Long Term Outcomes After Revascularisations Below the Knee with Paclitaxel Coated Devices: A Propensity Score Matched Cohort Analysis

Abstract

WHAT THIS PAPER ADDS In this retrospective cohort study of 14 738 patients and 6 568 propensity score matched patients with index revascularisation below the knee between 1 January 2010 and 31 December 2018, a reduction was observed in long term all cause mortality and the combined endpoints of amputation or death and cardiovascular event or death five years after the use of paclitaxel coated devices when compared with uncoated devices for the treatment of chronic limb threatening ischaemia. The study addressed a key question in vascular medicine and using long term real world evidence does not confirm the potential harm reported in randomised controlled trials. Objective: Endovascular revascularisation has become a standard approach for below knee lesions and paclitaxel coated devices have been widely used in patients with chronic limb threatening ischaemia. A recent metaanalysis reported higher mortality in paclitaxel coated devices compared with uncoated devices in femoropopliteal lesions. This study aimed to determine long term outcomes in below the knee interventions using paclitaxel coated devices in routine vascular care using a large and contemporary cohort. Methods: A large cohort was created using all inclusive health insurance claims data of patients covered by the second largest insurance fund in Germany. The cohort included patients with index revascularisation of arteries below the knee performed from 1 January 2010, to 31 December 2018. Only patients with first paclitaxel coated device exposure were included. The study cohort was stratified into balloon vs. stent treatment and patients with paclitaxel coated devices were matched with uncoated devices using propensity score. Outcomes were evaluated using the KaplaneMeier method and Cox regression. Results: There were 14 738 patients (mean age 77.6 years, 43.6% female) and 6 568 matched patients included in the study. Increasing use of paclitaxel coated devices was observed during the study period (6% in 2010 vs. 31% in 2018, p < .001), and a total of 2 611 (39.8%) deaths occurred within five years of follow up. In the propensity score matched Cox model, a paclitaxel related reduction of five year mortality (hazards ratio, HR 0.84, 95% confidence interval, CI 0.78e0.91), amputation or death (HR 0.87, 95% CI 0.81e0.94), and cardiovascular event or death (HR 0.86, 95% CI 0.80e0.92) were observed. Conclusion: In this propensity score matched cohort, reduced long term all cause mortality, reduced rates of amputation or death and cardiovascular event or death were observed at five years after the use of paclitaxel coated devices when compared with uncoated devices for the treatment of chronic limb threatening ischaemia.

Drug-Coated Balloon for Arteriovenous Access Stenosis in Hemodialysis Patients

“…Consequently, the FDA has recommended the use of DCBs only for highrisk patients with peripheral arterial diseases. Since the FDA advisory panel proposed their recommendation, several studies have evaluated the association of mortality with paclitaxel but the mortality signal was not replicated in most of them [44][45][46]. However, one meta-analysis by Rocha-Singh et al reported an association with an absolute increase in the mortality rate of 4.6% [47] and the exact reason for the mortality signal was reported; therefore, the mortality signal cannot be overlooked.…”

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

“…In a Germanywide propensity score-matched and adjusted analysis of the primary outcomes of 1) overall survival, 2) amputationfree survival and 3) freedom from major cardiovascular events, no evidence was found of increased complications in the femoropopliteal or crural artery in the paclitaxel group (37,914 and 14,738 pa- tients, respectively) after a 5-year followup period. Rather, an inverse association was discerned with improved outcomes following the index procedure, which could be confirmed in numerous sensitivity analyses [5,17].…”

“…In the BARMER cohort, which included almost 10% of insured persons in Germany and enables a patient-level evaluation, just 111 patients had received a coated stent and 138 patients a corresponding balloon by 2009. In 2018, the proportion of coated devices thus increased from 3% for the treatment of critical limb ischemia and 4% for the treatment of intermittent claudication (2010) to 39% and 48%, respectively [5,17]. A similar situation can be observed in practice patterns in the USA where around 50% of all procedures are today performed using coated stents or balloons [26].…”

“…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].…”

No Increased Mortality Risk Following Paclitaxel Treatment in a Large Swedish Registry Based Randomised Controlled Trial – Reassuring Patient Safety

“…Behrendt CA et al 5 performed two propensity score analyses (sometimes named "the poor man's RCT") in a large insurance fund database in Germany. They could not identify any increased mortality among patients treated with paclitaxel coated devices, either after intervention in the femoropopliteal, 6 or in the below the knee 6 segments. The Global CLTI Guidelines 7 could not give firm recommendations regarding the use of drug eluting devices.…”