Paclitaxel and Mortality Following Peripheral Angioplasty: An Adjusted and Case Matched Multicentre Analysis

Abstract

WHAT THIS PAPER ADDSRecent literature has suggested that there may be an association between the use of paclitaxel based endovascular therapy (PTX) and medium term mortality. This was based on a number of randomised trials of patients with claudication. Owing to a number of limitations such as lack of inclusion of patients with chronic limb threatening ischaemia (CLTI), and no availability of patient level data or adjustment for medication dose, no definitive conclusions can be made. This cohort study reported on 2071 patients with either claudication or CLTI, and after multiple adjustments for well established risk factors, showed no association between PTX and mortality.Objective: Paclitaxel based drug coated balloons (DCBs) and drug eluting stents (DESs) may be associated with increased mortality in patients with peripheral arterial occlusive disease (PAOD), based on a recent metaanalysis. This study, however, had a number of limitations, which have been discussed at great length among the vascular community. The aim of this research was to assess the association between paclitaxel based endovascular treatment (PTX) in the femoropopliteal (FeP) segment and mortality, adjusting for relevant risk factors and including patients with chronic limb threatening ischaemia (CLTI). Methods: This was a retrospective cohort study of a prospectively maintained multicentre (three sites) database of patients with claudication or CLTI. Patients having FeP angioplasty between 1 January 2014 and 30 May 2019 with or without PTX were included. Survival was compared in Cox regression analyses adjusted for parameters of the Charlson comorbidity index. A separate nested case matched (based on each individual's Charlson index) analysis was performed to compare mortality rates between those who received PTX and those who did not. Results: A total of 2 071 patients were analysed: 966 patients (46.6%) were treated with PTX (952 [46%] had CLTI and 1 119 [54%] severe claudication [Rutherford stage 3]). Over a 24 month median follow up, 456 (22.1%) patients died. Using multivariable Cox regression, PTX was not associated with mortality (HR 0.94, p ¼ .46), even when assessed separately for those with intermittent claudication (HR 1.30, p ¼ .15) or CLTI (HR 0.81, p ¼ .060). In the case matched analysis (885 matched pairs of patients), PTX was not associated with mortality (HR 0.89, p ¼ .17). Paclitaxel dose and use of a DCB or DES were not associated with mortality in any subanalysis. Conclusion: When relevant risk factors were taken into account, there were no associations between PTX and mid term mortality in patients with PAOD.

Sex Disparities in Long-Term Mortality after Paclitaxel Exposure in Patients with Peripheral Artery Disease: A Nationwide Claims-Based Cohort Study

“…This association was later confirmed in a patient-level meta-analysis and a separate meta-analysis concerning amputation-free survival after below-the-knee treatment [2,3]. During this ongoing controversy, multiple studies that used either real-world data from large administrative and clinical registries [4][5][6][7][8][9] or interim analyses from a large RCT [10] were not able to replicate this unsettling safety signal. Strikingly, analyses using observational datasets found an opposite signal, with improved survival in patients exposed to paclitaxel when compared with those not exposed [5,6].…”

Randomized controlled trials and real-world evidence for market access and surveillance of high-risk products—The example of paclitaxel

“…Indeed, a consensus is still not foreseeable today [4]. The fact is that the association observed between paclitaxel and mortality could also be confirmed in further patient-level analyses, while various independent observational studies of a high methodological quality were able to prove an inverse association [5,17,32,33,37].…”

“…A total of 2071 patients could be analysed in a mul-ticenter registry analysis at 3 hospitals in Great Britain and Greece. After a median follow-up period of 24 months, no higher mortality was observed in the group of patients treated with coated stents or balloons [33]. A retrospective singlecenter analysis is also available from Germany of balloon-supported angioplasties of the femoropopliteal artery from a high-volume centre.…”

One-year outcomes following primary stenting of infrapopliteal steno-occlusive arterial disease using a non-polymer sirolimus-eluting stent: Results from a prospective single-centre cohort study

“…The durability of PTA in the infrapopliteal segment is, however, challenged by issues such as vessel diameter, lesion length, presence of calcified atherosclerotic plaques or multilevel disease, and neointimal hyperplasia. Drug-coated balloons (DCBs) and drug-eluting tents (DESs) are increasingly used to address hyperplasia in this clinical context (PAOD), to improve, potentially, patency, and clinical outcomes ( 7 ). Randomised studies suggest the superiority of paclitaxel-based endovascular therapies in other segments (e.g., femoro-popliteal arteries) over plain balloon angioplasty (PBA) or bare metal stenting in terms of vessel patency ( 7 , 8 ).…”