Peripheral Vascular Disorders

A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.

The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.

“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”

“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.

Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.

VOYAGER PAD trial

The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).

Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.

“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.

[email protected]

SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.

A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.

The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.

“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”

“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.

Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.

VOYAGER PAD trial

The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).

Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.

“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.

[email protected]

SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.

A combined antithrombotic regimen of rivaroxaban plus aspirin was safe and effective for reducing ischemic events in patients with symptomatic peripheral artery disease who had just undergone peripheral artery revascularization in VOYAGER PAD, a multicenter randomized trial with nearly 6,600 patients.

The study and its results were a groundbreaking advance for this patient population, who until now have had no evidence-based treatment available, Mark P. Bonaca, MD, said on March 28 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

The study design excluded a small percentage of patients (about 2%) because of their very high bleeding-risk history. Among the treated patients, in those who received a combination of 2.5 mg rivaroxaban twice daily plus 100 mg of aspirin daily, bleeding events were more common, compared with control patients who received aspirin alone. But the patients who received both drugs showed no excess of fatal bleeds or intracranial hemorrhages, and the rate of ischemic events prevented by rivaroxaban plus aspirin exceeded the excess rate of bleeds by three- to sixfold, depending on how bleeding episodes were defined, noted Dr. Bonaca, executive director of CPC Clinical Research and CPC Community Health, an academic research organization affiliated with the University of Colorado at Denver in Aurora.

“This was a much anticipated and important trial. Those of us who treat patients with lower-limb peripheral artery disease have not had much evidence on how to treat these patients, particularly those who have just undergone revascularization. This trial gives us the evidence,” commented Mark A. Creager, MD, professor of medicine and director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. “The bleeding risk [from adding rivaroxaban treatment] was substantially less than the benefit from preventing major adverse limb events and major adverse cardiovascular events,” producing a “favorable balance” of benefit, compared with risk, Dr. Creager said in an interview. “In the right patients, the benefit greatly outweighed the risk.”

“This was an incredible trial that will advance care,” commented Joshua A. Beckman, MD, professor of medicine and director of Vascular Medicine at Vanderbilt University in Nashville, Tenn. “The treatment was beneficial for patients across a range of symptom severity, from claudication to critical limb ischemia,” and the results expand the range of patients proven to benefit from the rivaroxaban plus aspirin combination from the types of patients with peripheral artery disease (PAD) enrolled in the COMPASS trial. That pivotal trial showed similar benefit from the dual-antithrombotic regimen, but in patients who had both coronary artery disease as well as atherosclerotic disease in at least one additional vascular bed, such as lower-limb arteries (N Engl J Med. 2017 Oct 5;377[14]:1319-30). In addition to “bringing acute limb ischemia to the cardiovascular community,” the results also identified a very useful time point in the clinical presentation of these patients for starting a combined rivaroxaban plus aspirin regimen: when patients are hospitalized for their revascularization procedure, said Dr. Beckman, a designated discussant for the report.

Among the 6,564 patients randomized in the study, about two-thirds underwent endovascular revascularization within 10 days before starting their study treatment, and the remaining third had undergone surgical revascularization. The study focused on patients “with symptomatic PAD but without known coronary artery disease,” noted Dr. Bonaca.

VOYAGER PAD trial

The VOYAGER PAD (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular Or Surgical Limb Revascularization for Peripheral Artery Disease) trial enrolled patients during 2015-2018 at 534 sites in 34 countries. The study’s primary endpoint was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes, and was reduced during a median follow-up of 28 months from 19.9% with aspirin alone to 17.3% on the combined regimen, a 2.6% absolute difference and a 15% relative risk reduction that was statistically significant, an endpoint primarily driven by a reduction in acute limb ischemia. The primary safety endpoint was the rate of TIMI (Thrombolysis in Myocardial Infarction) major bleeds, which was 0.8% higher in the patients who received the anticoagulant, a 43% relative increase that just missed statistical significance. But that result demonstrated the small but important increased risk for bleeding events that the dual regimen produced in these patients, Dr. Bonaca said. Simultaneously with his report the findings also appeared in an article published online (N Engl J Med. 2020 Mar 28. doi: 10.1056/NEJMoa2000052).

Dr. Bonaca cautioned that one limitation of his report on the primary outcome of VOYAGER PAD is that the results of an important subgroup analysis won’t be known until a second report during the ACC online sessions on March 29, which will examine the impact that treatment with the antiplatelet drug clopidogrel had on both the efficacy and safety outcomes. Half of the enrolled patients received clopidogrel at the discretion of their treating physicians; addition or exclusion of concurrent clopidogrel treatment was outside of the study’s design. “Is efficacy the same with or without clopidogrel, and what is the bleeding cost,” especially in patients who receive three antithrombotic drugs? “It will be very important to understand,” Dr. Bonaca said.

“Until now, we had no idea of what was the best antithrombotic strategy for patients after a successful peripheral vascular intervention.” VOYAGER PAD was “an unprecedented vascular study that addressed an unmet patient need,” commented Roxana Mehran, MD, a designated discussant for the study and professor of medicine and director of Interventional Cardiovascular Research at Mount Sinai Medical Center in New York.

VOYAGER PAD was sponsored by Bayer and Janssen, the companies that market rivaroxaban (Xarelto). The institution that Dr. Bonaca directs has received research funding from Bayer and Janssen, and also from Amgen, Aralez, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi. Dr. Creager had no disclosures. Dr. Beckman has served as a data safety monitor for Bayer and for Novartis, and has been a consultant to Amgen, AstraZeneca, JanOne and Sanofi. Dr. Mehran has received research funding from Bayer and has been a consultant to Janssen, and she has also received research funding or been a consultant to several other companies.

[email protected]

SOURCE: Bonaca MP et al. ACC 20, Abstract 402-10.

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.

Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.

Pavel1964/Getty Images

Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.

Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.

“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”

The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.

Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.

Anthropometric data, peripheral BP, and aerobic capacity (peak VO₂) were also assessed at both study points.

Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.

Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.

For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.

The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.

In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.

The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.

Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO₂ didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.

The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.

Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”

The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.

[email protected]

SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.

Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.

Pavel1964/Getty Images

Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.

Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.

“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”

The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.

Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.

Anthropometric data, peripheral BP, and aerobic capacity (peak VO₂) were also assessed at both study points.

Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.

Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.

For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.

The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.

In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.

The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.

Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO₂ didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.

The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.

Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”

The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.

[email protected]

SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.

Persons who trained for a marathon showed improvement in age-related aortic stiffness and reduction in blood pressure in a study of 138 first-time completers of the London Marathon.

Pavel1964/Getty Images

Compared with pretraining values, the descending aortas of marathon completers were 9% more distensible at the level of the bifurcation of the pulmonary artery and 16% more distensible at the level of the diaphragm (P = .0009 and .002, respectively). There was no change in distensibility of the ascending aorta.

Additionally, central systolic BP dropped by 4 mm Hg and diastolic BP by 3 mm Hg by the time marathon training was completed.

“Training and completion of a first-time marathon result in beneficial reductions in BP and intrinsic aortic stiffening in healthy participants,” concluded Anish Bhuva, MBBS, and coinvestigators. “These changes are equivalent to approximately a 4-year reduction in vascular age.”

The study points to a role for exercise in the reduction of arterial stiffness, a known aging-related contributor to cardiovascular disease for which there currently is no good pharmacologic option, said Julio Chirinos, MD, Phd, in an accompanying editorial (J Am Coll Cardiol. 2020 Jan 6. doi: 10.1016/j.jacc.2019.11.007). The challenge lies in implementing exercise interventions on a large scale in societies where “there remains an immense paradoxical gap” between the known benefits of physical activity and increasingly sedentary populations, he added, calling for increased implementation research.

Using cardiovascular magnetic resonance to assess aortic distensibility, Dr. Bhuva, of the Institute of Cardiovascular Science, University College London, and colleagues assessed aortic BP and aortic stiffness at two points via the noninvasive imaging method. The first assessment was conducted before the study participants began marathon training; the second was obtained between 1 and 3 weeks after marathon completion, after any acute effects of the marathon had abated.

Anthropometric data, peripheral BP, and aerobic capacity (peak VO₂) were also assessed at both study points.

Although the study wasn’t designed to track individual training regimens, first-time London Marathon participants were given a 17-week “Beginner’s Training Plan” by event organizers, and asked to follow the plan while participating in the study. The goal of the beginner’s plan was marathon completion, with a schedule of about three runs weekly increasing in duration and intensity over the training period.

Participants had to be first-time marathon participants and running less than 2 hours per week at enrollment. Only those who completed the marathon were included in the data analysis, though baseline characteristics didn’t differ between completers and those who dropped out.

For 2016, the first study year, only participants aged 18-39 years were included, while in 2017, all ages were included in the study. The final age range was 21-69 years, with a mean age of 37; 51% of participants were female. Those with a history of hypertension or taking antihypertensive medication and those who had other significant medical conditions were excluded.

The differential increase in distensibility along the length of the aorta reflects known differences in tissue composition, agreed the authors and Dr. Chirinos, a cardiologist at the University of Pennsylvania, Philadelphia. In addition to the magnetic resonance–obtained distensibility measurements, the investigators conducted further calculations to adjust for baseline mean central arterial pressure, since arterial stiffness is a function both of intrinsic tissue characteristics and loading conditions.

In youth, aortic distensibility buffers the effect of pulse pressure on both the left ventricle and the peripheral vascular system. As the aorta and other large arteries stiffen predictably with age, isolated systolic hypertension can result. The stiffening “also favors adverse patterns of pulsatile left ventricular overload,” which can lead to left ventricular remodeling and, eventually, heart failure, noted Dr. Chirinos. Reduced aortic pliancy also allows pulse pressure variation to be transmitted downstream “into the microvasculature of target organs (such as the kidney and brain) that require high blood flow and thus operate at low arteriolar resistance,” he added.

The assessment that marathon training reversed aortic age by a median 3.9 years was derived from the baseline cross-sectional data regarding participants’ age and aortic stiffness. The effect size was largest in those older than 37 years and in those with higher baseline systolic BP, and men saw greater benefit by a median 1.4 years. Those with slower running times also saw greater benefit.

Study participants had small but significant reductions in heart rate, body fat percentage, and weight by the postmarathon assessment, but these differences were not associated with changes in aortic stiffness. Aerobic exercise capacity as measured by peak VO₂ didn’t change significantly from pre- to post training, but the fact that participants were semirecumbent during exercise testing (to allow concurrent echocardiography) may have affected results.

The real-world design of this study had the strengths of assessing free-living, healthy individuals who participated in a self-directed training plan. Dr. Bhuva and coauthors acknowledged that marathon training may include changes in diet, sleep, and other potentially confounding lifestyle factors, as well as improvement in lipid and glucose metabolism. Further, noted Dr. Chirinos, there was no control group. Also, results from individuals training for an endurance event may have limited generalizability to the general population.

Still, said Dr. Chirinos, the innovative study design took advantage of a large-scale athletic event to see how a realistic training regimen affected healthy individuals. “Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels.”

The study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre. Exercise testing equipment and technical support were provided by COSMED. Dr. Bhuva reported receiving funding from the British Heart Foundation. Dr. Chirinos reported having been a consultant or receiving research funding from multiple pharmaceutical companies and Microsoft; he is also an inventor of University of Pennsylvania–held patents for cardiovascular pharmaceutical agents.

[email protected]

SOURCE: Bhuva A et al. J Am Coll Cardiol. 2020 Jan;75(1):60-71.

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

[email protected]

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

[email protected]

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

PARIS – The Geriatric Nutritional Risk Index proved to be an independent predictor of 5-year overall survival as well as the composite of major adverse cardiovascular and limb events in a prospective cohort study of 1,219 patients with peripheral artery disease, Yae Matsuo, MD, reported at the annual congress of the European Society of Cardiology.

The Geriatric Nutritional Risk Index (GNRI) is a score calculated with a formula based upon a patient’s height, serum albumin, and the ratio between ideal and actual body weight (Am J Clin Nutr. 2005 Oct;82(4):777-83). The GNRI tool has been shown to be an accurate prognosticator for clinical outcomes in patients on hemodialysis and those with heart failure. However, it’s predictive accuracy hasn’t been evaluated in patients with PAD, according to Dr. Matsuo, a cardiologist at Kitakanto Cardiovascular Hospital in Shibukawa, Japan.

“The Geriatric Nutritional Risk Index is simple to calculate – so easy – and I think it’s a better predictor than BMI,” she said.

Fifty-six percent of the PAD patients had a GNRI score greater than 98, indicative of no increased risk of malnutrition and nutritional deficiencies. Their 5-year overall survival rate was 81%, compared with 62% in patients with a score of 92-98, 40% in those with a score of 82-91, and 23% with a score of less than 82. Other independent predictors of overall survival in multivariate analysis were age, estimated glomerular filtration rate, ankle brachial index, and C-reactive protein level.

A GNRI score above 98 was also predictive of significantly lower 5-year risk of both major adverse cardiovascular events and the composite of major adverse cardiovascular and limb events than in patients with a score of 98 or less.

The key remaining unanswered question is whether providing timely nutritional support to PAD patients with a low GNRI score will result in improved overall and limb survival and other outcomes.

Dr. Matsuo reported having no financial conflicts.

[email protected]

SOURCE: Matsuo Y. ESC CONGRESS 2019. Abstract P1956.

CHICAGO – Surgery and endovascular treatment for peripheral artery disease (PAD) among patients with claudication improves health status more in the setting of isolated iliac disease and multilevel disease than in other forms of PAD, which suggests that vascular specialists should give pause before pursuing interventions on superficial femoral and infrapopliteal artery lesions, a researcher of the PORTRAIT registry reported at the annual meeting of the Midwestern Vascular Surgery Society.

“Our analysis demonstrated that interventions for aortoiliac disease and multilevel disease appeared to improve overall health status more over time compared to femoral-popliteal disease and infrapopliteal disease,” said Todd R. Vogel, MD, of the University of Missouri Health System in Columbia.

The study evaluated improvement in Peripheral Artery Questionnaire (PAQ) scores from baseline to post intervention in 623 patients in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry. The patients were selected and combined with anatomic data on the nature of their claudication. Aortoiliac-only (AI) disease represented 20.4% (n = 127) of the study group, femoral-popliteal-only (FP) 35.5% (n = 221), infrapopliteal/distal (IP) 6.3% (n = 39), and multilevel disease (ML) 37.9% (n = 236).

In terms of demographics, patients in the AI group tended to be younger (average age of 61.2 years vs. 66.6 years for the study overall; P less than .001) and had a higher rate of smokers (96.1% former and current smokers vs. 90.7% overall; P less than .001). Otherwise, Dr. Vogel noted, demographics, smoking status, and severity of claudication were similar across the disease groups.

Rates of medical intervention were similar in the AI and ML disease groups, which were primarily endovascular procedures: 26% and 27%, respectively. The AI group had the highest rates of endovascular interventions, at 24%, with the FP group at 15%, IP at 11% and ML at 21%. Those who did not have surgery or endovascular aneurysm repair were treated medically.

“The AI group did significantly better at 3 months than the other groups,” Dr. Vogel pointed out, noting that at 12 months those patients had an average PAQ score of around 78 versus scores of around 75 for FP, 74 for IP, and 70 for ML.

“In the AI group, there’s also an immediate increase in quality of life that is sustained over time,” he said. At 3 months, PAQ scores in AI patients who had endovascular aneurysm repair increased 41 points over baseline, leveling off to a 38.8-point gain at 12 months, the highest gains across all disease groups and all treatment categories.

“However,” Dr. Vogel added, “the group with ML disease probably was the most improved over time on the PAQ scores,” he said, explaining that across the board, this group had lower baseline PAQ scores than all the other groups.

“No significant benefits were found with intervention versus medical management for FP and IP,” he said. “This suggests that intervention should be considered after medical management has been exhausted.”

Dr. Vogel also said the findings support aggressive treatment of AI and ML for symptomatic claudication. “This anatomic region represents the greatest potential benefit for improving overall health status in patients with symptomatic PAD,” he said.

Dr. Vogel had no relevant financial relationships to disclose.

CHICAGO – Surgery and endovascular treatment for peripheral artery disease (PAD) among patients with claudication improves health status more in the setting of isolated iliac disease and multilevel disease than in other forms of PAD, which suggests that vascular specialists should give pause before pursuing interventions on superficial femoral and infrapopliteal artery lesions, a researcher of the PORTRAIT registry reported at the annual meeting of the Midwestern Vascular Surgery Society.

“Our analysis demonstrated that interventions for aortoiliac disease and multilevel disease appeared to improve overall health status more over time compared to femoral-popliteal disease and infrapopliteal disease,” said Todd R. Vogel, MD, of the University of Missouri Health System in Columbia.

The study evaluated improvement in Peripheral Artery Questionnaire (PAQ) scores from baseline to post intervention in 623 patients in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry. The patients were selected and combined with anatomic data on the nature of their claudication. Aortoiliac-only (AI) disease represented 20.4% (n = 127) of the study group, femoral-popliteal-only (FP) 35.5% (n = 221), infrapopliteal/distal (IP) 6.3% (n = 39), and multilevel disease (ML) 37.9% (n = 236).

In terms of demographics, patients in the AI group tended to be younger (average age of 61.2 years vs. 66.6 years for the study overall; P less than .001) and had a higher rate of smokers (96.1% former and current smokers vs. 90.7% overall; P less than .001). Otherwise, Dr. Vogel noted, demographics, smoking status, and severity of claudication were similar across the disease groups.

Rates of medical intervention were similar in the AI and ML disease groups, which were primarily endovascular procedures: 26% and 27%, respectively. The AI group had the highest rates of endovascular interventions, at 24%, with the FP group at 15%, IP at 11% and ML at 21%. Those who did not have surgery or endovascular aneurysm repair were treated medically.

“The AI group did significantly better at 3 months than the other groups,” Dr. Vogel pointed out, noting that at 12 months those patients had an average PAQ score of around 78 versus scores of around 75 for FP, 74 for IP, and 70 for ML.

“In the AI group, there’s also an immediate increase in quality of life that is sustained over time,” he said. At 3 months, PAQ scores in AI patients who had endovascular aneurysm repair increased 41 points over baseline, leveling off to a 38.8-point gain at 12 months, the highest gains across all disease groups and all treatment categories.

“However,” Dr. Vogel added, “the group with ML disease probably was the most improved over time on the PAQ scores,” he said, explaining that across the board, this group had lower baseline PAQ scores than all the other groups.

“No significant benefits were found with intervention versus medical management for FP and IP,” he said. “This suggests that intervention should be considered after medical management has been exhausted.”

Dr. Vogel also said the findings support aggressive treatment of AI and ML for symptomatic claudication. “This anatomic region represents the greatest potential benefit for improving overall health status in patients with symptomatic PAD,” he said.

Dr. Vogel had no relevant financial relationships to disclose.

CHICAGO – Surgery and endovascular treatment for peripheral artery disease (PAD) among patients with claudication improves health status more in the setting of isolated iliac disease and multilevel disease than in other forms of PAD, which suggests that vascular specialists should give pause before pursuing interventions on superficial femoral and infrapopliteal artery lesions, a researcher of the PORTRAIT registry reported at the annual meeting of the Midwestern Vascular Surgery Society.

“Our analysis demonstrated that interventions for aortoiliac disease and multilevel disease appeared to improve overall health status more over time compared to femoral-popliteal disease and infrapopliteal disease,” said Todd R. Vogel, MD, of the University of Missouri Health System in Columbia.

The study evaluated improvement in Peripheral Artery Questionnaire (PAQ) scores from baseline to post intervention in 623 patients in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry. The patients were selected and combined with anatomic data on the nature of their claudication. Aortoiliac-only (AI) disease represented 20.4% (n = 127) of the study group, femoral-popliteal-only (FP) 35.5% (n = 221), infrapopliteal/distal (IP) 6.3% (n = 39), and multilevel disease (ML) 37.9% (n = 236).

In terms of demographics, patients in the AI group tended to be younger (average age of 61.2 years vs. 66.6 years for the study overall; P less than .001) and had a higher rate of smokers (96.1% former and current smokers vs. 90.7% overall; P less than .001). Otherwise, Dr. Vogel noted, demographics, smoking status, and severity of claudication were similar across the disease groups.

Rates of medical intervention were similar in the AI and ML disease groups, which were primarily endovascular procedures: 26% and 27%, respectively. The AI group had the highest rates of endovascular interventions, at 24%, with the FP group at 15%, IP at 11% and ML at 21%. Those who did not have surgery or endovascular aneurysm repair were treated medically.

“The AI group did significantly better at 3 months than the other groups,” Dr. Vogel pointed out, noting that at 12 months those patients had an average PAQ score of around 78 versus scores of around 75 for FP, 74 for IP, and 70 for ML.

“In the AI group, there’s also an immediate increase in quality of life that is sustained over time,” he said. At 3 months, PAQ scores in AI patients who had endovascular aneurysm repair increased 41 points over baseline, leveling off to a 38.8-point gain at 12 months, the highest gains across all disease groups and all treatment categories.

“However,” Dr. Vogel added, “the group with ML disease probably was the most improved over time on the PAQ scores,” he said, explaining that across the board, this group had lower baseline PAQ scores than all the other groups.

“No significant benefits were found with intervention versus medical management for FP and IP,” he said. “This suggests that intervention should be considered after medical management has been exhausted.”

Dr. Vogel also said the findings support aggressive treatment of AI and ML for symptomatic claudication. “This anatomic region represents the greatest potential benefit for improving overall health status in patients with symptomatic PAD,” he said.

Dr. Vogel had no relevant financial relationships to disclose.

The Food and Drug Administration has granted the Breakthrough Device Designation to the Virtue sirolimus-eluting balloon (SEB) for below-the-knee peripheral arterial disease, according to a statement from Orchestra BioMed.

According to the FDA, this designation indicates that the Virtue SEB could provide a “more effective treatment option ... for a life-threatening or irreversibly debilitating disease”; as the release notes, below-the-knee atherosclerosis presents a high rate of amputation and poor survival outcomes but has limited treatment options. The designation leads to expedited development, assessment, and review.

Darren R. Sherman, president, CEO, and cofounder of Orchestra BioMed, noted that the Virtue SEB “has the potential to improve long-term outcomes and reduce periprocedural complications” that can “extend hospital stay and increase cost of treatment.” The system had previously received this designation for coronary in-stent restenosis based upon the 3-year results of the European SABRE trial.

[email protected]

The Food and Drug Administration has granted the Breakthrough Device Designation to the Virtue sirolimus-eluting balloon (SEB) for below-the-knee peripheral arterial disease, according to a statement from Orchestra BioMed.

According to the FDA, this designation indicates that the Virtue SEB could provide a “more effective treatment option ... for a life-threatening or irreversibly debilitating disease”; as the release notes, below-the-knee atherosclerosis presents a high rate of amputation and poor survival outcomes but has limited treatment options. The designation leads to expedited development, assessment, and review.

Darren R. Sherman, president, CEO, and cofounder of Orchestra BioMed, noted that the Virtue SEB “has the potential to improve long-term outcomes and reduce periprocedural complications” that can “extend hospital stay and increase cost of treatment.” The system had previously received this designation for coronary in-stent restenosis based upon the 3-year results of the European SABRE trial.

[email protected]

The Food and Drug Administration has granted the Breakthrough Device Designation to the Virtue sirolimus-eluting balloon (SEB) for below-the-knee peripheral arterial disease, according to a statement from Orchestra BioMed.

According to the FDA, this designation indicates that the Virtue SEB could provide a “more effective treatment option ... for a life-threatening or irreversibly debilitating disease”; as the release notes, below-the-knee atherosclerosis presents a high rate of amputation and poor survival outcomes but has limited treatment options. The designation leads to expedited development, assessment, and review.

Darren R. Sherman, president, CEO, and cofounder of Orchestra BioMed, noted that the Virtue SEB “has the potential to improve long-term outcomes and reduce periprocedural complications” that can “extend hospital stay and increase cost of treatment.” The system had previously received this designation for coronary in-stent restenosis based upon the 3-year results of the European SABRE trial.

[email protected]

PARIS – For patients with peripheral artery disease, statin therapy is a literal lifeline, nearly halving mortality risk, according to new research presented at the annual congress of the European Society of Cardiology.

Patients with peripheral manifestations of cardiovascular disease “are a population with an extremely high risk to suffer a heart attack or a stroke,” said Joern Dopheide, MD, during a press conference at the meeting. Despite the known benefits of statins, including the reduction of all-cause and cardiovascular death and the reduction of morbidity, adherence to guideline-directed statin therapy is far from optimal, said Dr. Dopheide of Bern (Switzerland) University Hospital.

Patients with peripheral artery disease (PAD) not taking statins had a mortality rate of 34%, more than three times that of patients adherent to an intensified statin regimen. More surprisingly, patients who had been on a statin and then stopped the medication also had a mortality rate of 33%, indistinguishable from those who had never been treated with a statin.

Although statin adherence is low in general, it’s especially low in patients with PAD, said Dr. Dopheide. Still, he said, “few systematic data exist on the prognostic value of statin adherence and the correlation between adherence and cardiovascular outcome in PAD patients.”

Accordingly, Dr. Dopheide and his coinvestigators sought to determine the association between statin adherence and survival in PAD patients. The researchers obtained baseline and follow-up data for a cohort of 691 symptomatic PAD patients seen at a single site, looking at statin dosage, LDL cholesterol levels, and survival.

The patients were followed for a period of 50 months. Dr. Dopheide said that “Over the time course, we were able to increase the statin adherence from about 73% to about 81%, and parallel to that, we were able to reduce the LDL cholesterol levels from about 97 to 83 mg/dL, and we were able to increase the intensity of patients on statin therapy.”

Dr. Dopheide said that he and his colleagues saw a dose-response effect, so that the biggest drop in cholesterol was seen in patients on high statin doses, on more potent statins, or both.

Intensity was increased in some cases by upping statin dose – the mean statin dose climbed from 50 to 58 mg daily during the study period. An alternative strategy was to switch to a more potent statin such as atorvastatin or rosuvastatin; sometimes both intensity and dose were boosted.

“We were able to see that patients who were always on their statin therapy had a pretty low mortality rate of about 20%,” a figure that was halved for patients on more intensive statin therapy, who had a mortality rate of 10% across the study period, said Dr. Dopheide. “Patients in whom we started a statin therapy still profited from it, and had only a 15% mortality,” he added.

Some of the most surprising – and disturbing – study findings involved those who reduced their statin dose: “When patients discontinued their usual dose and decreased it, they suffered an even higher mortality rate, of nearly 43%. So that was kind of surprising and shocking to us.”

Identifying these high-risk patients and keeping them adherent is a substantial clinical challenge, but an important goal, said Dr. Dopheide. “We know that patients with peripheral arterial disease are a little more underrepresented in daily practice; it’s hard to identify them, especially when they are asymptomatic,” he acknowledged. However, once a PAD patient is identified, “One should at least keep the patient on the statin dosage they have,” or initiate statins if needed.

Further, warned Dr. Dopheide, “One should never discontinue statin or decrease the dosage,” adding that PAD patients should be informed that they are at “very high risk for myocardial infarction or stroke.” These patients “should regard their statin therapy as one of the most important and life-saving medications they can take,” he said.

Dr. Dopheide reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Dopheide, J., et al. ESC Congress 2019, Abstract P5363.

PARIS – For patients with peripheral artery disease, statin therapy is a literal lifeline, nearly halving mortality risk, according to new research presented at the annual congress of the European Society of Cardiology.

Patients with peripheral manifestations of cardiovascular disease “are a population with an extremely high risk to suffer a heart attack or a stroke,” said Joern Dopheide, MD, during a press conference at the meeting. Despite the known benefits of statins, including the reduction of all-cause and cardiovascular death and the reduction of morbidity, adherence to guideline-directed statin therapy is far from optimal, said Dr. Dopheide of Bern (Switzerland) University Hospital.

Patients with peripheral artery disease (PAD) not taking statins had a mortality rate of 34%, more than three times that of patients adherent to an intensified statin regimen. More surprisingly, patients who had been on a statin and then stopped the medication also had a mortality rate of 33%, indistinguishable from those who had never been treated with a statin.

Although statin adherence is low in general, it’s especially low in patients with PAD, said Dr. Dopheide. Still, he said, “few systematic data exist on the prognostic value of statin adherence and the correlation between adherence and cardiovascular outcome in PAD patients.”

Accordingly, Dr. Dopheide and his coinvestigators sought to determine the association between statin adherence and survival in PAD patients. The researchers obtained baseline and follow-up data for a cohort of 691 symptomatic PAD patients seen at a single site, looking at statin dosage, LDL cholesterol levels, and survival.

The patients were followed for a period of 50 months. Dr. Dopheide said that “Over the time course, we were able to increase the statin adherence from about 73% to about 81%, and parallel to that, we were able to reduce the LDL cholesterol levels from about 97 to 83 mg/dL, and we were able to increase the intensity of patients on statin therapy.”

Dr. Dopheide said that he and his colleagues saw a dose-response effect, so that the biggest drop in cholesterol was seen in patients on high statin doses, on more potent statins, or both.

Intensity was increased in some cases by upping statin dose – the mean statin dose climbed from 50 to 58 mg daily during the study period. An alternative strategy was to switch to a more potent statin such as atorvastatin or rosuvastatin; sometimes both intensity and dose were boosted.

“We were able to see that patients who were always on their statin therapy had a pretty low mortality rate of about 20%,” a figure that was halved for patients on more intensive statin therapy, who had a mortality rate of 10% across the study period, said Dr. Dopheide. “Patients in whom we started a statin therapy still profited from it, and had only a 15% mortality,” he added.

Some of the most surprising – and disturbing – study findings involved those who reduced their statin dose: “When patients discontinued their usual dose and decreased it, they suffered an even higher mortality rate, of nearly 43%. So that was kind of surprising and shocking to us.”

Identifying these high-risk patients and keeping them adherent is a substantial clinical challenge, but an important goal, said Dr. Dopheide. “We know that patients with peripheral arterial disease are a little more underrepresented in daily practice; it’s hard to identify them, especially when they are asymptomatic,” he acknowledged. However, once a PAD patient is identified, “One should at least keep the patient on the statin dosage they have,” or initiate statins if needed.

Further, warned Dr. Dopheide, “One should never discontinue statin or decrease the dosage,” adding that PAD patients should be informed that they are at “very high risk for myocardial infarction or stroke.” These patients “should regard their statin therapy as one of the most important and life-saving medications they can take,” he said.

Dr. Dopheide reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Dopheide, J., et al. ESC Congress 2019, Abstract P5363.

PARIS – For patients with peripheral artery disease, statin therapy is a literal lifeline, nearly halving mortality risk, according to new research presented at the annual congress of the European Society of Cardiology.

Patients with peripheral manifestations of cardiovascular disease “are a population with an extremely high risk to suffer a heart attack or a stroke,” said Joern Dopheide, MD, during a press conference at the meeting. Despite the known benefits of statins, including the reduction of all-cause and cardiovascular death and the reduction of morbidity, adherence to guideline-directed statin therapy is far from optimal, said Dr. Dopheide of Bern (Switzerland) University Hospital.

Patients with peripheral artery disease (PAD) not taking statins had a mortality rate of 34%, more than three times that of patients adherent to an intensified statin regimen. More surprisingly, patients who had been on a statin and then stopped the medication also had a mortality rate of 33%, indistinguishable from those who had never been treated with a statin.

Although statin adherence is low in general, it’s especially low in patients with PAD, said Dr. Dopheide. Still, he said, “few systematic data exist on the prognostic value of statin adherence and the correlation between adherence and cardiovascular outcome in PAD patients.”

Accordingly, Dr. Dopheide and his coinvestigators sought to determine the association between statin adherence and survival in PAD patients. The researchers obtained baseline and follow-up data for a cohort of 691 symptomatic PAD patients seen at a single site, looking at statin dosage, LDL cholesterol levels, and survival.

The patients were followed for a period of 50 months. Dr. Dopheide said that “Over the time course, we were able to increase the statin adherence from about 73% to about 81%, and parallel to that, we were able to reduce the LDL cholesterol levels from about 97 to 83 mg/dL, and we were able to increase the intensity of patients on statin therapy.”

Dr. Dopheide said that he and his colleagues saw a dose-response effect, so that the biggest drop in cholesterol was seen in patients on high statin doses, on more potent statins, or both.

Intensity was increased in some cases by upping statin dose – the mean statin dose climbed from 50 to 58 mg daily during the study period. An alternative strategy was to switch to a more potent statin such as atorvastatin or rosuvastatin; sometimes both intensity and dose were boosted.

“We were able to see that patients who were always on their statin therapy had a pretty low mortality rate of about 20%,” a figure that was halved for patients on more intensive statin therapy, who had a mortality rate of 10% across the study period, said Dr. Dopheide. “Patients in whom we started a statin therapy still profited from it, and had only a 15% mortality,” he added.

Some of the most surprising – and disturbing – study findings involved those who reduced their statin dose: “When patients discontinued their usual dose and decreased it, they suffered an even higher mortality rate, of nearly 43%. So that was kind of surprising and shocking to us.”

Identifying these high-risk patients and keeping them adherent is a substantial clinical challenge, but an important goal, said Dr. Dopheide. “We know that patients with peripheral arterial disease are a little more underrepresented in daily practice; it’s hard to identify them, especially when they are asymptomatic,” he acknowledged. However, once a PAD patient is identified, “One should at least keep the patient on the statin dosage they have,” or initiate statins if needed.

Further, warned Dr. Dopheide, “One should never discontinue statin or decrease the dosage,” adding that PAD patients should be informed that they are at “very high risk for myocardial infarction or stroke.” These patients “should regard their statin therapy as one of the most important and life-saving medications they can take,” he said.

Dr. Dopheide reported no outside sources of funding and no conflicts of interest.

[email protected]

SOURCE: Dopheide, J., et al. ESC Congress 2019, Abstract P5363.

A new assessment statement from the American Heart Association reviewed the strengths and limitations of current imaging techniques for critical limb ischemia (CLI), the severest form of peripheral arterial disease (PAD).

The main techniques discussed were the ankle-brachial index (ABI), toe-brachial index (TBI), toe systolic pressure, transcutaneous oximetry (TcPO₂) and skin perfusion pressure (SPP). The literature review also identified what the authors saw as opportunities for technology improvement.

“No single vascular test has been identified as the most important predictor of wound healing or major amputation for the threatened limb,” wrote Sanjay Misra, MD, of the Mayo Clinic in Rochester, Minn., and colleagues, on behalf of the American Heart Association Council on Peripheral Vascular Disease, the Council on Clinical Cardiology, and the Council on Cardiovascular and Stroke Nursing.

Of particular concern were limitations seen in the use of ABI, the most widely used assessment method. “Although ABI was first described to diagnose PAD, it has not been shown to be an accurate predictor of wound healing or major adverse limb events. Clearly, the ABI provides important prognostic information, including the risk of death, myocardial infarction, and stroke ... and should be performed in all patients suspected of having PAD,” but in about 30% of patients with angiographically documented CLI, the ABI is normal or noncompressible, the authors wrote.

And, although recent data indicate that toe pressure may be a better predictor of major adverse limb events and tibial disease in patients with CLI, especially among those with isolated below-knee disease, there was no solid evidence that ABI or TBI have the sensitivity or specificity to be used as perfusion tools to assess wound healing or limb salvage, the authors stated.

However, there may be some technological improvements on the horizon for assessing limb perfusion that might provide eventual benefits, according to the reviewers. These include the use of indigo carmine angiography to evaluate microcirculation and angiosomal revascularization, the use of CT perfusion or MRI to quantify perfusion and monitor treatment response, the use of contrast-enhanced ultrasound to assess calf muscle perfusion, and hyperspectral imaging.

Among the other issues of concern raised in the AHA statement were the significant demographic disparities that occur in detection and treatment of CLI. The authors noted differences in how CLI is diagnosed, the coexisting conditions that were present, and the disparities in treatment given based on sex and racial differences. For example, women were more likely to experience emergency hospitalization, have differences in blood flow, and have higher disability and death rates.

As for racial disparities, the reviewers found that black and Hispanic patients with CLI were more likely to have diabetes and chronic kidney disease, and were more likely to develop gangrene, compared with white patients, who were more likely to have ulcers and pain in their legs while at rest.

In terms of treatment, black patients were 78% more likely to receive lower extremity amputation for CLI, compared with their white peers, even after adjustment for socioeconomic status, access to facilities with revascularization services, and other factors, according to the report, which was published online in Circulation.

“CLI is a complex disease process with great morbidity. This statement highlights the importance of incorporating perfusion assessment into the care of CLI patients. Despite the high prevalence of CLI, strategies for perfusion assessment remain limited. New technologies offer potential opportunities to improve the precision and quality of CLI management,” the researchers concluded.

Dr. Misra and the majority of the authors reported having no relevant disclosures. Several authors reported receiving funding from the pharmaceutical and medical device industries.

[email protected]

SOURCE: Chandra S. et al. Circulation. 2019;140:00-00. doi: 10.1161/CIR.0000000000000708.

A new assessment statement from the American Heart Association reviewed the strengths and limitations of current imaging techniques for critical limb ischemia (CLI), the severest form of peripheral arterial disease (PAD).

The main techniques discussed were the ankle-brachial index (ABI), toe-brachial index (TBI), toe systolic pressure, transcutaneous oximetry (TcPO₂) and skin perfusion pressure (SPP). The literature review also identified what the authors saw as opportunities for technology improvement.

“No single vascular test has been identified as the most important predictor of wound healing or major amputation for the threatened limb,” wrote Sanjay Misra, MD, of the Mayo Clinic in Rochester, Minn., and colleagues, on behalf of the American Heart Association Council on Peripheral Vascular Disease, the Council on Clinical Cardiology, and the Council on Cardiovascular and Stroke Nursing.

Of particular concern were limitations seen in the use of ABI, the most widely used assessment method. “Although ABI was first described to diagnose PAD, it has not been shown to be an accurate predictor of wound healing or major adverse limb events. Clearly, the ABI provides important prognostic information, including the risk of death, myocardial infarction, and stroke ... and should be performed in all patients suspected of having PAD,” but in about 30% of patients with angiographically documented CLI, the ABI is normal or noncompressible, the authors wrote.

And, although recent data indicate that toe pressure may be a better predictor of major adverse limb events and tibial disease in patients with CLI, especially among those with isolated below-knee disease, there was no solid evidence that ABI or TBI have the sensitivity or specificity to be used as perfusion tools to assess wound healing or limb salvage, the authors stated.

However, there may be some technological improvements on the horizon for assessing limb perfusion that might provide eventual benefits, according to the reviewers. These include the use of indigo carmine angiography to evaluate microcirculation and angiosomal revascularization, the use of CT perfusion or MRI to quantify perfusion and monitor treatment response, the use of contrast-enhanced ultrasound to assess calf muscle perfusion, and hyperspectral imaging.

Among the other issues of concern raised in the AHA statement were the significant demographic disparities that occur in detection and treatment of CLI. The authors noted differences in how CLI is diagnosed, the coexisting conditions that were present, and the disparities in treatment given based on sex and racial differences. For example, women were more likely to experience emergency hospitalization, have differences in blood flow, and have higher disability and death rates.

As for racial disparities, the reviewers found that black and Hispanic patients with CLI were more likely to have diabetes and chronic kidney disease, and were more likely to develop gangrene, compared with white patients, who were more likely to have ulcers and pain in their legs while at rest.

In terms of treatment, black patients were 78% more likely to receive lower extremity amputation for CLI, compared with their white peers, even after adjustment for socioeconomic status, access to facilities with revascularization services, and other factors, according to the report, which was published online in Circulation.

“CLI is a complex disease process with great morbidity. This statement highlights the importance of incorporating perfusion assessment into the care of CLI patients. Despite the high prevalence of CLI, strategies for perfusion assessment remain limited. New technologies offer potential opportunities to improve the precision and quality of CLI management,” the researchers concluded.

Dr. Misra and the majority of the authors reported having no relevant disclosures. Several authors reported receiving funding from the pharmaceutical and medical device industries.

[email protected]

SOURCE: Chandra S. et al. Circulation. 2019;140:00-00. doi: 10.1161/CIR.0000000000000708.

A new assessment statement from the American Heart Association reviewed the strengths and limitations of current imaging techniques for critical limb ischemia (CLI), the severest form of peripheral arterial disease (PAD).

The main techniques discussed were the ankle-brachial index (ABI), toe-brachial index (TBI), toe systolic pressure, transcutaneous oximetry (TcPO₂) and skin perfusion pressure (SPP). The literature review also identified what the authors saw as opportunities for technology improvement.

“No single vascular test has been identified as the most important predictor of wound healing or major amputation for the threatened limb,” wrote Sanjay Misra, MD, of the Mayo Clinic in Rochester, Minn., and colleagues, on behalf of the American Heart Association Council on Peripheral Vascular Disease, the Council on Clinical Cardiology, and the Council on Cardiovascular and Stroke Nursing.

Of particular concern were limitations seen in the use of ABI, the most widely used assessment method. “Although ABI was first described to diagnose PAD, it has not been shown to be an accurate predictor of wound healing or major adverse limb events. Clearly, the ABI provides important prognostic information, including the risk of death, myocardial infarction, and stroke ... and should be performed in all patients suspected of having PAD,” but in about 30% of patients with angiographically documented CLI, the ABI is normal or noncompressible, the authors wrote.

And, although recent data indicate that toe pressure may be a better predictor of major adverse limb events and tibial disease in patients with CLI, especially among those with isolated below-knee disease, there was no solid evidence that ABI or TBI have the sensitivity or specificity to be used as perfusion tools to assess wound healing or limb salvage, the authors stated.

However, there may be some technological improvements on the horizon for assessing limb perfusion that might provide eventual benefits, according to the reviewers. These include the use of indigo carmine angiography to evaluate microcirculation and angiosomal revascularization, the use of CT perfusion or MRI to quantify perfusion and monitor treatment response, the use of contrast-enhanced ultrasound to assess calf muscle perfusion, and hyperspectral imaging.

Among the other issues of concern raised in the AHA statement were the significant demographic disparities that occur in detection and treatment of CLI. The authors noted differences in how CLI is diagnosed, the coexisting conditions that were present, and the disparities in treatment given based on sex and racial differences. For example, women were more likely to experience emergency hospitalization, have differences in blood flow, and have higher disability and death rates.

As for racial disparities, the reviewers found that black and Hispanic patients with CLI were more likely to have diabetes and chronic kidney disease, and were more likely to develop gangrene, compared with white patients, who were more likely to have ulcers and pain in their legs while at rest.

In terms of treatment, black patients were 78% more likely to receive lower extremity amputation for CLI, compared with their white peers, even after adjustment for socioeconomic status, access to facilities with revascularization services, and other factors, according to the report, which was published online in Circulation.

“CLI is a complex disease process with great morbidity. This statement highlights the importance of incorporating perfusion assessment into the care of CLI patients. Despite the high prevalence of CLI, strategies for perfusion assessment remain limited. New technologies offer potential opportunities to improve the precision and quality of CLI management,” the researchers concluded.

Dr. Misra and the majority of the authors reported having no relevant disclosures. Several authors reported receiving funding from the pharmaceutical and medical device industries.

[email protected]

SOURCE: Chandra S. et al. Circulation. 2019;140:00-00. doi: 10.1161/CIR.0000000000000708.

Paclitaxel-coated devices, which are used to treat peripheral artery disease (PAD), appear to have a nearly 60% higher mortality risk than uncoated devices, according to a letter to health care providers from the Food and Drug Administration.

This letter updates details about long-term follow-up data and panel conclusions reviewed by the Food and Drug Administration, as well as recommendations from the agency regarding these devices. On Jan. 17, 2019, the FDA notified providers regarding an apparent increased late mortality risk seen with paclitaxel-eluting stents and paclitaxel-coated balloons placed in the femoropopliteal artery in patients with PAD. The agency issued an update March 15.

In a public meeting June 19-20, the Circulatory System Devices Panel of the Medical Devices Advisory Committee discussed long-term follow-up data that demonstrated a 57% relative increase in mortality among PAD patients treated with paclitaxel-coated devices when compared with those receiving uncoated devices. The panel concluded that the late mortality signal was real and warranted further study and action, a conclusion with which the FDA has concurred.

Among other recommendations issued by the FDA, health care professionals should continue to closely monitor patients who’ve already received the devices and fully discuss the risks and benefits of these devices with patients. The FDA has decided that, given the demonstrated short-term benefits of these devices, clinical studies may continue and should collect long-term safety and effectiveness data.

The magnitude of this late mortality signal should be interpreted with caution, the FDA noted in the update, because of the wide confidence intervals (although the relative risk was 1.57, the 95% confidence interval was 1.16-2.13, which translates to 16%-113% higher relative risk), pooling studies of different devices that weren’t meant to be combined, missing data, and other reasons.

The full letter, including more detailed data and the full list of recommendations, is available on the FDA’s website.

[email protected]

Paclitaxel-coated devices, which are used to treat peripheral artery disease (PAD), appear to have a nearly 60% higher mortality risk than uncoated devices, according to a letter to health care providers from the Food and Drug Administration.

This letter updates details about long-term follow-up data and panel conclusions reviewed by the Food and Drug Administration, as well as recommendations from the agency regarding these devices. On Jan. 17, 2019, the FDA notified providers regarding an apparent increased late mortality risk seen with paclitaxel-eluting stents and paclitaxel-coated balloons placed in the femoropopliteal artery in patients with PAD. The agency issued an update March 15.

In a public meeting June 19-20, the Circulatory System Devices Panel of the Medical Devices Advisory Committee discussed long-term follow-up data that demonstrated a 57% relative increase in mortality among PAD patients treated with paclitaxel-coated devices when compared with those receiving uncoated devices. The panel concluded that the late mortality signal was real and warranted further study and action, a conclusion with which the FDA has concurred.

Among other recommendations issued by the FDA, health care professionals should continue to closely monitor patients who’ve already received the devices and fully discuss the risks and benefits of these devices with patients. The FDA has decided that, given the demonstrated short-term benefits of these devices, clinical studies may continue and should collect long-term safety and effectiveness data.

The magnitude of this late mortality signal should be interpreted with caution, the FDA noted in the update, because of the wide confidence intervals (although the relative risk was 1.57, the 95% confidence interval was 1.16-2.13, which translates to 16%-113% higher relative risk), pooling studies of different devices that weren’t meant to be combined, missing data, and other reasons.

The full letter, including more detailed data and the full list of recommendations, is available on the FDA’s website.

[email protected]

Paclitaxel-coated devices, which are used to treat peripheral artery disease (PAD), appear to have a nearly 60% higher mortality risk than uncoated devices, according to a letter to health care providers from the Food and Drug Administration.

This letter updates details about long-term follow-up data and panel conclusions reviewed by the Food and Drug Administration, as well as recommendations from the agency regarding these devices. On Jan. 17, 2019, the FDA notified providers regarding an apparent increased late mortality risk seen with paclitaxel-eluting stents and paclitaxel-coated balloons placed in the femoropopliteal artery in patients with PAD. The agency issued an update March 15.

In a public meeting June 19-20, the Circulatory System Devices Panel of the Medical Devices Advisory Committee discussed long-term follow-up data that demonstrated a 57% relative increase in mortality among PAD patients treated with paclitaxel-coated devices when compared with those receiving uncoated devices. The panel concluded that the late mortality signal was real and warranted further study and action, a conclusion with which the FDA has concurred.

Among other recommendations issued by the FDA, health care professionals should continue to closely monitor patients who’ve already received the devices and fully discuss the risks and benefits of these devices with patients. The FDA has decided that, given the demonstrated short-term benefits of these devices, clinical studies may continue and should collect long-term safety and effectiveness data.

The magnitude of this late mortality signal should be interpreted with caution, the FDA noted in the update, because of the wide confidence intervals (although the relative risk was 1.57, the 95% confidence interval was 1.16-2.13, which translates to 16%-113% higher relative risk), pooling studies of different devices that weren’t meant to be combined, missing data, and other reasons.

The full letter, including more detailed data and the full list of recommendations, is available on the FDA’s website.

[email protected]

Adults who quit smoking reduced their risk for peripheral artery disease in the short term, but remained at increased risk for up to 30 years, compared with never-smokers, based on data from more than 13,000 adults in a community-based study.

Courtesy Journal of the American College of Cardiology

Most reports on the impact of smoking cessation on cardiovascular disease have focused on coronary heart disease (CHD), and stroke, while data on the effects of smoking cessation on peripheral artery disease (PAD) are limited, wrote Ning Ding, MBBS, SCM, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, Md., and colleagues.

To compare the impact of smoking on PAD, CHD, and stroke, the researchers used data from the Atherosclerosis Risk in Communities (ARIC) study, which included 15,792 adults aged 45-64 years in four communities. The findings were published in the Journal of the American College of Cardiology.

The study population of 13,355 individuals had no baseline history of PAD, CHD, or stroke. Over a median 26 years of follow-up, the researchers identified 492 cases of PAD, 1,798 cases of CHD, and 1,106 cases of stroke.

The risk of all three conditions began to decline within 5 years of smoking cessation, which could be encouraging to smokers who wish to quit, the researchers noted. In addition, the longer the duration of smoking cessation, the lower the risk for all three conditions (See central illustration).

However, a significantly elevated risk remained for PAD for up to 30 years after smoking cessation and for CHD for up to 20 years after smoking cessation, compared with never-smokers.

The researchers also found a roughly fourfold increased risk for PAD for smokers who smoked for 40 or more pack-years, compared with never-smokers, which was greater than the 2.1 hazard ratio for CHD and 1.8 HR for stroke. In addition, current smokers of at least one pack per day had a significantly greater risk of PAD, compared with never-smokers (HR, 5.36) that was higher than the risk for CHD or stroke (HR, 2.38 and HR, 1.88, respectively).

The study findings were limited by several factors including the reliance on self-reports, potential misclassification of data, and the potential exclusion of mild PAD cases that did not require hospitalization, the researchers noted. However, the results support the value of encouraging smokers to quit and support the need to include PAD risk in public health information, they said. “Although public statements about smoking and [cardiovascular disease] have been focusing on CHD and stroke, our results indicate the need to take account of PAD as well for comprehensively acknowledging the effect of smoking on overall cardiovascular health,” they added.

The ARIC study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. Lead author Dr. Ding had no financial conflicts to disclose; coauthors disclosed relationships with Bristol-Myers Squibb and Fukuda Denshi.

SOURCE: Ding N et al. J Am Coll Cardiol. 2019 Jul 22;74:498-507. doi: 10.1016/j.jacc.2019.06.003.

Adults who quit smoking reduced their risk for peripheral artery disease in the short term, but remained at increased risk for up to 30 years, compared with never-smokers, based on data from more than 13,000 adults in a community-based study.

Courtesy Journal of the American College of Cardiology

Most reports on the impact of smoking cessation on cardiovascular disease have focused on coronary heart disease (CHD), and stroke, while data on the effects of smoking cessation on peripheral artery disease (PAD) are limited, wrote Ning Ding, MBBS, SCM, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, Md., and colleagues.

To compare the impact of smoking on PAD, CHD, and stroke, the researchers used data from the Atherosclerosis Risk in Communities (ARIC) study, which included 15,792 adults aged 45-64 years in four communities. The findings were published in the Journal of the American College of Cardiology.

The study population of 13,355 individuals had no baseline history of PAD, CHD, or stroke. Over a median 26 years of follow-up, the researchers identified 492 cases of PAD, 1,798 cases of CHD, and 1,106 cases of stroke.

The risk of all three conditions began to decline within 5 years of smoking cessation, which could be encouraging to smokers who wish to quit, the researchers noted. In addition, the longer the duration of smoking cessation, the lower the risk for all three conditions (See central illustration).

However, a significantly elevated risk remained for PAD for up to 30 years after smoking cessation and for CHD for up to 20 years after smoking cessation, compared with never-smokers.

The researchers also found a roughly fourfold increased risk for PAD for smokers who smoked for 40 or more pack-years, compared with never-smokers, which was greater than the 2.1 hazard ratio for CHD and 1.8 HR for stroke. In addition, current smokers of at least one pack per day had a significantly greater risk of PAD, compared with never-smokers (HR, 5.36) that was higher than the risk for CHD or stroke (HR, 2.38 and HR, 1.88, respectively).

The study findings were limited by several factors including the reliance on self-reports, potential misclassification of data, and the potential exclusion of mild PAD cases that did not require hospitalization, the researchers noted. However, the results support the value of encouraging smokers to quit and support the need to include PAD risk in public health information, they said. “Although public statements about smoking and [cardiovascular disease] have been focusing on CHD and stroke, our results indicate the need to take account of PAD as well for comprehensively acknowledging the effect of smoking on overall cardiovascular health,” they added.

The ARIC study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. Lead author Dr. Ding had no financial conflicts to disclose; coauthors disclosed relationships with Bristol-Myers Squibb and Fukuda Denshi.

SOURCE: Ding N et al. J Am Coll Cardiol. 2019 Jul 22;74:498-507. doi: 10.1016/j.jacc.2019.06.003.

Adults who quit smoking reduced their risk for peripheral artery disease in the short term, but remained at increased risk for up to 30 years, compared with never-smokers, based on data from more than 13,000 adults in a community-based study.

Courtesy Journal of the American College of Cardiology

Most reports on the impact of smoking cessation on cardiovascular disease have focused on coronary heart disease (CHD), and stroke, while data on the effects of smoking cessation on peripheral artery disease (PAD) are limited, wrote Ning Ding, MBBS, SCM, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, Md., and colleagues.

To compare the impact of smoking on PAD, CHD, and stroke, the researchers used data from the Atherosclerosis Risk in Communities (ARIC) study, which included 15,792 adults aged 45-64 years in four communities. The findings were published in the Journal of the American College of Cardiology.

The study population of 13,355 individuals had no baseline history of PAD, CHD, or stroke. Over a median 26 years of follow-up, the researchers identified 492 cases of PAD, 1,798 cases of CHD, and 1,106 cases of stroke.

The risk of all three conditions began to decline within 5 years of smoking cessation, which could be encouraging to smokers who wish to quit, the researchers noted. In addition, the longer the duration of smoking cessation, the lower the risk for all three conditions (See central illustration).

However, a significantly elevated risk remained for PAD for up to 30 years after smoking cessation and for CHD for up to 20 years after smoking cessation, compared with never-smokers.

The researchers also found a roughly fourfold increased risk for PAD for smokers who smoked for 40 or more pack-years, compared with never-smokers, which was greater than the 2.1 hazard ratio for CHD and 1.8 HR for stroke. In addition, current smokers of at least one pack per day had a significantly greater risk of PAD, compared with never-smokers (HR, 5.36) that was higher than the risk for CHD or stroke (HR, 2.38 and HR, 1.88, respectively).

The study findings were limited by several factors including the reliance on self-reports, potential misclassification of data, and the potential exclusion of mild PAD cases that did not require hospitalization, the researchers noted. However, the results support the value of encouraging smokers to quit and support the need to include PAD risk in public health information, they said. “Although public statements about smoking and [cardiovascular disease] have been focusing on CHD and stroke, our results indicate the need to take account of PAD as well for comprehensively acknowledging the effect of smoking on overall cardiovascular health,” they added.

The ARIC study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. Lead author Dr. Ding had no financial conflicts to disclose; coauthors disclosed relationships with Bristol-Myers Squibb and Fukuda Denshi.

SOURCE: Ding N et al. J Am Coll Cardiol. 2019 Jul 22;74:498-507. doi: 10.1016/j.jacc.2019.06.003.