The FDA issued an advisory August 7 updating healthcare providers and the public on its stance regarding the long-term safety of paclitaxel-coated and -eluting devices, sharing that its expert panel had indeed identified a late mortality signal associated with the devices.
The agency’s update comes six months after a correction in Circulation revealed the results of the 2016 Zilver PTX trial had been “inadvertently reversed” to reflect a long-term survival benefit with paclitaxel-eluting stents compared to percutaneous transluminal angioplasty (PTA) in patients with peripheral artery disease (PAD). In reality, paclitaxel patients saw a steeper five-year mortality rate than their PTA peers—16.9% compared to 10.2%, respectively.
That reversal, paired with the results of a meta-analysis that found all-cause mortality at two and five years was higher among those treated for femoropopliteal disease with paclitaxel balloons and stents, pushed the FDA to launch its own review. A panel debated the subject for two days in June, ultimately issuing a vague, nonbinding recommendation to continue sales of paclitaxel devices so long as they’re used as indicated.
Throughout the process, the FDA has retained its stance that the benefits of paclitaxel-coated devices continue to outweigh the risks, so long as the therapies are used appropriately. The agency didn’t repeat that statement in its August update, writing instead that its panel acknowledged a late mortality signal associated with the use of paclitaxel-coated devices.
“The Panel and the FDA agreed that the magnitude of the signal should be interpreted with caution because of multiple limitations in the available data including wide confidence intervals due to a small sample size, pooling of studies of different paclitaxel-coated devices that were not intended to be combined, substantial amounts of missing study data, no clear evidence of a paclitaxel dose effect on mortality and no identified pathophysiologic mechanisms for the late deaths,” the agency said in its statement.
“The panel determined, and the FDA concurs, that additional clinical study data are needed to fully evaluate the late mortality signal.”
Though two clinical trials were halted months ago due to mounting evidence of a mortality burden with paclitaxel devices, the FDA recommended clinical studies should continue and “should collect long-term safety (including mortality) and effectiveness data.” The agency also recommended:
- Close monitoring of patients who have already been treated with paclitaxel-coated and -eluting devices
- Physicians discuss the potential increased risk of long-term mortality with patients considering paclitaxel devices, as well as provide alternate options for PAD treatment
- Physicians weigh the risks and benefits of paclitaxel devices with individual patients as part of the informed consent process
- Patients with paclitaxel devices control their other CV risk factors and receive professional guidance on healthy lifestyle changes
- Anyone who experiences an adverse event or suspected adverse event voluntarily report those events through MedWatch, the FDA’s safety information and adverse event reporting program
The FDA said it’s continuing to work with manufacturers of paclitaxel devices, as well as clinical investigators, to gather more clinical evidence related to the long-term safety of paclitaxel-coated balloons and paclitaxel-eluting stents.