Expert opinion on Paclitaxel published in CVIR

July 31, 2023

In 2018, a meta-analysis from Katsanos et al. sounded the alarm for a possible link between the use of Paclitaxel coated devices and increased mortality.

The topic has remained controversial ever since – but a recently published re-analysis of old data and new outcomes on the link between Paclitaxel coated and eluting devices and mortality concluded that this link was not supported and these devices should be used in PAD treatment. Simultaneously, the FDA issued a letter to physicians supporting the use of DCBs and DESs on the grounds of their safety and efficacy.

The editorial can be read here via CVIR.

We spoke to Prof. Stefan Müller-Hülsbeck to hear his thoughts on this development.

Prof. Müller-Hülsbeck

You are the first author on the expert opinion with a re-analysis of old data and new outcomes which was recently published in CVIR. What was the impetus for the new meta-analysis?

Müller-Hülsbeck: First of all, it needs some clarification – we didn’t initiate and publish the results from a new meta-analysis done by ourselves. Rather, we collected some of the most recent publications and brought them into context with our daily practice in the cathlab during treatment of PAD patients. In short, we once again highlighted the fact that disparate study designs, mixed data sources, and variable ascertainment rates may explain differences in reported mortality outcomes. It must be highlighted that these RCTs were designed to make conclusions about short-term, limb-related endpoints, and not long-term mortality.

What were the main findings of the new analysis?

Müller-Hülsbeck: In recent pooled randomized trial data with updated vital status (vital status serves as an indicator of whether a patient is alive or deceased) ascertainment (re-analysis of the trials used for Katsanos), paclitaxel was associated with improved efficacy but was not associated with increased mortality. Data collections even reported advantages in survival with drug-based therapies using Paclitaxel. [1][2][3][4]

The FDA published a long-awaited update letter to healthcare providers about the use of paclitaxel-coated devices, almost simultaneously to your paper. Where did your findings overlap? Where did they differ?

Müller-Hülsbeck: There is an overwhelming overlap and no differences can be identified. Based on the FDA’s review of the totality of the available data and analyses, they have determined that the data does not support an excess mortality risk for paclitaxel-coated devices. We are not in a position to give such a statement, but we totally are in line with this statement. We conclude that, in the absence of a proven risk of mortality of PCDs, we advocate that the benefits of Paclitaxel coated device use in the femoropopliteal segment in terms of increased primary patency and reduced TLR warrant their use in the routine treatment of patients with femoropopliteal disease. The FDA added recommendations for health care providers to discuss the risks and benefits of all available PAD treatment options, including paclitaxel-coated devices, with our patients and we should continue routine monitoring of patients treated with paclitaxel-coated balloons and paclitaxel-eluting stents. The most important FDA message is that we need to ensure patients receive optimal medical therapy for PAD and, last but not least, any adverse events or suspected adverse events needs to be reported (to the FDA). We fully support these recommendations.

We will expect that other authorities will adapt their recommendations for using paclitaxel-based devices for PAD treatment.

In June 2023, the Endovascular Subcommittee launched a member survey on the use of drug-eluting devices for PAD. Can you already share some findings with us?

Müller-Hülsbeck: This survey and the results are of outmost importance for our community. With a growing body of evidence and recent statements refuting the mortality signal with available data (FDA, CIRSE), a large majority of respondents believe in the safety of these devices and practice is increasing. However, the situation clearly pinpointed the fragility of a system that was primarily based on short-term studies and focused endpoints.

What do you expect the clinical impact of these publications to be? How has your own clinical practice been affected?

Müller-Hülsbeck: Immediately after the Katsanos publication, we were afraid that we had harmed a lot of our patients. We internally evaluated our available data and stopped using these devices for a short period. When discussions started about metaphorical tsunami destroying confidence in PTX, and after my participation in the expert panel meeting in Washington, concerns about these findings and confidence in PTX came back. This resulted in a return to routine use of these devices and new alternatives which are limus-based, and the use of these devices was included in every informed consent process.

1. Schneider PA, Brodmann M, Mauri L, Laird J, Soga Y, Micari A, Ansel G, Shishehbor MH, Krishnan P, Gao Q, Ouriel K, Zeller T. Paclitaxel exposure: Long-term safety and effectiveness of a drug-coated balloon for claudication in pooled randomized trials. Catheter Cardiovasc Interv. 2020 Nov;96(5):1087-1099
2. Dake MD, Ansel GM, Bosiers M, Holden A, Iida O, Jaff MR, Lottes AE, O’Leary EE, Saunders AT, Schermerhorn M, Yokoi H, Zeller T. Paclitaxel-Coated Zilver PTX Drug-Eluting Stent Treatment Does Not Result in Increased Long-Term All-Cause Mortality Compared to Uncoated Devices. Cardiovasc Intervent Radiol. 2020 Jan;43(1):8-19
3. Secemsky EA, Kundi H, Weinberg I, Jaff MR, Krawisz A, Parikh SA, Beckman JA, Mustapha J, Rosenfield K, Yeh RW. Association of Survival With Femoropopliteal Artery Revascularization With Drug-Coated Devices. JAMA Cardiol. 2019 Apr 1;4(4):332-340
4. Freisinger E et al. Mortality after use of paclitaxel-based devices in peripheral arteries: a real-world safety analysis, Eur Heart J 2020 Oct 7;41(38):3732-3739.