There is no sign of increased all-cause mortality following the use of paclitaxel-coated devices for the treatment of symptomatic peripheral arterial occlusive disease, a new study based on German claims data attests in the European Journal of Vascular and Endovascular Surgery.
The study investigators set out to determine the survival of patients after use of paclitaxel-coated devices using a propensity score matched retrospective analysis of German health insurance claims. BARMER is the second largest insurance fund in Germany, and lead author Christian-Alexander Behrendt (University Medical Centre Hamburg-Eppendorf, Hamburg, Germany) and colleagues used this dataset to identify index femoropopliteal arterial interventions between 1 January 2010 and 31 December 2018. To ensure first paclitaxel exposure, patients with prior deployment of paclitaxel were excluded.
The study cohort—37,914 patients; mean age 73.3 years; 48.8% female—was stratified into patients with chronic limb threatening ischaemia (CLTI) and intermittent claudication, then into balloon versus stent cohorts. Within each stratum, paclitaxel was compared with uncoated devices.
Contextualising this research by highlighting how multiple US and European guidelines have recommended drug-eluting devices as “first-line treatments in the femoropopliteal segment”, Behrendt et al cite a 2018 meta-analysis published in the Journal of the American Heart Association (JAHA) as the cause for heightened scrutiny on these devices in recent months. The JAHA meta-analysis, authored by Konstantinos Katsanos (School of Medicine, University of Patras, Patras, Greece) and colleagues, evaluated data from 28 randomised controlled trials, and reported a higher risk of death at two and five years following the use of paclitaxel-coated balloons and paclitaxel-eluting stents in the femoropopliteal arteries.
However, this finding was not repeated in analyses involving “real-world data”. As reported in this newspaper, Eva Freisinger (University Hospital Münster, Münster, Germany) also used the BARMER dataset to conduct a real-world safety analysis of paclitaxel-based devices in peripheral arteries, concluding in the European Heart Journal that the use of drug-eluting devices is “safe for endovascular therapy of the lower limbs”. Indeed, Freisinger et al explicitly stated: “Particularly with regard to long-term mortality, neither drug-coated balloons nor drug-eluting stents was associated with increased risk compared to non-drug-eluting devices”.
The present study is differentiated from that of Freisinger et al by restricting the included patients to ensure a more homogenous study population. Behrendt and his co-investigators write: “Aiming to add to the existing evidence, the current approach rested on a rigorous study design involving a more homogeneous study population (only femoropopliteal segment, no prior major amputation), with a lookback period of up to five years and follow-up periods (left and right censoring) of five years.”
In this most recent analysis of the BARMER insurance claims dataset, Behrendt and co-authors also have opposing conclusions to the Katsanos et al JAHA meta-analysis. They report that paclitaxel-coated balloons and stents were associated with improved overall survival (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.77–0.90), amputation-free survival (HR 0.85, 95% CI 0.78–0.91), and freedom from major cardiovascular events (HR 0.82, 95% CI 0.77–0.89) versus uncoated devices at five years for CLTI. In the intermittent claudication cohort, mortality was significantly lower after using drug-coated balloons (HR 0.87, 95% CI 0.76–0.99) or combined drug-coated balloons and drug-eluting stents (HR 0.88, 95% CI 0.80–0.98).
Additionally, Behrendt et al note that the annual proportion of paclitaxel use increased from 3% to 39% during the study period for CLTI, and from 4% to 48% for intermittent claudicants (both p<0.001).
“In this propensity score matched retrospective analysis of health insurance claims,” the authors summarise, “comprising a rapidly increasing proportion of paclitaxel-coated devices in the treatment of peripheral arterial occlusive disease, higher long-term survival, amputation-free survival, and adverse cardiovascular event-free survival after the treatment of CLTI with paclitaxel-coated devices (both balloon and stent) was found, when compared with the uncoated control group. In patients with intermittent claudication, paclitaxel-coated devices were associated with higher long-term survival only, visible in the group where balloons and stents were combined and for balloons but not for stents. Unlike any other prior analysis, a persistent, robust, and positive association of paclitaxel exposure and survival is documented for a wide range of subgroups.”