Paclitaxel-coated devices found safe in new study—but the debate isn’t over

Paclitaxel-coated devices were found safe for the treatment of femoropopliteal artery revascularization in a JAMA Cardiology study published Feb. 12—the latest installment in a continuing debate over whether drug-coated stents and balloons raise long-term mortality risk in patients with peripheral artery disease (PAD).

Eric A. Secemsky, MD, MSc, of Beth Israel Deaconess Medical Center in Boston, and colleagues launched their nationwide cohort study of 16,560 Centers for Medicare and Medicaid Services (CMS) beneficiaries in an attempt to clarify the results of a handful of recent studies, including a concerning meta-analysis published in the Journal of the American Heart Association last December.

The analysis, which pooled results from 28 randomized controlled trials and considered a total of 4,663 patients with PAD, found significantly higher two- and five-year mortality rates in patients implanted with paclitaxel-coated stents or balloons (7.2 percent and 14.7 percent, respectively) compared to those with bare-metal stents (3.8 percent and 8.1 percent, respectively). The study raised eyebrows about the long-term safety of paclitaxel-coated devices and prompted both an FDA investigation and the temporary suspension of two clinical trials.

For their work, Secemsky and his co-authors reviewed CMS data for patients admitted for femoropopliteal artery revascularization at 1,883 U.S. hospitals in 2016. Nearly half of the study pool had a history of tobacco use, 60 percent had diabetes and 51 percent had critical limb ischemia at baseline.

Drug-coated devices, including drug-eluting stents (DES) and drug-coated balloons (DCB), were used in 36.2 percent of patients, according to the researchers. After a mean follow-up of 389 days, treatment with drug-coated devices was associated with a lower cumulative incidence of all-cause mortality compared with treatment using non-coated devices through 600 days post-procedure (32.5 percent versus 34.3 percent). Uncoated devices included bare-metal stents and uncoated percutaneous transluminal angioplasty balloons.

When the team broke their results down further, they found revascularization with drug-coated devices in patients with critical limb ischemia was associated with a 38.1 percent cumulative incidence of mortality through 600 days post-procedure, compared to a 40.1 percent incidence in patients without drug-coated devices. Still, there wasn’t a significant difference in survival between drug-coated and non-drug-coated treatments in patients without critical limb ischemia (26.5 percent and 29 percent, respectively).

Secemsky et al. observed similar survival trends when treatment was stratified by using a DCB alone or DES with or without DCB. After multivariable adjustment, drug-coated devices weren’t linked to a difference in all-cause mortality compared to non-drug-coated devices.

“At first blush, the study provides reassurance that, in real-world practice, the mortality signal seen in the systematic review and meta-analysis is not borne out,” Jay Giri, MD, MPH, of the University of Pennsylvania Perelman Center, wrote in a related editorial. “So, were those prior findings spurious? Unfortunately, there are a number of reasons why it is not easy to draw a direct comparison between the two analyses.”

Most notably, he said, was the fact that Secemsky and colleagues’ study only followed patients for a median of 389 days, and the meta-analysis that sparked this debate didn’t find any danger with paclitaxel-coated devices until after the two-year mark. Since that analysis was published, a host of studies have found the In.Pact Admiral DCB, Ranger SFA DCB, Zilver PTX DES, Stellarex DCB and Lutonix DCB devices safe at both three and five years.

“What should clinicians do now?” Giri wrote. “Currently, there is insufficient evidence to place a blanket moratorium on the use of paclitaxel-eluting balloons and paclitaxel-eluting stents out of concerns for long-term safety, and the [earlier analysis] remains hypothesis-generating. However, 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.

“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.”