In the Journals

No evidence of paclitaxel-related mortality risk in real-world PAD cohort

Jay Giri
Jay Giri

In a cohort of CMS beneficiaries with peripheral artery disease, there was no evidence that those revascularized with a drug-coated device had increased risk for mortality compared with those who were not, researchers reported in JAMA Cardiology.

As Cardiology Today’s Intervention previously reported, a summary-level meta-analysis published in December found that patients with PAD who had a revascularization procedure with a paclitaxel-coated device had elevated risk for mortality compared with controls at 2 and 5 years. As a result, the FDA launched an investigation and two ongoing trials were temporarily halted. Subsequent analyses using patient-level data have not found any evidence of a mortality risk related to paclitaxel-coated devices.

For the present study, Eric A. Secemsky, MD, MSc, from the division of cardiology and the Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center and Harvard Medical School, and colleagues retrospectively analyzed 16,560 CMS beneficiaries (mean age, 73 years; 47% men; 51% with critical limb ischemia) admitted to 1,883 centers for femoropopliteal artery revascularization in 2016.

Patients were stratified by whether they were treated with a drug-coated device (drug-coated balloon or drug-eluting stent) or an uncoated device (percutaneous transluminal angioplasty or bare-metal stent).

The primary outcome was all-cause mortality. Median follow-up was 389 days.

No mortality risk

Compared with the uncoated group, the drug-coated group had a lower cumulative incidence of death up to 600 days (32.5% vs. 34.3%; log-rank P = .007), Secemsky and colleagues wrote.

There was a trend favoring patients treated with a DCB compared with PTA (log-rank P = .06) and no difference in mortality between patients treated with a DES compared with a BMS (log-rank P = .56), according to the researchers.

After adjustment for patient, procedure and hospital characteristics, there was no difference between drug-coated and uncoated devices in all-cause mortality (adjusted HR = 0.97; 95% CI, 0.91-1.04), Secemsky and colleagues wrote.

The mortality findings were consistent in those with CLI (aHR = 0.93; 95% CI, 0.85-1.01), those without CLI (aHR = 0.94; 95% CI, 0.85-1.03), those treated with DCBs alone (aHR = 0.94; 95% CI, 0.86-1.03) and those treated with DES with or without DCB (aHR = 0.97; 95% CI, 0.89-1.06).

“Further review of patient-level trial data and real-world registries will be valuable in providing greater evidence of the safety of drug-coated devices used for peripheral artery revascularization,” the researchers wrote.

Path remains unclear

In an invited commentary, Jay Giri, MD, MPH, director of peripheral intervention and assistant professor of medicine at the Hospital of the University of Pennsylvania and a Cardiology Today Next Gen Innovator, wrote that the new analysis does not necessarily disprove the previous one because it is possible confounders were not eliminated; the follow-up was not as long; and the population was higher-risk than that analyzed in the previous study, which means a paclitaxel-related mortality risk could be “washed out” by other competing mortality risks.

“A careful risk-benefit discussion with patients about the uncertainty in long-term outcomes with these devices is warranted in the context of their greater efficacy with regard to revascularization outcomes,” Giri wrote. “The good news is that several efforts are underway to more carefully understand the issue, with planned long-term analyses of [randomized controlled trials] by individual industry sponsors in preparation. (The first of these was recently published and is reassuring). Most importantly, a pooled individual patient-level analysis of trials from all industry stakeholders is also in the works.” – by Erik Swain

Disclosures: Secemsky reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Giri reports he serves on an advisory board for AstraZeneca, receives institutional research funds from Recor Medical and St. Jude Medical and serves on the board of the PERT Consortium, a 501(c)3 nonprofit organization.

Jay Giri
Jay Giri

In a cohort of CMS beneficiaries with peripheral artery disease, there was no evidence that those revascularized with a drug-coated device had increased risk for mortality compared with those who were not, researchers reported in JAMA Cardiology.

As Cardiology Today’s Intervention previously reported, a summary-level meta-analysis published in December found that patients with PAD who had a revascularization procedure with a paclitaxel-coated device had elevated risk for mortality compared with controls at 2 and 5 years. As a result, the FDA launched an investigation and two ongoing trials were temporarily halted. Subsequent analyses using patient-level data have not found any evidence of a mortality risk related to paclitaxel-coated devices.

For the present study, Eric A. Secemsky, MD, MSc, from the division of cardiology and the Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center and Harvard Medical School, and colleagues retrospectively analyzed 16,560 CMS beneficiaries (mean age, 73 years; 47% men; 51% with critical limb ischemia) admitted to 1,883 centers for femoropopliteal artery revascularization in 2016.

Patients were stratified by whether they were treated with a drug-coated device (drug-coated balloon or drug-eluting stent) or an uncoated device (percutaneous transluminal angioplasty or bare-metal stent).

The primary outcome was all-cause mortality. Median follow-up was 389 days.

No mortality risk

Compared with the uncoated group, the drug-coated group had a lower cumulative incidence of death up to 600 days (32.5% vs. 34.3%; log-rank P = .007), Secemsky and colleagues wrote.

There was a trend favoring patients treated with a DCB compared with PTA (log-rank P = .06) and no difference in mortality between patients treated with a DES compared with a BMS (log-rank P = .56), according to the researchers.

After adjustment for patient, procedure and hospital characteristics, there was no difference between drug-coated and uncoated devices in all-cause mortality (adjusted HR = 0.97; 95% CI, 0.91-1.04), Secemsky and colleagues wrote.

The mortality findings were consistent in those with CLI (aHR = 0.93; 95% CI, 0.85-1.01), those without CLI (aHR = 0.94; 95% CI, 0.85-1.03), those treated with DCBs alone (aHR = 0.94; 95% CI, 0.86-1.03) and those treated with DES with or without DCB (aHR = 0.97; 95% CI, 0.89-1.06).

“Further review of patient-level trial data and real-world registries will be valuable in providing greater evidence of the safety of drug-coated devices used for peripheral artery revascularization,” the researchers wrote.

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Path remains unclear

In an invited commentary, Jay Giri, MD, MPH, director of peripheral intervention and assistant professor of medicine at the Hospital of the University of Pennsylvania and a Cardiology Today Next Gen Innovator, wrote that the new analysis does not necessarily disprove the previous one because it is possible confounders were not eliminated; the follow-up was not as long; and the population was higher-risk than that analyzed in the previous study, which means a paclitaxel-related mortality risk could be “washed out” by other competing mortality risks.

“A careful risk-benefit discussion with patients about the uncertainty in long-term outcomes with these devices is warranted in the context of their greater efficacy with regard to revascularization outcomes,” Giri wrote. “The good news is that several efforts are underway to more carefully understand the issue, with planned long-term analyses of [randomized controlled trials] by individual industry sponsors in preparation. (The first of these was recently published and is reassuring). Most importantly, a pooled individual patient-level analysis of trials from all industry stakeholders is also in the works.” – by Erik Swain

Disclosures: Secemsky reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Giri reports he serves on an advisory board for AstraZeneca, receives institutional research funds from Recor Medical and St. Jude Medical and serves on the board of the PERT Consortium, a 501(c)3 nonprofit organization.

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