FDA removes red flag for paclitaxel-coated devices after review finds data do not support mortality risk

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paclitaxel update issued by US FDA
FDA has issued new guidance for the use of paclitaxel coated devices in peripheral arterial disease

In a letter to healthcare providers dated 11 July 2023, the US Food and Drug Administration (FDA) communicates that the risk of mortality associated with paclitaxel-coated devices to treat peripheral arterial disease (PAD) is no longer supported based on the totality of the available data and analyses.

This update signals a lowering of the red flag raised in a 2019 letter from the Administration—published in response to a meta-analysis that indicated a late mortality signal—warning that treatment of PAD with paclitaxel-coated balloons and paclitaxel-eluting stents was “potentially associated with increased mortality”. 

Alongside the letter, the US FDA has updated its recommendations for healthcare providers regarding the use of paclitaxel-coated balloons and stents for PAD. As well as removing reference to the possibility of increased mortality with these devices, the amended guidance softens the language around the monitoring of patients who have been treated with paclitaxel-coated stents and balloons, stating that healthcare providers should continue ‘routine’ rather than ‘close’ monitoring of these patients, as had previously been stated. 

The safety of paclitaxel—used in peripheral interventions to prevent restenosis—was called into question by data put forward in 2018 by Konstantinos Katsanos (University of Patras, Patras, Greece) et al that pointed to an increased risk of death at two and five years following the use of paclitaxel-coated balloons and paclitaxel-eluting stents in the femoropopliteal artery. 

The FDA responded, notifying healthcare providers in early 2019 about a late mortality signal in patients treated for PAD in the femoropopliteal artery with paclitaxel-coated balloons and paclitaxel-eluting stents. Their most recent update on the topic, prior to that shared on 11 July 2023, was posted in August 2019. 

In its new update, the FDA notes that “additional data from the pivotal randomised controlled trials (RCTs) has become available,” and that the Administration has worked with device manufacturers and external stakeholders to develop the protocol and analysis plan for new data generation. 

The FDA references the fact that device manufacturers collaborated in an updated meta-analysis, which included “additional studies, more complete vital status information, and longer-term follow-up compared to prior studies”. Patient follow-up in these studies ranged from two to five years, the Administration notes, and led it to conclude that the updated RCT meta-analysis “does not indicate that the use of paclitaxel-coated devices is associated with a late mortality signal”. 

Furthermore, the FDA states that it also reviewed additional analyses of the risk for late mortality, including the SWEDEPAD trial interim analysis, the VOYAGER PAD study, the German BARMER Health Insurance study, the US Veterans Health Administration study and the Medicare SAFE-PAD study. “None of these studies, with mean or median follow-up ranging from 1.7 to 3.5 years, found a risk for late mortality associated with paclitaxel-coated devices,” the FDA communicates, adding that longer-term follow-up in several of these studies is ongoing.

Timeline of events

Click here for an in-depth run through of the key developments in the paclitaxel story.


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