An unplanned interim analysis of a randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices found that there was no difference in all-cause mortality.
These findings were published online Wednesday in The New England Journal of Medicine.
Peripheral artery disease is a worldwide health problem. Endovascular interventions are indicated to prevent amputations and alleviate symptoms. Paclitaxel is an antiproliferative agent that is used on drug-coated balloons and drug-coated stents, which are used to reduce the risk of restenosis. A recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease.
Joakkim Nordanstig, MD, PhD, of Gothenburg University, Sweden, and co-investigators conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry clinical trial, The Swedish Drug Elution Trial in Peripheral Arterial Disease (SWEDEPAD).
At the time of this analysis, 2,289 patients had been randomly assigned to treatment with drug-coated devices (1,149 patients) or treatment with uncoated devices (1,140 patients). Paclitaxel was used as the coating agent for all the drug-coated devices. Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1,480 patients) or intermittent claudication (809 patients). The single endpoint for this interim analysis was all-cause mortality.
During a mean follow-up of 2.49 years (no patients lost to follow-up), 574 patients died: 293 (25.5%) in the drug-coated-device group and 281 (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92-1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively).
There are some limitations to this trial. The trial design is open-label and, thus, has potential to introduce bias. More importantly, this interim analysis was not a prespecified part of the trial protocol. However, it was needed given the recent meta-analysis that brought into question the safety of paclitaxel-coated devices.
Despite these limitations, this unplanned interim analysis of a randomized trial did not show a significantly higher all-cause mortality rate with paclitaxel-coated devices during 1 to 4 years of follow-up.
The authors explained that there were two reasons why they published the unplanned interim analysis of the trial.
“First, we sought to reduce patients’ and physicians’ concerns regarding the safety of paclitaxel-coated devices, and second, we considered the data to be important to support completion of ongoing trials investigating the efficacy of such devices in peripheral artery disease,” Nordanstig and colleagues wrote.
Both the SWEDEPAD 1 and 2 trials had been stopped after the meta-analysis to which the Nordanstig and colleagues’ paper refers was published, in December 2018. Enrollment for both studies was resumed in March 2019.
Another trial, BASIL-3, also stopped after the Katsanos and colleagues meta-analysis, but it resumed enrollment in September 2019.
Nordanstig J, James S, Andersson M, et al. Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease. N Engl J Med 2020 Dec 9. DOI: 10.1056/NEJMoa2005206 (Article in press).