Do not use paclitaxel drug-coated balloons (DCBs) or drug-eluting stents (DESs) in the routine treatment of patients with intermittent claudication until further notice, a medical device alert (MDA) issued today by the UK Medicines and Healthcare products Regulatory Agency (MHRA) announces, “as the potential mortality risk generally outweighs the benefits”. However, the use of DCBs and DESs 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 restenosis and reduced life expectancy, the MDA accedes.
The MDA makes the following recommendations concerning the ongoing use of paclitaxel-coated balloons and implantable drug-eluting stents in the treatment of patients with peripheral arterial disease (PAD):
1. Do not use paclitaxel drug-coated balloons (DCBs) or drug-eluting stents (DESs) in the routine treatment of patients with intermittent claudication until further notice, as the potential mortality risk generally outweighs the benefits.
2. Use of paclitaxel DCBs and DESs in patients with critical limb ischaemia remains an appropriate option in accordance with National Institute of Care Excellence (NICE) guidance, as the benefits may outweigh the risks. This is because these patients generally have a higher risk of irreversible ischemic damage resulting from restenosis, and a lower life expectancy.
3. Assess the relative risks on an individual patient basis, and if this supports use of a paclitaxel DCB or DES, ensure that:
a) the process of informed consent includes a risk-benefit discussion regarding the uncertainty in long-term outcomes with these devices, and the current evidence which indicates an increased mortality rate
b) the patient receives enhanced life-long follow-up.
4. Ensure local procedures accounting for duty of candour are in place for the continued management of patients who have already been treated with paclitaxel DCBs an DESs. Consider the need for enhanced patient follow-up, and the provision of information and advice to address patient concerns arising from the current uncertainty in long-term outcomes with these devices.
5. Where enhanced patient follow-up is appropriate this may include telephone consultations or review in the community, and any serious adverse events and cause of death should be reported.
6. Report adverse events involving these devices through your local incident reporting system and/or your national incident reporting authority as appropriate: England, Scotland, Northern Ireland, Wales. You should also report directly to manufacturers if your local or national systems do not.
These recommendations are addressed to interventional radiologists and vascular surgeons, and, according to the MHRA announcement, should be actioned by 2 July 2019.
The MDA calls for more data, saying that “A review of results from clinical trials on the use of these devices in patients with arterio-venous fistula remains outstanding. These results should be shared when available to enable assessment of use in this population.”
The announcement adds: “In all cases where paclitaxel DCBs or DESs are used, there needs to be fully informed consent and an enhanced, long-term patient follow-up. Formal long-term surveillance is essential to improve understanding of the safety and performance of these devices following their market approval.”
These recommendations come one day after an independent expert advisory group (EAG) advised MHRA to limit the use of paclitaxel devices to patients with critical limb ischaemia (CLI). The EAG was set up in response to a meta-analysis of randomised controlled trials published 6 December 2018 in the Journal of the American Heart Association (JAHA) by Konstantinos Katsanos (Patras, Greece) et al that reported a statistically significant increased all-cause mortality from two to five years post treatment with paclitaxel DCBs and DESs used in the femoropopliteal arteries in patients with intermittent claudication compared with patients treated with plain balloons or bare-metal stents. MHRA say that “These findings raised significant concerns on their [paclitaxel devices] use in routine clinical practice and clinical trials”.
The MDA states: “It is accepted that the causal relationship between paclitaxel-coated devices and mortality is not yet understood and requires further evaluation. However, having taken account of the EAG’s findings, together with other relevant information and opinions, MHRA considers the current evidence does not support the routine use of paclitaxel DCBs or DESs in patients with intermittent claudication.
“We will review the need to update this advice as further evidence emerges, including the findings of an ongoing meta-analysis using the patient level data from the randomised controlled trials reviewed by Katsanos et al. To build on the current evidence base, the ongoing and completed trials that have reported results from one or two-year follow-up should continue or reopen patient follow-up to try to establish the longer-term mortality status of all patients, up to at least five years post-treatment.
“The risk-benefit profile for patients with other vascular indications may be different to those for intermittent claudication and requires further clinical evidence to be reviewed before conclusions can be drawn.”