Internal BIBA MedTech data show that perceptions on paclitaxel devices have shifted considerably in the twelve months that have elapsed since Konstantinos Katsanos (Patras, Greece) et al published their meta-analysis in the Journal of the American Heart Association (JAHA) alleging an increased death rate in patients treated with paclitaxel-coated balloons or paclitaxel-eluting stents in the femoropopliteal arteries. A recent survey reports that for 43% of physicians, the leading cause for this increased concern is due to published statements from regulatory bodies and international societies. Exactly one year on from the initial JAHA publication, Vascular News collates these position statements.
Society for Cardiovascular Angiography and Interventions (SCAI):
After reviewing the Katsanos et al meta-analysis, experts from the Society for Cardiovascular Angiography and Interventions (SCAI) concluded in a statement published on 25 January 2019 that the methods used by Katsanos et al were appropriate and within constraints of trial-level meta-analysis. However, the society statement said: “It is important to note that SCAI believes the associations are hypothesis-generating and require further investigation with patient-level data.”
Cardiovascular and Interventional Radiological Society of Europe (CIRSE):
On 29 March 2019, CIRSE made the following recommendations:
- In the majority of patients undergoing lower limb recanalisation therapies, alternatives to drug-eluting devices should be used.
- For some individual patients at particularly high risk for restenosis, clinicians may decide that the benefits of using a paclitaxel-coated device may outweigh the risks.
- Drug-eluting devices should only be used after a full informed consent process that has discussed the mortality implications from the Katsanos meta-analysis.
- All patients who have already received paclitaxel-eluting devices should be followed up to assess for a potential effect on mortality.
Medicines and Healthcare products Regulatory Agency (MHRA):
The MHRA issued a medical device alert (MDA) on 4 June 2019 warning physicians not to use paclitaxel-coated balloons or paclitaxel-eluting stents in the routine treatment of patients with intermittent claudication until further notice, “as the potential mortality risk generally outweighs the benefits”. However, the agency accedes that use of these devices may still be considered in patients with critical limb ischaemia, taking National Institute of Care Excellence (NICE) guidance into consideration, in view of their increased risk of stenosis and reduced life expectancy. This MDA was published one day after an independent expert advisory group (EAG), consisting of leading UK clinicians from multiple specialties (including interventional radiology, vascular surgery, toxicology and statistics) advised the MHRA to limit the use of paclitaxel devices to patients with CLI. The EAG was established following the publication of the Katsanos et al meta-analysis.
Society for Vascular Surgery (SVS):
The SVS Vascular Quality Initiative (VQI) used large, multicentre registries as datasets for the analysis of vascular patient care in the USA. At the SVS annual meeting (12–15 June, National Harbour, USA), Daniel Bertges (Burlington, USA) demonstrated how the VQI could potentially be used for surveillance of the safety of new peripheral arterial devices. “In this large, real-world sample,” he shared, “there is no difference in mortality at a mean of 12.4 months. The results are similar for patients treated with paclitaxel-coated balloons or paclitaxel-eluting stents. Certainly, a longer registry follow-up is required and ongoing, and we hope that the VQI Peripheral Vascular Interventions Registry will be part of that cumulative body of evidence on this important topic.”
In Spring 2019, the SVS formed a Paclitaxel Safety Task Force, with the mission of facilitating the performance and interpretation of an Individual Patient Data meta-analysis using patient-level randomised controlled trial data from industry partners.
US Food and Drug Administration (FDA):
The FDA admitted in an update from 7 August 2019 that treatment of peripheral arterial disease (PAD) with paclitaxel-coated balloons and paclitaxel-eluting stents is potentially associated with increased mortality. While the regulatory body reported the presence of the mortality signal in its own analysis, it said that the magnitude of the signal should be interpreted with caution due to several limitations in the available data. The FDA advises diligent patient monitoring, that the Katsanos et al meta-analysis be included in the patient consent process, that the device risks and benefits are discussed prior to treatment, and that physicians report any adverse events experienced with the use of paclitaxel-coated balloons and/or paclitaxel-eluting stents. These recommendations are based on the agency’s analysis of long-term follow-up data from premarket trials. The FDA is working with manufacturers and investigators to update device labels and to garner additional clinical evidence for assessment of the long-term safety of these devices.