Paclitaxel-Based Devices for the Treatment of PAD: Balancing Clinical Efficacy with Possible Risk

Paclitaxel-based endovascular devices have become the standard of care in symptomatic, medication-refractory peripheral artery disease (PAD) and in critical limb ischemia (CLI). This review examines the data on the efficacy and safety of these devices relative to standard balloon angioplasty (PTA) and bare metal stents (BMS).

Randomized controlled trials (RCTs) have found that peripheral devices coated with paclitaxel result in superior patency rates and decreased target lesion revascularization (TLR) compared with non-drug-coated devices. Recently, a meta-analysis of randomized controlled trials unexpectedly reported an increase in mortality in patients treated with paclitaxel-coated devices (PCDs), resulting in the pausing of ongoing trials and a warning of safety from the FDA. Observational data that has been published since this time has not supported this safety concern. PAD is a common disease that severely impacts quality and length of life. PCDs are a promising therapy for patients with PAD, offering a more effective and durable intervention when compared with traditional PTA/BMS. A meta-analysis of RCTs identified a signal of harm with these devices which has now been replicated by the FDA. However, there is significant missing data from the trials analyzed by the meta-analysis and FDA, no plausible mechanism linking paclitaxel to death, and no correlation between paclitaxel dose and mortality. Analyses in observational data have found no safety signal. An FDA panel evaluating the validity of this late-mortality signal recently adjourned, emphasizing that the available data is incomplete. PCDs will remain on the market, and an active discussion is underway for developing an approach for improved post-market surveillance, device-labeling, and cause of death adjudication.