A systematic review and meta-analysis, recently published in the Journal of Endovascular Therapy, found no difference in short- to midterm mortality among patients who underwent dialysis access treatment using a drug-coated balloon compared with percutaneous transluminal angioplasty with an uncoated balloon. “With proven benefit and no evidence of harm,” say the authors, they recommend “ongoing use of [paclitaxel-coated balloons] for the failing dialysis access”.
“To our knowledge, there has been no systematic review and meta-analysis specifically investigating mortality following paclitaxel-coated device use in the treatment of the dysfunctional dialysis access circuit,” comment Krystal Dinh (Westmead Hospital, Westmead, Australia) and colleagues, the study investigators.
The aim of this study, therefore, was to perform a systematic review and meta-analysis of eight randomised controlled trials to investigate the risk of all-cause mortality in patients who underwent dialysis access treatment using paclitaxel-coated devices compared with percutaneous transluminal angioplasty with an uncoated balloon.
At the pooled mean follow-up of 13.5 months, all-cause mortality—the primary outcome—was similar in the paclitaxel-coated balloon and percutaneous transluminal angioplasty groups, at 13.8% and 11.2%, respectively (RR 1.26, 95% confidence interval [CI] 0.85–0.89, p=0.25).
In addition, subgroup analysis confirmed that there were no statistically significant differences in mortality at six, 12, and 24 months after treatment. Six-month follow-up data was available in all eight studies included in the meta-analysis and showed results of 5.2% vs. 4.8%, respectively (RR 1.24, 95% CI 0.62–2.47, p=0.55); at 12-months, for which there were six studies’ worth of data, the results were 6.3% vs. 6% (RR 1.06, 95% CI 0.43–2.63, p=0.9); and 24-month follow-up data, available across three studies, revealed figures of 19% vs. 13.5% (RR 1.38, 95% CI 0.9–2.12, p=0.14).
Dinh and colleagues remark that the present analysis was performed to assess the single endpoint of mortality “in direct response” to the meta-analysis published by Katsanos et al in December 2018, which identified higher mortality rates in patients with peripheral arterial disease (PAD) who underwent endovascular treatment of the femoropopliteal arteries with paclitaxel-coated balloons and stents compared to a similar group where no paclitaxel was used.
“In contrast to those findings, our study found no association for patients undergoing treatment for the failing [dialysis access],” the authors state. They recognise that although the meta-analysis by Katsanos and colleagues did not include patients undergoing treatment for dialysis access stenosis, the US Food and Drug Administration warning letter that followed in March 2019 did not distinguish between paclitaxel-coated devices used for the treatment of PAD and dialysis access failure.
In response to this, Dinh and colleagues postulate: “The potential issues of patient safety and medicolegal liability are likely to result in reduced use of paclitaxel-coated devices, a technology shown to reduce reintervention rates”.
They emphasise the fact that paclitaxel-coated balloons are “proven to avoid restenosis and reintervention”, and, “in the absence of a safety signal,” recommend ongoing use while further study is undertaken.
The investigators note a few limitations of the present study. Firstly, the number of studies and participants analysed in the meta-analysis was smaller than that of Katsanos et al. In addition, the duration of follow-up in the included studies was short, with only three extending to the 24-month follow-up, and none extended to the four to five years reported in the Katsanos et al study, which render Dinh and colleagues “unable to make any inferences about long-term mortality outcomes”. Finally, like the Katsanos et al study, the present analysis was a summary-level meta-analysis that was unable to collect patient level data and specific causes of death. The authors believe that “additional insights would certainly be gained if we had access to cause and time of death results”.
They recognise that while it is unclear whether the drug paclitaxel was responsible for the increased death rates observed by Katsanos et al, it is “very likely” that any increased risk would be difficult to detect, and less relevant due to the significant risk of life that is known to result from increased repeat interventions and venous catheters in this high-risk population.
The authors conclude: “It is important that we interpret the paclitaxel safety signal alongside a complete understanding of the evidence for patient benefit that may be gained through the use of paclitaxel-coated balloon angioplasty in [dialysis access]”.