Treating From Below: A Physician Perspective on Pedal Access and the Lutonix® 018 DCB

This article first appeared in Cath Lab Digest, Volume 27 - Issue 11 - November 2019 

Can you tell us about your lab and practice?

I am the Director of Vascular Surgery at Memorial Hermann Northeast Hospital in Humble, Texas. The group that I am affiliated with is called Vital Heart and Vein, LLC. I am one of two vascular surgeons in a multispecialty practice, with mostly other cardiologists. I have a broad-based vascular practice where I diagnose and treat the entire spectrum of vascular disease, and we have a very large peripheral arterial disease (PAD) patient population. I do advanced invasive peripheral vascular intervention, pedal intervention, and alternative access. I would consider myself a very aggressive interventionalist- surgeon who offers a wide base of therapy, but the majority of my peripheral practice is based on a very aggressive, minimally invasive endovascular intervention of PAD.

People in southern parts of the United States often talk about being in the “diabetes belt.” Does your area fall under that description?

Absolutely. We serve a patient population with a very high incidence of obesity, diabetes, and end stage renal disease on hemodialysis. We see a lot of patients with advanced peripheral vascular disease, multilevel disease, gangrene, and tissue loss. Certainly, the majority of our patients are Rutherford IV, V, and VI class patients. Treating just a claudicant is rare. Much of our practice deals with limb salvage, and since we instituted an aggressive peripheral program six years ago, our limb salvage rate has gone up and the number of amputations we have performed in the past five years has gone down significantly. Prior to institution of our limb salvage program, we did 40-50 amputations per year and now that number is <10 amputations per year. We have a “limb salvage team” at the hospital that includes a vascular surgeon, a podiatrist, a wound care specialist, and a hospitalist, who manages all the comorbidities of the patient, including diabetes or hypertension, or whatever comorbidities they may have. If a patient comes into the emergency department with gangrene of their foot, a wound, or rest pain, for example, it initiates the activation of a limb salvage team, which triggers my involvement as well as those additional team member physicians I mentioned earlier. Treating these patients is a group effort, requiring us to work together in order to salvage limbs. As a vascular surgeon/interventionalist, my job is restoring circulation. The podiatrist debrides and removes all grossly necrotic tissue, a wound care specialist initiates wound care, and, if possible and warranted, outpatient hyperbaric therapy. Finally, the hospitalist or internist manages comorbidities, working to get the patient’s hypertension and/or diabetes under control in order help enhance wound salvage and healing.

What is your typical algorithm for restoring circulation?

My algorithm is fairly simple. In patients with symptomatic PAD, I of course begin with a duplex ultrasound and ankle-brachial indices, and do a thorough physical exam. Generally, I start most angiograms with a standard retrograde contralateral femoral approach and do a diagnostic angiogram. Depending on the nature of the pathology, I will elect to either stay with an up-and-over approach or get pedal access. If I have prior imaging, I may start the case entirely from a pedal approach; close to 50% of my cases are done in this fashion. I find that the pedal approach makes it much easier to treat chronic total occlusions and other complex lesions. In cases where there is a tortuous aorto-iliac system, the pedal approach makes the procedure much easier and more time efficient. Typical treatment is luminal crossing of a lesion, and orbital atherectomy paired with a drug-coated balloon (DCB). I use stents selectively.

Speaking of DCBs, there has been a significant amount of conversation in the community lately as it relates to the meta-analysis by Katsanos et al¹ and the subsequent FDA Letters to Health Care Providers. What has been your reaction regarding the potential for increased mortality after 2 years?

I am skeptical of the results of the meta-analysis for many reasons. Two come from the paper itself, which stated that the study could not explore undetected sources of heterogeneity between the treatment groups due to the lack of patient level data and that ultimately, a plausible mechanism between paclitaxel and death could not be established.

In my opinion, the mortality observed in this study is probably not related to paclitaxel, but the simple fact that the patients who received treatment with a drug-coated balloon suffered from advanced peripheral vascular disease and the presence of multiple comorbidities. These patients most likely died from their comorbidities, whether diabetic related, heart related, stroke, or anything similar, rather than paclitaxel.

I have treated perhaps 1,800 legs over the past six years. The results from the meta-analysis and subsequent FDA letters have not changed my practice.

Which DCBs do you currently use in your practice?

I use the Lutonix^® DCB.

Why do you use the Lutonix^® DCB?

For several reasons. First, because it has delivered excellent results in terms of safety and efficacy, not only in multiple clinical trials, but in my patients as well.

Second is the choice of drug dose and excipient. The Lutonix^® DCB has a low dose of 2 mg/mm², which in preclinical work conducted by the company, was shown to deliver a similar concentration of paclitaxel to the arterial wall at twenty-four hours (compared to a higher dose competitive device).² Similarly, samples gathered from animal testing showed a downstream paclitaxel tissue concentration of less than one percent of a higher dose competitive device at twenty-eight days.³ Given the choice, I prefer to use less drug to deliver a similar dose to the tissue, with less skeletal muscle necrosis and vascular changes.

Third, all diameters and lengths of the Lutonix^® 018 DCB can go through a 5 French (Fr) sheath or smaller (the 4 mm Lutonix^® 018 DCB is 4 Fr). In some of the other DCBs, increasing beyond a 4 mm balloon requires upsizing to a 6 Fr sheath. It allows me more versatility in treating from an alternative access site. For instance, if I am going to do pedal access and place a 5 Fr sheath in a tibial vessel, I don’t have to upsize my sheath if I want to treat a popliteal or a superficial femoral artery (SFA) from below. I can stay with that 5 Fr sheath, whereas if I use another balloon, it would require upsizing the sheath.

Finally, in my experience, the Lutonix^® 018 DCB is versatile, offers great pushability, and easy lesion crossing, especially for navigation through tortuous anatomy. I have used the Lutonix^® 018 DCB in several SFA and popliteal lesions from tibial or retrograde access. It uses the same formulation of paclitaxel as the Lutonix^® 035 Drug-Coated Balloons. I find the .018-inch size is particularly useful, especially with the .014-inch ViperWire (CSI). If you are trying to push an 035-inch DCB over the ViperWire, sometimes it may not be able to track, for whatever reason. The new 018-inch balloon tracks over the ViperWire very easily and as a result, it saves a step. If I used an 035-inch balloon, it would require that I place a catheter, exchange out the ViperWire for an .035-inch wire, and then put the 035-inch balloon back in. Now I can leave in the ViperWire, or the .014-inch or .018-inch wire that is in place, use a Lutonix^® 018 DCB, and treat the area I need to treat.

Can you talk more about your use of pedal access?

Pedal access has revolutionized intervention today. It has brought increased success by permitting the use of multiple approaches to cross difficult lesions. Pedal access has increased limb salvage rates in our practice, because if you can’t cross the lesion from above, you can cross and treat from below as well. It has reduced the rate of access site complications, because smaller diameter sheaths are used in the tibial vessels and we typically don’t see a lot of complications from pedal access. Intervention through a larger sheath (6 or 7 Fr) in the femoral area increases risk of access site complications such as hematoma, pseudoaneurysm, or retroperitoneal hematoma, which can increase hospital stay and costs. The use of pedal access can help address those concerns. How I decide to use pedal access depends on the nature of the lesion. If a patient has an ostial lesion, let’s say a chronic total occlusion of the SFA at the ostium, I find it easier to treat retrograde from a tibial access. Going from above means you can’t figure out where the ostium is located, because it is not visible on angiography. Coming from below, typically the distal popliteal and the distal SFA offer a nice rail to work with in order to cross that lesion from below. If a lesion has a convex appearance, it is often difficult for the wire to find the true lumen of the artery. Wires like to bounce off that convexity and go subintimal, so going retrograde in those situations is also helpful. The presence of chronic total occlusions or ostial lesions of the SFA make pedal access my go-to in these situations. I can treat from a single access site.

Can you describe a recent case?

This morning we had a patient (Figure 1) who had previously undergone a bilateral femoral popliteal (fempop) bypass, so she already had incisions in her groin. She was complaining of recurrent claudication of her left leg. An office ultrasound showed that she had a 50-60% lesion of her popliteal artery just beyond the distal anastomosis of the bypass graft. We chose not to try and stick through a hostile groin, and navigate a wire and catheter from above. In this situation, we accessed the posterior artery retrograde, placed a 4 Fr sheath, and guided a wire beyond the stenosis and the popliteal artery just beyond the fempop bypass. We performed vessel preparation and then used a short shaft Lutonix^® 018 DCB to treat the area with an excellent result. The procedure itself took no longer than 15-20 minutes. We were able to avoid potential complications accessing the groin, keep our sheath size at 4 Fr in the tibial vessel, cross the lesion, and treat it from below. The Lutonix^® 018 DCB can inflate up to a 7 mm diameter, but in this case, we used a 5 mm balloon and achieved a great result without having to worry about shutting down the graft or sticking a hostile groin.

An 018-inch DCB adds another tool to your toolbox. It allows you to be versatile and use alternative access, and the great thing about these balloons is that they are so smooth; they have great pushability, which is helpful in tortuous anatomy. Using a smaller diameter balloon to treat the SFA and popliteal arteries from retrograde access improves our chances of success in treating claudication. 

Limitations associated with this pre-clinical study include: Pathologic findings are limited to healthy swine and do not account for the fact that human PAD presents with co-morbidities; and transferring pre-clinical findings in healthy animal arteries to humans with peripheral arterial disease is complex, as lesions can be complicated by fibrosis, necrosis, and calcification.  This study was funded by Lutonix, Inc. (New Hope, Minnesota).

Financial support for this article has been provided by Becton Dickinson and Company.

Disclosure: Dr. Kousta Foteh reports no conflicts of interest regarding the content herein.

Dr. Kousta Foteh can be contacted at kfoteh@me.com.

References

1. https://www.fda.gov/medical-devices/letters-health-care-providers/august-7-2019-update-treatment-peripheral-arterial-disease-paclitaxel-coated-balloons-and-paclitaxelKatsanos 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. doi: 10.1161/JAHA.118.011245.
2. Data obtained from two data sets. Lutonix^® data from Virmani Pre-Clinical animal data GLP study. Medtronic from Medtronic’s own reported data, Dr. Melder, LINC presentation 2012.  Bench test data on file.  Bench results may not be indicative of clinical performance. Different test methods may yield different results.
3. Kolodgie FD, Pacheco E, Yahagi K, Mori H, Ladich E, Virmani R. Comparison of particulate embolization after femoral artery treatment with IN.PACT admiral versus Lutonix 035 paclitaxel-coated balloons in healthy swine. J Vasc Interv Radiol. 2016 Nov; 27(11): 1676-1685.e2. doi: 10.1016/j.jvir.2016.06.036.
    

The opinions and clinical experiences presented herein reflect those of the author, are for informational purposes only, and may not be representative of what others may experience. The results from this case study may not be predictive for all patients. Individual results may vary depending on a variety of patient-specific attributes.

In August 2019, the U.S. Food and Drug Administration (FDA) issued an updated letter to health care providers noting an increased risk in late mortality (2-3 years post-treatment) with paclitaxel-coated devices when used to treat peripheral arterial disease in the femoropopliteal artery as 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-coated device exposure. Physicians should discuss this late mortality signal and the benefits and risks of available treatment options with their patients. BD will continue to work collaboratively with the FDA and industry for additional safety data collection and inform labeling as appropriate. These communications as well as information about the FDA Panel meeting can be found at: https://www.fda.gov/medical-devices/letters-health-care-providers/august-7-2019-update-treatment-peripheral-arterial-disease-paclitaxel-coated-balloons-and-paclitaxel.

Indications

The LUTONIX 018 Drug Coated Balloon PTA catheter is indicated for percutaneous transluminal angioplasty, after appropriate vessel preparation, of de novo, restenotic, or in-stent restenotic lesions up to 300mm in length in native superficial femoral or popliteal arteries with reference vessel diameters of 4-7mm.

The LUTONIX 018 Drug Coated Balloon PTA catheter is indicated for percutaneous transluminal angioplasty, after pre-dilatation, for treatment of stenotic lesions of dysfunctional native arteriovenous dialysis fistulae that are 4 mm to 7 mm in diameter and up to 80 mm in length.

Contraindications

The LUTONIX® Catheter is contraindicated for use in: 1) Patients who cannot receive recommended anti-platelet and/or anticoagulant therapy. 2) Women who are breastfeeding, pregnant, or are intending to become pregnant or men intending to father children. It is unknown whether paclitaxel will be excreted in human milk and there is a potential for adverse reaction in nursing infants from paclitaxel exposure. 3) Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the delivery system. Potential adverse events which may be associated with a peripheral balloon dilatation procedure include: Additional intervention • Allergic reaction to drugs, excipients, or contrast medium • Amputation/loss of limb • Aneurysm or pseudoaneurysm • Arrhythmias • Embolization • Hematoma • Hemorrhage, including bleeding at the puncture site • Hypotension/hypertension • Inflammation • Occlusion • Pain or tenderness • Pneumothorax or hemothorax • Sepsis/infection • Shock • Stroke • Thrombosis • Vessel dissection, perforation, rupture, or spasm. Although systemic effects are not anticipated, refer to the Physicians’ Desk Reference for more information on the potential adverse events observed with paclitaxel. Potential adverse events, not described in the above source, which may be unique to the paclitaxel drug coating include: Allergic/immunologic reaction to the drug coating paclitaxel • Alopecia • Anemia • Blood product transfusion • Gastrointestinal symptoms • Hematologic dyscrasia (including leukopenia neutropenia, thrombocytopenia) • Hepatic enzyme changes • Histologic changes in vessel wall, including inflammation, cellular damage, or necrosis • Myalgia/Arthralgia • Myelosuppression • Peripheral neuropathy

Please consult package insert for more detailed safety information and instructions for use.

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