June 15, 2020
European IFUs for Paclitaxel-Coated Devices Will Contain New Warning
June 15, 2020—Manufacturers and marketers of paclitaxel-coated balloons and stents used in the treatment of lower extremity peripheral arterial disease are issuing a Field Safety Notice regarding updates to the indications for use (IFU) for these devices throughout Europe.
As specified in the Field Safety Notice, which has been posted online by the United Kingdom's Medicines & Healthcare Products Regulatory Agency (MHRA), these updates include a warning and summary of the findings by Katsanos et al published in Journal of the American Heart Association in December 2018 and are to be supplemented with the clinical data specific to each device concerned (eg, Kaplan Meier mortality estimates at 2, 3, and 5 years for that treatment device versus control device).
According to the communication, the French competent authority, Agence Nationale de Sécurité du Medicament et des Produits de Santé, requested all manufacturers to add a warning and clinical summary related to the meta-analysis data to European IFUs in response to the Katsanos meta-analysis. The meta-analysis describes an increased risk of death at 2 and 5 years after treatment with paclitaxel‐coated balloons and stents in the femoropopliteal artery in the studies analyzed, but it has been controversial.
The European Union IFU warning states: "A signal for increased risk of late mortality has been identified following the use of paclitaxel-coated balloons and paclitaxel-eluting stents for femoropopliteal arterial disease beginning approximately 2–3 years post-treatment compared with the use of non-drug–coated devices. There is uncertainty regarding the magnitude and mechanism for the increased late mortality risk, including the impact of repeat paclitaxel-coated device exposure. Physicians should discuss this late mortality signal and the benefits and risks of available treatment options with their patients."
The notice advises:
- The indications and contraindications of the devices remain unchanged.
- No product batch/lot is being recalled in relation to this field safety notice.
- “[T]he benefits of paclitaxel-coated devices (eg, reduced reinterventions) should be considered in individual patients along with potential risks (eg, late mortality)."
- Physicians should discuss this late mortality signal and the benefits and risks of available treatment options with their patients.
- Health care professionals should inform patients and their follow-up physicians of the nature of the devices used during the procedure.
The communication lists the affected medical devices: BioPath (BioSensors International); Eluvia (Boston Scientific); In.Pact Admiral and In.Pact Pacific (Medtronic); Luminor (iVascular); Lutonix (BD Interventional); Passeo-18 Lux (Biotronik); Ranger and Ranger SL (Boston Scientific); SeQuent Please OTW (B. Braun Melsungen AG); Stellarex (Philips); and Zilver PTX (Cook Medical).
In the United States, the FDA issued an update in August 2019 that, among other recommendations and actions, advised that the agency was having manufacturers update their labeling for paclitaxel-coated devices to include information about the late mortality signal.