No sign of paclitaxel-related mortality risk in VOYAGER PAD cohort
At 3.5 years after lower-extremity revascularization, there was no difference in mortality in the VOYAGER PAD cohort between patients with peripheral artery disease treated with paclitaxel-coated devices and those not treated with them.
In addition, the beneficial treatment effect of rivaroxaban (Xarelto, Janssen/Bayer) was consistent regardless of whether patients underwent an endovascular procedure with paclitaxel-coated devices, researchers reported at TCT Connect.
“The objectives of the current analysis were in patients enrolled in VOYAGER who underwent endovascular lower-extremity revascularization to assess whether the use of paclitaxel-coated devices is associated with all-cause mortality and to elucidate whether the effect of rivaroxaban is consistent with vs. without drug-coated device use,” Connie N. Hess, MD, MHS, interventional cardiologist and associate professor of medicine at the University of Colorado and clinician-scientist at CPC Clinical Research, said during a press conference. “In 2018, there was a meta-analysis that demonstrated an association between mortality and drug-coated device use. There were some significant limitations with this analysis, including a lot of missing data from pivotal trials at 5 years, calling into question the accuracy of these results.”
Among the cohort, 4,379 patients underwent an endovascular procedure, of whom 31% were treated with a drug-coated device. The researchers used inverse probability of treatment weighting to account for differences between those who had an endovascular procedure with a drug-coated device and those had an endovascular procedure without a drug-coated device.
Median follow-up was 31 months and ascertainment of mortality was achieved in 99.6% of patients.
There was no difference in mortality between those treated with drug-coated devices (12.1%) and those treated with other devices (12.6%; HR = 0.95; 95% CI, 0.83-1.09), Hess said, noting the results did not change in a sensitivity analysis using stabilized weights (HR = 0.95; 95% CI, 0.77-1.18).
The primary outcome from the main VOYAGER PAD analysis, defined as acute limb ischemia, major amputation of vascular etiology, MI, ischemic stroke or CV death, favored those assigned rivaroxaban over those assigned placebo in both those treated with drug-coated devices and those not treated with them (P for interaction = .88), she said.
“We found no mortality risk or benefit associated with drug-coated device use,” Hess said. “We also demonstrated that the effect of rivaroxaban on reducing ischemic limb and cardiovascular outcomes is consistent regardless of drug-coated device use. There have been many studies published on the issue of paclitaxel and mortality with mixed results. VOYAGER PAD addresses the limitations of many currently available data.”
In a discussion at the press conference, Robert Lookstein, MD, MHCDL, FSIR, FAHA, FSVM, professor of radiology and surgery at Icahn School of Medicine at Mount Sinai, said: “The fact that this study has 99.6% ascertainment of vital status at 3.5-year follow-up is an incredible milestone. The fact that there’s no difference in mortality at that level of follow-up with that level of ascertainment ... starts to raise the question of whether it’s time to shut the door on the paclitaxel controversy. The entire vascular community has been waiting for a prospective, independently adjudicated trial to make determinations of whether we can put this behind us, and I think this trial is it.”
During the press conference discussion, Peter A. Schneider, MD, professor of surgery in the department of surgery, division of vascular and endovascular surgery at the University of California, San Francisco, said: “The two things we missed on the initial randomized trials of paclitaxel were the follow-up data, thus introducing ascertainment bias, and also very good control of periprocedural and follow-up medications, thus the possibility of a treatment bias. Those were eliminated here, and now under randomized controlled trial conditions, we see no effect on mortality of paclitaxel. These data support some of the thoughts we’ve had about how paclitaxel was implicated in mortality in the first place. It could have been trial design all along.”
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Hess CN, et al. Endovascular 1: Late-breaking clinical trials and science. Presented at: TCT Connect; Oct. 14-18, 2020 (virtual meeting).