The UK Medicines and Healthcare products Regulatory Agency (MHRA) acted to limit the future use of paclitaxel-eluting stents and paclitaxel-coated balloons in routine clinical care following recommendations from the independent Expert Advisory Group (EAG) on the use of these devices.
The independent EAG was formed following the publication of a meta-analysis published by Konstantinos Katsanos (Patras, Greece) et al late last year in the Journal of the American Heart Association (JAHA) that raised concerns amongst the medical community for reporting an increased risk of death at two and five years after using paclitaxel devices in the femoropopliteal artery. The EAG consists of leading UK clinicians from multiple specialties, including interventional radiology, vascular surgery, toxicology and statistics.
The group reviewed the findings of the Katsanos et al paper, and concluded that the statistical analysis used by the investigators was robust. The EAG also considers that “there is a possible dose dependent effect of the use of paclitaxel-coated/-eluting devices on mortality although no scientific or clinical explanation is currently available.
“There are some established causal links between multiple factors and mortality, but the association of increased mortality and the use of paclitaxel-coated/-eluting devices is established by randomised controlled trials which control for confounding in known factors. There is no evidence to suggest that confounding persisted within these studies. Current knowledge gaps include dose-time relationship, outcomes of paclitaxel coated balloons versus paclitaxel eluting stents, patient factors, effect on patients with claudication compared with those with critical limb ischaemia, peer-reviewed publication of commercial evidence, mechanistic explanation, and biological evidence.”
The EAG was tasked with providing recommendations to the MHRA on the benefits and risks of the use of these devices in the treatment of peripheral arterial disease (PAD).
The expert group recommends that these devices not be used to treat patients with intermittent claudication, saying that this is a condition that may be treated effectively with other devices and therapies. However, for patients with critical limb ischaemia (CLI), the EAG advise that the devices may still be considered “where it is felt that the benefits outweigh the risks and taking NICE guidance into consideration in conjunction with appropriate informed consent and an enhanced patient follow-up”.
After receiving the recommendations, the MHRA has acted to limit the future use of these devices in routine clinical care, until more is known on this issue. Writing on their website, the MHRA encourages “anyone, patient, carer or healthcare professional, who is aware of a safety complication or adverse event associated with a medical device, to report to us via the Yellow Card scheme”.
The EAG recommends that future research is undertaken to evaluate the causal relationship between these devices and mortality. In line with the EAG’s recommendations, the MHRA will consider the available evidence supporting the use of these devices for other conditions.
The EAG also conclude that paclitaxel devices “may still be considered a treatment option within ethically approved trials following appropriate informed consent. In particular, currently suspended RCTs involving patients with CLI should consider resumption in recruitment.” This comes days after the investigators of the SWEDEPAD trials announce their intention to explore the possibility of resuming enrolment.
The US Food and Drug Administration (FDA) is leading a review of patient-level data from clinical trials involving these devices. The MHRA will take this review into account going forward, saying on their website that they “will consider any further information concerning the safety of these devices. It will take any regulatory action and update its guidance where necessary”.