No Mortality Difference Found With Paclitaxel-Coated Devices in Interim Analysis of SWEDEPAD Trial

December 9, 2020—In The New England Journal of Medicine (NEJM), Joakim Nordanstig, MD, et al published findings from an unplanned interim analysis of all-cause mortality in the SWEDEPAD clinical trial, in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices. The results did not show a significant difference between the groups in the incidence of death during 1 to 4 years of follow-up, concluded the investigators in NEJM.

BACKGROUND

SWEDEPAD, the Swedish drug-elution trial in peripheral arterial disease, is a multicenter, randomized, open-label, registry-based clinical trial based on the National Quality Registry for Vascular Surgery (Swedvasc) platform. SWEDEPAD is led by Principal Investigator Mårten Falkenberg, MD, and Dr. Nordanstig, who serves as Steering Committee Chair.

In December 2018, the SWEDEPAD 1 and 2 trials were paused to review mortality data from the trials after concerns were raised by Konstantinos Katsanos, MD, et al in a study published in Journal of the American Heart Association. As previously reported, the Katsanos et al systematic review and meta‐analysis of randomized controlled trials evaluating paclitaxel‐coated balloons and stents in the femoral and/or popliteal arteries concluded that there is an increased risk of death after application of these devices in this anatomy. In May 2019, SWEDEPAD investigators announced the intention to resume recruitment of patients after reviewing the data.

SWEDEPAD INTERIM ANALYSIS

Nordanstig et al report in NEJM that at the time of the unplanned interim analysis, 2,289 patients had been randomly assigned to treatment with drug-coated devices (n = 1,149 patients) or treatment with uncoated devices (n = 1,140). 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. No patients were lost to follow-up.

During a mean follow-up of 2.49 years, 574 patients died, including 293 (25.5%) patients in the drug-coated–device group and 281 (24.6%) patients in the uncoated-device group (hazard ratio, 1.06; 95% CI, 0.92-1.22). The 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), reported the investigators in NEJM.

The SWEDEPAD investigators emphasized that the interim analysis was not planned or prespecified but rather initiated in response to mortality concerns identified elsewhere. Other limitations include the potential of bias introduction due to its open-label design (although perhaps less concern when evaluating hard endpoints such as mortality), and the potential effects of low event rates in the claudication groups and whether the use of “low-dose” devices had any influence on the results.