A recent meta-analysis published in the Journal of Vascular and Interventional Radiology supports evidence that paclitaxel-coated balloons may pose more risk than reward for patients with symptoms of critical limb ischemia (CLI).
CLI is a common manifestation of infrapopliteal obstructive arterial disease in humans, first author Konstantinos Katsanos, MD, MSc, PhD, and colleagues said in JVIR, and it’s not rare for those symptoms to result in death or limb loss. CLI can be treated with endovascular or surgical revascularization—both of which are considered valid—but in an era of noninvasive innovation, many patients opt for the former approach.
“Endovascular therapies of infrapopliteal arterial occlusions are often preferred considering their inherently less invasive nature and because of multiple patient background comorbidities or absence of a suitable vein conduit,” Katsanos, of Patras University Hospital in Patras, Greece, and co-authors wrote. “Hence, percutaneous revascularization has been developed as mainstream treatment of below-the-knee arterial occlusive disease, offering long-term clinical outcomes comparable to open bypass surgery.”
Treating CLI with paclitaxel-coated balloons has historically been effective, but in recent months paclitaxel-coated and -eluting devices have come under intense scrutiny. A correction in Circulation nearly a year ago triggered a series of events that concluded with an FDA investigation, and last June the agency issued a nonbinding recommendation to continue the sales of paclitaxel-coated devices for patients with peripheral artery disease (PAD).
Still, the FDA recognized a need for better long-term clinical data on the subject. The Circulation correction inverted the results of the 2016 Silver PTX trial, finding the study’s five-year mortality results were “inadvertently reversed” to reflect a long-term survival benefit with paclitaxel-eluting stents compared to percutaneous transluminal angioplasty for PAD patients. In reality, that study found a significantly higher mortality rates in patients treated with the paclitaxel stents, throwing the safety of such therapies into question.
Katsanos et al.’s review and meta-analysis of randomized controlled studies compared treatment of the infrapopliteal arteries with paclitaxel-coated balloons to treatment with conventional balloon angioplasty for CLI. The authors defined their primary safety and efficacy endpoint as amputation-free survival (AFS); a secondary efficacy endpoint was target lesion revascularization (TLR).
The team identified eight randomized controlled trials that involved a total of 1,420 patients, 97% of whom presented with symptoms of CLI. They found that AFS was “significantly worse” for paclitaxel patients—those treated with the coated balloons saw a 13.7% crude risk of death or limb loss compared to the control group’s 9.4%.
Katsanos and colleagues also reported that TLR was heavily reduced in the case of paclitaxel balloons, with paclitaxel patients experiencing an 11.8% crude risk of TLR compared to the 25.6% crude risk in conventional angioplasty patients. The harm signal was most obvious when examining higher-dose devices.
“The findings of this study add to the evidence underpinning some major safety concerns about use of paclitaxel in lower limb angioplasties,” the authors wrote. “There appears to be increased risk of death or major limb loss during the first year when paclitaxel-coated balloons are applied in the infrapopliteal arteries for CLI treatment. Actual causes for this detrimental clinical outcome remain largely unknown, but downstream and systemic paclitaxel embolization is a plausible mechanism.”
The team said further multicenter studies with longer-term follow-up are “urgently warranted.”