In the latest twist in the debate over the long-term safety of paclitaxel-coated balloons and stents, a correction published Feb. 19 in Circulation said the five-year mortality results of the Zilver PTX randomized trial were “inadvertently reversed.” They originally showed there was a long-term survival advantage with the paclitaxel-eluting stent compared to percutaneous transluminal angioplasty (PTA) in patients with peripheral artery disease (PAD), but that finding should have been flipped.
The five-year all-cause mortality rates in the corrected version of the 2016 study are now 16.9 percent in the drug-eluting stent (DES) group and 10.2 percent in the PTA group. Those figures were initially reversed and had been cited as evidence of the long-term safety of paclitaxel devices, which came under scrutiny following the publication of a meta-analysis in December.
That study, which pooled results from 28 randomized controlled trials, found all-cause mortality rates at two and five years were higher among those treated for femoropopliteal disease with paclitaxel balloons and stents compared to control patients who received uncoated devices. Relative increases in mortality associated with the drug-coated devices reached 68 percent at two years and 93 percent at five years.
In the fallout from that critical meta-analysis, the FDA announced it was looking into the potential safety signal, and two trials evaluating drug-coated devices for the treatment of peripheral artery disease were halted. Trial investigators and device manufacturers rushed to report patient-level data from their respective studies at the Leipzig Interventional Course in late January, which the Society for Cardiovascular Angiography and Interventions (SCAI) highlighted as it weighed in on the budding concerns with paclitaxel devices.
Both the FDA and SCAI said at the time of their statements they believed the benefits of paclitaxel-coated balloons and stents continued to outweigh their risks when used for appropriate indications. The FDA is conducting its own review of the available long-term follow-up data for paclitaxel-coated products, including a focus on the causes of death, the doses of paclitaxel delivered and patient characteristics that may affect clinical outcomes.
The new correction in Circulation is sure to play into future conversations on this topic going forward, as it changes the five-year mortality advantage from the Zilver PTX to the PTA arm of that trial. However, the Zilver PTX trial is one of many that will likely be pooled together in future patient-level analyses evaluating paclitaxel-coated balloons and stents against other products.