Safety of Paclitaxel Drug-Eluting Technology: Data Support Continued Use

by Mia DeFino

On the second day of the 9th annual AMP Symposium, the morning general session Drug Delivery Beyond Revascularization covered many analyses and clinical trial updates on the efficacy and safety of paclitaxel drug-eluting technology that recently have had safety concerns raised by the Food and Drug Administration (January, March, and August 2019).

Peter Soukas, MD, from Brown Medical School and Cardiovascular Institute, presented on drug technology below the knee (BTK), showing that there are many randomized trials that have examined treatment of short lesions, but there are few trials that have looked at longer lesions and whether drug-eluting stents (DES) or drug-coated balloons (DCB) are more effective. Overall, DES has proven beneficial for BTK, but this is limited by proximal vessel location, cost, and need for prolonged dual antiplatelet therapy (DAPT). DCB for BTK has failed to show superiority over percutaneous transluminal angioplasty (PTA) in randomized controlled trials, likely due to several reasons: high prevalence of diffuse, occlusive, and calcified disease; dissections; recoil; impaired retention/release kinetics; and distal embolization.

Bret Wiechmann, MD, from the University of Florida, shared 1-year results from the IMPERIAL head-to-head Eluvia DES versus Zilver PTX DES trial. Both primary non-inferiority effectiveness (primary patency) and safety endpoints (major adverse events, stent thrombosis, and stent fractures) were met and held across subgroup analyses in diabetics and patients with chronic total occlusion (CTO). Eluvia was also found to be superior to Zilver PTX for primary patency at 12 months (P= .0144) in a post-hoc analysis, and there were consistent primary patency results with Eluvia regardless of lesion complexity characteristics. Dr. Wiechmann also presented combined safety results from Eluvia with a holistic view of all of Boston Scientific’s long-term clinical data on paclitaxel-eluting devices that showed no difference in all-cause mortality when compared to non-coated devices.

“The IN.PACT Clinical Program is the largest, independently adjudicated cohort treated with DCB for femoropopliteal disease with data through 5 years,” said Marianne Brodmann, MD, from the Medical University Graz. The results from this independent patient-level meta-analysis demonstrate no correlation between exposure to paclitaxel and mortality through 5 years, and paclitaxel dose was not identified as a predictor of mortality by a multivariable Cox regression model. It was observed that DCB patients who died were older and had more comorbidities. Dr. Brodmann encouraged real-world comparative studies to understand the role of follow-up visit compliance with lower mortality risk and to better understand long-term safety of paclitaxel products. Dr. Brodmann also presented on the Ranger DCB clinical study that is a clinical program with a robust series of randomized studies generating Level 1 evidence, and she commented on the excitement relating to the results from COMPARE 1 and Ranger II SFA studies.

“The Lutonix Long SFA Global Registry demonstrated durable benefits at 24 months for the Lutonix DCB in real-world patients,” said Michael Lichtenberg, MD, from the Arnsberg Vascular Clinic. The registry captured data from patients in Europe who had claudication or ischemic rest for two years after being treated with the Lutonix drug-coated percutaneous transluminal angioplasty (PTA) dilation catheter. He also presented data from the Lutonix Global SFA registry that showed favorable and sustainable freedom from TLR at 24 months in complex lesions (calcified, CTOs) and diabetics.

The ILLUMENATE Trial evaluated the CVI Paclitaxel-coated PTA Catheter compared to the bare PTA balloon catheter for the treatment of de-novo or post-PTA occluded/stenotic or reoccluded/restenotic (except for in-stent) SFA and/or popliteal arteries. Sean Lyden, MD, from The Cleveland Clinic Lerner College of Medicine showed data from the trial that demonstrated durable safety and patency through 3 years and functional and quality of life improvements observed from baseline through 3 years for the DCB cohorts. Also, no mortality signal was observed versus PTA at 3 years.

Understanding the evidence that supports the use of certain treatments is essential for providing options to patients and optimal outcomes. Craig Walker, MD, from Tulane Medical School Cardiovascular Institute of the South, discussed the evidence behind the use of atherectomy and drug technology in CLI. He mentioned that he uses atherectomy devices and DCBs frequently and often uses the two approaches together. Most atherectomy devices are different from each other, yet they often are lumped together in results for best practices and use guidelines. Dr. Walker called for more research and clinical studies to generate evidence for atherectomy coupled with drug delivery in CLI therapy.

Arnaud Kerzmann, MD, from CHU Liège presented on a 3 center European experience where renal failure and Rutherford classification 4-6 were the only factors impacting survival. Results from the Zilver PASS trial comparing an endovascular versus open surgical approach were presented by Constantino Peña, MD, on behalf of the investigators of this trial. Dr. Peña mentioned that the final 12-month and preliminary 24-month results show at least a non-inferiority of Zilver PTX versus prosthetic bypass surgery above the knee, with similar patency results and less complications.

Eric Secemsky, MD, MSc, FACC, FSVM, of Harvard Medical School, urged the audience to find ways to use real-world data to evaluate the safety of different devices in the CLI population that is treated. His presentation focused on three different analyses of Medicare data over different time periods and with both ICD-9 and ICD-10 diagnosis codes. All three analyses showed no differences in survival following treatment with drug-coated versus non-drug-coated devices in unadjusted, adjusted, and subgroup analyses. He recommended continued analyses as more data continue to become available. He said that he uses these analyses to discuss the safety of drug-coated devices with his patients.