Arrhythmias & EP

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.

There was no difference in risk between individual DOAC medications.

The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.

Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.

The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.

According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).

Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.

Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.

“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.

The study is limited by the potential for residual confounding, the investigators noted.

The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.

The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.

There was no difference in risk between individual DOAC medications.

The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.

Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.

The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.

According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).

Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.

Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.

“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.

The study is limited by the potential for residual confounding, the investigators noted.

The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.

The direct oral anticoagulant (DOAC) drugs apixaban, dabigatran, and rivaroxaban are associated with a lower risk of osteoporotic fracture than is warfarin in patients with atrial fibrillation (AFib), according to a new retrospective analysis.

There was no difference in risk between individual DOAC medications.

The study drew from an EHR database of the Hong Kong Hospital Authority. It was led by Wallis C.Y. Lau, PhD, of the University of Hong Kong and appeared online May 19 in Annals of Internal Medicine.

Warfarin is suspected to contribute to osteoporotic fracturing in AFib patients, but previous studies returned mixed results. The more recently introduced DOACs were not tested for fracture risks, and it hasn’t been determined if individual DOACs have different risks. The question is even more important in AFib, in which patients are older and often have comorbidities that could predispose them to fractures.

The study included 23,515 patients with AFib who used anticoagulants. 3,241 used apixaban, 6,867 dabigatran, 3,866 rivaroxaban, and 9,541 used warfarin. The median follow-up was 423 days.

According to Cox proportional hazards model analyses, DOAC use was associated with fewer fractures than was warfarin (hazard ratio for apixaban vs. warfarin, 0.62; 95% confidence interval, 0.41-0.94; HR for dabigatran, 0.65; 95% CI, 0.49-0.86; HR for rivaroxaban, 0.52; 95% CI, 0.37-0.73). Subanalyses in men and women showed similar results (P for interaction >.05).

Head-to-head comparisons between individual DOACs yielded no statistically significant differences in osteoporotic fracture risk.

Although the findings couldn’t absolutely rule out a difference in osteoporotic fracture risk between different DOACs, the authors argue that any clinical significance would likely be small.

“Given the supportive evidence from experimental settings, findings from our study using clinical data, and the indirect evidence provided by the previous meta-analysis of randomized, controlled trials, there exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” the authors wrote.

The study is limited by the potential for residual confounding, the investigators noted.

The study was funded by the University of Hong Kong and University College London Strategic Partnership Fund.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 19. doi: 10.7326/M19-3671.

Among patients with atrial fibrillation, use of direct oral anticoagulants is linked to lower osteoporotic fracture risk versus warfarin, results of a recent population-based cohort study show.

iStock/Thinkstock

The choice of direct oral anticoagulant (DOAC) didn’t appear to have an impact, as each individual agent yielded a substantially lower risk of fracture versus the vitamin K antagonist, with risk reductions ranging from 38% to 48%, according to the study authors.

This is one of the latest reports to suggest DOACs could have an edge over warfarin for preventing fractures, providing new evidence that “may help inform the benefit risk assessment” when it comes to choosing an anticoagulant for a patient with atrial fibrillation (AFib) in the clinic, wrote the authors, led by Wallis C.Y. Lau, PhD, with the University College London.

“There exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” Dr. Lau and coauthors wrote in a report on the study that appears in Annals of Internal Medicine.

The case is especially compelling since fracture risk is “often neglected” when choosing an anticoagulant, the authors wrote. Surgeries to treat fracture are difficult because of the need for perioperative management of anticoagulation as “a balance between the risk for stroke and excessive bleeding must be achieved,” they added.

Based on these data, physicians should strongly consider DOACs as an alternative to vitamin K antagonists to reduce the risk of osteoporosis over the long term in patients with AFib, according to Victor Lawrence Roberts, MD, a Florida endocrinologist.

“Osteoporosis takes years, sometimes decades to develop, and if you then overlay warfarin on top of a readily evolving metabolic bone disease, you probably accelerate that process, said Dr. Roberts, professor of internal medicine at the University of Central Florida, Orlando, and editorial advisory board member of Internal Medicine News.

There’s a considerable amount of concerning preclinical data that warfarin could increase osteoporotic fracture risk. Of note, vitamin K antagonists modulate osteocalcin, a calcium-binding bone matrix protein, Dr. Roberts said.

“Osteocalcin is important for bone metabolism and health, and inhibiting osteocalcin will inhibit the ability to have a healthy bone matrix,” he explained.

The impact of anticoagulants on fracture risk is particularly relevant to patients with AFib, according to Dr. Lau and colleagues, who referenced one 2017 report showing a higher incidence of hip fracture among AFib patients versus those without AFib.

In their more recent study, Dr. Lau and colleagues reviewed electronic health records in a Hong Kong database for 23,515 older adults with a new diagnosis of AFib who received a new prescription of warfarin or DOACs including apixaban, dabigatran, or rivaroxaban.

DOAC use was consistently associated with a lower risk of osteoporotic fractures versus warfarin, regardless of the DOAC considered. The hazard ratios were 0.62 (95% confidence interval, 0.41-0.94) for apixaban, 0.65 (95% CI, 0.49-0.86) for dabigatran, and 0.52 (95% CI, 0.37-0.73) for rivaroxaban versus warfarin, the report showed.

Head-to-head comparisons between DOACS didn’t yield any statistically significant differences, though the analyses were underpowered in this respect, according to the investigators.

“This study can only rule out more than a twofold higher or a 50% lower relative risk for osteoporotic fractures between individual DOACs,” they wrote. “However, any absolute risk differences were small and would likely be of minor clinical significance.”

The reduced risk of fracture for DOACs versus warfarin was consistent in men and women with AFib, suggesting that women may particularly benefit from DOACs, given that they have a higher risk of fracture than men, the investigators added.

The results of this study suggest yet another benefit of DOACs over warfarin in patients with AFib, according to internist Noel Deep, MD, who is the chief medical officer of Aspirus Langlade Hospital in Antigo, Wisconsin.

“The lower risk of osteoporotic fractures with DOACS, in addition to other advantages such as lower risk of intracranial bleeding, once- or twice-daily consistent dosing, no dietary restrictions, and no blood tests to regulate the dose might be another reason that physicians may favor them over warfarin in older individuals requiring anticoagulation,” Dr. Deep said in an interview.

Results of this and several other recent studies may help in recommending DOACs to internal medicine patients who have a diagnosis of AFib requiring anticoagulation, according to Dr. Deep, who is also a physician at Aspirus Antigo Clinic and a member of Internal Medicine News’ editorial advisory board. These include a 2019 U.S.-based study of more than 167,000 patients with AFib (JAMA Intern Med. 2019;180[2]:245‐253) showing that use of DOACs, particularly apixaban, were linked to lower fracture risk versus warfarin use. Similarly, a Danish national registry study also published in 2019 showed that the absolute risk of osteoporotic fractures was low overall and significantly lower in patients who received DOACs (J Am Coll Cardiol. 2019;74[17]:2150-2158).

Funding for the study came from the University of Hong Kong and University College London Strategic Planning Fund. The study authors reported disclosures related to Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, IQVIA, and others.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 18. doi: 10.7326/M19-3671.

Among patients with atrial fibrillation, use of direct oral anticoagulants is linked to lower osteoporotic fracture risk versus warfarin, results of a recent population-based cohort study show.

iStock/Thinkstock

The choice of direct oral anticoagulant (DOAC) didn’t appear to have an impact, as each individual agent yielded a substantially lower risk of fracture versus the vitamin K antagonist, with risk reductions ranging from 38% to 48%, according to the study authors.

This is one of the latest reports to suggest DOACs could have an edge over warfarin for preventing fractures, providing new evidence that “may help inform the benefit risk assessment” when it comes to choosing an anticoagulant for a patient with atrial fibrillation (AFib) in the clinic, wrote the authors, led by Wallis C.Y. Lau, PhD, with the University College London.

“There exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” Dr. Lau and coauthors wrote in a report on the study that appears in Annals of Internal Medicine.

The case is especially compelling since fracture risk is “often neglected” when choosing an anticoagulant, the authors wrote. Surgeries to treat fracture are difficult because of the need for perioperative management of anticoagulation as “a balance between the risk for stroke and excessive bleeding must be achieved,” they added.

Based on these data, physicians should strongly consider DOACs as an alternative to vitamin K antagonists to reduce the risk of osteoporosis over the long term in patients with AFib, according to Victor Lawrence Roberts, MD, a Florida endocrinologist.

“Osteoporosis takes years, sometimes decades to develop, and if you then overlay warfarin on top of a readily evolving metabolic bone disease, you probably accelerate that process, said Dr. Roberts, professor of internal medicine at the University of Central Florida, Orlando, and editorial advisory board member of Internal Medicine News.

There’s a considerable amount of concerning preclinical data that warfarin could increase osteoporotic fracture risk. Of note, vitamin K antagonists modulate osteocalcin, a calcium-binding bone matrix protein, Dr. Roberts said.

“Osteocalcin is important for bone metabolism and health, and inhibiting osteocalcin will inhibit the ability to have a healthy bone matrix,” he explained.

The impact of anticoagulants on fracture risk is particularly relevant to patients with AFib, according to Dr. Lau and colleagues, who referenced one 2017 report showing a higher incidence of hip fracture among AFib patients versus those without AFib.

In their more recent study, Dr. Lau and colleagues reviewed electronic health records in a Hong Kong database for 23,515 older adults with a new diagnosis of AFib who received a new prescription of warfarin or DOACs including apixaban, dabigatran, or rivaroxaban.

DOAC use was consistently associated with a lower risk of osteoporotic fractures versus warfarin, regardless of the DOAC considered. The hazard ratios were 0.62 (95% confidence interval, 0.41-0.94) for apixaban, 0.65 (95% CI, 0.49-0.86) for dabigatran, and 0.52 (95% CI, 0.37-0.73) for rivaroxaban versus warfarin, the report showed.

Head-to-head comparisons between DOACS didn’t yield any statistically significant differences, though the analyses were underpowered in this respect, according to the investigators.

“This study can only rule out more than a twofold higher or a 50% lower relative risk for osteoporotic fractures between individual DOACs,” they wrote. “However, any absolute risk differences were small and would likely be of minor clinical significance.”

The reduced risk of fracture for DOACs versus warfarin was consistent in men and women with AFib, suggesting that women may particularly benefit from DOACs, given that they have a higher risk of fracture than men, the investigators added.

The results of this study suggest yet another benefit of DOACs over warfarin in patients with AFib, according to internist Noel Deep, MD, who is the chief medical officer of Aspirus Langlade Hospital in Antigo, Wisconsin.

“The lower risk of osteoporotic fractures with DOACS, in addition to other advantages such as lower risk of intracranial bleeding, once- or twice-daily consistent dosing, no dietary restrictions, and no blood tests to regulate the dose might be another reason that physicians may favor them over warfarin in older individuals requiring anticoagulation,” Dr. Deep said in an interview.

Results of this and several other recent studies may help in recommending DOACs to internal medicine patients who have a diagnosis of AFib requiring anticoagulation, according to Dr. Deep, who is also a physician at Aspirus Antigo Clinic and a member of Internal Medicine News’ editorial advisory board. These include a 2019 U.S.-based study of more than 167,000 patients with AFib (JAMA Intern Med. 2019;180[2]:245‐253) showing that use of DOACs, particularly apixaban, were linked to lower fracture risk versus warfarin use. Similarly, a Danish national registry study also published in 2019 showed that the absolute risk of osteoporotic fractures was low overall and significantly lower in patients who received DOACs (J Am Coll Cardiol. 2019;74[17]:2150-2158).

Funding for the study came from the University of Hong Kong and University College London Strategic Planning Fund. The study authors reported disclosures related to Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, IQVIA, and others.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 18. doi: 10.7326/M19-3671.

Among patients with atrial fibrillation, use of direct oral anticoagulants is linked to lower osteoporotic fracture risk versus warfarin, results of a recent population-based cohort study show.

iStock/Thinkstock

The choice of direct oral anticoagulant (DOAC) didn’t appear to have an impact, as each individual agent yielded a substantially lower risk of fracture versus the vitamin K antagonist, with risk reductions ranging from 38% to 48%, according to the study authors.

This is one of the latest reports to suggest DOACs could have an edge over warfarin for preventing fractures, providing new evidence that “may help inform the benefit risk assessment” when it comes to choosing an anticoagulant for a patient with atrial fibrillation (AFib) in the clinic, wrote the authors, led by Wallis C.Y. Lau, PhD, with the University College London.

“There exists a compelling case for evaluating whether the risk for osteoporotic fractures should be considered at the point of prescribing an oral anticoagulant to minimize fracture risk,” Dr. Lau and coauthors wrote in a report on the study that appears in Annals of Internal Medicine.

The case is especially compelling since fracture risk is “often neglected” when choosing an anticoagulant, the authors wrote. Surgeries to treat fracture are difficult because of the need for perioperative management of anticoagulation as “a balance between the risk for stroke and excessive bleeding must be achieved,” they added.

Based on these data, physicians should strongly consider DOACs as an alternative to vitamin K antagonists to reduce the risk of osteoporosis over the long term in patients with AFib, according to Victor Lawrence Roberts, MD, a Florida endocrinologist.

“Osteoporosis takes years, sometimes decades to develop, and if you then overlay warfarin on top of a readily evolving metabolic bone disease, you probably accelerate that process, said Dr. Roberts, professor of internal medicine at the University of Central Florida, Orlando, and editorial advisory board member of Internal Medicine News.

There’s a considerable amount of concerning preclinical data that warfarin could increase osteoporotic fracture risk. Of note, vitamin K antagonists modulate osteocalcin, a calcium-binding bone matrix protein, Dr. Roberts said.

“Osteocalcin is important for bone metabolism and health, and inhibiting osteocalcin will inhibit the ability to have a healthy bone matrix,” he explained.

The impact of anticoagulants on fracture risk is particularly relevant to patients with AFib, according to Dr. Lau and colleagues, who referenced one 2017 report showing a higher incidence of hip fracture among AFib patients versus those without AFib.

In their more recent study, Dr. Lau and colleagues reviewed electronic health records in a Hong Kong database for 23,515 older adults with a new diagnosis of AFib who received a new prescription of warfarin or DOACs including apixaban, dabigatran, or rivaroxaban.

DOAC use was consistently associated with a lower risk of osteoporotic fractures versus warfarin, regardless of the DOAC considered. The hazard ratios were 0.62 (95% confidence interval, 0.41-0.94) for apixaban, 0.65 (95% CI, 0.49-0.86) for dabigatran, and 0.52 (95% CI, 0.37-0.73) for rivaroxaban versus warfarin, the report showed.

Head-to-head comparisons between DOACS didn’t yield any statistically significant differences, though the analyses were underpowered in this respect, according to the investigators.

“This study can only rule out more than a twofold higher or a 50% lower relative risk for osteoporotic fractures between individual DOACs,” they wrote. “However, any absolute risk differences were small and would likely be of minor clinical significance.”

The reduced risk of fracture for DOACs versus warfarin was consistent in men and women with AFib, suggesting that women may particularly benefit from DOACs, given that they have a higher risk of fracture than men, the investigators added.

The results of this study suggest yet another benefit of DOACs over warfarin in patients with AFib, according to internist Noel Deep, MD, who is the chief medical officer of Aspirus Langlade Hospital in Antigo, Wisconsin.

“The lower risk of osteoporotic fractures with DOACS, in addition to other advantages such as lower risk of intracranial bleeding, once- or twice-daily consistent dosing, no dietary restrictions, and no blood tests to regulate the dose might be another reason that physicians may favor them over warfarin in older individuals requiring anticoagulation,” Dr. Deep said in an interview.

Results of this and several other recent studies may help in recommending DOACs to internal medicine patients who have a diagnosis of AFib requiring anticoagulation, according to Dr. Deep, who is also a physician at Aspirus Antigo Clinic and a member of Internal Medicine News’ editorial advisory board. These include a 2019 U.S.-based study of more than 167,000 patients with AFib (JAMA Intern Med. 2019;180[2]:245‐253) showing that use of DOACs, particularly apixaban, were linked to lower fracture risk versus warfarin use. Similarly, a Danish national registry study also published in 2019 showed that the absolute risk of osteoporotic fractures was low overall and significantly lower in patients who received DOACs (J Am Coll Cardiol. 2019;74[17]:2150-2158).

Funding for the study came from the University of Hong Kong and University College London Strategic Planning Fund. The study authors reported disclosures related to Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, IQVIA, and others.

SOURCE: Lau WCY et al. Ann Intern Med. 2020 May 18. doi: 10.7326/M19-3671.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.

“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.

“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.

In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.

Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.

“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.

In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.

Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.

[email protected]

Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.

“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.

“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.

In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.

Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.

“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.

In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.

Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.

[email protected]

Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.

“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.

“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.

In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.

Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.

“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.

In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.

Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.

[email protected]

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

The implantable defibrillator with subcutaneous leads, designed in part to minimize the risk for potentially serious lead-related complications, has reached a milestone by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.

Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.

At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.

The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.

Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.

“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.

“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.

This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.

In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.

A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.

“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”

In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”

Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.

The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.

The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.

The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.

Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.

The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
 

This article first appeared on Medscape.com.

Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.

The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.

“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.

Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.

This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.

These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.

“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.

The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.

Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.

Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.

SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.

[email protected]

Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.

The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.

“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.

Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.

This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.

These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.

“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.

The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.

Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.

Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.

SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.

[email protected]

Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.

The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.

“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.

Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.

This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.

These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.

“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.

The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.

Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.

Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.

SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.

[email protected]

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

[email protected]

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

[email protected]

Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.

The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.

The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
 

S-ICDs maintain ‘niche’ status despite advantages

The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.

“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”

The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”

“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
 

Device improvements boost performance

The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.

The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.

In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.

“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”

UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.

[email protected]

Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.

“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.

“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.

Evidence builds for coffee’s safety

The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”

“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
 

What the study did

The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.

The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.

The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.

A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
 

What it tells us

While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”

“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.

The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.

[email protected]

SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.

Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.

“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.

“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.

Evidence builds for coffee’s safety

The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”

“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
 

What the study did

The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.

The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.

The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.

A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
 

What it tells us

While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”

“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.

The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.

[email protected]

SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.

Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.

“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.

“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.

Evidence builds for coffee’s safety

The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”

“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
 

What the study did

The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.

The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.

The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.

A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
 

What it tells us

While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”

“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.

The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.

[email protected]

SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.

As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.

The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.

“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.

The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.

The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.

“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”

The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.

“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”

The document also includes eight guiding principles such as:
 

• The expectation that response levels will be different between regions, and even within a given region.
• A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
• A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
• In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.

Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.

Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”

As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”

Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.

“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”

That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.

The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.

“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.

Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.

“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”

“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.

Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.

“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”

Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.

Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.

“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?

“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”

Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.

This article first appeared on Medscape.com.