In December 2018, the Journal of the American Heart Association published “Risk of death following application of paclitaxel‐coated balloons and stents in the femoropopliteal artery of the leg: A systematic review and meta‐analysis of randomized controlled trials” by Konstantinos Katsanos et al.
This hotly-discussed and -contested article reported an increased mortality rate with the use of paclitaxel devices for the treatment of femoropopliteal artery disease. These findings were subsequently validated by a Food and Drug Administration (FDA) analysis—a potentially concerning signal of increased long-term mortality in study subjects treated with paclitaxel-coated products compared to patients treated with uncoated devices. In response, the FDA released three communications (Jan. 17, March 15 and Aug. 7, 2019) to healthcare providers about the use of paclitaxel devices. In June 2019, the FDA convened a panel with expert input to assess safety and further recommendations regarding paclitaxel devices. Since that time, there have been multiple publications reviewing the trial data as well as administrative databases which have not confirmed the mortality signal.
In September 2016, the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) began recording device-specific data (including paclitaxel devices) in the Peripheral Vascular Intervention (PVI) registry. VQI is the only clinical registry that records device-specific information which allows identification of paclitaxel technology and correlation with detailed patient, clinical and outcomes data.
An early analysis of VQI data was presented at the FDA panel and at the SVS Vascular Annual Meeting in June 2019, reporting lower one-year mortality in claudicants treated with paclitaxel devices compared to non- paclitaxel devices (1.6% vs. 4.4%; HR=0.59; 95% CI, 0.39–0.89, p=0.01). Similar mortality was observed in patients with chronic limb-threatening ischemia for paclitaxel vs. non-paclitaxel devices (12.8% vs. 15.5%; HR=0.85; 95% CI 0.72–1.0; p=0.05). In brief, the mortality signal associated with paclitaxel technology was not seen in the PVI registry at a median of 17 months (range 10–22 months). The study has undergone peer review and is anticipated for publication in Circulation: Cardiovascular Interventions.
As the SVS VQI PVI registry is in the unique position of being the only clinical registry to have device identification and line-by-line patient clinical and outcomes data, it is important to use this information to further study the potential mortality signal. In response to this need, the SVS Patient Safety Organization (PSO) developed two studies to investigate paclitaxel outcomes in real-world practice.
First, we have engaged the Vascular Implant Surveillance and Interventional Outcomes Network (VISION), a coordinated registry network with proven methodology to match VQI patients to Medicare claims. VISION is supported by the Medical Device Epidemiology Network (MDEpiNet), a global public- private partnership with the aim of advancing a national patient-centered medical device evaluation and surveillance system.
VISION is led by Phil Goodney, MD, and Art Sedrakyan, MD, who directs the MDEpiNet Coordinating Center at Weill Cornell Medicine in New York under a cooperative agreement with the FDA and its Center for Devices and Radiological Health (CDRH).
One of the limitations of the VQI registry is that most follow-up is limited to one year. Linking VQI patient data in a protected manner to CMS claims data allows investigators to extend the period of study prior to device identification in the VQI and beyond the one-year VQI follow-up.
The VISION analysis is examining mortality, reintervention and major amputation after paclitaxel treatment. This ongoing analysis will leverage the strengths of the VQI PVI registry with the Medicare claims database.
Second, we have launched an active surveillance program of paclitaxel mortality using Data Extraction and Longitudinal Trend Analysis (DELTA) in collaboration with Frederic Resnic, MD, at Lahey Hospital & Medical Center in Burlington, Massachusetts. DELTA is an open source software application for risk-adjusted analysis of clinical registry outcomes. DELTA is designed for early signal detection and will allow real-time monitoring of any mortality signal.
If identified, this would be immediately reported to the VQI membership. Further details about the study are available on clinicaltrials.gov under the identifier NCT04110288. We anticipate being able to report the results to VQI members in the coming months.
One of the values of the VQI is it is a large, robust and clinically-detailed registry that allows analysis of relevant outcomes in a real-world population. In collaboration with our partners at VISION and DELTA, we hope to use VQI data to help better define the role of paclitaxel technology in clinical practice.
Daniel Bertges is associate professor of surgery at the University of Vermont Medical Center in Burlington, Vermont, and chair of the SVS VQI PVI Committee. Jens Eldrup-Jorgensen is professor of surgery at Tufts University School of Medicine in Boston and a vascular surgeon at Maine Medical Center in Portland, Maine. He is the SVS PSO medical director.