Batya Swift Yasgur, MA, LSW

The American Heart Association (AHA) and seven other medical societies have issued interim guidance to inform treatment of victims of cardiac arrest with suspected or confirmed COVID-19, focusing on reducing provider exposure, and prioritizing oxygenation and ventilation strategies, goals of care, and appropriateness of resuscitation.

“We were very specific in calling this ‘interim guidance’ based on expert opinion because things are evolving so quickly and we are learning more and more every day as more and more patients with COVID-19 are taken care of,” corresponding author Comilla Sasson, MD, PhD, vice president, Emergency Cardiovascular Care (ECC) Science and Innovation, American Heart Association, told theheart.org | Medscape Cardiology.

“We wanted this to be a starting point for providing the clinical guidance that everyone is looking for and, as we collect more data, the guidance will change, as it has for CDC [Centers for Disease Control and Prevention] and WHO [World Health Organization],” she said.

“The guidance sought to balance the provision of timely, high-quality resuscitation to patients while simultaneously protecting rescuers,” she added.

The guidance was published online April 9 in Circulation. The AHA produced the guidelines in collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, the Society of Critical Care Anesthesiologists, and the American Society of Anesthesiologists, with support from the American Association of Critical Care Nurses and National EMS Physicians.
 

Respiratory Etiologies

“We think of cardiac arrest in adults, especially as related to cardiac etiologies, but we are now thinking of it in COVID-19 more as hypoxemia or respiratory failure, which can predispose patients to cardiac arrest,” Sasson explained.

Healthcare workers are the “highest-risk profession” for contracting the COVID-19, with resuscitations carrying “added risk” for several reasons, the authors note.

Administering CPR involves performing numerous aerosol-generating procedures that can cause viral particles to remain suspended in the air and be inhaled by those nearby, with a half-life of approximately 1 hour, they point out.

Moreover, resuscitation efforts “require numerous providers to work in close proximity to one another and the patient,” and the high-stress emergent nature of these events may result in lapses in infection-control procedures.

The guidance is designed “to protect not only the patient but also the provider and involves strategies regarding oxygenation and ventilation that differ from what we’ve done in the past since we have a strong feeling that this is a different disease process that may require different approaches than what we’ve dealt with in the past,” Sasson commented.

Reducing Provider Exposure

Providers should don PPE to protect both themselves and their colleagues from unnecessary exposure, the authors advise, noting that recommendations for PPE standards may “vary considerably,” so health or emergency medical services (EMS) standards should be taken into account.

Moreover, it is important to allow only the most essential providers into the room or on the scene. In keeping with reducing the number of rescuers, the authors recommend replacing manual chest compressions with mechanical CPR devices for patients who meet height and weight criteria in settings with “protocols and expertise in place for their use.”

COVID-19 status should be communicated to any new providers prior to their arrival on the scene, the authors stress.
 

Oxygenation and Ventilation Strategies

“Reducing risk of aerosolization during the process of intubation is key,” Sasson emphasized.

For this reason, a high-efficiency particulate air HEPA filter (if available) should be attached to any manual or mechanical ventilation device, specifically in the path of exhaled gas, before any breaths are administered.

Moreover, it is important to intubate early with a cuffed tube and connect to a mechanical ventilator, if possible. The intubator should be engaged with the “highest chance of first-pass success,” and chest compression should be paused to intubate.

To further increase the chance of a successful first intubation, use of video laryngoscopy (if available) is helpful.

Additional guidance includes:

• Using a bag-mask device (or T-piece in neonates) with a HEPA filter and a tight seal prior to intubation
• Considering passive oxygenation with non-rebreathing face mask as an alternative to bag-mask device for short duration (in adults)
• Considering supraglottic airway if intubation is delayed
• Minimizing closed circuit disconnections.

Resuscitation Considerations

“One big take-home point of the guidance is to consider resuscitation appropriateness, starting with goals of care when the patient comes to us, and continuing or stopping resuscitation when needed, based on the discussion with the family as well as local protocol,” Sasson said.

A variety of factors need to be taken into account, including age, comorbidities, and illness severity to determine the appropriateness of resuscitation, and “the likelihood of success” must be balanced “against the risk to rescuers and patients from whom resources are being diverted,” the authors state.

An Array of Scenarios

“We divided bystander CPR into adults vs pediatrics and into those who are living with a person who is in cardiac arrest – because they have already been exposed [to COVID-19] – vs those who are not living with the patient,” Sasson reported. “We also addressed the role of lay bystanders.”

For lay rescuers:

• Household members should perform at least hands-only CPR, if willing and able to do so
• Use of a face mark or cloth covering of the mouth and nose of the rescuer and/or patient may reduce the risk of transmission to a nonhousehold member
• In children, lay rescuers should perform chest compressions and “consider mouth-to-mouth resuscitation,” especially if they are household members.
• If available, an automated external defibrillator should be used to assess and treat victims of out-of-hospital cardiac arrest (OHCA).

The authors offer additional guidance for in-hospital cardiac arrest (IHCA), including addressing advanced care directives, closing the door when possible to prevent airborne contamination of adjacent space, and considering leaving the patient on a mechanical ventilator with HEPA filter.

They additionally address the special needs of neonates, recommending the presence of a “skilled attendant prepared to resuscitate, irrespective of COVID-19 status,” and stressing the importance of PPE since the mother may be a “potential source of aerosolization for the neonatal team.” Additional measures include avoidance of routine airway suctioning and the use of endotracheal medications.

Critically ill pregnant women with COVID-19 are more vulnerable to acute decompensation because of the cardiopulmonary physiological changes associated with pregnancy, the authors note. Preparation for a potential perimortem delivery should take place after 4 minutes of resuscitation and be initiated early in the resuscitation algorithm so as to allow specialized obstetrical and neonatal teams with PPE to convene.

“We will be continually updating this guidance and we are encouraging people to ask questions,” Sasson summarized.

She noted that a hospital-based COVID-19 registry is being formed to collect “clinically relevant data” that will inform and update the current guidance.

Sasson reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
 

This article first appeared on Medscape.com.

The American Heart Association (AHA) and seven other medical societies have issued interim guidance to inform treatment of victims of cardiac arrest with suspected or confirmed COVID-19, focusing on reducing provider exposure, and prioritizing oxygenation and ventilation strategies, goals of care, and appropriateness of resuscitation.

“We were very specific in calling this ‘interim guidance’ based on expert opinion because things are evolving so quickly and we are learning more and more every day as more and more patients with COVID-19 are taken care of,” corresponding author Comilla Sasson, MD, PhD, vice president, Emergency Cardiovascular Care (ECC) Science and Innovation, American Heart Association, told theheart.org | Medscape Cardiology.

“We wanted this to be a starting point for providing the clinical guidance that everyone is looking for and, as we collect more data, the guidance will change, as it has for CDC [Centers for Disease Control and Prevention] and WHO [World Health Organization],” she said.

“The guidance sought to balance the provision of timely, high-quality resuscitation to patients while simultaneously protecting rescuers,” she added.

The guidance was published online April 9 in Circulation. The AHA produced the guidelines in collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, the Society of Critical Care Anesthesiologists, and the American Society of Anesthesiologists, with support from the American Association of Critical Care Nurses and National EMS Physicians.
 

Respiratory Etiologies

“We think of cardiac arrest in adults, especially as related to cardiac etiologies, but we are now thinking of it in COVID-19 more as hypoxemia or respiratory failure, which can predispose patients to cardiac arrest,” Sasson explained.

Healthcare workers are the “highest-risk profession” for contracting the COVID-19, with resuscitations carrying “added risk” for several reasons, the authors note.

Administering CPR involves performing numerous aerosol-generating procedures that can cause viral particles to remain suspended in the air and be inhaled by those nearby, with a half-life of approximately 1 hour, they point out.

Moreover, resuscitation efforts “require numerous providers to work in close proximity to one another and the patient,” and the high-stress emergent nature of these events may result in lapses in infection-control procedures.

The guidance is designed “to protect not only the patient but also the provider and involves strategies regarding oxygenation and ventilation that differ from what we’ve done in the past since we have a strong feeling that this is a different disease process that may require different approaches than what we’ve dealt with in the past,” Sasson commented.

Reducing Provider Exposure

Providers should don PPE to protect both themselves and their colleagues from unnecessary exposure, the authors advise, noting that recommendations for PPE standards may “vary considerably,” so health or emergency medical services (EMS) standards should be taken into account.

Moreover, it is important to allow only the most essential providers into the room or on the scene. In keeping with reducing the number of rescuers, the authors recommend replacing manual chest compressions with mechanical CPR devices for patients who meet height and weight criteria in settings with “protocols and expertise in place for their use.”

COVID-19 status should be communicated to any new providers prior to their arrival on the scene, the authors stress.
 

Oxygenation and Ventilation Strategies

“Reducing risk of aerosolization during the process of intubation is key,” Sasson emphasized.

For this reason, a high-efficiency particulate air HEPA filter (if available) should be attached to any manual or mechanical ventilation device, specifically in the path of exhaled gas, before any breaths are administered.

Moreover, it is important to intubate early with a cuffed tube and connect to a mechanical ventilator, if possible. The intubator should be engaged with the “highest chance of first-pass success,” and chest compression should be paused to intubate.

To further increase the chance of a successful first intubation, use of video laryngoscopy (if available) is helpful.

Additional guidance includes:

• Using a bag-mask device (or T-piece in neonates) with a HEPA filter and a tight seal prior to intubation
• Considering passive oxygenation with non-rebreathing face mask as an alternative to bag-mask device for short duration (in adults)
• Considering supraglottic airway if intubation is delayed
• Minimizing closed circuit disconnections.

Resuscitation Considerations

“One big take-home point of the guidance is to consider resuscitation appropriateness, starting with goals of care when the patient comes to us, and continuing or stopping resuscitation when needed, based on the discussion with the family as well as local protocol,” Sasson said.

A variety of factors need to be taken into account, including age, comorbidities, and illness severity to determine the appropriateness of resuscitation, and “the likelihood of success” must be balanced “against the risk to rescuers and patients from whom resources are being diverted,” the authors state.

An Array of Scenarios

“We divided bystander CPR into adults vs pediatrics and into those who are living with a person who is in cardiac arrest – because they have already been exposed [to COVID-19] – vs those who are not living with the patient,” Sasson reported. “We also addressed the role of lay bystanders.”

For lay rescuers:

• Household members should perform at least hands-only CPR, if willing and able to do so
• Use of a face mark or cloth covering of the mouth and nose of the rescuer and/or patient may reduce the risk of transmission to a nonhousehold member
• In children, lay rescuers should perform chest compressions and “consider mouth-to-mouth resuscitation,” especially if they are household members.
• If available, an automated external defibrillator should be used to assess and treat victims of out-of-hospital cardiac arrest (OHCA).

The authors offer additional guidance for in-hospital cardiac arrest (IHCA), including addressing advanced care directives, closing the door when possible to prevent airborne contamination of adjacent space, and considering leaving the patient on a mechanical ventilator with HEPA filter.

They additionally address the special needs of neonates, recommending the presence of a “skilled attendant prepared to resuscitate, irrespective of COVID-19 status,” and stressing the importance of PPE since the mother may be a “potential source of aerosolization for the neonatal team.” Additional measures include avoidance of routine airway suctioning and the use of endotracheal medications.

Critically ill pregnant women with COVID-19 are more vulnerable to acute decompensation because of the cardiopulmonary physiological changes associated with pregnancy, the authors note. Preparation for a potential perimortem delivery should take place after 4 minutes of resuscitation and be initiated early in the resuscitation algorithm so as to allow specialized obstetrical and neonatal teams with PPE to convene.

“We will be continually updating this guidance and we are encouraging people to ask questions,” Sasson summarized.

She noted that a hospital-based COVID-19 registry is being formed to collect “clinically relevant data” that will inform and update the current guidance.

Sasson reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
 

This article first appeared on Medscape.com.

The American Heart Association (AHA) and seven other medical societies have issued interim guidance to inform treatment of victims of cardiac arrest with suspected or confirmed COVID-19, focusing on reducing provider exposure, and prioritizing oxygenation and ventilation strategies, goals of care, and appropriateness of resuscitation.

“We were very specific in calling this ‘interim guidance’ based on expert opinion because things are evolving so quickly and we are learning more and more every day as more and more patients with COVID-19 are taken care of,” corresponding author Comilla Sasson, MD, PhD, vice president, Emergency Cardiovascular Care (ECC) Science and Innovation, American Heart Association, told theheart.org | Medscape Cardiology.

“We wanted this to be a starting point for providing the clinical guidance that everyone is looking for and, as we collect more data, the guidance will change, as it has for CDC [Centers for Disease Control and Prevention] and WHO [World Health Organization],” she said.

“The guidance sought to balance the provision of timely, high-quality resuscitation to patients while simultaneously protecting rescuers,” she added.

The guidance was published online April 9 in Circulation. The AHA produced the guidelines in collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, the Society of Critical Care Anesthesiologists, and the American Society of Anesthesiologists, with support from the American Association of Critical Care Nurses and National EMS Physicians.
 

Respiratory Etiologies

“We think of cardiac arrest in adults, especially as related to cardiac etiologies, but we are now thinking of it in COVID-19 more as hypoxemia or respiratory failure, which can predispose patients to cardiac arrest,” Sasson explained.

Healthcare workers are the “highest-risk profession” for contracting the COVID-19, with resuscitations carrying “added risk” for several reasons, the authors note.

Administering CPR involves performing numerous aerosol-generating procedures that can cause viral particles to remain suspended in the air and be inhaled by those nearby, with a half-life of approximately 1 hour, they point out.

Moreover, resuscitation efforts “require numerous providers to work in close proximity to one another and the patient,” and the high-stress emergent nature of these events may result in lapses in infection-control procedures.

The guidance is designed “to protect not only the patient but also the provider and involves strategies regarding oxygenation and ventilation that differ from what we’ve done in the past since we have a strong feeling that this is a different disease process that may require different approaches than what we’ve dealt with in the past,” Sasson commented.

Reducing Provider Exposure

Providers should don PPE to protect both themselves and their colleagues from unnecessary exposure, the authors advise, noting that recommendations for PPE standards may “vary considerably,” so health or emergency medical services (EMS) standards should be taken into account.

Moreover, it is important to allow only the most essential providers into the room or on the scene. In keeping with reducing the number of rescuers, the authors recommend replacing manual chest compressions with mechanical CPR devices for patients who meet height and weight criteria in settings with “protocols and expertise in place for their use.”

COVID-19 status should be communicated to any new providers prior to their arrival on the scene, the authors stress.
 

Oxygenation and Ventilation Strategies

“Reducing risk of aerosolization during the process of intubation is key,” Sasson emphasized.

For this reason, a high-efficiency particulate air HEPA filter (if available) should be attached to any manual or mechanical ventilation device, specifically in the path of exhaled gas, before any breaths are administered.

Moreover, it is important to intubate early with a cuffed tube and connect to a mechanical ventilator, if possible. The intubator should be engaged with the “highest chance of first-pass success,” and chest compression should be paused to intubate.

To further increase the chance of a successful first intubation, use of video laryngoscopy (if available) is helpful.

Additional guidance includes:

• Using a bag-mask device (or T-piece in neonates) with a HEPA filter and a tight seal prior to intubation
• Considering passive oxygenation with non-rebreathing face mask as an alternative to bag-mask device for short duration (in adults)
• Considering supraglottic airway if intubation is delayed
• Minimizing closed circuit disconnections.

Resuscitation Considerations

“One big take-home point of the guidance is to consider resuscitation appropriateness, starting with goals of care when the patient comes to us, and continuing or stopping resuscitation when needed, based on the discussion with the family as well as local protocol,” Sasson said.

A variety of factors need to be taken into account, including age, comorbidities, and illness severity to determine the appropriateness of resuscitation, and “the likelihood of success” must be balanced “against the risk to rescuers and patients from whom resources are being diverted,” the authors state.

An Array of Scenarios

“We divided bystander CPR into adults vs pediatrics and into those who are living with a person who is in cardiac arrest – because they have already been exposed [to COVID-19] – vs those who are not living with the patient,” Sasson reported. “We also addressed the role of lay bystanders.”

For lay rescuers:

• Household members should perform at least hands-only CPR, if willing and able to do so
• Use of a face mark or cloth covering of the mouth and nose of the rescuer and/or patient may reduce the risk of transmission to a nonhousehold member
• In children, lay rescuers should perform chest compressions and “consider mouth-to-mouth resuscitation,” especially if they are household members.
• If available, an automated external defibrillator should be used to assess and treat victims of out-of-hospital cardiac arrest (OHCA).

The authors offer additional guidance for in-hospital cardiac arrest (IHCA), including addressing advanced care directives, closing the door when possible to prevent airborne contamination of adjacent space, and considering leaving the patient on a mechanical ventilator with HEPA filter.

They additionally address the special needs of neonates, recommending the presence of a “skilled attendant prepared to resuscitate, irrespective of COVID-19 status,” and stressing the importance of PPE since the mother may be a “potential source of aerosolization for the neonatal team.” Additional measures include avoidance of routine airway suctioning and the use of endotracheal medications.

Critically ill pregnant women with COVID-19 are more vulnerable to acute decompensation because of the cardiopulmonary physiological changes associated with pregnancy, the authors note. Preparation for a potential perimortem delivery should take place after 4 minutes of resuscitation and be initiated early in the resuscitation algorithm so as to allow specialized obstetrical and neonatal teams with PPE to convene.

“We will be continually updating this guidance and we are encouraging people to ask questions,” Sasson summarized.

She noted that a hospital-based COVID-19 registry is being formed to collect “clinically relevant data” that will inform and update the current guidance.

Sasson reports no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
 

This article first appeared on Medscape.com.

The controversy regarding the safety of treating peripheral artery disease (PAD) with paclitaxel-coated devices has only deepened in the new year, with two recent studies suggesting opposite safety findings.
 

The debate began with a 2018 meta-analysis showing a late mortality signal associated with paclitaxel drug-coated balloons (DCBs) that sent reverberations through the interventional cardiology community (J Am Heart Assoc. 2018 Dec 18;7[24]:e011245).

Now, in a new meta-analysis involving eight randomized controlled trials (RCTs) and more than 1,400 patients with critical limb ischemia (CLI), the same researchers found significantly more early amputations and deaths in those treated with DCB below the knee, compared with conventional balloon angioplasty.

“The findings of our latest report add to previous evidence underpinning major safety concerns around use of paclitaxel in lower limb angioplasties – increased long-term patient mortality in cases of intermittent claudication,” lead author Konstantinos Katsanos MD, MSc, PhD, Patras University Hospital, Greece, said in an interview.

By contrast, a retrospective study of insurance claims in Germany showed no heightened mortality with paclitaxel-coated balloons and stents, compared with uncoated devices, in close to 38,000 patients with PAD.

On the contrary, use of paclitaxel-coated devices was associated with higher long-term survival, better amputation-free survival (AFS), and lower rates of major cardiovascular events in the treatment of chronic limb-threatening ischemia (CLTI).

These findings “emphasize the difference between population-based evidence and randomized trials,” lead author Christian-Alexander Behrendt, MD, University Medical Center Hamburg-Eppendorf, Germany, said in an interview.

Downstream “showers”

In the new meta-analysis led by Dr. Katsanos, published online Jan. 15, the 1,420 patients were treated with five different DCBs and 97% had CLI (J Vasc Intervent Radiol 2020 Feb;31[2]:202-12).

In up to 1-year follow-up, the paclitaxel DCB group had fewer target lesion revascularizations (TLR) than those of the uncoated device group (11.8% vs. 25.6%; risk ratio, 0.53; 95% confidence interval, 0.35-0.81) but worse AFS (13.7% vs. 9.4%; hazard ratio [HR], 1.52; 95% CI, 1.12-2.07).

The latter finding was driven by nonsignificant increased risks for all-cause death (odds ratio [OR], 1.39; 95% CI, 0.94-2.07) and major amputations (OR, 1.63; 95% CI, 0.92-2.90).

In dose-subgroup analyses, AFS was significantly worse in cases with high-dose (3.0-3.5 mcg/mm²) devices, but not in the single trial with a low-dose DCB (2.0 mcg/mm²).

“Considering the well-described downstream ‘showers’ of paclitaxel particles with current drug-coated balloons, we hypothesize that nontarget paclitaxel embolization is a plausible mechanism for distal foot and systemic toxicity,” Dr. Katsanos said.

Short time frame

Eric Secemsky, MD, of Harvard Medical School, and director of vascular intervention at Beth Israel Deaconess Medical Center, Boston, suggested in an interview that this theorized mechanism of harm in below-the-knee procedures could potentially shed light on a similar mechanism at play in above-the-knee procedures.

“We didn’t understand why people could potentially be dying in above-the-knee [procedures], and the suggestion here is that these devices might perhaps be causing particular embolization or maybe delayed wound healing,” Dr. Secemsky speculated.

However, “I don’t know that this is true, so I am cautious to say this is true,” he emphasized.

Dr. Secemsky said a strength of the Katsanos analysis is that the RCTs included more than 1,000 patients, but noted that it is hard to vet the quality and rigor of the data, as some of the studies have not yet been published. He also noted that paclitaxel-coated devices are not approved by the Food and Drug Administration in the United States for below-the-knee procedures.

Moreover, he continued, “two studies were driving the signal of harm: the IN.PACT DEEP, which included an iteration of their DCB that is no longer being tested; and the unpublished SINGA-PACLI trial. Those studies contributed most of the adverse events seen in this meta-analysis.”

In addition, the trials had different lengths of follow-up (6-12 months), he said. “Thus, the five trials with data available to 12 months are driving the 1-year findings, whereas three RCTs, including the primary RCT showing safety [Lutonix-BTK trial], only contribute data to 6 months.”

For this reason, “we are not too excited about this meta-analysis as of now, [because] all it tells us is that we need more data to support the safety of drug-coated devices in this population,” Dr. Secemsky said.

Dr. Katsanos explained that, “to address the differences in follow-up period and number of cases lost to follow-up, the primary endpoint was calculated on the log-hazard scale and expressed as a hazard ratio, as recommended for time-to-event outcomes.”

He highlighted that a short-term time frame of 6 months to 1 year was chosen “because it is clinically relevant to limb-threatening CLI.”

Sensitivity tests also “showed consistent direction and magnitude of the summary treatment effects in case of both AFS and freedom from TLR,” Dr. Katsanos emphasized.

Lower mortality, fewer amputations

The second study, published online Jan. 8, drew on health insurance claims in the German BARMER database to analyze 37,914 patients (mean age, 73.3 years, 49% female) and 21,546 propensity-score-matched patients with symptomatic CLTI or intermittent claudication (IC) with an index revascularization during 2010-2018 (Eur J Vasc Endovasc Surg. 2020 Jan 8. doi: 10.1016/j.ejvs.2019.12.034).

Patients were first stratified by CLTI or IC, and then by balloon vs. stent use. Paclitaxel-coated devices were then compared with uncoated devices within each stratum. The primary outcome was all-cause mortality at the end of follow-up.

From 2010 to 2018, the annual use of paclitaxel-coated devices increased dramatically from 3% to 39% in the CLTI group and from 4% to 48% in the IC group (P less than .001 for both).

A total of 2,454 deaths occurred within 5 years of follow-up (median, 2.7 years; longest, 8 years).

A Cox proportional hazards model (based on propensity-score-matched cohorts at 5 years) showed that, compared with uncoated devices, use of paclitaxel-coated devices in the CLTI group was associated with several improvements:

• Overall survival: HR, 0.83; 95% CI, 0.77-0.90.
• Amputation-free survival: HR, 0.85; 95% CI, 0.78-0.91.
• Major cardiovascular events: HR, 0.82; 95% CI, 0.77-0.88.

In the IC group, mortality was significantly better with DCB (HR, 0.87; 95% CI, 0.76-0.99) or a combination of DCB and drug-eluting stents (HR, 0.88; 95% CI, 0.80-0.98) than with uncoated devices, but similar for DES alone (HR, 0.91; 95% CI, 0.77-1.08).

No benefit was found for paclitaxel-coated devices in the IC group for AFS (HR, 0.91; 95% CI, 0.82-1.00) or major cardiovascular events (HR, 0.93; 95% CI, 0.87-1.00).

The authors acknowledge that “unmeasured confounding” may partly explain the results. It may be that patients revascularized with DCB or DES “are more likely to be treated in highly specialized trial centers with clear follow-up protocol.”

Moreover, these patients may have received “the best treatment,” including statin therapy, added Dr. Behrendt.

More evidence needed

Dr. Secemsky, who was not involved with either study, said the German investigators “did a wonderful job with this analysis in a large population of several thousand patients, showing nicely that after accounting for differences in comorbidities, the patients had no evidence of harm with [paclitaxel-coated] devices through 5 years.”

However, he cautioned, median follow-up time was just over 2 years. “Although the investigators had data all the way out to 5 years, over time, the number of patients contributing data became smaller, which results in more uncertainty with these longer-term findings,” he said. “As such, we still need to look at additional long-term data in this patient population to confirm the safety of these devices.”

At present, the “major consideration we want to address is whether it’s safe to use these devices, and we’re undertaking these analyses to examine safety, not to see if they improve mortality,” although the present study “has a suggestion of mortality benefit,” Dr. Secemsky said.

Dr. Katsanos added that paclitaxel-coated balloons “remain under investigation for below-knee arteries and critical limb ischemia,” with “a few randomized controlled trials on the way.”

“We need definitive evidence from high-quality multicenter controlled trials that these devices may improve wound healing and limb salvage without any systemic mortality risk,” he said.

Dr. Katsanos receives personal fees from Boston Scientific and Philips Healthcare. The study by Dr. Behrendt was part of the IDOMENEO project funded by the German Joint Federal Committee. Dr. Behrendt reports no relevant financial relationships. Dr. Secemsky reports institutional grants from Cook Medical, BD Bard, Medtronic, Beth Israel Deaconess Medical Center, and Boston Scientific, and reports consultancy for Cook Medical, BD Bard, and Medtronic.
 

This article first appeared on Medscape.com.

The controversy regarding the safety of treating peripheral artery disease (PAD) with paclitaxel-coated devices has only deepened in the new year, with two recent studies suggesting opposite safety findings.
 

The debate began with a 2018 meta-analysis showing a late mortality signal associated with paclitaxel drug-coated balloons (DCBs) that sent reverberations through the interventional cardiology community (J Am Heart Assoc. 2018 Dec 18;7[24]:e011245).

Now, in a new meta-analysis involving eight randomized controlled trials (RCTs) and more than 1,400 patients with critical limb ischemia (CLI), the same researchers found significantly more early amputations and deaths in those treated with DCB below the knee, compared with conventional balloon angioplasty.

“The findings of our latest report add to previous evidence underpinning major safety concerns around use of paclitaxel in lower limb angioplasties – increased long-term patient mortality in cases of intermittent claudication,” lead author Konstantinos Katsanos MD, MSc, PhD, Patras University Hospital, Greece, said in an interview.

By contrast, a retrospective study of insurance claims in Germany showed no heightened mortality with paclitaxel-coated balloons and stents, compared with uncoated devices, in close to 38,000 patients with PAD.

On the contrary, use of paclitaxel-coated devices was associated with higher long-term survival, better amputation-free survival (AFS), and lower rates of major cardiovascular events in the treatment of chronic limb-threatening ischemia (CLTI).

These findings “emphasize the difference between population-based evidence and randomized trials,” lead author Christian-Alexander Behrendt, MD, University Medical Center Hamburg-Eppendorf, Germany, said in an interview.

Downstream “showers”

In the new meta-analysis led by Dr. Katsanos, published online Jan. 15, the 1,420 patients were treated with five different DCBs and 97% had CLI (J Vasc Intervent Radiol 2020 Feb;31[2]:202-12).

In up to 1-year follow-up, the paclitaxel DCB group had fewer target lesion revascularizations (TLR) than those of the uncoated device group (11.8% vs. 25.6%; risk ratio, 0.53; 95% confidence interval, 0.35-0.81) but worse AFS (13.7% vs. 9.4%; hazard ratio [HR], 1.52; 95% CI, 1.12-2.07).

The latter finding was driven by nonsignificant increased risks for all-cause death (odds ratio [OR], 1.39; 95% CI, 0.94-2.07) and major amputations (OR, 1.63; 95% CI, 0.92-2.90).

In dose-subgroup analyses, AFS was significantly worse in cases with high-dose (3.0-3.5 mcg/mm²) devices, but not in the single trial with a low-dose DCB (2.0 mcg/mm²).

“Considering the well-described downstream ‘showers’ of paclitaxel particles with current drug-coated balloons, we hypothesize that nontarget paclitaxel embolization is a plausible mechanism for distal foot and systemic toxicity,” Dr. Katsanos said.

Short time frame

Eric Secemsky, MD, of Harvard Medical School, and director of vascular intervention at Beth Israel Deaconess Medical Center, Boston, suggested in an interview that this theorized mechanism of harm in below-the-knee procedures could potentially shed light on a similar mechanism at play in above-the-knee procedures.

“We didn’t understand why people could potentially be dying in above-the-knee [procedures], and the suggestion here is that these devices might perhaps be causing particular embolization or maybe delayed wound healing,” Dr. Secemsky speculated.

However, “I don’t know that this is true, so I am cautious to say this is true,” he emphasized.

Dr. Secemsky said a strength of the Katsanos analysis is that the RCTs included more than 1,000 patients, but noted that it is hard to vet the quality and rigor of the data, as some of the studies have not yet been published. He also noted that paclitaxel-coated devices are not approved by the Food and Drug Administration in the United States for below-the-knee procedures.

Moreover, he continued, “two studies were driving the signal of harm: the IN.PACT DEEP, which included an iteration of their DCB that is no longer being tested; and the unpublished SINGA-PACLI trial. Those studies contributed most of the adverse events seen in this meta-analysis.”

In addition, the trials had different lengths of follow-up (6-12 months), he said. “Thus, the five trials with data available to 12 months are driving the 1-year findings, whereas three RCTs, including the primary RCT showing safety [Lutonix-BTK trial], only contribute data to 6 months.”

For this reason, “we are not too excited about this meta-analysis as of now, [because] all it tells us is that we need more data to support the safety of drug-coated devices in this population,” Dr. Secemsky said.

Dr. Katsanos explained that, “to address the differences in follow-up period and number of cases lost to follow-up, the primary endpoint was calculated on the log-hazard scale and expressed as a hazard ratio, as recommended for time-to-event outcomes.”

He highlighted that a short-term time frame of 6 months to 1 year was chosen “because it is clinically relevant to limb-threatening CLI.”

Sensitivity tests also “showed consistent direction and magnitude of the summary treatment effects in case of both AFS and freedom from TLR,” Dr. Katsanos emphasized.

Lower mortality, fewer amputations

The second study, published online Jan. 8, drew on health insurance claims in the German BARMER database to analyze 37,914 patients (mean age, 73.3 years, 49% female) and 21,546 propensity-score-matched patients with symptomatic CLTI or intermittent claudication (IC) with an index revascularization during 2010-2018 (Eur J Vasc Endovasc Surg. 2020 Jan 8. doi: 10.1016/j.ejvs.2019.12.034).

Patients were first stratified by CLTI or IC, and then by balloon vs. stent use. Paclitaxel-coated devices were then compared with uncoated devices within each stratum. The primary outcome was all-cause mortality at the end of follow-up.

From 2010 to 2018, the annual use of paclitaxel-coated devices increased dramatically from 3% to 39% in the CLTI group and from 4% to 48% in the IC group (P less than .001 for both).

A total of 2,454 deaths occurred within 5 years of follow-up (median, 2.7 years; longest, 8 years).

A Cox proportional hazards model (based on propensity-score-matched cohorts at 5 years) showed that, compared with uncoated devices, use of paclitaxel-coated devices in the CLTI group was associated with several improvements:

• Overall survival: HR, 0.83; 95% CI, 0.77-0.90.
• Amputation-free survival: HR, 0.85; 95% CI, 0.78-0.91.
• Major cardiovascular events: HR, 0.82; 95% CI, 0.77-0.88.

In the IC group, mortality was significantly better with DCB (HR, 0.87; 95% CI, 0.76-0.99) or a combination of DCB and drug-eluting stents (HR, 0.88; 95% CI, 0.80-0.98) than with uncoated devices, but similar for DES alone (HR, 0.91; 95% CI, 0.77-1.08).

No benefit was found for paclitaxel-coated devices in the IC group for AFS (HR, 0.91; 95% CI, 0.82-1.00) or major cardiovascular events (HR, 0.93; 95% CI, 0.87-1.00).

The authors acknowledge that “unmeasured confounding” may partly explain the results. It may be that patients revascularized with DCB or DES “are more likely to be treated in highly specialized trial centers with clear follow-up protocol.”

Moreover, these patients may have received “the best treatment,” including statin therapy, added Dr. Behrendt.

More evidence needed

Dr. Secemsky, who was not involved with either study, said the German investigators “did a wonderful job with this analysis in a large population of several thousand patients, showing nicely that after accounting for differences in comorbidities, the patients had no evidence of harm with [paclitaxel-coated] devices through 5 years.”

However, he cautioned, median follow-up time was just over 2 years. “Although the investigators had data all the way out to 5 years, over time, the number of patients contributing data became smaller, which results in more uncertainty with these longer-term findings,” he said. “As such, we still need to look at additional long-term data in this patient population to confirm the safety of these devices.”

At present, the “major consideration we want to address is whether it’s safe to use these devices, and we’re undertaking these analyses to examine safety, not to see if they improve mortality,” although the present study “has a suggestion of mortality benefit,” Dr. Secemsky said.

Dr. Katsanos added that paclitaxel-coated balloons “remain under investigation for below-knee arteries and critical limb ischemia,” with “a few randomized controlled trials on the way.”

“We need definitive evidence from high-quality multicenter controlled trials that these devices may improve wound healing and limb salvage without any systemic mortality risk,” he said.

Dr. Katsanos receives personal fees from Boston Scientific and Philips Healthcare. The study by Dr. Behrendt was part of the IDOMENEO project funded by the German Joint Federal Committee. Dr. Behrendt reports no relevant financial relationships. Dr. Secemsky reports institutional grants from Cook Medical, BD Bard, Medtronic, Beth Israel Deaconess Medical Center, and Boston Scientific, and reports consultancy for Cook Medical, BD Bard, and Medtronic.
 

This article first appeared on Medscape.com.

The controversy regarding the safety of treating peripheral artery disease (PAD) with paclitaxel-coated devices has only deepened in the new year, with two recent studies suggesting opposite safety findings.
 

The debate began with a 2018 meta-analysis showing a late mortality signal associated with paclitaxel drug-coated balloons (DCBs) that sent reverberations through the interventional cardiology community (J Am Heart Assoc. 2018 Dec 18;7[24]:e011245).

Now, in a new meta-analysis involving eight randomized controlled trials (RCTs) and more than 1,400 patients with critical limb ischemia (CLI), the same researchers found significantly more early amputations and deaths in those treated with DCB below the knee, compared with conventional balloon angioplasty.

“The findings of our latest report add to previous evidence underpinning major safety concerns around use of paclitaxel in lower limb angioplasties – increased long-term patient mortality in cases of intermittent claudication,” lead author Konstantinos Katsanos MD, MSc, PhD, Patras University Hospital, Greece, said in an interview.

By contrast, a retrospective study of insurance claims in Germany showed no heightened mortality with paclitaxel-coated balloons and stents, compared with uncoated devices, in close to 38,000 patients with PAD.

On the contrary, use of paclitaxel-coated devices was associated with higher long-term survival, better amputation-free survival (AFS), and lower rates of major cardiovascular events in the treatment of chronic limb-threatening ischemia (CLTI).

These findings “emphasize the difference between population-based evidence and randomized trials,” lead author Christian-Alexander Behrendt, MD, University Medical Center Hamburg-Eppendorf, Germany, said in an interview.

Downstream “showers”

In the new meta-analysis led by Dr. Katsanos, published online Jan. 15, the 1,420 patients were treated with five different DCBs and 97% had CLI (J Vasc Intervent Radiol 2020 Feb;31[2]:202-12).

In up to 1-year follow-up, the paclitaxel DCB group had fewer target lesion revascularizations (TLR) than those of the uncoated device group (11.8% vs. 25.6%; risk ratio, 0.53; 95% confidence interval, 0.35-0.81) but worse AFS (13.7% vs. 9.4%; hazard ratio [HR], 1.52; 95% CI, 1.12-2.07).

The latter finding was driven by nonsignificant increased risks for all-cause death (odds ratio [OR], 1.39; 95% CI, 0.94-2.07) and major amputations (OR, 1.63; 95% CI, 0.92-2.90).

In dose-subgroup analyses, AFS was significantly worse in cases with high-dose (3.0-3.5 mcg/mm²) devices, but not in the single trial with a low-dose DCB (2.0 mcg/mm²).

“Considering the well-described downstream ‘showers’ of paclitaxel particles with current drug-coated balloons, we hypothesize that nontarget paclitaxel embolization is a plausible mechanism for distal foot and systemic toxicity,” Dr. Katsanos said.

Short time frame

Eric Secemsky, MD, of Harvard Medical School, and director of vascular intervention at Beth Israel Deaconess Medical Center, Boston, suggested in an interview that this theorized mechanism of harm in below-the-knee procedures could potentially shed light on a similar mechanism at play in above-the-knee procedures.

“We didn’t understand why people could potentially be dying in above-the-knee [procedures], and the suggestion here is that these devices might perhaps be causing particular embolization or maybe delayed wound healing,” Dr. Secemsky speculated.

However, “I don’t know that this is true, so I am cautious to say this is true,” he emphasized.

Dr. Secemsky said a strength of the Katsanos analysis is that the RCTs included more than 1,000 patients, but noted that it is hard to vet the quality and rigor of the data, as some of the studies have not yet been published. He also noted that paclitaxel-coated devices are not approved by the Food and Drug Administration in the United States for below-the-knee procedures.

Moreover, he continued, “two studies were driving the signal of harm: the IN.PACT DEEP, which included an iteration of their DCB that is no longer being tested; and the unpublished SINGA-PACLI trial. Those studies contributed most of the adverse events seen in this meta-analysis.”

In addition, the trials had different lengths of follow-up (6-12 months), he said. “Thus, the five trials with data available to 12 months are driving the 1-year findings, whereas three RCTs, including the primary RCT showing safety [Lutonix-BTK trial], only contribute data to 6 months.”

For this reason, “we are not too excited about this meta-analysis as of now, [because] all it tells us is that we need more data to support the safety of drug-coated devices in this population,” Dr. Secemsky said.

Dr. Katsanos explained that, “to address the differences in follow-up period and number of cases lost to follow-up, the primary endpoint was calculated on the log-hazard scale and expressed as a hazard ratio, as recommended for time-to-event outcomes.”

He highlighted that a short-term time frame of 6 months to 1 year was chosen “because it is clinically relevant to limb-threatening CLI.”

Sensitivity tests also “showed consistent direction and magnitude of the summary treatment effects in case of both AFS and freedom from TLR,” Dr. Katsanos emphasized.

Lower mortality, fewer amputations

The second study, published online Jan. 8, drew on health insurance claims in the German BARMER database to analyze 37,914 patients (mean age, 73.3 years, 49% female) and 21,546 propensity-score-matched patients with symptomatic CLTI or intermittent claudication (IC) with an index revascularization during 2010-2018 (Eur J Vasc Endovasc Surg. 2020 Jan 8. doi: 10.1016/j.ejvs.2019.12.034).

Patients were first stratified by CLTI or IC, and then by balloon vs. stent use. Paclitaxel-coated devices were then compared with uncoated devices within each stratum. The primary outcome was all-cause mortality at the end of follow-up.

From 2010 to 2018, the annual use of paclitaxel-coated devices increased dramatically from 3% to 39% in the CLTI group and from 4% to 48% in the IC group (P less than .001 for both).

A total of 2,454 deaths occurred within 5 years of follow-up (median, 2.7 years; longest, 8 years).

A Cox proportional hazards model (based on propensity-score-matched cohorts at 5 years) showed that, compared with uncoated devices, use of paclitaxel-coated devices in the CLTI group was associated with several improvements:

• Overall survival: HR, 0.83; 95% CI, 0.77-0.90.
• Amputation-free survival: HR, 0.85; 95% CI, 0.78-0.91.
• Major cardiovascular events: HR, 0.82; 95% CI, 0.77-0.88.

In the IC group, mortality was significantly better with DCB (HR, 0.87; 95% CI, 0.76-0.99) or a combination of DCB and drug-eluting stents (HR, 0.88; 95% CI, 0.80-0.98) than with uncoated devices, but similar for DES alone (HR, 0.91; 95% CI, 0.77-1.08).

No benefit was found for paclitaxel-coated devices in the IC group for AFS (HR, 0.91; 95% CI, 0.82-1.00) or major cardiovascular events (HR, 0.93; 95% CI, 0.87-1.00).

The authors acknowledge that “unmeasured confounding” may partly explain the results. It may be that patients revascularized with DCB or DES “are more likely to be treated in highly specialized trial centers with clear follow-up protocol.”

Moreover, these patients may have received “the best treatment,” including statin therapy, added Dr. Behrendt.

More evidence needed

Dr. Secemsky, who was not involved with either study, said the German investigators “did a wonderful job with this analysis in a large population of several thousand patients, showing nicely that after accounting for differences in comorbidities, the patients had no evidence of harm with [paclitaxel-coated] devices through 5 years.”

However, he cautioned, median follow-up time was just over 2 years. “Although the investigators had data all the way out to 5 years, over time, the number of patients contributing data became smaller, which results in more uncertainty with these longer-term findings,” he said. “As such, we still need to look at additional long-term data in this patient population to confirm the safety of these devices.”

At present, the “major consideration we want to address is whether it’s safe to use these devices, and we’re undertaking these analyses to examine safety, not to see if they improve mortality,” although the present study “has a suggestion of mortality benefit,” Dr. Secemsky said.

Dr. Katsanos added that paclitaxel-coated balloons “remain under investigation for below-knee arteries and critical limb ischemia,” with “a few randomized controlled trials on the way.”

“We need definitive evidence from high-quality multicenter controlled trials that these devices may improve wound healing and limb salvage without any systemic mortality risk,” he said.

Dr. Katsanos receives personal fees from Boston Scientific and Philips Healthcare. The study by Dr. Behrendt was part of the IDOMENEO project funded by the German Joint Federal Committee. Dr. Behrendt reports no relevant financial relationships. Dr. Secemsky reports institutional grants from Cook Medical, BD Bard, Medtronic, Beth Israel Deaconess Medical Center, and Boston Scientific, and reports consultancy for Cook Medical, BD Bard, and Medtronic.
 

This article first appeared on Medscape.com.