including women and patients with diabetes, obesity, and severe as well as moderate elevations in TGs at baseline, Dr. Bergmark reported.

Olezarsen is a N-acetylgalactosamine–conjugated antisense oligonucleotide targeting APOC3 RNA. The results of this randomized trial, called BRIDGE-TIMI 73a, are consistent with other evidence that inhibiting expression of ApoC-III lowers the levels of TGs and other lipid subfractions to a degree that would predict clinical benefit.

In this study, 154 patients at 24 sites in North America were randomized in a 1:1 ratio to 50 or 80 mg olezarsen. Those in each of these cohorts were then randomized in a 3:1 ratio to active therapy or placebo. All therapies were administered by subcutaneous injection once per month.

Patients were eligible for the trial if they had moderate hypertriglyceridemia, defined as a level of 150-499 mg/dL, and elevated CV risk or if they had severe hypertriglyceridemia (≥ 500 mg/dL) with or without other evidence of elevated CV risk. The primary endpoint was a change in TGs at 6 months. Complete follow-up was available in about 97% of patients regardless of treatment assignment.

With a slight numerical advantage for the higher dose, the TG reductions were 49.1% for the 50-mg dose and 53.1% for the 80-mg dose relative to no significant change in the placebo group (P < .001 for both olezarsen doses). The reductions in ApoC-III, an upstream driver of TG production and a CV risk factor, were 64.2% and 73.2% relative to placebo (both P < .001), respectively, Dr. Bergmark reported.

In those with moderate hypertriglyceridemia, normal TG levels, defined as < 150 mg/dL, were reached at 6 months in 85.7% and 93.3% in the 40-mg and 80-mg dose groups, respectively. Relative to these reductions, normalization was seen in only 11.8% of placebo patients (P < .001).
 

TG Lowering Might Not Be Best Endpoint

The primary endpoint in this trial was a change in TGs, but this target was questioned by an invited ACC discussant, Daniel Soffer, MD, who is both an adjunct professor assistant professor of medicine at Penn Medicine, Philadelphia, and current president of the National Lipid Association.

Dr. Soffer noted that highly elevated TGs are a major risk factor for acute pancreatitis, so this predicts a clinical benefit for this purpose, but he thought the other lipid subfractions are far more important for the goal of reducing atherosclerotic cardiovascular disease (ASCVD).

Indeed, he said categorically that it is not TGs that drive ASCVD risk and therefore not what is the real importance of these data. Rather, “it is the non-HDL cholesterol and ApoB lowering” that will drive the likely benefits from this therapy in CV disease.

In addition to the TG reductions, olezarsen did, in fact, produce significant reductions in many of the lipid subfractions associated with increased CV risk. While slightly more favorable in most cases with the higher dose of olezarsen, even the lower dose reduced Apo C-III from baseline by 64.2% (P < .001), VLDL by 46.2% (P < .001), remnant cholesterol by 46.6% (P < .001), ApoB by 18.2% (P < .001), and non-HDL cholesterol by 25.4% (P < .001). HDL cholesterol was increased by 39.6% (P < .001).

These favorable effects on TG and other lipid subfractions were achieved with a safety profile that was reassuring, Dr. Bergmark said. Serious adverse events leading to discontinuation occurred in 0%, 1.7%, and 1.8% of the placebo, lower-dose, and higher-dose arms, respectively. These rates did not differ significantly.
 

Increased Liver Enzymes Is Common

Liver enzymes were significantly elevated (P < .001) for both doses of olezarsen vs placebo, but liver enzymes > 3× the upper limit of normal did not reach significance on either dose of olezarsen relative to placebo. Low platelet counts and reductions in kidney function were observed in a minority of patients but were generally manageable, according to Dr. Bergmark. There was no impact on hemoglobin A1c levels.

Further evaluation of change in hepatic function is planned in the ongoing extension studies.

Characterizing these results as “exciting,” Neha J. Pagidipati, MD, a member of the Duke Clinical Research Institute and an assistant professor at the Duke School of Medicine, Durham, North Carolina, said that identifying a drug effective for hypertriglyceridemia is likely to be a major advance. While elevated TGs are “one of the toughest” lipid abnormalities to manage, “there is not much out there to offer for treatment.”

She, like Dr. Soffer, was encouraged by the favorable effects on multiple lipid abnormalities associated with increased CV risk, but she said the ultimate clinical utility of this or other agents that lower TGs for ASCVD requires a study showing a change in CV events.

Dr. Bergmark reported financial relationships with 15 pharmaceutical companies, including Ionis, which provided funding for the BRIDGE-TIMI 73a trial. Soffer had financial relationships with Akcea, Amgen, Amryt, AstraZeneca, Ionis, Novartis, Regeneron, and Verve. Dr. Pagidipati had financial relationships with more than 10 pharmaceutical companies but was not involved in the design of management of the BRIDGE-TIMI 73a trial.

A version of this article first appeared on Medscape.com.

ATLANTA — A novel antisense therapy called olezarsen reduced triglycerides (TGs) by approximately 50% with either of the two study doses relative to placebo and did so with a low relative risk for adverse events, new data from a phase 2b trial showed.

“The reduction in triglycerides was greater than that currently possible with any available therapy,” reported Brian A. Bergmark, MD, an interventional cardiologist at Brigham and Women’s Hospital, Boston.

The drug also produced meaningful improvements in multiple other lipid subfractions associated with increased cardiovascular (CV) risk, including ApoC-III, very low–density lipoprotein (VLDL) cholesterol, ApoB, and non-LDL cholesterol. High-density lipoprotein (HDL) cholesterol levels were significantly raised.

The results were presented on April 7 as a late breaker at the American College of Cardiology (ACC) Scientific Session 2024 and published online simultaneously in The New England Journal of Medicine.
 

No Major Subgroup Failed to Respond

The effect was seen across all the key subgroups evaluated, including women and patients with diabetes, obesity, and severe as well as moderate elevations in TGs at baseline, Dr. Bergmark reported.

Olezarsen is a N-acetylgalactosamine–conjugated antisense oligonucleotide targeting APOC3 RNA. The results of this randomized trial, called BRIDGE-TIMI 73a, are consistent with other evidence that inhibiting expression of ApoC-III lowers the levels of TGs and other lipid subfractions to a degree that would predict clinical benefit.

In this study, 154 patients at 24 sites in North America were randomized in a 1:1 ratio to 50 or 80 mg olezarsen. Those in each of these cohorts were then randomized in a 3:1 ratio to active therapy or placebo. All therapies were administered by subcutaneous injection once per month.

Patients were eligible for the trial if they had moderate hypertriglyceridemia, defined as a level of 150-499 mg/dL, and elevated CV risk or if they had severe hypertriglyceridemia (≥ 500 mg/dL) with or without other evidence of elevated CV risk. The primary endpoint was a change in TGs at 6 months. Complete follow-up was available in about 97% of patients regardless of treatment assignment.

With a slight numerical advantage for the higher dose, the TG reductions were 49.1% for the 50-mg dose and 53.1% for the 80-mg dose relative to no significant change in the placebo group (P < .001 for both olezarsen doses). The reductions in ApoC-III, an upstream driver of TG production and a CV risk factor, were 64.2% and 73.2% relative to placebo (both P < .001), respectively, Dr. Bergmark reported.

In those with moderate hypertriglyceridemia, normal TG levels, defined as < 150 mg/dL, were reached at 6 months in 85.7% and 93.3% in the 40-mg and 80-mg dose groups, respectively. Relative to these reductions, normalization was seen in only 11.8% of placebo patients (P < .001).
 

TG Lowering Might Not Be Best Endpoint

The primary endpoint in this trial was a change in TGs, but this target was questioned by an invited ACC discussant, Daniel Soffer, MD, who is both an adjunct professor assistant professor of medicine at Penn Medicine, Philadelphia, and current president of the National Lipid Association.

Dr. Soffer noted that highly elevated TGs are a major risk factor for acute pancreatitis, so this predicts a clinical benefit for this purpose, but he thought the other lipid subfractions are far more important for the goal of reducing atherosclerotic cardiovascular disease (ASCVD).

Indeed, he said categorically that it is not TGs that drive ASCVD risk and therefore not what is the real importance of these data. Rather, “it is the non-HDL cholesterol and ApoB lowering” that will drive the likely benefits from this therapy in CV disease.

In addition to the TG reductions, olezarsen did, in fact, produce significant reductions in many of the lipid subfractions associated with increased CV risk. While slightly more favorable in most cases with the higher dose of olezarsen, even the lower dose reduced Apo C-III from baseline by 64.2% (P < .001), VLDL by 46.2% (P < .001), remnant cholesterol by 46.6% (P < .001), ApoB by 18.2% (P < .001), and non-HDL cholesterol by 25.4% (P < .001). HDL cholesterol was increased by 39.6% (P < .001).

These favorable effects on TG and other lipid subfractions were achieved with a safety profile that was reassuring, Dr. Bergmark said. Serious adverse events leading to discontinuation occurred in 0%, 1.7%, and 1.8% of the placebo, lower-dose, and higher-dose arms, respectively. These rates did not differ significantly.
 

Increased Liver Enzymes Is Common

Liver enzymes were significantly elevated (P < .001) for both doses of olezarsen vs placebo, but liver enzymes > 3× the upper limit of normal did not reach significance on either dose of olezarsen relative to placebo. Low platelet counts and reductions in kidney function were observed in a minority of patients but were generally manageable, according to Dr. Bergmark. There was no impact on hemoglobin A1c levels.

Further evaluation of change in hepatic function is planned in the ongoing extension studies.

Characterizing these results as “exciting,” Neha J. Pagidipati, MD, a member of the Duke Clinical Research Institute and an assistant professor at the Duke School of Medicine, Durham, North Carolina, said that identifying a drug effective for hypertriglyceridemia is likely to be a major advance. While elevated TGs are “one of the toughest” lipid abnormalities to manage, “there is not much out there to offer for treatment.”

She, like Dr. Soffer, was encouraged by the favorable effects on multiple lipid abnormalities associated with increased CV risk, but she said the ultimate clinical utility of this or other agents that lower TGs for ASCVD requires a study showing a change in CV events.

Dr. Bergmark reported financial relationships with 15 pharmaceutical companies, including Ionis, which provided funding for the BRIDGE-TIMI 73a trial. Soffer had financial relationships with Akcea, Amgen, Amryt, AstraZeneca, Ionis, Novartis, Regeneron, and Verve. Dr. Pagidipati had financial relationships with more than 10 pharmaceutical companies but was not involved in the design of management of the BRIDGE-TIMI 73a trial.

A version of this article first appeared on Medscape.com.

TOPLINE:

In people with type 2 diabetes (T2D), higher levels of arm and trunk fat are associated with an increased risk for cardiovascular disease (CVD) and mortality, while higher levels of leg fat are associated with a reduced risk for these conditions.

METHODOLOGY:

• People with T2D have a twofold to fourfold higher risk for CVD and mortality, and evidence shows obesity management helps delay complications and premature death, but an elevated body mass index (BMI) may be insufficient to measure obesity.
• In the “obesity paradox,” people with elevated BMI may have a lower CVD risk than people of normal weight.
• Researchers prospectively investigated how regional body fat accumulation was associated with CVD risk in 21,472 people with T2D (mean age, 58.9 years; 60.7% men; BMI about 29-33) from the UK Biobank (2006-2010), followed up for a median of 7.7 years.
• The regional body fat distribution in arms, trunk, and legs was assessed using bioelectrical impedance analysis.
• The primary outcomes were the incidence of CVD, all-cause mortality, and CVD mortality.

TAKEAWAY:

• Participants in the highest quartile of arm fat percentage (multivariate-adjusted hazard ratio [HR], 1.63; 95% CI, 1.29-2.05) and trunk fat percentage (HR, 1.27; 95% CI, 1.06-1.52) were at a higher risk for CVD than those in the lowest quartile.
• However, participants in the highest quartile of leg fat percentage had a lower risk for CVD than those in the lowest quartile (HR, 0.72; 95% CI, 0.58-0.90).
• A nonlinear relationship was observed between higher leg fat percentage and lower CVD risk and between higher trunk fat percentage and higher CVD risk, whereas a linear relationship was noted between higher arm fat percentage and higher CVD risk.
• The patterns of association were similar for both all-cause mortality and CVD mortality. Overall patterns were similar for men and women.

IN PRACTICE:

“Our findings add to the understanding of body fat distribution in patients with T2D, which highlights the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among patients with T2D,” wrote the authors.

SOURCE:

The study led by Zixin Qiu, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

As body fat was measured only once at the beginning of the study, its changing association over time could not be assessed. Moreover, the findings were primarily based on predominantly White UK adults, potentially restricting their generalizability to other population groups. Furthermore, diabetes was diagnosed using self-reported medical history, medication, and hemoglobin A1c levels, implying that some cases may have gone undetected at baseline. 

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Hubei Province Science Fund for Distinguished Young Scholars, and Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with type 2 diabetes (T2D), higher levels of arm and trunk fat are associated with an increased risk for cardiovascular disease (CVD) and mortality, while higher levels of leg fat are associated with a reduced risk for these conditions.

METHODOLOGY:

• People with T2D have a twofold to fourfold higher risk for CVD and mortality, and evidence shows obesity management helps delay complications and premature death, but an elevated body mass index (BMI) may be insufficient to measure obesity.
• In the “obesity paradox,” people with elevated BMI may have a lower CVD risk than people of normal weight.
• Researchers prospectively investigated how regional body fat accumulation was associated with CVD risk in 21,472 people with T2D (mean age, 58.9 years; 60.7% men; BMI about 29-33) from the UK Biobank (2006-2010), followed up for a median of 7.7 years.
• The regional body fat distribution in arms, trunk, and legs was assessed using bioelectrical impedance analysis.
• The primary outcomes were the incidence of CVD, all-cause mortality, and CVD mortality.

TAKEAWAY:

• Participants in the highest quartile of arm fat percentage (multivariate-adjusted hazard ratio [HR], 1.63; 95% CI, 1.29-2.05) and trunk fat percentage (HR, 1.27; 95% CI, 1.06-1.52) were at a higher risk for CVD than those in the lowest quartile.
• However, participants in the highest quartile of leg fat percentage had a lower risk for CVD than those in the lowest quartile (HR, 0.72; 95% CI, 0.58-0.90).
• A nonlinear relationship was observed between higher leg fat percentage and lower CVD risk and between higher trunk fat percentage and higher CVD risk, whereas a linear relationship was noted between higher arm fat percentage and higher CVD risk.
• The patterns of association were similar for both all-cause mortality and CVD mortality. Overall patterns were similar for men and women.

IN PRACTICE:

“Our findings add to the understanding of body fat distribution in patients with T2D, which highlights the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among patients with T2D,” wrote the authors.

SOURCE:

The study led by Zixin Qiu, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

As body fat was measured only once at the beginning of the study, its changing association over time could not be assessed. Moreover, the findings were primarily based on predominantly White UK adults, potentially restricting their generalizability to other population groups. Furthermore, diabetes was diagnosed using self-reported medical history, medication, and hemoglobin A1c levels, implying that some cases may have gone undetected at baseline. 

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Hubei Province Science Fund for Distinguished Young Scholars, and Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with type 2 diabetes (T2D), higher levels of arm and trunk fat are associated with an increased risk for cardiovascular disease (CVD) and mortality, while higher levels of leg fat are associated with a reduced risk for these conditions.

METHODOLOGY:

• People with T2D have a twofold to fourfold higher risk for CVD and mortality, and evidence shows obesity management helps delay complications and premature death, but an elevated body mass index (BMI) may be insufficient to measure obesity.
• In the “obesity paradox,” people with elevated BMI may have a lower CVD risk than people of normal weight.
• Researchers prospectively investigated how regional body fat accumulation was associated with CVD risk in 21,472 people with T2D (mean age, 58.9 years; 60.7% men; BMI about 29-33) from the UK Biobank (2006-2010), followed up for a median of 7.7 years.
• The regional body fat distribution in arms, trunk, and legs was assessed using bioelectrical impedance analysis.
• The primary outcomes were the incidence of CVD, all-cause mortality, and CVD mortality.

TAKEAWAY:

• Participants in the highest quartile of arm fat percentage (multivariate-adjusted hazard ratio [HR], 1.63; 95% CI, 1.29-2.05) and trunk fat percentage (HR, 1.27; 95% CI, 1.06-1.52) were at a higher risk for CVD than those in the lowest quartile.
• However, participants in the highest quartile of leg fat percentage had a lower risk for CVD than those in the lowest quartile (HR, 0.72; 95% CI, 0.58-0.90).
• A nonlinear relationship was observed between higher leg fat percentage and lower CVD risk and between higher trunk fat percentage and higher CVD risk, whereas a linear relationship was noted between higher arm fat percentage and higher CVD risk.
• The patterns of association were similar for both all-cause mortality and CVD mortality. Overall patterns were similar for men and women.

IN PRACTICE:

“Our findings add to the understanding of body fat distribution in patients with T2D, which highlights the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among patients with T2D,” wrote the authors.

SOURCE:

The study led by Zixin Qiu, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

As body fat was measured only once at the beginning of the study, its changing association over time could not be assessed. Moreover, the findings were primarily based on predominantly White UK adults, potentially restricting their generalizability to other population groups. Furthermore, diabetes was diagnosed using self-reported medical history, medication, and hemoglobin A1c levels, implying that some cases may have gone undetected at baseline. 

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Hubei Province Science Fund for Distinguished Young Scholars, and Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

A version of this article 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.

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.

Little blue pill meets a little blue light.

A digital application can improve erectile function, according to new research presented at the European Association of Urology (EAU) Annual Congress on April 8, 2024.

Researchers developed a 12-week, self-managed program to treat erectile dysfunction (ED). The program is delivered to patients’ mobile devices and encourages users to do cardiovascular training, pelvic floor exercises, and physiotherapy. It also provides information about ED, sexual therapy, and stress management.

“The treatment of ED through physical activity and/or lifestyle changes is recommended in current European guidelines but is not well established in clinical practice,” according to the researchers.

App or Waitlist

The app, known as Kranus Edera, was created by Kranus Health. It is available by prescription in Germany and France.

To study the effectiveness of the app, investigators conducted a randomized controlled trial at the University Hospital Münster in Germany.

The study included 241 men who had scores of 21 or less on the International Index of Erectile Function (IIEF-5).

About half of the participants were randomly assigned to get the app. The rest were placed on a waiting list for the technology and served as a control group.

After 12 weeks, those who received the app reported significantly greater improvement on the IIEF-5, with a gain of 4.5 points vs a 0.2-point improvement for men in the control group (P < .0001).

Men who received the app also reported gains in measures of quality of life (20.5 vs −0.04) and patient activation (11.1 vs 0.64).

Nearly nine in 10 people who used the app did so several times per week, the researchers reported.

Sabine Kliesch, MD, with University Hospital Münster, led the study, which was presented at a poster session on April 8 at the EAU Congress in Paris.

Fully Reimbursed in Germany

In Germany, Kranus Edera has been included on a government list of digital health apps that are fully reimbursed by insurers, partly based on the results of the clinical trial. The cost there is €235 (about $255).

Patients typically notice improvements in 2-4 weeks, according to the company’s website. Patients who are taking a phosphodiesterase-5 enzyme inhibitor for ED may continue taking the medication, although they may no longer need it or they may be able to reduce the dose after treatment with the app, it says.

Kranus also has virtual treatments for incontinence in women and voiding dysfunction.

The app is meant to save doctors time by providing patients with detailed explanations and guidance within the app itself, said Laura Wiemer, MD, senior medical director of Kranus.

The app’s modules help reinforce guideline-recommended approaches to the treatment of ED “in playful ways with awards, motivational messages, and individual adjustments to help achieve better adherence and compliance of the patient,” Dr. Wiemer told this news organization.

Kranus plans to expand to the United States in 2024, she said.

A version of this article appeared on Medscape.com.

Little blue pill meets a little blue light.

A digital application can improve erectile function, according to new research presented at the European Association of Urology (EAU) Annual Congress on April 8, 2024.

Researchers developed a 12-week, self-managed program to treat erectile dysfunction (ED). The program is delivered to patients’ mobile devices and encourages users to do cardiovascular training, pelvic floor exercises, and physiotherapy. It also provides information about ED, sexual therapy, and stress management.

“The treatment of ED through physical activity and/or lifestyle changes is recommended in current European guidelines but is not well established in clinical practice,” according to the researchers.

App or Waitlist

The app, known as Kranus Edera, was created by Kranus Health. It is available by prescription in Germany and France.

To study the effectiveness of the app, investigators conducted a randomized controlled trial at the University Hospital Münster in Germany.

The study included 241 men who had scores of 21 or less on the International Index of Erectile Function (IIEF-5).

About half of the participants were randomly assigned to get the app. The rest were placed on a waiting list for the technology and served as a control group.

After 12 weeks, those who received the app reported significantly greater improvement on the IIEF-5, with a gain of 4.5 points vs a 0.2-point improvement for men in the control group (P < .0001).

Men who received the app also reported gains in measures of quality of life (20.5 vs −0.04) and patient activation (11.1 vs 0.64).

Nearly nine in 10 people who used the app did so several times per week, the researchers reported.

Sabine Kliesch, MD, with University Hospital Münster, led the study, which was presented at a poster session on April 8 at the EAU Congress in Paris.

Fully Reimbursed in Germany

In Germany, Kranus Edera has been included on a government list of digital health apps that are fully reimbursed by insurers, partly based on the results of the clinical trial. The cost there is €235 (about $255).

Patients typically notice improvements in 2-4 weeks, according to the company’s website. Patients who are taking a phosphodiesterase-5 enzyme inhibitor for ED may continue taking the medication, although they may no longer need it or they may be able to reduce the dose after treatment with the app, it says.

Kranus also has virtual treatments for incontinence in women and voiding dysfunction.

The app is meant to save doctors time by providing patients with detailed explanations and guidance within the app itself, said Laura Wiemer, MD, senior medical director of Kranus.

The app’s modules help reinforce guideline-recommended approaches to the treatment of ED “in playful ways with awards, motivational messages, and individual adjustments to help achieve better adherence and compliance of the patient,” Dr. Wiemer told this news organization.

Kranus plans to expand to the United States in 2024, she said.

A version of this article appeared on Medscape.com.

Little blue pill meets a little blue light.

A digital application can improve erectile function, according to new research presented at the European Association of Urology (EAU) Annual Congress on April 8, 2024.

Researchers developed a 12-week, self-managed program to treat erectile dysfunction (ED). The program is delivered to patients’ mobile devices and encourages users to do cardiovascular training, pelvic floor exercises, and physiotherapy. It also provides information about ED, sexual therapy, and stress management.

“The treatment of ED through physical activity and/or lifestyle changes is recommended in current European guidelines but is not well established in clinical practice,” according to the researchers.

App or Waitlist

The app, known as Kranus Edera, was created by Kranus Health. It is available by prescription in Germany and France.

To study the effectiveness of the app, investigators conducted a randomized controlled trial at the University Hospital Münster in Germany.

The study included 241 men who had scores of 21 or less on the International Index of Erectile Function (IIEF-5).

About half of the participants were randomly assigned to get the app. The rest were placed on a waiting list for the technology and served as a control group.

After 12 weeks, those who received the app reported significantly greater improvement on the IIEF-5, with a gain of 4.5 points vs a 0.2-point improvement for men in the control group (P < .0001).

Men who received the app also reported gains in measures of quality of life (20.5 vs −0.04) and patient activation (11.1 vs 0.64).

Nearly nine in 10 people who used the app did so several times per week, the researchers reported.

Sabine Kliesch, MD, with University Hospital Münster, led the study, which was presented at a poster session on April 8 at the EAU Congress in Paris.

Fully Reimbursed in Germany

In Germany, Kranus Edera has been included on a government list of digital health apps that are fully reimbursed by insurers, partly based on the results of the clinical trial. The cost there is €235 (about $255).

Patients typically notice improvements in 2-4 weeks, according to the company’s website. Patients who are taking a phosphodiesterase-5 enzyme inhibitor for ED may continue taking the medication, although they may no longer need it or they may be able to reduce the dose after treatment with the app, it says.

Kranus also has virtual treatments for incontinence in women and voiding dysfunction.

The app is meant to save doctors time by providing patients with detailed explanations and guidance within the app itself, said Laura Wiemer, MD, senior medical director of Kranus.

The app’s modules help reinforce guideline-recommended approaches to the treatment of ED “in playful ways with awards, motivational messages, and individual adjustments to help achieve better adherence and compliance of the patient,” Dr. Wiemer told this news organization.

Kranus plans to expand to the United States in 2024, she said.

A version of this article appeared on Medscape.com.