Ted Bosworth

CHICAGO – Renal denervation, relative to a sham procedure, was linked with statistically significant reductions in blood pressure in the newly completed SPYRAL HTN–ON MED trial, but several factors are likely to have worked in concert to prevent the study from meeting its primary endpoint.

Of these differences, probably none was more important than the substantially higher proportion of patients in the sham group that received additional BP-lowering medications over the course of the study, David E. Kandzari, MD, reported at the American Heart Association scientific sessions.

Ted Bosworth/MDedge News

The SPYRAL HTN–ON MED pivotal trial followed the previously completed SPYRAL HTN–ON MED pilot study, which did show a significant BP-lowering effect on antihypertensive medications followed radiofrequency denervation. In a recent update of the pilot study, the effect was persistent out to 3 years.

In the SPYRAL HTN–ON MED program, patients on their second screening visit were required to have a systolic pressure of between 140 and 170 mm Hg on 24-hour ambulatory BP monitoring (ABPM) while taking up to three antihypertensive medications. Patients who entered the study were randomized to renal denervation or sham control while maintaining their baseline antihypertensive therapies.

The previously reported pilot study comprised 80 patients. The expansion pivotal trial added 257 more patients for a total cohort of 337 patients. The primary efficacy endpoint was based on a Bayesian analysis of change in 24-hour systolic ABPM at 6 months for those in the experimental arm versus those on medications alone. Participants from both the pilot and pivotal trials were included.

The prespecified definition of success for renal denervation was a 97.5% threshold for probability of superiority on the basis of this Bayesian analysis. However, the Bayesian analysis was distorted by differences in the pilot and expansion cohorts, which complicated the superiority calculation. As a result, the analysis only yielded a 51% probability of superiority, a level substantially below the predefined threshold.

Despite differences seen in BP control in favor of renal denervation, several factors were identified that likely contributed to the missed primary endpoint. One stood out.

“Significant differences in medication prescriptions were disproportionate in favor of the sham group,” reported Dr. Kandzari, chief of Piedmont Heart Institute, Atlanta. He said these differences, which were a violation of the protocol mandate, led to a “bias toward the null” for the primary outcome.

The failure to meet the primary outcome was particularly disappointing in the wake of the favorable pilot study and the SPYRAL HTN–OFF MED pivotal trial, which were both positive.

In the pilot study, which did not have a medication imbalance, a 7.3–mm Hg reduction (P = .004) in 24-hour ABPM was seen at 6 months. Relative reductions in office-based systolic pressure reductions for renal denervation versus sham were 6.6 mm Hg (P = .03) and 4.0 mm Hg (P = .03) for the pilot and expansions groups, respectively.

On the basis of a Win ratio derived from a hierarchical analysis of ABMP and medication burden reduction, the 1.50 advantage (P = .005) for the renal denervation arm in the newly completed SPYRAL HTN–ON MED trial was also compelling.

At study entry, the median number of medications was 1.9 in both the renal denervation and sham arms. At the end of 6 months, the median number of medications was unchanged in the experimental arm but rose to 2.1 (P = .01) in the sham group. Similarly, there was little change in the medication burden from the start to the end of the trial in the denervation group (2.8 vs. 3.0), but a statistically significant change in the sham group (2.9 vs. 3.5; P = .04).

Furthermore, the net percentage change of patients receiving medications favoring BP reduction over the course of the study did not differ between the experimental and control arms of the pilot cohort, but was more than 10 times higher among controls in the expansion group (1.9% vs. 21.8%; P < .0001).

Medication changes over the course of the SPYRAL HTN–ON MED trial were even greater in some specific subgroups. Among Black participants, for example, 14.2% of those randomized to renal denervation and 54.6% of those randomized to the sham group increased their antihypertensive therapies over the course of the study.

The COVID-19 epidemic is suspected of playing another role in the negative results, according to Dr. Kandzari. After a brief pause in enrollment, the SPYRAL HTN–ON MED trial was resumed, but approximately 80% of the expansion cohort data were collected during this period. When compared, variances in office and 24-hour ABPM were observed for participants who were or were not evaluated during COVID.

“Significant differences in 24-hour ABPM patterns pre- and during COVID may reflect changes in patient behavior and lifestyle,” Dr. Kandzari speculated.

The data from this study differ from essentially all of the other studies in the SPYRAL HTN program as well as several other sham-controlled studies with renal denervation, according to Dr. Kandzari.

Ted Bosworth/MDedge News

The AHA-invited discussant, Ajay J. Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, largely agreed that several variables appeared to conspire against a positive result in this trial, but he zeroed in on the imbalance of antihypertensive medications.

“Any trial that attempts to show a difference between renal denervation and a sham procedure must insure that antihypertensive medications are the same in the two arms. They cannot be different,” he said.

As an active investigator in the field of renal denervation, Dr. Kirtane thinks the evidence does support a benefit from renal denervation, but he believes data are still needed to determine which patients are candidates.

“Renal denervation is not going to be a replacement for previous established therapies, but it will be an adjunct,” he predicted. The preponderance of evidence supports clinically meaningful reductions in BP with this approach, “but we need to determine who to consider [for this therapy] and to have realistic expectations about the degree of benefit.”

Dr. Kandzari reported financial relationships with Abbott Vascular, Ablative Solutions, Biotronik, Boston Scientific, CSI, Medtronic Cardiovascular, OrbusNeich, and Teleflex. Dr. Kirtane reported financial relationships with Abbott Vascular, Abiomed, Boston Scientific, Cardiovascular Systems, Cathworks, Chiesi, Medtronic, Opens, Philipps, Regeneron, ReCor Medical, Siemens, Spectranetics, and Zoll.
 

CHICAGO – Renal denervation, relative to a sham procedure, was linked with statistically significant reductions in blood pressure in the newly completed SPYRAL HTN–ON MED trial, but several factors are likely to have worked in concert to prevent the study from meeting its primary endpoint.

Of these differences, probably none was more important than the substantially higher proportion of patients in the sham group that received additional BP-lowering medications over the course of the study, David E. Kandzari, MD, reported at the American Heart Association scientific sessions.

Ted Bosworth/MDedge News

The SPYRAL HTN–ON MED pivotal trial followed the previously completed SPYRAL HTN–ON MED pilot study, which did show a significant BP-lowering effect on antihypertensive medications followed radiofrequency denervation. In a recent update of the pilot study, the effect was persistent out to 3 years.

In the SPYRAL HTN–ON MED program, patients on their second screening visit were required to have a systolic pressure of between 140 and 170 mm Hg on 24-hour ambulatory BP monitoring (ABPM) while taking up to three antihypertensive medications. Patients who entered the study were randomized to renal denervation or sham control while maintaining their baseline antihypertensive therapies.

The previously reported pilot study comprised 80 patients. The expansion pivotal trial added 257 more patients for a total cohort of 337 patients. The primary efficacy endpoint was based on a Bayesian analysis of change in 24-hour systolic ABPM at 6 months for those in the experimental arm versus those on medications alone. Participants from both the pilot and pivotal trials were included.

The prespecified definition of success for renal denervation was a 97.5% threshold for probability of superiority on the basis of this Bayesian analysis. However, the Bayesian analysis was distorted by differences in the pilot and expansion cohorts, which complicated the superiority calculation. As a result, the analysis only yielded a 51% probability of superiority, a level substantially below the predefined threshold.

Despite differences seen in BP control in favor of renal denervation, several factors were identified that likely contributed to the missed primary endpoint. One stood out.

“Significant differences in medication prescriptions were disproportionate in favor of the sham group,” reported Dr. Kandzari, chief of Piedmont Heart Institute, Atlanta. He said these differences, which were a violation of the protocol mandate, led to a “bias toward the null” for the primary outcome.

The failure to meet the primary outcome was particularly disappointing in the wake of the favorable pilot study and the SPYRAL HTN–OFF MED pivotal trial, which were both positive.

In the pilot study, which did not have a medication imbalance, a 7.3–mm Hg reduction (P = .004) in 24-hour ABPM was seen at 6 months. Relative reductions in office-based systolic pressure reductions for renal denervation versus sham were 6.6 mm Hg (P = .03) and 4.0 mm Hg (P = .03) for the pilot and expansions groups, respectively.

On the basis of a Win ratio derived from a hierarchical analysis of ABMP and medication burden reduction, the 1.50 advantage (P = .005) for the renal denervation arm in the newly completed SPYRAL HTN–ON MED trial was also compelling.

At study entry, the median number of medications was 1.9 in both the renal denervation and sham arms. At the end of 6 months, the median number of medications was unchanged in the experimental arm but rose to 2.1 (P = .01) in the sham group. Similarly, there was little change in the medication burden from the start to the end of the trial in the denervation group (2.8 vs. 3.0), but a statistically significant change in the sham group (2.9 vs. 3.5; P = .04).

Furthermore, the net percentage change of patients receiving medications favoring BP reduction over the course of the study did not differ between the experimental and control arms of the pilot cohort, but was more than 10 times higher among controls in the expansion group (1.9% vs. 21.8%; P < .0001).

Medication changes over the course of the SPYRAL HTN–ON MED trial were even greater in some specific subgroups. Among Black participants, for example, 14.2% of those randomized to renal denervation and 54.6% of those randomized to the sham group increased their antihypertensive therapies over the course of the study.

The COVID-19 epidemic is suspected of playing another role in the negative results, according to Dr. Kandzari. After a brief pause in enrollment, the SPYRAL HTN–ON MED trial was resumed, but approximately 80% of the expansion cohort data were collected during this period. When compared, variances in office and 24-hour ABPM were observed for participants who were or were not evaluated during COVID.

“Significant differences in 24-hour ABPM patterns pre- and during COVID may reflect changes in patient behavior and lifestyle,” Dr. Kandzari speculated.

The data from this study differ from essentially all of the other studies in the SPYRAL HTN program as well as several other sham-controlled studies with renal denervation, according to Dr. Kandzari.

Ted Bosworth/MDedge News

The AHA-invited discussant, Ajay J. Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, largely agreed that several variables appeared to conspire against a positive result in this trial, but he zeroed in on the imbalance of antihypertensive medications.

“Any trial that attempts to show a difference between renal denervation and a sham procedure must insure that antihypertensive medications are the same in the two arms. They cannot be different,” he said.

As an active investigator in the field of renal denervation, Dr. Kirtane thinks the evidence does support a benefit from renal denervation, but he believes data are still needed to determine which patients are candidates.

“Renal denervation is not going to be a replacement for previous established therapies, but it will be an adjunct,” he predicted. The preponderance of evidence supports clinically meaningful reductions in BP with this approach, “but we need to determine who to consider [for this therapy] and to have realistic expectations about the degree of benefit.”

Dr. Kandzari reported financial relationships with Abbott Vascular, Ablative Solutions, Biotronik, Boston Scientific, CSI, Medtronic Cardiovascular, OrbusNeich, and Teleflex. Dr. Kirtane reported financial relationships with Abbott Vascular, Abiomed, Boston Scientific, Cardiovascular Systems, Cathworks, Chiesi, Medtronic, Opens, Philipps, Regeneron, ReCor Medical, Siemens, Spectranetics, and Zoll.
 

CHICAGO – Renal denervation, relative to a sham procedure, was linked with statistically significant reductions in blood pressure in the newly completed SPYRAL HTN–ON MED trial, but several factors are likely to have worked in concert to prevent the study from meeting its primary endpoint.

Of these differences, probably none was more important than the substantially higher proportion of patients in the sham group that received additional BP-lowering medications over the course of the study, David E. Kandzari, MD, reported at the American Heart Association scientific sessions.

Ted Bosworth/MDedge News

The SPYRAL HTN–ON MED pivotal trial followed the previously completed SPYRAL HTN–ON MED pilot study, which did show a significant BP-lowering effect on antihypertensive medications followed radiofrequency denervation. In a recent update of the pilot study, the effect was persistent out to 3 years.

In the SPYRAL HTN–ON MED program, patients on their second screening visit were required to have a systolic pressure of between 140 and 170 mm Hg on 24-hour ambulatory BP monitoring (ABPM) while taking up to three antihypertensive medications. Patients who entered the study were randomized to renal denervation or sham control while maintaining their baseline antihypertensive therapies.

The previously reported pilot study comprised 80 patients. The expansion pivotal trial added 257 more patients for a total cohort of 337 patients. The primary efficacy endpoint was based on a Bayesian analysis of change in 24-hour systolic ABPM at 6 months for those in the experimental arm versus those on medications alone. Participants from both the pilot and pivotal trials were included.

The prespecified definition of success for renal denervation was a 97.5% threshold for probability of superiority on the basis of this Bayesian analysis. However, the Bayesian analysis was distorted by differences in the pilot and expansion cohorts, which complicated the superiority calculation. As a result, the analysis only yielded a 51% probability of superiority, a level substantially below the predefined threshold.

Despite differences seen in BP control in favor of renal denervation, several factors were identified that likely contributed to the missed primary endpoint. One stood out.

“Significant differences in medication prescriptions were disproportionate in favor of the sham group,” reported Dr. Kandzari, chief of Piedmont Heart Institute, Atlanta. He said these differences, which were a violation of the protocol mandate, led to a “bias toward the null” for the primary outcome.

The failure to meet the primary outcome was particularly disappointing in the wake of the favorable pilot study and the SPYRAL HTN–OFF MED pivotal trial, which were both positive.

In the pilot study, which did not have a medication imbalance, a 7.3–mm Hg reduction (P = .004) in 24-hour ABPM was seen at 6 months. Relative reductions in office-based systolic pressure reductions for renal denervation versus sham were 6.6 mm Hg (P = .03) and 4.0 mm Hg (P = .03) for the pilot and expansions groups, respectively.

On the basis of a Win ratio derived from a hierarchical analysis of ABMP and medication burden reduction, the 1.50 advantage (P = .005) for the renal denervation arm in the newly completed SPYRAL HTN–ON MED trial was also compelling.

At study entry, the median number of medications was 1.9 in both the renal denervation and sham arms. At the end of 6 months, the median number of medications was unchanged in the experimental arm but rose to 2.1 (P = .01) in the sham group. Similarly, there was little change in the medication burden from the start to the end of the trial in the denervation group (2.8 vs. 3.0), but a statistically significant change in the sham group (2.9 vs. 3.5; P = .04).

Furthermore, the net percentage change of patients receiving medications favoring BP reduction over the course of the study did not differ between the experimental and control arms of the pilot cohort, but was more than 10 times higher among controls in the expansion group (1.9% vs. 21.8%; P < .0001).

Medication changes over the course of the SPYRAL HTN–ON MED trial were even greater in some specific subgroups. Among Black participants, for example, 14.2% of those randomized to renal denervation and 54.6% of those randomized to the sham group increased their antihypertensive therapies over the course of the study.

The COVID-19 epidemic is suspected of playing another role in the negative results, according to Dr. Kandzari. After a brief pause in enrollment, the SPYRAL HTN–ON MED trial was resumed, but approximately 80% of the expansion cohort data were collected during this period. When compared, variances in office and 24-hour ABPM were observed for participants who were or were not evaluated during COVID.

“Significant differences in 24-hour ABPM patterns pre- and during COVID may reflect changes in patient behavior and lifestyle,” Dr. Kandzari speculated.

The data from this study differ from essentially all of the other studies in the SPYRAL HTN program as well as several other sham-controlled studies with renal denervation, according to Dr. Kandzari.

Ted Bosworth/MDedge News

The AHA-invited discussant, Ajay J. Kirtane, MD, director of the Cardiac Catheterization Laboratories at Columbia University, New York, largely agreed that several variables appeared to conspire against a positive result in this trial, but he zeroed in on the imbalance of antihypertensive medications.

“Any trial that attempts to show a difference between renal denervation and a sham procedure must insure that antihypertensive medications are the same in the two arms. They cannot be different,” he said.

As an active investigator in the field of renal denervation, Dr. Kirtane thinks the evidence does support a benefit from renal denervation, but he believes data are still needed to determine which patients are candidates.

“Renal denervation is not going to be a replacement for previous established therapies, but it will be an adjunct,” he predicted. The preponderance of evidence supports clinically meaningful reductions in BP with this approach, “but we need to determine who to consider [for this therapy] and to have realistic expectations about the degree of benefit.”

Dr. Kandzari reported financial relationships with Abbott Vascular, Ablative Solutions, Biotronik, Boston Scientific, CSI, Medtronic Cardiovascular, OrbusNeich, and Teleflex. Dr. Kirtane reported financial relationships with Abbott Vascular, Abiomed, Boston Scientific, Cardiovascular Systems, Cathworks, Chiesi, Medtronic, Opens, Philipps, Regeneron, ReCor Medical, Siemens, Spectranetics, and Zoll.
 

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.

In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.

Ted Bosworth/MDedge News

“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.

The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.

The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
 

Saphenous vein availability determined cohort

Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.

Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.

In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.

The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).

The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).

BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”

The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.

After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).

For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.

The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.

Level 1 evidence provided for intervention choice

Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.

Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.

Ted Bosworth/MDedge News

A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.

In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.

Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
 

Results not necessarily relevant to all

These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.

Ted Bosworth/MDedge News

Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.

In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.

Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.

Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.

Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.

CHICAGO – A stepwise care pathway was associated with a substantial reduction in the number of invasive tests performed and a major improvement in outcomes, relative to usual management, in patients suspected of coronary artery disease (CAD), according to 1-year results of the multinational, randomized PRECISE trial.

The care pathway is appropriate for patients with nonacute chest pain or equivalent complaints that have raised suspicion of CAD, and it is extremely simple, according to the description from the principal investigator, Pamela S. Douglas, MD, given in her presentation at the annual scientific sessions of the American Heart Association.

Ted Bosworth/MDedge News

Unlike the highly complex diagnostic algorithms shunting suspected CAD patients to the vast array of potential evaluations, the newly tested protocol, characterized as a “precision strategy,” divides patients into those who are immediate candidates for invasive testing and those who are not. The discriminator is the PROMISE minimal risk assessment score, a tool already validated.

Those deemed candidates for testing on the basis of an elevated score undergo computed coronary CT angiography (cCTA). In those who are not, testing is deferred.
 

Strategy is simple but effective

Although simple, this pathway is highly effective, judging by the results of the PRECISE trial, which tested the strategy in 2,103 patients at 65 sites in North America and Europe. The primary outcome was a composite of major adverse cardiovascular events (MACE) that included death, nonfatal MI, and catheterization without observed CAD.

After a median follow-up of 11.8 months, the primary MACE endpoint was reached in about 11.3% of those in the usual-care group, which was more than twofold higher than the 4.2% in the precision strategy group. The unadjusted risk reduction was 65% but rose to more than 70% (hazard ratio, 0.29; P < .001) after adjustment for gender and baseline characteristics.

In the arm randomized to the precision strategy, 16% were characterized as low risk and received no further testing. Almost all the others underwent cCTA alone (48%) or cCTA with fractional flow reserve (FFR) (31%). Stress echocardiography, treadmill electrocardiography, and other functional studies were performed in the small proportion of remaining patients.
 

cCTA performed in just 15% of usual care

In the usual-care arm, cCTA with or without FFR was only performed in 15%. More than 80% of patients underwent evaluations with one or more of an array of functional tests. For example, one-third were evaluated with single photon emission CT/PET and nearly as many underwent stress echocardiography testing. Only 7% in usual care underwent no testing after referral.

Within the MACE composite endpoint, almost all the relative benefit in the precision strategy arm was derived from the endpoint of angiography performed without evidence of obstructive CAD (2.6% vs. 10.2%). Rates of all-cause mortality and MI were not significantly different.

Important for the safety and utility of the precision strategy, there “were no deaths or MI events among those assigned deferred testing ” in that experimental arm, according to Dr. Douglas, professor of research in cardiovascular diseases at Duke University, Durham, N.C.

Instead, those in the precision strategy arm were far less likely to undergo catheterization without finding CAD (20% vs. 60%) and far less likely to undergo catheterization without revascularization (28% vs. 70%).

In addition, the group randomized to the precision strategy were more likely to be placed on risk reducing therapies following testing. Although the higher proportion of patients placed on antihypertensive therapy did not reach statistical significance (P = .1), the increased proportions placed on lipid therapy (P < .001) and antiplatelet therapy (P < .001) did.

Citing a study in JAMA Cardiology that found that more than 25% of patients presenting with stable chest pain have normal coronary arteries, Dr. Douglas said that the precision strategy as shown in the PRECISE trial addresses several agreed-upon goals in guidelines from the AHA, the European Society of Cardiology and the U.K.’s National Institute for Health and Care Excellence. These goals include reducing unnecessary testing by risk stratification, improving diagnostic yield of the testing that is performed, and avoiding the costs and complications of unneeded invasive testing.

New protocol called preferred approach

On the basis of these results, Dr. Douglas called the precision strategy “a preferred approach in evaluating patients with stable symptoms and suspected coronary disease.”

Julie Indik, MD, PhD, a professor of medicine at the University of Arizona, Tuscon, said that application of this approach in routine care could have “a major impact on care” by avoiding unnecessary tests with no apparent adverse effect on outcomes.

Although not demonstrated in this study, Dr. Indik suggested that the large number of patients tested for CAD each year – she estimated 4 million visits – means that less testing is likely to have a major impact on the costs of care, and she praised “the practical, efficient” approach of the precision strategy.

Ted Bosworth/MDedge News

Ron Blankstein, MD, director of cardiac computed tomography, Brigham and Women’s Hospital, Boston, also said these data “have both economic and safety implications.” As an AHA-invited discussant of this study, he emphasized that this is a strategy that should only be applied to lower risk patients with no prior history of CAD, but, in this group, he believes these data “will inform future guidelines.”

Dr. Douglas declined to speculate on whether the precision strategy will be incorporated into future guidelines, but she did say that the PRECISE data demonstrate that this approach improves quality of care.

In an interview, Dr. Douglas suggested that this care pathway could provide a basis on which to demonstrate improved outcomes with more efficient use of resources, a common definition of quality care delivery.

Dr. Douglas reported financial relationships with Caption Health, Kowa, and Heartflow, which provided funding for the PRECISE trial. Dr. Indik reported no potential conflicts of interest. Dr. Blankstein reported financial relationships with Amgen, Caristo Diagnostics, and Novartis.

CHICAGO – A stepwise care pathway was associated with a substantial reduction in the number of invasive tests performed and a major improvement in outcomes, relative to usual management, in patients suspected of coronary artery disease (CAD), according to 1-year results of the multinational, randomized PRECISE trial.

The care pathway is appropriate for patients with nonacute chest pain or equivalent complaints that have raised suspicion of CAD, and it is extremely simple, according to the description from the principal investigator, Pamela S. Douglas, MD, given in her presentation at the annual scientific sessions of the American Heart Association.

Ted Bosworth/MDedge News

Unlike the highly complex diagnostic algorithms shunting suspected CAD patients to the vast array of potential evaluations, the newly tested protocol, characterized as a “precision strategy,” divides patients into those who are immediate candidates for invasive testing and those who are not. The discriminator is the PROMISE minimal risk assessment score, a tool already validated.

Those deemed candidates for testing on the basis of an elevated score undergo computed coronary CT angiography (cCTA). In those who are not, testing is deferred.
 

Strategy is simple but effective

Although simple, this pathway is highly effective, judging by the results of the PRECISE trial, which tested the strategy in 2,103 patients at 65 sites in North America and Europe. The primary outcome was a composite of major adverse cardiovascular events (MACE) that included death, nonfatal MI, and catheterization without observed CAD.

After a median follow-up of 11.8 months, the primary MACE endpoint was reached in about 11.3% of those in the usual-care group, which was more than twofold higher than the 4.2% in the precision strategy group. The unadjusted risk reduction was 65% but rose to more than 70% (hazard ratio, 0.29; P < .001) after adjustment for gender and baseline characteristics.

In the arm randomized to the precision strategy, 16% were characterized as low risk and received no further testing. Almost all the others underwent cCTA alone (48%) or cCTA with fractional flow reserve (FFR) (31%). Stress echocardiography, treadmill electrocardiography, and other functional studies were performed in the small proportion of remaining patients.
 

cCTA performed in just 15% of usual care

In the usual-care arm, cCTA with or without FFR was only performed in 15%. More than 80% of patients underwent evaluations with one or more of an array of functional tests. For example, one-third were evaluated with single photon emission CT/PET and nearly as many underwent stress echocardiography testing. Only 7% in usual care underwent no testing after referral.

Within the MACE composite endpoint, almost all the relative benefit in the precision strategy arm was derived from the endpoint of angiography performed without evidence of obstructive CAD (2.6% vs. 10.2%). Rates of all-cause mortality and MI were not significantly different.

Important for the safety and utility of the precision strategy, there “were no deaths or MI events among those assigned deferred testing ” in that experimental arm, according to Dr. Douglas, professor of research in cardiovascular diseases at Duke University, Durham, N.C.

Instead, those in the precision strategy arm were far less likely to undergo catheterization without finding CAD (20% vs. 60%) and far less likely to undergo catheterization without revascularization (28% vs. 70%).

In addition, the group randomized to the precision strategy were more likely to be placed on risk reducing therapies following testing. Although the higher proportion of patients placed on antihypertensive therapy did not reach statistical significance (P = .1), the increased proportions placed on lipid therapy (P < .001) and antiplatelet therapy (P < .001) did.

Citing a study in JAMA Cardiology that found that more than 25% of patients presenting with stable chest pain have normal coronary arteries, Dr. Douglas said that the precision strategy as shown in the PRECISE trial addresses several agreed-upon goals in guidelines from the AHA, the European Society of Cardiology and the U.K.’s National Institute for Health and Care Excellence. These goals include reducing unnecessary testing by risk stratification, improving diagnostic yield of the testing that is performed, and avoiding the costs and complications of unneeded invasive testing.

New protocol called preferred approach

On the basis of these results, Dr. Douglas called the precision strategy “a preferred approach in evaluating patients with stable symptoms and suspected coronary disease.”

Julie Indik, MD, PhD, a professor of medicine at the University of Arizona, Tuscon, said that application of this approach in routine care could have “a major impact on care” by avoiding unnecessary tests with no apparent adverse effect on outcomes.

Although not demonstrated in this study, Dr. Indik suggested that the large number of patients tested for CAD each year – she estimated 4 million visits – means that less testing is likely to have a major impact on the costs of care, and she praised “the practical, efficient” approach of the precision strategy.

Ted Bosworth/MDedge News

Ron Blankstein, MD, director of cardiac computed tomography, Brigham and Women’s Hospital, Boston, also said these data “have both economic and safety implications.” As an AHA-invited discussant of this study, he emphasized that this is a strategy that should only be applied to lower risk patients with no prior history of CAD, but, in this group, he believes these data “will inform future guidelines.”

Dr. Douglas declined to speculate on whether the precision strategy will be incorporated into future guidelines, but she did say that the PRECISE data demonstrate that this approach improves quality of care.

In an interview, Dr. Douglas suggested that this care pathway could provide a basis on which to demonstrate improved outcomes with more efficient use of resources, a common definition of quality care delivery.

Dr. Douglas reported financial relationships with Caption Health, Kowa, and Heartflow, which provided funding for the PRECISE trial. Dr. Indik reported no potential conflicts of interest. Dr. Blankstein reported financial relationships with Amgen, Caristo Diagnostics, and Novartis.

CHICAGO – A stepwise care pathway was associated with a substantial reduction in the number of invasive tests performed and a major improvement in outcomes, relative to usual management, in patients suspected of coronary artery disease (CAD), according to 1-year results of the multinational, randomized PRECISE trial.

The care pathway is appropriate for patients with nonacute chest pain or equivalent complaints that have raised suspicion of CAD, and it is extremely simple, according to the description from the principal investigator, Pamela S. Douglas, MD, given in her presentation at the annual scientific sessions of the American Heart Association.

Ted Bosworth/MDedge News

Unlike the highly complex diagnostic algorithms shunting suspected CAD patients to the vast array of potential evaluations, the newly tested protocol, characterized as a “precision strategy,” divides patients into those who are immediate candidates for invasive testing and those who are not. The discriminator is the PROMISE minimal risk assessment score, a tool already validated.

Those deemed candidates for testing on the basis of an elevated score undergo computed coronary CT angiography (cCTA). In those who are not, testing is deferred.
 

Strategy is simple but effective

Although simple, this pathway is highly effective, judging by the results of the PRECISE trial, which tested the strategy in 2,103 patients at 65 sites in North America and Europe. The primary outcome was a composite of major adverse cardiovascular events (MACE) that included death, nonfatal MI, and catheterization without observed CAD.

After a median follow-up of 11.8 months, the primary MACE endpoint was reached in about 11.3% of those in the usual-care group, which was more than twofold higher than the 4.2% in the precision strategy group. The unadjusted risk reduction was 65% but rose to more than 70% (hazard ratio, 0.29; P < .001) after adjustment for gender and baseline characteristics.

In the arm randomized to the precision strategy, 16% were characterized as low risk and received no further testing. Almost all the others underwent cCTA alone (48%) or cCTA with fractional flow reserve (FFR) (31%). Stress echocardiography, treadmill electrocardiography, and other functional studies were performed in the small proportion of remaining patients.
 

cCTA performed in just 15% of usual care

In the usual-care arm, cCTA with or without FFR was only performed in 15%. More than 80% of patients underwent evaluations with one or more of an array of functional tests. For example, one-third were evaluated with single photon emission CT/PET and nearly as many underwent stress echocardiography testing. Only 7% in usual care underwent no testing after referral.

Within the MACE composite endpoint, almost all the relative benefit in the precision strategy arm was derived from the endpoint of angiography performed without evidence of obstructive CAD (2.6% vs. 10.2%). Rates of all-cause mortality and MI were not significantly different.

Important for the safety and utility of the precision strategy, there “were no deaths or MI events among those assigned deferred testing ” in that experimental arm, according to Dr. Douglas, professor of research in cardiovascular diseases at Duke University, Durham, N.C.

Instead, those in the precision strategy arm were far less likely to undergo catheterization without finding CAD (20% vs. 60%) and far less likely to undergo catheterization without revascularization (28% vs. 70%).

In addition, the group randomized to the precision strategy were more likely to be placed on risk reducing therapies following testing. Although the higher proportion of patients placed on antihypertensive therapy did not reach statistical significance (P = .1), the increased proportions placed on lipid therapy (P < .001) and antiplatelet therapy (P < .001) did.

Citing a study in JAMA Cardiology that found that more than 25% of patients presenting with stable chest pain have normal coronary arteries, Dr. Douglas said that the precision strategy as shown in the PRECISE trial addresses several agreed-upon goals in guidelines from the AHA, the European Society of Cardiology and the U.K.’s National Institute for Health and Care Excellence. These goals include reducing unnecessary testing by risk stratification, improving diagnostic yield of the testing that is performed, and avoiding the costs and complications of unneeded invasive testing.

New protocol called preferred approach

On the basis of these results, Dr. Douglas called the precision strategy “a preferred approach in evaluating patients with stable symptoms and suspected coronary disease.”

Julie Indik, MD, PhD, a professor of medicine at the University of Arizona, Tuscon, said that application of this approach in routine care could have “a major impact on care” by avoiding unnecessary tests with no apparent adverse effect on outcomes.

Although not demonstrated in this study, Dr. Indik suggested that the large number of patients tested for CAD each year – she estimated 4 million visits – means that less testing is likely to have a major impact on the costs of care, and she praised “the practical, efficient” approach of the precision strategy.

Ted Bosworth/MDedge News

Ron Blankstein, MD, director of cardiac computed tomography, Brigham and Women’s Hospital, Boston, also said these data “have both economic and safety implications.” As an AHA-invited discussant of this study, he emphasized that this is a strategy that should only be applied to lower risk patients with no prior history of CAD, but, in this group, he believes these data “will inform future guidelines.”

Dr. Douglas declined to speculate on whether the precision strategy will be incorporated into future guidelines, but she did say that the PRECISE data demonstrate that this approach improves quality of care.

In an interview, Dr. Douglas suggested that this care pathway could provide a basis on which to demonstrate improved outcomes with more efficient use of resources, a common definition of quality care delivery.

Dr. Douglas reported financial relationships with Caption Health, Kowa, and Heartflow, which provided funding for the PRECISE trial. Dr. Indik reported no potential conflicts of interest. Dr. Blankstein reported financial relationships with Amgen, Caristo Diagnostics, and Novartis.

CHICAGO – With more than 15 years of follow-up from two related trials, the best conduit for the second most important target vessel in coronary artery bypass grafting (CABG) appears to be resolved.

The radial artery (RA) graft is linked with a lower risk of major adverse cardiac events (MACE) relative to a saphenous vein (SV) or the free right internal thoracic artery (FRITA).

On the basis of these findings, “a radial artery graft should be considered in all isolated CABG operations unless there are contraindications,” reported David L. Hare, MBBS, director of research in the department of cardiology, University of Melbourne.

For the primary graft, there is general agreement that the left internal thoracic artery (LITA) is the first choice for the left anterior descending vessel, but the optimal graft for the second most important target has never been established, according to Dr. Hare.

Almost 25 years ago, two randomized controlled trials called RAPCO-RITA and RAPCO-SV were initiated to address the question. There is now 15 years of follow-up for both of the RAPCO (Radial Artery Patency and Clinical Outcomes) trials, which were presented together at the American Heart Association scientific sessions.
 

Two trials conducted simultaneously

The RAPCO-RITA trial randomized CABG patients less than 70 years of age (less than 60 years in those with diabetes) to grafting of the second target vessel with an RA or FRITA graft. The RAPCO-SV trial randomized those 70 years or older (60 years or older with diabetes) to an RA or SV graft.

The two primary endpoints were graft patency at 10 years and a composite MACE at 10 years. The assessment of the MACE endpoint, which consisted of cardiovascular mortality, acute myocardial infarction, and coronary revascularization, was later amended to include a comparison at 15 years.

Ten-year patency results, favoring the RA in both studies, were previously published in Circulation. In the new data presented at the meeting, the RA was associated with a significant reduction in MACE relative to the comparator graft in both studies.

“The main driver was a reduction in all-cause mortality,” Dr. Hare reported.

In RAPCO-RITA, 394 patients were randomized with follow-up data available for all but 1 patient at 15 years. Similarly, only 1 patient was lost to follow-up among the 225 randomized in RAPCO-SV. In both studies, baseline characteristics were well balanced.

MACE curves separate at 5 years

In RAPCO-RITA, the MACE survival curves began to separate at about 5 years and then gradually widened. By 15 years, the lower rate of MACE in the RA group (38% vs. 48%) translated into a 26% relative reduction (hazard ratio, 0.74; P = .04).

In RAPCO-SV, the pattern was similar, by 15 years, the rates of MACE were 60% and 73% for the RA and SV groups, respectively, translating into a 29% relative reduction (HR, 0.71; P = .04).

There was no heterogeneity in benefit across prespecified subgroups such as presence or absence of diabetes, gender, or age. In RAPCO-RITA, there was 8% absolute and 31% relative reduction in all-cause mortality. In RAPCO-SV, the absolute and relative reductions were 11% and 26%.

When the trial was initiated, Dr. Hare hypothesized that RITA would prove more durable than RA, so the outcome was not anticipated.

“This is the first randomized controlled trial program to address the question,” said Dr. Hare, who noted that there have been numerous retrospective and case control analyses that have produced mixed results in the past.
 

Discussant praises trial quality

The AHA-invited discussant, Marc Ruel, MD, chair of cardiac surgery, University of Ottawa (Ont.) Heart Institute, called these data “important,” and he congratulated Dr. Hare for conducting the first randomized trial to address the question about second graft durability.

However, he noted that, although the study was randomized, it was not blinded, and he questioned whether postoperative care, in particular, was similar. He also pointed out that the MACE rate seemed high, particularly among the older patients randomized in RAPCO-SV.

“All of the patients were referred to an independently run CABG rehab program that was quite separate from the trial but that provided identical mandated care,” Dr. Hare responded, indicating that there was no opportunity for differences in postprocedural management.

In the United States, the SV graft is often preferred on the basis of easy harvesting and handling characteristics, according to Dr. Hare, who estimated that fewer than 10% of the 200,000 CABG procedures performed in the United States employ the RA conduit for second target vessels. He believes the RAPCO trials data support a change.

“My personal view is [that, on the basis of] this data, given that it is from a controlled trial rather than from patient-level meta-analyses, all isolated CABG operations should be using a radial graft if it is suitable,” Dr. Hare said.

Dr. Hare reports financial relationships with Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, CSL-Biotherapies, Lundbeck, Menarini, Merck, Novartis, Pfizer, Regeneron, Sanofi, Servier, and Vifor. Dr. Ruel reports financial relationships with Cryolife, Edwards, and Medtronic.

CHICAGO – With more than 15 years of follow-up from two related trials, the best conduit for the second most important target vessel in coronary artery bypass grafting (CABG) appears to be resolved.

The radial artery (RA) graft is linked with a lower risk of major adverse cardiac events (MACE) relative to a saphenous vein (SV) or the free right internal thoracic artery (FRITA).

On the basis of these findings, “a radial artery graft should be considered in all isolated CABG operations unless there are contraindications,” reported David L. Hare, MBBS, director of research in the department of cardiology, University of Melbourne.

For the primary graft, there is general agreement that the left internal thoracic artery (LITA) is the first choice for the left anterior descending vessel, but the optimal graft for the second most important target has never been established, according to Dr. Hare.

Almost 25 years ago, two randomized controlled trials called RAPCO-RITA and RAPCO-SV were initiated to address the question. There is now 15 years of follow-up for both of the RAPCO (Radial Artery Patency and Clinical Outcomes) trials, which were presented together at the American Heart Association scientific sessions.
 

Two trials conducted simultaneously

The RAPCO-RITA trial randomized CABG patients less than 70 years of age (less than 60 years in those with diabetes) to grafting of the second target vessel with an RA or FRITA graft. The RAPCO-SV trial randomized those 70 years or older (60 years or older with diabetes) to an RA or SV graft.

The two primary endpoints were graft patency at 10 years and a composite MACE at 10 years. The assessment of the MACE endpoint, which consisted of cardiovascular mortality, acute myocardial infarction, and coronary revascularization, was later amended to include a comparison at 15 years.

Ten-year patency results, favoring the RA in both studies, were previously published in Circulation. In the new data presented at the meeting, the RA was associated with a significant reduction in MACE relative to the comparator graft in both studies.

“The main driver was a reduction in all-cause mortality,” Dr. Hare reported.

In RAPCO-RITA, 394 patients were randomized with follow-up data available for all but 1 patient at 15 years. Similarly, only 1 patient was lost to follow-up among the 225 randomized in RAPCO-SV. In both studies, baseline characteristics were well balanced.

MACE curves separate at 5 years

In RAPCO-RITA, the MACE survival curves began to separate at about 5 years and then gradually widened. By 15 years, the lower rate of MACE in the RA group (38% vs. 48%) translated into a 26% relative reduction (hazard ratio, 0.74; P = .04).

In RAPCO-SV, the pattern was similar, by 15 years, the rates of MACE were 60% and 73% for the RA and SV groups, respectively, translating into a 29% relative reduction (HR, 0.71; P = .04).

There was no heterogeneity in benefit across prespecified subgroups such as presence or absence of diabetes, gender, or age. In RAPCO-RITA, there was 8% absolute and 31% relative reduction in all-cause mortality. In RAPCO-SV, the absolute and relative reductions were 11% and 26%.

When the trial was initiated, Dr. Hare hypothesized that RITA would prove more durable than RA, so the outcome was not anticipated.

“This is the first randomized controlled trial program to address the question,” said Dr. Hare, who noted that there have been numerous retrospective and case control analyses that have produced mixed results in the past.
 

Discussant praises trial quality

The AHA-invited discussant, Marc Ruel, MD, chair of cardiac surgery, University of Ottawa (Ont.) Heart Institute, called these data “important,” and he congratulated Dr. Hare for conducting the first randomized trial to address the question about second graft durability.

However, he noted that, although the study was randomized, it was not blinded, and he questioned whether postoperative care, in particular, was similar. He also pointed out that the MACE rate seemed high, particularly among the older patients randomized in RAPCO-SV.

“All of the patients were referred to an independently run CABG rehab program that was quite separate from the trial but that provided identical mandated care,” Dr. Hare responded, indicating that there was no opportunity for differences in postprocedural management.

In the United States, the SV graft is often preferred on the basis of easy harvesting and handling characteristics, according to Dr. Hare, who estimated that fewer than 10% of the 200,000 CABG procedures performed in the United States employ the RA conduit for second target vessels. He believes the RAPCO trials data support a change.

“My personal view is [that, on the basis of] this data, given that it is from a controlled trial rather than from patient-level meta-analyses, all isolated CABG operations should be using a radial graft if it is suitable,” Dr. Hare said.

Dr. Hare reports financial relationships with Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, CSL-Biotherapies, Lundbeck, Menarini, Merck, Novartis, Pfizer, Regeneron, Sanofi, Servier, and Vifor. Dr. Ruel reports financial relationships with Cryolife, Edwards, and Medtronic.

CHICAGO – With more than 15 years of follow-up from two related trials, the best conduit for the second most important target vessel in coronary artery bypass grafting (CABG) appears to be resolved.

The radial artery (RA) graft is linked with a lower risk of major adverse cardiac events (MACE) relative to a saphenous vein (SV) or the free right internal thoracic artery (FRITA).

On the basis of these findings, “a radial artery graft should be considered in all isolated CABG operations unless there are contraindications,” reported David L. Hare, MBBS, director of research in the department of cardiology, University of Melbourne.

For the primary graft, there is general agreement that the left internal thoracic artery (LITA) is the first choice for the left anterior descending vessel, but the optimal graft for the second most important target has never been established, according to Dr. Hare.

Almost 25 years ago, two randomized controlled trials called RAPCO-RITA and RAPCO-SV were initiated to address the question. There is now 15 years of follow-up for both of the RAPCO (Radial Artery Patency and Clinical Outcomes) trials, which were presented together at the American Heart Association scientific sessions.
 

Two trials conducted simultaneously

The RAPCO-RITA trial randomized CABG patients less than 70 years of age (less than 60 years in those with diabetes) to grafting of the second target vessel with an RA or FRITA graft. The RAPCO-SV trial randomized those 70 years or older (60 years or older with diabetes) to an RA or SV graft.

The two primary endpoints were graft patency at 10 years and a composite MACE at 10 years. The assessment of the MACE endpoint, which consisted of cardiovascular mortality, acute myocardial infarction, and coronary revascularization, was later amended to include a comparison at 15 years.

Ten-year patency results, favoring the RA in both studies, were previously published in Circulation. In the new data presented at the meeting, the RA was associated with a significant reduction in MACE relative to the comparator graft in both studies.

“The main driver was a reduction in all-cause mortality,” Dr. Hare reported.

In RAPCO-RITA, 394 patients were randomized with follow-up data available for all but 1 patient at 15 years. Similarly, only 1 patient was lost to follow-up among the 225 randomized in RAPCO-SV. In both studies, baseline characteristics were well balanced.

MACE curves separate at 5 years

In RAPCO-RITA, the MACE survival curves began to separate at about 5 years and then gradually widened. By 15 years, the lower rate of MACE in the RA group (38% vs. 48%) translated into a 26% relative reduction (hazard ratio, 0.74; P = .04).

In RAPCO-SV, the pattern was similar, by 15 years, the rates of MACE were 60% and 73% for the RA and SV groups, respectively, translating into a 29% relative reduction (HR, 0.71; P = .04).

There was no heterogeneity in benefit across prespecified subgroups such as presence or absence of diabetes, gender, or age. In RAPCO-RITA, there was 8% absolute and 31% relative reduction in all-cause mortality. In RAPCO-SV, the absolute and relative reductions were 11% and 26%.

When the trial was initiated, Dr. Hare hypothesized that RITA would prove more durable than RA, so the outcome was not anticipated.

“This is the first randomized controlled trial program to address the question,” said Dr. Hare, who noted that there have been numerous retrospective and case control analyses that have produced mixed results in the past.
 

Discussant praises trial quality

The AHA-invited discussant, Marc Ruel, MD, chair of cardiac surgery, University of Ottawa (Ont.) Heart Institute, called these data “important,” and he congratulated Dr. Hare for conducting the first randomized trial to address the question about second graft durability.

However, he noted that, although the study was randomized, it was not blinded, and he questioned whether postoperative care, in particular, was similar. He also pointed out that the MACE rate seemed high, particularly among the older patients randomized in RAPCO-SV.

“All of the patients were referred to an independently run CABG rehab program that was quite separate from the trial but that provided identical mandated care,” Dr. Hare responded, indicating that there was no opportunity for differences in postprocedural management.

In the United States, the SV graft is often preferred on the basis of easy harvesting and handling characteristics, according to Dr. Hare, who estimated that fewer than 10% of the 200,000 CABG procedures performed in the United States employ the RA conduit for second target vessels. He believes the RAPCO trials data support a change.

“My personal view is [that, on the basis of] this data, given that it is from a controlled trial rather than from patient-level meta-analyses, all isolated CABG operations should be using a radial graft if it is suitable,” Dr. Hare said.

Dr. Hare reports financial relationships with Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, CSL-Biotherapies, Lundbeck, Menarini, Merck, Novartis, Pfizer, Regeneron, Sanofi, Servier, and Vifor. Dr. Ruel reports financial relationships with Cryolife, Edwards, and Medtronic.

CHICAGO – Despite a 25% reduction in triglycerides (TGs) along with similar reductions in very-low-density lipoprotein (VLDL), and remnant cholesterol, a novel agent failed to provide any protection in a multinational trial against a composite endpoint of major adverse cardiovascular events (MACE) in patients with type 2 diabetes.

“Our data further highlight the complexity of lipid mediators of residual risk among patients with insulin resistance who are receiving statin therapy,” reported Aruna Das Pradhan, MD, of Harvard Medical School, Boston, and Queen Mary University, London.

Ted Bosworth/MDedge News

No benefit from fibrates seen in statin era

“We have not seen a significant cardiovascular event reduction with a fibrate in the statin era,” according to Karol Watson, MD, PhD, director of the UCLA Women’s Cardiovascular Health Center, Los Angeles.

Ted Bosworth/MDedge News

Lipid profile improved as predicted

Yet, in regard to an improvement in the lipid profile, pemafibrate performed as predicted. When compared to placebo 4 months into the trial, pemafibrate was associated with median reductions of 26.2% in TGs, 25.8% in VLDL, and 25.6% in remnant cholesterol, which is cholesterol transported in TG-rich lipoproteins after lipolysis and lipoprotein remodeling.

Furthermore, pemafibrate was associated with a median 27.6% reduction relative to placebo in apolipoprotein C-III and a median 4.8% reduction in apolipoprotein E, all of which would be expected to reduce CV risk.

The findings of PROMINENT were published online in the New England Journal of Medicine immediately after their presentation.

The findings of this study do not eliminate any hope for lowering residual CV risk with TG reductions, but they do suggest the relationship with other lipid subfractions is complex, according to Salim S. Virani, MD, PhD, a professor of cardiology at Baylor College of Medicine, Houston.

“I think that the lack of efficacy despite TG lowering may be largely due to a lack of an overall decrease in the apolipoprotein B level,” speculated Dr. Virani, who wrote an editorial that accompanied publication of the PROMINENT results.

He noted that pemafibrate is implicated in converting remnant cholesterol to LDL cholesterol, which might be one reason for a counterproductive effect on CV risk.

“In order for therapies that lower TG levels to be effective, they probably have to have mechanisms to increase clearance of TG-rich remnant lipoprotein cholesterol particles rather than just converting remnant lipoproteins to LDL,” Dr. Virani explained in an attempt to unravel the interplay of these variables.

Although this study enrolled patients “who would be predicted to have the most benefit from a TG-lowering strategy,” Dr. Watson agreed that these results do not necessarily extend to other means of lowering TG. However, it might draw into question the value of pemafibrate and perhaps other drugs in this class for treatment of hypertriglyceridemia. In addition to a lack of CV benefit, treatment was not without risks, including a higher rate of thromboembolism and adverse renal events.

Dr. Das Pradhan reported financial relationships with Denka, Medtelligence, Optum, Novo Nordisk, and Kowa, which provided funding for this trial. Dr. Watson reported financial relationships with Amarin, Amgen, Boehringer-Ingelheim, and Esperion.

CHICAGO – Despite a 25% reduction in triglycerides (TGs) along with similar reductions in very-low-density lipoprotein (VLDL), and remnant cholesterol, a novel agent failed to provide any protection in a multinational trial against a composite endpoint of major adverse cardiovascular events (MACE) in patients with type 2 diabetes.

“Our data further highlight the complexity of lipid mediators of residual risk among patients with insulin resistance who are receiving statin therapy,” reported Aruna Das Pradhan, MD, of Harvard Medical School, Boston, and Queen Mary University, London.

Ted Bosworth/MDedge News

No benefit from fibrates seen in statin era

“We have not seen a significant cardiovascular event reduction with a fibrate in the statin era,” according to Karol Watson, MD, PhD, director of the UCLA Women’s Cardiovascular Health Center, Los Angeles.

Ted Bosworth/MDedge News

Lipid profile improved as predicted

Yet, in regard to an improvement in the lipid profile, pemafibrate performed as predicted. When compared to placebo 4 months into the trial, pemafibrate was associated with median reductions of 26.2% in TGs, 25.8% in VLDL, and 25.6% in remnant cholesterol, which is cholesterol transported in TG-rich lipoproteins after lipolysis and lipoprotein remodeling.

Furthermore, pemafibrate was associated with a median 27.6% reduction relative to placebo in apolipoprotein C-III and a median 4.8% reduction in apolipoprotein E, all of which would be expected to reduce CV risk.

The findings of PROMINENT were published online in the New England Journal of Medicine immediately after their presentation.

The findings of this study do not eliminate any hope for lowering residual CV risk with TG reductions, but they do suggest the relationship with other lipid subfractions is complex, according to Salim S. Virani, MD, PhD, a professor of cardiology at Baylor College of Medicine, Houston.

“I think that the lack of efficacy despite TG lowering may be largely due to a lack of an overall decrease in the apolipoprotein B level,” speculated Dr. Virani, who wrote an editorial that accompanied publication of the PROMINENT results.

He noted that pemafibrate is implicated in converting remnant cholesterol to LDL cholesterol, which might be one reason for a counterproductive effect on CV risk.

“In order for therapies that lower TG levels to be effective, they probably have to have mechanisms to increase clearance of TG-rich remnant lipoprotein cholesterol particles rather than just converting remnant lipoproteins to LDL,” Dr. Virani explained in an attempt to unravel the interplay of these variables.

Although this study enrolled patients “who would be predicted to have the most benefit from a TG-lowering strategy,” Dr. Watson agreed that these results do not necessarily extend to other means of lowering TG. However, it might draw into question the value of pemafibrate and perhaps other drugs in this class for treatment of hypertriglyceridemia. In addition to a lack of CV benefit, treatment was not without risks, including a higher rate of thromboembolism and adverse renal events.

Dr. Das Pradhan reported financial relationships with Denka, Medtelligence, Optum, Novo Nordisk, and Kowa, which provided funding for this trial. Dr. Watson reported financial relationships with Amarin, Amgen, Boehringer-Ingelheim, and Esperion.

CHICAGO – Despite a 25% reduction in triglycerides (TGs) along with similar reductions in very-low-density lipoprotein (VLDL), and remnant cholesterol, a novel agent failed to provide any protection in a multinational trial against a composite endpoint of major adverse cardiovascular events (MACE) in patients with type 2 diabetes.

“Our data further highlight the complexity of lipid mediators of residual risk among patients with insulin resistance who are receiving statin therapy,” reported Aruna Das Pradhan, MD, of Harvard Medical School, Boston, and Queen Mary University, London.

Ted Bosworth/MDedge News

No benefit from fibrates seen in statin era

“We have not seen a significant cardiovascular event reduction with a fibrate in the statin era,” according to Karol Watson, MD, PhD, director of the UCLA Women’s Cardiovascular Health Center, Los Angeles.

Ted Bosworth/MDedge News

Lipid profile improved as predicted

Yet, in regard to an improvement in the lipid profile, pemafibrate performed as predicted. When compared to placebo 4 months into the trial, pemafibrate was associated with median reductions of 26.2% in TGs, 25.8% in VLDL, and 25.6% in remnant cholesterol, which is cholesterol transported in TG-rich lipoproteins after lipolysis and lipoprotein remodeling.

Furthermore, pemafibrate was associated with a median 27.6% reduction relative to placebo in apolipoprotein C-III and a median 4.8% reduction in apolipoprotein E, all of which would be expected to reduce CV risk.

The findings of PROMINENT were published online in the New England Journal of Medicine immediately after their presentation.

The findings of this study do not eliminate any hope for lowering residual CV risk with TG reductions, but they do suggest the relationship with other lipid subfractions is complex, according to Salim S. Virani, MD, PhD, a professor of cardiology at Baylor College of Medicine, Houston.

“I think that the lack of efficacy despite TG lowering may be largely due to a lack of an overall decrease in the apolipoprotein B level,” speculated Dr. Virani, who wrote an editorial that accompanied publication of the PROMINENT results.

He noted that pemafibrate is implicated in converting remnant cholesterol to LDL cholesterol, which might be one reason for a counterproductive effect on CV risk.

“In order for therapies that lower TG levels to be effective, they probably have to have mechanisms to increase clearance of TG-rich remnant lipoprotein cholesterol particles rather than just converting remnant lipoproteins to LDL,” Dr. Virani explained in an attempt to unravel the interplay of these variables.

Although this study enrolled patients “who would be predicted to have the most benefit from a TG-lowering strategy,” Dr. Watson agreed that these results do not necessarily extend to other means of lowering TG. However, it might draw into question the value of pemafibrate and perhaps other drugs in this class for treatment of hypertriglyceridemia. In addition to a lack of CV benefit, treatment was not without risks, including a higher rate of thromboembolism and adverse renal events.

Dr. Das Pradhan reported financial relationships with Denka, Medtelligence, Optum, Novo Nordisk, and Kowa, which provided funding for this trial. Dr. Watson reported financial relationships with Amarin, Amgen, Boehringer-Ingelheim, and Esperion.

NASHVILLE, Tenn. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O₂ saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

NASHVILLE, Tenn. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O₂ saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

NASHVILLE, Tenn. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O₂ saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

NASHVILLE, TENN. – For children with uncontrolled asthma on standard therapies and meeting criteria of a type 2 (T2) inflammatory phenotype, a prospective 1-year extension from a phase 3 trial supports the biologic dupilumab as a potential treatment standard, according to the investigator who presented the findings at the annual meeting of the American College of Chest Physicians (CHEST).

“The appropriate candidate is a child with the T2 inflammatory phenotype who is still experiencing exacerbations on at least a medium dose of inhaled corticosteroids plus a second controller medication,” said Leonard B. Bacharier, MD, section chief, division of pediatric allergy, immunology, and pulmonary medicine, Vanderbilt University Medical Center, Nashville, Tenn.

By T2 inflammatory phenotype, Dr. Bacharier specified that key features include an eosinophil count of at least 150 cells/mL and a FENO level of at least 20 ppb. If children meet these and inadequate standard-therapy response criteria, Dr. Bacharier thinks the extension data support dupilumab as a routine therapy despite the cost.

“As a pediatrician, I think it is really important that children with asthma finish their childhood with the best bone health and the lowest risk of other steroid-associated adverse events,” Dr. Bacharier said.

Over the course of the 1-year extension, called EXCURSION, there was no evidence of diminished efficacy nor of any new safety signal. In other words, patients have remained well controlled for 2 years with a well-tolerated therapy. Dr. Bacharier pointed out, however, that one of the most compelling reasons to consider this as a potential standard was the very low rates at which patients required a course of steroids.

At the end of 1 year in the extension trial, called VOYAGE, the unadjusted annualized total number of steroid courses per patient was 0.414 in the dupilumab group vs. 0.816 in the placebo group. At the end of EXCURSION, following an additional year of therapy, the rate was 0.152.

“This means that fewer than 2 patients out of 10 required prednisone in the previous year,” Dr. Bacharier said.

The EXCURSION extension study did not capture data on steroid-related adverse events, but Dr. Bacharier said that these data are reassuring for both acute and long-term risks of steroid exposure.

“We know that the adverse effects associated with oral steroids are related to cumulative exposure. The more you receive, the greater the risk of adverse effects,” he said.

In patients who were randomly assigned to placebo in the VOYAGE trial and then switched to dupilumab in the EXCURSION extension, steroid exposure was also very low, but whether evaluated as annualized total courses (0.152 vs. 0.181) or by proportion of patients with any steroid intake (10.5% vs. 13.2%), there was a numerical advantage for starting and remaining on dupilumab over the 2-year follow-up.

In VOYAGE, which was published last year in the New England Journal of Medicine, 408 children from ages 6 to 11 years were randomly assigned in a 2:1 ratio to dupilumab or matching placebo. For children weighing less than 30 kg, the dose was 200 mg. For those who weighed less, the dose was 100 mg. Both doses were administered every 2 weeks.

As previously reported, the study met the primary endpoint of annualized rate of severe asthma exacerbations, which was 0.31 in the dupilumab group vs. 0.75 in the placebo group, a relative reduction of 59.3% (P < .001). Dupilumab was also superior on several secondary endpoints, including measures of lung function and asthma control.

The EXCURSION extension study enrolled 365 of the patients who participated in VOYAGE. This included 125 of the 135 randomly assigned to placebo and 240 of the 273 randomly assigned to dupilumab. Those initially randomly assigned to placebo were transitioned to dupilumab. The same weight-based dosing was employed.

At baseline, the children enrolled in VOYAGE had an annualized rate of 2.560 severe exacerbations. At the end of VOYAGE, this rate was 0.330. At the end of EXCURSION after 2 years on dupilumab, the rate was 0.118. In the group switched from placebo to dupilumab, the rate was 0.124.

During EXCURSION, treatment-emergent adverse events occurred in 2.5% of those who remained on dupilumab and 0.8% of those switched from placebo to dupilumab. Three patients (1.3%) permanently discontinued therapy because of a treatment-related event. The most common adverse events involved upper respiratory complaints, such as nasopharyngitis, pharyngitis, upper respiratory tract infections, and rhinitis influenza, but all were reported in fewer than 10% of patients. Other reported side effects, such as injection-site reactions and diarrhea, occurred in 5% or fewer of patients.

“Over the 2 years, dupilumab was well tolerated, and there was evidence of an increased risk of adverse events for longer exposure,” Dr. Bacharier reported.

It is for this reason that Dr. Bacharier concluded that children with repeated exacerbations requiring steroids despite standard therapies should be considered for dupilumab if they also meet criteria for the T2 inflammatory phenotype. This last point is important.

“In children with low levels of eosinophil and low phenol, we are not seeing these kinds of response,” Dr. Bacharier said. Rather, in the absence of eosinophilia, “there is probably no difference between dupilumab and placebo.”

An important steroid-sparing effect is “suggested” by the data, but Sally E. Wenzel, MD, director of the University of Pittsburgh Asthma and Environmental Lung Health Institute in Pittsburgh, characterized the idea that dupilumab is emerging to be a standard in uncontrolled asthma in children with the T2 phenotype as “a bit premature.”

She challenged the conclusion that the EXCURSION data associated dupilumab with a reduction in annualized steroid courses over time. While the number was lower after 2 years of treatment than after 1, Dr. Wenzel pointed out that all patients were on dupilumab in the second year, “so we don’t know what really happens without treatment.” She said there are other potential explanations, including the possibility that aging children have less active disease.

More importantly, Dr. Wenzel said in an interview that she would also hesitate to urge biologics in every child who meets the criteria that Dr. Bacharier outlined.

“The most important concern is that we do not know how long one should continue the dupilumab and if the long-term treatment adversely or positively affects a growing immune system,” she said.

There is reason to be concerned that blockage of an entire immune pathway with a biologic could adversely affect autoimmunity as well as susceptibility to cancer, according to Dr. Wenzel. She hopes this does not prove to be the case, but she encouraged prudence until there are more data to judge.

While extension data for dupilumab “sound good,” she thinks moving toward any type of standard of care with biologics in children “has to be done with caution and constant evaluation and reevaluation.”

Dr. Bacharier disclosed relationships with AstraZeneca, GlaxoSmithKline, Regeneron and Sanofi. The two latter companies collaborated on the development and marketing of dupilumab. Dr. Wenzel disclosed relationships with AstraZeneca, GlaxoSmithKline, Knopp Pharmaceuticals, Pieris, and Sanofi-Regeneron.

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

NASHVILLE, TENN. – For children with uncontrolled asthma on standard therapies and meeting criteria of a type 2 (T2) inflammatory phenotype, a prospective 1-year extension from a phase 3 trial supports the biologic dupilumab as a potential treatment standard, according to the investigator who presented the findings at the annual meeting of the American College of Chest Physicians (CHEST).

“The appropriate candidate is a child with the T2 inflammatory phenotype who is still experiencing exacerbations on at least a medium dose of inhaled corticosteroids plus a second controller medication,” said Leonard B. Bacharier, MD, section chief, division of pediatric allergy, immunology, and pulmonary medicine, Vanderbilt University Medical Center, Nashville, Tenn.

By T2 inflammatory phenotype, Dr. Bacharier specified that key features include an eosinophil count of at least 150 cells/mL and a FENO level of at least 20 ppb. If children meet these and inadequate standard-therapy response criteria, Dr. Bacharier thinks the extension data support dupilumab as a routine therapy despite the cost.

“As a pediatrician, I think it is really important that children with asthma finish their childhood with the best bone health and the lowest risk of other steroid-associated adverse events,” Dr. Bacharier said.

Over the course of the 1-year extension, called EXCURSION, there was no evidence of diminished efficacy nor of any new safety signal. In other words, patients have remained well controlled for 2 years with a well-tolerated therapy. Dr. Bacharier pointed out, however, that one of the most compelling reasons to consider this as a potential standard was the very low rates at which patients required a course of steroids.

At the end of 1 year in the extension trial, called VOYAGE, the unadjusted annualized total number of steroid courses per patient was 0.414 in the dupilumab group vs. 0.816 in the placebo group. At the end of EXCURSION, following an additional year of therapy, the rate was 0.152.

“This means that fewer than 2 patients out of 10 required prednisone in the previous year,” Dr. Bacharier said.

The EXCURSION extension study did not capture data on steroid-related adverse events, but Dr. Bacharier said that these data are reassuring for both acute and long-term risks of steroid exposure.

“We know that the adverse effects associated with oral steroids are related to cumulative exposure. The more you receive, the greater the risk of adverse effects,” he said.

In patients who were randomly assigned to placebo in the VOYAGE trial and then switched to dupilumab in the EXCURSION extension, steroid exposure was also very low, but whether evaluated as annualized total courses (0.152 vs. 0.181) or by proportion of patients with any steroid intake (10.5% vs. 13.2%), there was a numerical advantage for starting and remaining on dupilumab over the 2-year follow-up.

In VOYAGE, which was published last year in the New England Journal of Medicine, 408 children from ages 6 to 11 years were randomly assigned in a 2:1 ratio to dupilumab or matching placebo. For children weighing less than 30 kg, the dose was 200 mg. For those who weighed less, the dose was 100 mg. Both doses were administered every 2 weeks.

As previously reported, the study met the primary endpoint of annualized rate of severe asthma exacerbations, which was 0.31 in the dupilumab group vs. 0.75 in the placebo group, a relative reduction of 59.3% (P < .001). Dupilumab was also superior on several secondary endpoints, including measures of lung function and asthma control.

The EXCURSION extension study enrolled 365 of the patients who participated in VOYAGE. This included 125 of the 135 randomly assigned to placebo and 240 of the 273 randomly assigned to dupilumab. Those initially randomly assigned to placebo were transitioned to dupilumab. The same weight-based dosing was employed.

At baseline, the children enrolled in VOYAGE had an annualized rate of 2.560 severe exacerbations. At the end of VOYAGE, this rate was 0.330. At the end of EXCURSION after 2 years on dupilumab, the rate was 0.118. In the group switched from placebo to dupilumab, the rate was 0.124.

During EXCURSION, treatment-emergent adverse events occurred in 2.5% of those who remained on dupilumab and 0.8% of those switched from placebo to dupilumab. Three patients (1.3%) permanently discontinued therapy because of a treatment-related event. The most common adverse events involved upper respiratory complaints, such as nasopharyngitis, pharyngitis, upper respiratory tract infections, and rhinitis influenza, but all were reported in fewer than 10% of patients. Other reported side effects, such as injection-site reactions and diarrhea, occurred in 5% or fewer of patients.

“Over the 2 years, dupilumab was well tolerated, and there was evidence of an increased risk of adverse events for longer exposure,” Dr. Bacharier reported.

It is for this reason that Dr. Bacharier concluded that children with repeated exacerbations requiring steroids despite standard therapies should be considered for dupilumab if they also meet criteria for the T2 inflammatory phenotype. This last point is important.

“In children with low levels of eosinophil and low phenol, we are not seeing these kinds of response,” Dr. Bacharier said. Rather, in the absence of eosinophilia, “there is probably no difference between dupilumab and placebo.”

An important steroid-sparing effect is “suggested” by the data, but Sally E. Wenzel, MD, director of the University of Pittsburgh Asthma and Environmental Lung Health Institute in Pittsburgh, characterized the idea that dupilumab is emerging to be a standard in uncontrolled asthma in children with the T2 phenotype as “a bit premature.”

She challenged the conclusion that the EXCURSION data associated dupilumab with a reduction in annualized steroid courses over time. While the number was lower after 2 years of treatment than after 1, Dr. Wenzel pointed out that all patients were on dupilumab in the second year, “so we don’t know what really happens without treatment.” She said there are other potential explanations, including the possibility that aging children have less active disease.

More importantly, Dr. Wenzel said in an interview that she would also hesitate to urge biologics in every child who meets the criteria that Dr. Bacharier outlined.

“The most important concern is that we do not know how long one should continue the dupilumab and if the long-term treatment adversely or positively affects a growing immune system,” she said.

There is reason to be concerned that blockage of an entire immune pathway with a biologic could adversely affect autoimmunity as well as susceptibility to cancer, according to Dr. Wenzel. She hopes this does not prove to be the case, but she encouraged prudence until there are more data to judge.

While extension data for dupilumab “sound good,” she thinks moving toward any type of standard of care with biologics in children “has to be done with caution and constant evaluation and reevaluation.”

Dr. Bacharier disclosed relationships with AstraZeneca, GlaxoSmithKline, Regeneron and Sanofi. The two latter companies collaborated on the development and marketing of dupilumab. Dr. Wenzel disclosed relationships with AstraZeneca, GlaxoSmithKline, Knopp Pharmaceuticals, Pieris, and Sanofi-Regeneron.

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

NASHVILLE, TENN. – For children with uncontrolled asthma on standard therapies and meeting criteria of a type 2 (T2) inflammatory phenotype, a prospective 1-year extension from a phase 3 trial supports the biologic dupilumab as a potential treatment standard, according to the investigator who presented the findings at the annual meeting of the American College of Chest Physicians (CHEST).

“The appropriate candidate is a child with the T2 inflammatory phenotype who is still experiencing exacerbations on at least a medium dose of inhaled corticosteroids plus a second controller medication,” said Leonard B. Bacharier, MD, section chief, division of pediatric allergy, immunology, and pulmonary medicine, Vanderbilt University Medical Center, Nashville, Tenn.

By T2 inflammatory phenotype, Dr. Bacharier specified that key features include an eosinophil count of at least 150 cells/mL and a FENO level of at least 20 ppb. If children meet these and inadequate standard-therapy response criteria, Dr. Bacharier thinks the extension data support dupilumab as a routine therapy despite the cost.

“As a pediatrician, I think it is really important that children with asthma finish their childhood with the best bone health and the lowest risk of other steroid-associated adverse events,” Dr. Bacharier said.

Over the course of the 1-year extension, called EXCURSION, there was no evidence of diminished efficacy nor of any new safety signal. In other words, patients have remained well controlled for 2 years with a well-tolerated therapy. Dr. Bacharier pointed out, however, that one of the most compelling reasons to consider this as a potential standard was the very low rates at which patients required a course of steroids.

At the end of 1 year in the extension trial, called VOYAGE, the unadjusted annualized total number of steroid courses per patient was 0.414 in the dupilumab group vs. 0.816 in the placebo group. At the end of EXCURSION, following an additional year of therapy, the rate was 0.152.

“This means that fewer than 2 patients out of 10 required prednisone in the previous year,” Dr. Bacharier said.

The EXCURSION extension study did not capture data on steroid-related adverse events, but Dr. Bacharier said that these data are reassuring for both acute and long-term risks of steroid exposure.

“We know that the adverse effects associated with oral steroids are related to cumulative exposure. The more you receive, the greater the risk of adverse effects,” he said.

In patients who were randomly assigned to placebo in the VOYAGE trial and then switched to dupilumab in the EXCURSION extension, steroid exposure was also very low, but whether evaluated as annualized total courses (0.152 vs. 0.181) or by proportion of patients with any steroid intake (10.5% vs. 13.2%), there was a numerical advantage for starting and remaining on dupilumab over the 2-year follow-up.

In VOYAGE, which was published last year in the New England Journal of Medicine, 408 children from ages 6 to 11 years were randomly assigned in a 2:1 ratio to dupilumab or matching placebo. For children weighing less than 30 kg, the dose was 200 mg. For those who weighed less, the dose was 100 mg. Both doses were administered every 2 weeks.

As previously reported, the study met the primary endpoint of annualized rate of severe asthma exacerbations, which was 0.31 in the dupilumab group vs. 0.75 in the placebo group, a relative reduction of 59.3% (P < .001). Dupilumab was also superior on several secondary endpoints, including measures of lung function and asthma control.

The EXCURSION extension study enrolled 365 of the patients who participated in VOYAGE. This included 125 of the 135 randomly assigned to placebo and 240 of the 273 randomly assigned to dupilumab. Those initially randomly assigned to placebo were transitioned to dupilumab. The same weight-based dosing was employed.

At baseline, the children enrolled in VOYAGE had an annualized rate of 2.560 severe exacerbations. At the end of VOYAGE, this rate was 0.330. At the end of EXCURSION after 2 years on dupilumab, the rate was 0.118. In the group switched from placebo to dupilumab, the rate was 0.124.

During EXCURSION, treatment-emergent adverse events occurred in 2.5% of those who remained on dupilumab and 0.8% of those switched from placebo to dupilumab. Three patients (1.3%) permanently discontinued therapy because of a treatment-related event. The most common adverse events involved upper respiratory complaints, such as nasopharyngitis, pharyngitis, upper respiratory tract infections, and rhinitis influenza, but all were reported in fewer than 10% of patients. Other reported side effects, such as injection-site reactions and diarrhea, occurred in 5% or fewer of patients.

“Over the 2 years, dupilumab was well tolerated, and there was evidence of an increased risk of adverse events for longer exposure,” Dr. Bacharier reported.

It is for this reason that Dr. Bacharier concluded that children with repeated exacerbations requiring steroids despite standard therapies should be considered for dupilumab if they also meet criteria for the T2 inflammatory phenotype. This last point is important.

“In children with low levels of eosinophil and low phenol, we are not seeing these kinds of response,” Dr. Bacharier said. Rather, in the absence of eosinophilia, “there is probably no difference between dupilumab and placebo.”

An important steroid-sparing effect is “suggested” by the data, but Sally E. Wenzel, MD, director of the University of Pittsburgh Asthma and Environmental Lung Health Institute in Pittsburgh, characterized the idea that dupilumab is emerging to be a standard in uncontrolled asthma in children with the T2 phenotype as “a bit premature.”

She challenged the conclusion that the EXCURSION data associated dupilumab with a reduction in annualized steroid courses over time. While the number was lower after 2 years of treatment than after 1, Dr. Wenzel pointed out that all patients were on dupilumab in the second year, “so we don’t know what really happens without treatment.” She said there are other potential explanations, including the possibility that aging children have less active disease.

More importantly, Dr. Wenzel said in an interview that she would also hesitate to urge biologics in every child who meets the criteria that Dr. Bacharier outlined.

“The most important concern is that we do not know how long one should continue the dupilumab and if the long-term treatment adversely or positively affects a growing immune system,” she said.

There is reason to be concerned that blockage of an entire immune pathway with a biologic could adversely affect autoimmunity as well as susceptibility to cancer, according to Dr. Wenzel. She hopes this does not prove to be the case, but she encouraged prudence until there are more data to judge.

While extension data for dupilumab “sound good,” she thinks moving toward any type of standard of care with biologics in children “has to be done with caution and constant evaluation and reevaluation.”

Dr. Bacharier disclosed relationships with AstraZeneca, GlaxoSmithKline, Regeneron and Sanofi. The two latter companies collaborated on the development and marketing of dupilumab. Dr. Wenzel disclosed relationships with AstraZeneca, GlaxoSmithKline, Knopp Pharmaceuticals, Pieris, and Sanofi-Regeneron.

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

NASHVILLE, TENN. – In a growing number of states, pulmonologists face serious legal consequences for advising women who have an underlying medical condition that places them at risk for life-threatening complications from pregnancy or childbirth, according to a panel of experts assembled for a special session at the annual meeting of the American College of Chest Physicians.

Following the June 24 decision by the U.S. Supreme Court to overturn Roe v. Wade, several states were swift to enact tight restrictions on abortion. These restrictions include bans on elective abortions for almost any reason. Worded in various ways, the new laws typically include exceptions when the health of the mother is threatened, but these exceptions must be navigated carefully.

As a general rule, “there is no clear and specific definition of when the mother’s life is at risk. These laws are vague on purpose,” said Rebecca Cohen, MD, division chief, Complex Family Planning, University of Colorado at Denver, Aurora.

The remarks were relevant to any clinician who advises women regarding pregnancy termination, but Dr. Cohen’s advice was tailored to pulmonologists. Advances have reduced the proportion of women with severe lung diseases, such as pulmonary arterial hypertension or interstitial lung disease, that make pregnancy untenable, but serious risks persist.

Clinicians need to assume a defensive posture, and the first step is to understand the laws, according to Dr. Cohen. For this, she recommended the nongovernmental Guttmacher Institute as a resource. With a focus on sexual and reproductive health, this research institute maintains a state-by-state summary of laws that govern pregnancy termination. The laws are being reconsidered across the country, and Dr. Cohen said the website updates its summaries accordingly.

In states with the most rigorous restrictions, the risks to physicians are substantial. Pulmonologists need to recognize that they might face legal consequences from merely advising a patient to terminate her pregnancy if the medical need is ambiguous or unclear, according to Dr. Cohen.

“If the advice is interpreted as aiding and abetting an elective abortion, it is a felony offense in some states,” Dr. Cohen said.

In states with restrictive laws, pregnancy prevention is the safest approach for women of childbearing age who face life-threatening complications in the event of pregnancy, according to Dr. Cohen. This might reasonably include a step beyond standard contraception. Dr. Cohen mentioned such approaches as period tracking to double down.

In addition, for women of childbearing age with health problems that might result in complications in the event of a pregnancy, it is appropriate to establish this fact in the medical record. This history could prove useful for maximizing options when making decisions in the best interest of the mother’s health in the event of contraception failure.

In addition, pulmonologists who counsel women about the potential for pregnancy termination should consider establishing a relationship with the legal department at the institution where they work, according to Dr. Cohen. In specific cases in which termination is recommended, she further advised building documentation with participation from additional medical specialists, such as an obstetrician who manages high-risk pregnancies.

“There is no guarantee that any given documentation is adequate,” Dr. Cohen warned. She indicated that consensus from multiple clinicians can strengthen the legal defense if one is necessary.

For some serious lung conditions that are incompatible with pregnancy, the threat to the mother’s life can occur early, according to Deborah Jo Levine, MD, a clinical instructor in the division of pulmonary, allergy, and critical care medicine, Stanford (Calif.) University.

As a result, “you need to identify at-risk patients early and develop a plan promptly,” said Dr. Levine, who joined Dr. Cohen on the special panel at the CHEST 2022 meeting. Even when termination is medically appropriate, restrictive laws are making these services harder to find.

In the case of a pregnancy likely to pose a high risk of complications owing to the patient’s having lung disease, “it is important to involve a high-risk ob quickly,” Dr. Levine warned. “In some cases, termination poses less risk if performed early.”

Sunjay R. Devarajan, MD, assistant professor of pulmonary medicine and critical care, Baylor College of Medicine, Houston, has faced this issue in a state that has some of the most restrictive laws. Even when there is no debate about the necessity of a medically indicated abortion, he cautioned that abortion services are becoming harder to find.

“A recent patient who had a complicated unintentional pregnancy on our service had to go out of state for pregnancy termination,” Dr. Devarajan said. He noted that this option is not available to all women, particularly in states such as his own in which most bordering states also now have highly restrictive abortion laws.

On the basis of this experience, he is thinking more defensively. Now that clinicians can be drawn into legal proceedings even when pregnancy termination is indicated, he agreed that clinicians must become familiar with the local laws.

“We are doing better in managing pregnancies in women with serious lung diseases, but termination is still the prudent approach in some cases,” Dr. Devarajan said. He indicated that he considered the advice offered by Dr. Cohen helpful in avoiding complications for the patient and the physician.

Dr. Cohen, Dr. Levine, and Dr. Devarajan have disclosed no relevant financial relationships.

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

NASHVILLE, TENN. – In a growing number of states, pulmonologists face serious legal consequences for advising women who have an underlying medical condition that places them at risk for life-threatening complications from pregnancy or childbirth, according to a panel of experts assembled for a special session at the annual meeting of the American College of Chest Physicians.

Following the June 24 decision by the U.S. Supreme Court to overturn Roe v. Wade, several states were swift to enact tight restrictions on abortion. These restrictions include bans on elective abortions for almost any reason. Worded in various ways, the new laws typically include exceptions when the health of the mother is threatened, but these exceptions must be navigated carefully.

As a general rule, “there is no clear and specific definition of when the mother’s life is at risk. These laws are vague on purpose,” said Rebecca Cohen, MD, division chief, Complex Family Planning, University of Colorado at Denver, Aurora.

The remarks were relevant to any clinician who advises women regarding pregnancy termination, but Dr. Cohen’s advice was tailored to pulmonologists. Advances have reduced the proportion of women with severe lung diseases, such as pulmonary arterial hypertension or interstitial lung disease, that make pregnancy untenable, but serious risks persist.

Clinicians need to assume a defensive posture, and the first step is to understand the laws, according to Dr. Cohen. For this, she recommended the nongovernmental Guttmacher Institute as a resource. With a focus on sexual and reproductive health, this research institute maintains a state-by-state summary of laws that govern pregnancy termination. The laws are being reconsidered across the country, and Dr. Cohen said the website updates its summaries accordingly.

In states with the most rigorous restrictions, the risks to physicians are substantial. Pulmonologists need to recognize that they might face legal consequences from merely advising a patient to terminate her pregnancy if the medical need is ambiguous or unclear, according to Dr. Cohen.

“If the advice is interpreted as aiding and abetting an elective abortion, it is a felony offense in some states,” Dr. Cohen said.

In states with restrictive laws, pregnancy prevention is the safest approach for women of childbearing age who face life-threatening complications in the event of pregnancy, according to Dr. Cohen. This might reasonably include a step beyond standard contraception. Dr. Cohen mentioned such approaches as period tracking to double down.

In addition, for women of childbearing age with health problems that might result in complications in the event of a pregnancy, it is appropriate to establish this fact in the medical record. This history could prove useful for maximizing options when making decisions in the best interest of the mother’s health in the event of contraception failure.

In addition, pulmonologists who counsel women about the potential for pregnancy termination should consider establishing a relationship with the legal department at the institution where they work, according to Dr. Cohen. In specific cases in which termination is recommended, she further advised building documentation with participation from additional medical specialists, such as an obstetrician who manages high-risk pregnancies.

“There is no guarantee that any given documentation is adequate,” Dr. Cohen warned. She indicated that consensus from multiple clinicians can strengthen the legal defense if one is necessary.

For some serious lung conditions that are incompatible with pregnancy, the threat to the mother’s life can occur early, according to Deborah Jo Levine, MD, a clinical instructor in the division of pulmonary, allergy, and critical care medicine, Stanford (Calif.) University.

As a result, “you need to identify at-risk patients early and develop a plan promptly,” said Dr. Levine, who joined Dr. Cohen on the special panel at the CHEST 2022 meeting. Even when termination is medically appropriate, restrictive laws are making these services harder to find.

In the case of a pregnancy likely to pose a high risk of complications owing to the patient’s having lung disease, “it is important to involve a high-risk ob quickly,” Dr. Levine warned. “In some cases, termination poses less risk if performed early.”

Sunjay R. Devarajan, MD, assistant professor of pulmonary medicine and critical care, Baylor College of Medicine, Houston, has faced this issue in a state that has some of the most restrictive laws. Even when there is no debate about the necessity of a medically indicated abortion, he cautioned that abortion services are becoming harder to find.

“A recent patient who had a complicated unintentional pregnancy on our service had to go out of state for pregnancy termination,” Dr. Devarajan said. He noted that this option is not available to all women, particularly in states such as his own in which most bordering states also now have highly restrictive abortion laws.

On the basis of this experience, he is thinking more defensively. Now that clinicians can be drawn into legal proceedings even when pregnancy termination is indicated, he agreed that clinicians must become familiar with the local laws.

“We are doing better in managing pregnancies in women with serious lung diseases, but termination is still the prudent approach in some cases,” Dr. Devarajan said. He indicated that he considered the advice offered by Dr. Cohen helpful in avoiding complications for the patient and the physician.

Dr. Cohen, Dr. Levine, and Dr. Devarajan have disclosed no relevant financial relationships.

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

NASHVILLE, TENN. – In a growing number of states, pulmonologists face serious legal consequences for advising women who have an underlying medical condition that places them at risk for life-threatening complications from pregnancy or childbirth, according to a panel of experts assembled for a special session at the annual meeting of the American College of Chest Physicians.

Following the June 24 decision by the U.S. Supreme Court to overturn Roe v. Wade, several states were swift to enact tight restrictions on abortion. These restrictions include bans on elective abortions for almost any reason. Worded in various ways, the new laws typically include exceptions when the health of the mother is threatened, but these exceptions must be navigated carefully.

As a general rule, “there is no clear and specific definition of when the mother’s life is at risk. These laws are vague on purpose,” said Rebecca Cohen, MD, division chief, Complex Family Planning, University of Colorado at Denver, Aurora.

The remarks were relevant to any clinician who advises women regarding pregnancy termination, but Dr. Cohen’s advice was tailored to pulmonologists. Advances have reduced the proportion of women with severe lung diseases, such as pulmonary arterial hypertension or interstitial lung disease, that make pregnancy untenable, but serious risks persist.

Clinicians need to assume a defensive posture, and the first step is to understand the laws, according to Dr. Cohen. For this, she recommended the nongovernmental Guttmacher Institute as a resource. With a focus on sexual and reproductive health, this research institute maintains a state-by-state summary of laws that govern pregnancy termination. The laws are being reconsidered across the country, and Dr. Cohen said the website updates its summaries accordingly.

In states with the most rigorous restrictions, the risks to physicians are substantial. Pulmonologists need to recognize that they might face legal consequences from merely advising a patient to terminate her pregnancy if the medical need is ambiguous or unclear, according to Dr. Cohen.

“If the advice is interpreted as aiding and abetting an elective abortion, it is a felony offense in some states,” Dr. Cohen said.

In states with restrictive laws, pregnancy prevention is the safest approach for women of childbearing age who face life-threatening complications in the event of pregnancy, according to Dr. Cohen. This might reasonably include a step beyond standard contraception. Dr. Cohen mentioned such approaches as period tracking to double down.

In addition, for women of childbearing age with health problems that might result in complications in the event of a pregnancy, it is appropriate to establish this fact in the medical record. This history could prove useful for maximizing options when making decisions in the best interest of the mother’s health in the event of contraception failure.

In addition, pulmonologists who counsel women about the potential for pregnancy termination should consider establishing a relationship with the legal department at the institution where they work, according to Dr. Cohen. In specific cases in which termination is recommended, she further advised building documentation with participation from additional medical specialists, such as an obstetrician who manages high-risk pregnancies.

“There is no guarantee that any given documentation is adequate,” Dr. Cohen warned. She indicated that consensus from multiple clinicians can strengthen the legal defense if one is necessary.

For some serious lung conditions that are incompatible with pregnancy, the threat to the mother’s life can occur early, according to Deborah Jo Levine, MD, a clinical instructor in the division of pulmonary, allergy, and critical care medicine, Stanford (Calif.) University.

As a result, “you need to identify at-risk patients early and develop a plan promptly,” said Dr. Levine, who joined Dr. Cohen on the special panel at the CHEST 2022 meeting. Even when termination is medically appropriate, restrictive laws are making these services harder to find.

In the case of a pregnancy likely to pose a high risk of complications owing to the patient’s having lung disease, “it is important to involve a high-risk ob quickly,” Dr. Levine warned. “In some cases, termination poses less risk if performed early.”

Sunjay R. Devarajan, MD, assistant professor of pulmonary medicine and critical care, Baylor College of Medicine, Houston, has faced this issue in a state that has some of the most restrictive laws. Even when there is no debate about the necessity of a medically indicated abortion, he cautioned that abortion services are becoming harder to find.

“A recent patient who had a complicated unintentional pregnancy on our service had to go out of state for pregnancy termination,” Dr. Devarajan said. He noted that this option is not available to all women, particularly in states such as his own in which most bordering states also now have highly restrictive abortion laws.

On the basis of this experience, he is thinking more defensively. Now that clinicians can be drawn into legal proceedings even when pregnancy termination is indicated, he agreed that clinicians must become familiar with the local laws.

“We are doing better in managing pregnancies in women with serious lung diseases, but termination is still the prudent approach in some cases,” Dr. Devarajan said. He indicated that he considered the advice offered by Dr. Cohen helpful in avoiding complications for the patient and the physician.

Dr. Cohen, Dr. Levine, and Dr. Devarajan have disclosed no relevant financial relationships.

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