VOYAGER PAD: No mortality risk/benefit with paclitaxel-coated devices in lower extremity revascularization

The use of paclitaxel drug-coated devices did not appear to affect mortality risk in patients with symptomatic peripheral artery disease (PAD) who underwent endovascular lower extremity revascularization, according to subgroup analysis of the VOYAGER PAD* trial.

In the trial, 6,564 patients with symptomatic lower extremity PAD who had undergone revascularization were randomized 1:1 to receive rivaroxaban (2.5 mg BID) or placebo, in addition to aspirin (100 mg/day).

Previously published results showed a significantly reduced risk of the primary endpoint (acute limb ischaemia, major amputation for vascular causes, myocardial infarction, ischaemic stroke, and cardiovascular death) with rivaroxaban vs placebo (3-year incidence: 17.3 percent vs 19.9 percent; hazard ratio [HR], 0.85; p=0.0085). [N Engl J Med 2020;382:1994-2004]

The present analysis assessed if the primary outcome was consistent regardless of use of paclitaxel drug-coated devices and included 4,379 patients who underwent endovascular index lower extremity revascularization. Of these, 31 percent were treated with a drug-coated device, of whom 78, 17, and 5 percent received drug-coated balloon, drug-coated stent, and both, respectively. The patients were followed up for a median 31 months. [TCT Connect 2020, Endovascular 1: Late-Breaking Clinical Trials and Science]

In weighted analysis comprising 4,316 patients, 394 deaths occurred. All-cause mortality was comparable between the drug-coated and non-drug-coated device groups (12.1 percent vs 12.6 percent; HR, 0.95, 95 percent confidence interval [CI], 0.83–1.09; p=0.49). The deaths were primarily due to cardiovascular causes (54 and 62 percent of deaths in the drug-coated and non-drug-coated device groups, respectively).

The findings were consistent regardless of device type, namely comparisons between using drug-coated balloon and percutaneous transluminal angioplasty (HR, 0.99, 95 percent CI, 0.82–1.20) or between drug-eluting stent and bare metal stent (HR, 1.04, 95 percent CI, 0.84–1.28).

The reduced risk of the primary endpoint with rivaroxaban vs placebo also did not differ with device type (HR, 0.87, 95 percent CI, 0.65–1.15 for drug-coated device and HR, 0.89, 95 percent CI, 0.74–1.07 for non-drug-coated device; p_interaction=0.88).

“Endovascular revascularization is indicated for improvement of symptoms and limb salvage in symptomatic PAD,” said Associate Professor Connie Hess from the University of Colorado School of Medicine, Aurora, Colorado, US, at TCT Connect 2020.

Its success, however, is limited by restenosis, with paclitaxel drug-coated devices introduced to attenuate restenosis risk and improve patency.

Previous research on mortality risk associated with paclitaxel-coated device use has been inconclusive, with some studies suggesting an increased risk, [J Am Heart Assoc 2018;7:e011245; Circulation 2020;141:1859-1869] and others demonstrating no mortality risk. [Catheter Cardiovasc Interv 2020;doi:10.1002/ccd.29152; Eur Heart J 2020;41:3732-3739]

“[In this analysis,] IPTW** successfully adjusted for known confounders and showed no mortality risk or benefit associated with drug-coated devices, including in subgroups by device type,” said Hess.

“This analysis from VOYAGER PAD addresses many of the limitations of currently available data regarding mortality and paclitaxel and adds to the literature examining the safety of drug-coated devices,” she continued.

“[In addition,] the benefit of rivaroxaban 2.5 mg twice daily with aspirin vs aspirin alone on reducing ischaemic limb and cardiovascular outcomes after revascularization for symptomatic PAD is consistent regardless of drug-coated device use,” she said.