Paclitaxel-coated devices do not increase mortality risk

An updated patient-level meta-analysis refutes claims that paclitaxel-coated devices for femoropopliteal interventional procedures heighten the risk of death. The recent study presented at TCT 2023 has found no association between exposure to paclitaxel and mortality.

This finding provides “reassurance to patients, physicians, and regulators on the safety of paclitaxel-coated devices.” [Lancet 2023;doi:10.1016/S0140-6736(23)02189-X]

In 2018, a summary-level meta-analysis of 28 randomized controlled trials on femoropopliteal disease reported a higher risk of mortality for paclitaxel-coated devices relative to uncoated control devices. [https://www.tctmd.com/news/paclitaxel-safety-questions-pad-will-capstone-data-close-door]

However, the updated meta-analysis showed no significant increase in death among patients treated with paclitaxel-coated devices in intention-to-treat (ITT), as-treated, and two crossover analyses. Ten trials, including a total of 2,666 participants, comparing paclitaxel-coated and control devices met the eligibility criteria of this patient-level pooled analysis. Median follow-up was 4.9 years.

The investigators, led by Dr William A. Gray from Lankenau Heart Institute, Wynnewood, Pennsylvania, US, used Cox regression models to examine the impact of paclitaxel exposure on death risk in both ITT (primary analysis) and three as-treated analysis sets accounting for treatment group crossover at the index procedure and over time. They also assessed the effect of paclitaxel dose and baseline covariates.

The meta-analysis revealed no significant increase in deaths in patients treated with paclitaxel-coated devices. [Lancet 2023;doi:10.1016/S0140-6736(23)02189-X]

These results were consistent in the ITT analysis (hazard ratio [HR], 1.14, 95 percent confidence interval [CI], 0.93‒1.40), the as-treated analysis (HR, 1.13, 95 percent CI, 0.92‒1.39), and in two crossover analyses: when late crossovers were censored (HR, 1.07, 95 percent CI, 0.87‒1.31) and when crossovers were analysed from the date of paclitaxel exposure (HR, 1.04, 95 percent CI, 0.84‒1.28).

Additionally, paclitaxel dose had no significant impact on the risk of mortality.

Capstone

“Until this particular analysis was done, it was really difficult to say that the case was closed,” senior author Gray said in a news release. “So, I think when you look at the totality of the data that has been collected and analysed over more than 4 years, this is the capstone.” [https://www.tctmd.com/news/paclitaxel-safety-questions-pad-will-capstone-data-close-door]

Just recently, the US Food and Drug Administration (FDA) reversed its restrictions on the use of paclitaxel-based therapies in peripheral vascular interventions as a result of the 2018 study. This decision was based on the “review of the totality of the available data and analyses.”

The FDA also wrote in their letter to healthcare providers that an “updated RCT meta-analysis does not indicate that the use of paclitaxel-coated devices is associated with a late mortality risk.” [https://www.tctmd.com/news/paclitaxel-safety-questions-pad-will-capstone-data-close-door]

Dr Venita R Chandra from Stanford University Medical Center, California, US, supported the findings of Gray and colleagues regarding the paclitaxel debate.

“I feel like it's a breath of fresh air to just finally, pretty confidently, have touched everyone's concerns and elegantly addressed the deficiencies of prior work,” Chandra said. “This is, I think, the final straw on the camel's back of good work to take this controversy away and let us focus on other things.”