By: Rajesh V. Swaminathan, MD, and Faisal Latif, MD, FACC, FSCAI
Contributors: Mehdi Shishehbor, DO, MPH, PhD; Herbert D. Aronow, MD, MPH; Sahil A. Parikh, MD; Jayant Bagai, MD, FSCAI
Paclitaxel-containing devices (PCDs) are frequently utilized in femoropopliteal endovascular procedures, as they improve short- and intermediate-term primary patency rates.1–4 However, in a 2018 systematic review and meta-analysis, Katsanos et. al. identified a late mortality signal among patients who underwent endovascular procedures with PCDs compared with those where PCDs were not used.5 Similar findings from a recent meta-analysis were seen with PCD use in below-the-knee interventions for critical limb ischemia.6
The interventional community is now left with difficult decisions regarding how and when to use these devices in current clinical practice, leading to variability in practice patterns. To date, there is no mechanistic explanation for the study findings, and emerging patient-level data do not support a long-term mortality difference between PCDs and control groups.7–9 However, until there is further clarity on this issue, health care providers are encouraged to follow the Food and Drug Administration’s (FDA’s) recommendations.
The purpose of this Tip of the Month is to offer some suggestions for how to utilize PCDs and to review current recommendations from the FDA.
Immediate Implementation Steps:
- Review the updated FDA letter to health care providers. Here is the link.10
- Have discussions with your patients prior to the procedure about PCDs. Patients should be informed about the potential long-term risks in the context of improving intermediate-term quality of life. Patient preferences and alternative therapies, including non-PCDs, should be discussed. Document this conversation in the medical record and in the procedural informed consent document. The basis for your conversation can be derived from the updated labeling in the Instructions for Use11 on currently available PCDs:
“A signal for increased risk of late mortality has been identified following the use of paclitaxel-coated balloons and paclitaxel-eluting stents for femoropopliteal arterial disease beginning approximately 2–3 years post-treatment compared with the use of non-drug coated devices. There is uncertainty regarding the magnitude and mechanism for the increased late mortality risk, including the impact of repeat paclitaxel device exposure. Physicians should discuss this late mortality signal and the benefits and risks of available treatment options with their patients.”
- Limit your use of PCDs to select patients who are at high risk for restenosis and repeat femoropopliteal interventions and when the patient feels the benefits would outweigh the risk of late mortality. Having a discussion prior to the procedure to set this context will ensure a patient-centered approach to the ideal goals of therapy.
- Provide close follow-up along with optimal peripheral artery disease (PAD) medical therapy, including counseling on smoking cessation and exercise.
- Consider reporting any adverse events noted periprocedurally or during follow-up to the FDA via MedWatch, the FDA Safety Information and Adverse Event Reporting Program.12
The Registry Assessment of Peripheral Interventional Devices (RAPID) is an MDEpiNet project. This public-private partnership brings together resources from health care professionals, industry, patient groups, payers, academia, and government to advance a national patient-centered medical device evaluation and surveillance system.13 RAPID III (Pathways) was launched in June 2019 specifically to address safety concerns of PCDs and serves as an ideal use case for the program. Pathways currently has five working groups, each addressing a different task for a collaborative approach to evaluating PCD safety concerns.
SCAI physician leaders, along with other representatives from other professional societies, are members of the Multispecialty Paclitaxel Coalition. This international coalition, which also includes patient advocates, holds regular meetings to discuss recommendations in the context of emerging data.
Previously halted clinical trials utilizing PCDs have restarted. A number of ongoing, large-scale observational studies using the Centers for Medicare and Medicaid Services (CMS), national pharmacy claims, and other datasets are also underway.
PCDs remain on the market for the treatment of femoropopliteal disease when alternative therapies are not optimal and when the risk of restenosis or recurrent intervention is high. Data highlighting the benefits and potential risks should be discussed with patients so that an informed decision can be made. Multistakeholder panels representing professional organizations and societies whose members care for patients with PAD are convening regularly and collaborating with the FDA to develop further recommendations regarding optimal PCD use.
- Dake MD, Ansel GM, Jaff MR et al. Paclitaxel‐eluting stents show superiority to balloon angioplasty and bare metal stents in femoropopliteal disease: twelve‐month Zilver PTX randomized study results. Circ Cardiovasc Interv. 2011 Oct 1;4(5):495–504.
- Rosenfield K, Jaff MR, White CJ et al. Trial of a Paclitaxel‐Coated Balloon for Femoropopliteal Artery Disease. N Engl J Med. 2015 Jul 9;373(2):145–53.
- Tepe G, Laird J, Schneider P et al. Drug‐coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12‐month results from the IN.PACT SFA randomized trial. Circulation. 2015 Feb 3;131(5):495–502.
- Krishnan P, Faries P, Niazi K et al. Stellarex Drug‐Coated Balloon for Treatment of Femoropopliteal Disease: Twelve‐Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies. Circulation. 2017 Sep 19;136(12):1102–1113.
- Katsanos K, Spiliopoulos S, Kitrou P et al. 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. J Am Heart Assoc. 2018 Dec 18;7(24):e011245.
- Katsanos K, Spiliopoulos S, Kitrou P et al. Risk of Death and Amputation with Use of Paclitaxel-Coated Balloons in the Infrapopliteal Arteries for Treatment of Critical Limb Ischemia: A Systematic Review and Meta‐Analysis of Randomized Controlled trials. J Vasc Interv Radiol. 2020 Feb;31(2):202–212.
- Schneider PA, Laird JR, Doros G et al. Mortality Not Correlated With Paclitaxel Exposure: An Independent Patient-Level Meta-Analysis of a Drug-Coated Balloon. J Am Coll Cardiol. 2019 May 28;73(20):2550–563.
- Ouriel K, Adelman MA, Rosenfield K et al. Safety of Paclitaxel-Coated Balloon Angioplasty for Femoropopliteal Peripheral Artery Disease. JACC Cardiovasc Interv. 2019 Dec 23;12(24):2515–2524.
- Dake MD, Ansel GM, Bosiers M et al. Paclitaxel-Coated Zilver PTX Drug-Eluting Stent Treatment Does Not Result in Increased Long-Term All-Cause Mortality Compared to Uncoated Devices. Cardiovasc Intervent Radiol 2020;43(1):8–19.
- U.S. Food and Drug Administration. “August 7, 2019 UPDATE: Treatment of Peripheral Arterial Disease with Paclitaxel-Coated Balloons and Paclitaxel-Eluting Stents Potentially Associated with Increased Mortality.” Accessed: February 24, 2020, https://www.fda.gov/medical-devices/letters-health-care-providers/august-7-2019-update-treatment-peripheral-arterial-disease-paclitaxel-coated-balloons-and-paclitaxel.
- Rachal, Maria. “Paclitaxel device makers roll out revised labels, fresh safety analyses.” MedTechDive. Accessed: February 24, 2020, https://www.medtechdive.com/news/paclitaxel-medical-devices-new-labels-safety-analyses/564134/.
- U.S. Food and Drug Administration. “Reporting Serious Problems to FDA.” Accessed: February 24, 2020, https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program/reporting-serious-problems-fda.
- Medical Device Epidemiology Network. “RAPID – Registry Assessment of Peripheral Interventional Devices (RAPID).” Accessed: February 24, 2020, https://www.sciencedirect.com/science/article/pii/S0741521417321298.
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