There was no increased risk of long‐term, all‐cause mortality associated with paclitaxel-coated device (PCD) use among patients undergoing femoropopliteal peripheral endovascular intervention within the Veterans Health Administration (VHA). This is the conclusion of Jorge Antonio Gutierrez (Duke University Medical Center, Durham, USA) and colleagues, published ahead of print in the Journal of the American Heart Association (JAHA). Theirs was the first study examining the impact of PCD use on mortality with the VHA; they found that in more than 10,000 veterans with peripheral arterial disease (PAD) undergoing femoropopliteal intervention, the rates of two‐year and three‐year all‐cause mortality were similar among patients undergoing revascularisation with PCD (drug-coated balloons [DCB] and/or drug-eluting stents [DES]) and non‐PCD (percutaneous angioplasty balloon and/or bare metal stent) devices.
“The long‐term safety of PCDs for peripheral endovascular intervention is uncertain,” Gutierrez et al write. They therefore used data from the VHA to evaluate the association between PCDs, long‐term mortality, and cause of death, aiming to shed further light on the controversy first sparked in December 2018 by Konstantinos Katsanos (University of Patras, Patras, Greece) and colleagues, who reported in JAHA a potential association between increased mortality and PCD use in the leg.
In the present study, the investigators used the Veterans Administration Corporate Data Warehouse in conjunction with International Classification of Diseases, Tenth Revision (ICD‐10) Procedure Coding System, Current Procedural Terminology, and Healthcare Common Procedure Coding System codes to identify patients with PAD treated within the Veterans Administration for femoropopliteal artery revascularisation between 1 October 2015 and 30 June 2019. An adjusted Cox regression, using stabilised inverse probability-weighted estimates, was used to evaluate the association between PCDs and long‐term survival. They also obtained cause of death data using the National Death Index.
In total, 10,505 patients underwent femoropopliteal peripheral endovascular intervention; 2,265 (21.6%) with a PCD and 8,240 (78.4%) with a non‐PCD (percutaneous angioplasty balloon and/or bare metal stent). Survival rates at two years (77.4% vs. 79.7%) and three years (70.7% vs. 71.8%) were similar between PCD and non‐PCD groups, respectively.
The adjusted hazard for all‐cause mortality for patients treated with a PCD versus non‐PCD was 1.06 (95% confidence interval [CI], 0.95–1.18; p=0.3013). Among patients who died between 1 October 2015 and 31 December 2017, the cause of death according to treatment group, PCD versus non‐PCD, was similar.
Gutierrez et al state: “All‐cause mortality risk related to exposure to PCD was no different when stratified according to claudication or chronic limb-threatening ischaemia (CLTI) presentations. […] After adjustment for treatment assignment, no statistically significant risk in all‐cause mortality was observed between the use of PCD and non‐PCD devices.”
“The endovascular community is now left with difficult decisions regarding when to use PCDs in clinical practice”
Before the reporting of a late mortality signal in the 2018 Katsanos et al meta‐analysis, PCDs were frequently used in femoropopliteal endovascular procedures, as they improved short‐term and intermediate‐term primary patency rates, Gutierrez and colleagues write. The late mortality signal was confirmed by a subsequent analysis from the US Food and Drug Administration of long‐term follow‐up data from pivotal premarket randomised trials for PCD, and most recently by an individual patient data meta‐analysis of US commercially available PCDs.
“However,” the authors of the present study explain, “limitations with these early studies have been recognised, including small sample sizes, substantial amounts of missing data, and poor patient follow‐up”.
They continue: “Nevertheless, PCDs now carry revised package labelling with information detailing the potential for late mortality. Globally, international clinical trials were initially halted (SWEDEPAD [Swedish drug‐elution trial in peripheral arterial disease] and BASIL‐3 [Bypass versus angioplasty in severe ischaemia of the leg]), and the UK Medical and Healthcare Products Regulatory Agency has advised against PCD use in intermittent claudication. The endovascular community is now left with difficult decisions regarding when to use PCDs in clinical practice, leading to wide variability in practice patterns. The Circulatory System Devices Panel and the US Food and Drug Administration acknowledge that additional clinical study data, particularly those evaluating long‐term safety of PCDs, are needed.”
FDA guidance “remains clear” amid developing situation, editorial concludes
An editorial on the new findings were simultaneously published ahead of print in JAHA. Douglas E Drachman and Joseph M Garasic (both Massachusetts General Hospital, Boston, USA) conclude in ‘Paclitaxel-coated devices: Safety and efficacy are in the PVI of the beholder’ that, “For now, the guidance from the [FDA] remains clear: reserve use of PCDs for anatomic and clinical situations where their efficacy may be most advantageous and where their risk is lowest, while participating in shared, individualised consideration of risk and benefit with our patients.”
Considering future directions, they add: “With a growing body of data, including randomised controlled assessments on the horizon, our understanding of the safety and efficacy of PCDs continues to evolve, as will our optimal interventional strategies for the care of patients with symptomatic lower-extremity [PAD].”