The main advantage of endovascular intervention is a quicker recovery period. Most people recover within a few days of having balloon angioplasty or a stent inserted, whereas it can take over 6 weeks to recover from bypass surgery. Endovascular intervention also means avoiding the risks associated with general anaesthesia.
A: Percutaneous transluminal angioplasty was first performed at the University of Oregon Hospital on 16 January 1964 by Dr Charles Theodore Dotter[1].
The patient was Laura Shaw, an 82-year-old woman with a painful left foot, who had refused amputation. Within minutes, the foot was warm and hyperemic. The pain disappeared and the ulcer healed. The patient died of congestive heart failure 3 years later.
Learn more about peripheral artery disease here.
Where there is persistent lifestyle-limiting claudication, the 2016 ACC/AHA guidelines recommend the use of endovascular interventions, including drug-coated balloons and drug-eluting stents, as well as atherectomy. Bypass surgery may sometimes be used[2].
Medical therapies and structured exercise are the first recommended treatments for femoropopliteal artery disease.
Medical approaches include antiplatelet agents, statins, antihypertensive agents, oral anticoagulants, cilotstazol, pentoxifylline, and chelation therapy. Smoking cessation and glycemic control are also recommended[3].
ELEGANCE (NCT04674969) is a 5-year global perspective, non-randomized, open-label, multi-center registry set up in December 2020 to collect real-world data - including health economic data - from patients treated with the Eluvia™ drug-eluting stent or Ranger™ drug-coated balloon for lesions located in the peripheral vasculature.
The primary endpoints are major adverse events (target lesion revascularizations [TLRs], major limb amputations, deaths) and primary patency and freedom from clinically-driven TLRs at 12 months. Estimated enrolment is about 5,000 patients, with a special instruction to ensure inclusion of diverse patient populations usually under-represented in PVD trials, including more complex lesions and in populations at risk such as patients with diabetes[4].
Drug-Eluting Stents (DES) FAQs
Figure 1: Eluvia Drug-Eluting Vascular Stent System
A drug-eluting stent is a peripheral or coronary stent that is placed into narrowed or diseased peripheral or coronary arteries to release a drug to block cell proliferation. Stents usually consist of a metallic scaffold, which helps to keep the artery patent, and a polymer containing an antiproliferative drug. The drug is released over a period of weeks to months following the procedure. Stents also prevent the acute vascular recoil that’s seen with balloon angioplasty.
Drug-eluting stents are coated with antiproliferative medications that prevent inflammation and restenosis of the artery in the long term.
In peripheral arterial disease, a drug-eluting stent prevents the development of fibrosis, which - together with thrombi - could otherwise block the stented artery, a process called restenosis (learn more about restenosis here.
The IMPERIAL trial (NCT02574481) was the world’s first, head-to-head randomized controlled trial (RCT) of drug-eluting stents Eluvia and Zilver PTX
The primary efficacy and safety endpoints at 12 months were primary patency and major adverse events (clinically-driven target lesion revascularization [TLR], major limb amputation, death)[5].
The primary outcomes were non-inferiority for both efficacy and safety endpoints at 12 months. Primary patency was 86.6% (231/266) for Eluvia vs 81.4% (106/130) for Zilver PTX (5.3% difference, p<0.0001). The clinically-driven TLR rate showed 50% reduction with Eluvia at 4.5% (13/287) vs. Zilver PTX at 9.0% (13/145)[6].
The EMINENT trial (number) is the largest RCT (2:1) comparing the Eluvia drug-eluting vascular stent system to self-expanding bare metal stents (BMS).
The results for Eluvia at 12 months demonstrated superiority with a statistically significant primary patency of 84.5% versus 76.3% for BMS[7]. Eluvia also demonstrated sustained clinical improvement without reintervention over BMS through 1-year[8]
Figure 2: EMINENT trial: 1-Year Primary Patency Results[9]
Eluvia DES sustains drug release over the long term. The longer elution period of Eluvia compared with Zilver PTX may have contributed to the superior efficacy of Eluvia in the IMPERIAL trial, in which there was a 50% reduction in target lesion revascularizations (TLRs) at 24 months[10].
Figure 3: Eluvia's elution period compared with traditional drug-coated stents
Drug-Coated Balloons (DCB) FAQs
Figure 4: Ranger Paclitaxel-Coated PTA Balloon Catheter
A drug-coated balloon is a semi-compliant balloon that carries antiproliferative drugs on its outer surface. When the balloon is inflated, it presses particles of the drug into the vessel wall. The drug is released at a high concentration in a short space of time.
As well as expanding the lumen of the artery, a drug-coated balloon carries the antiproliferative drug, e.g. paclitaxel, to the target lesion. The drug adheres to the balloon membrane and is partially hidden below the folds which are wrapped around the shaft of the balloon. Upon balloon inflation, solid drug particles are pushed into the vessel wall. The drug’s very low solubility minimizes premature loss, dissolution and elimination[11].
The COMPARE trial (NCT02701543) was the world’s first head-to-head, prospective, noninferiority, RCT (1:1), comparing low dose Ranger DCB (2 μg/mm2) to high dose IN.PACT DCB (3.5 μg/mm2).
The primary efficacy and safety endpoints at 12 months were primary patency and freedom from major adverse events (death through 1 month, major amputation, clinically-driven TLRs)[12].
Primary patency was 83.0% in the low-dose Ranger DCB vs. 81.5% in the high-dose IN.PACT DCB (1.5% difference, p= <0.01). Freedom from major adverse events was 92.6% in the high-dose IN.PACT DCB vs. 91.0% in the low-dose Ranger DCB. Ranger demonstrated similar patency and efficacy at 12 months, with half the total drug dose of IN.PACT DCB[13].
The RANGER II prospective, multi-center RCT compared the Ranger drug-coated balloon to uncoated balloons (3:1) with follow-up through five years.
At 2 years, the primary efficacy and safety endpoints were primary patency and freedom from major adverse events (clinically-driven target lesion revascularization [TLR], major limb amputation, death)[14].
Ranger DCB demonstrated superiority over uncoated balloon PTA, with a primary patency of 84.0% compared to 71.4% for PTA (figure 5). Ranger also demonstrated low reintervention rates regardless of patient gender.
Primary patency was 82.9% in the Ranger DCB vs. 66.3% in the uncoated balloon PTA (16.6% difference, p= <0.0001). Freedom from major adverse events was 94.1% in the Ranger DCB vs. 83.0% in the PTA (11.1% difference, p= 0.0017).
Figure 5: RANGER II trial: DCB Ranger vs. PTA at 2 Years[15]
Resources
[1] Payne MM. Charles Theodore Dotter. The father of intervention. Tex Heart Inst J 2001;28:28-38. Secemsky EA, Shen C, Schermerhorn M, et al. Longitudinal assessment of safety of femoropopliteal endovascular treatment with paclitaxel-coated devices among Medicare beneficiaries: The SAFE-PAD study. JAMA Intern Med 2021;181:1071-80.
[2] Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary. Vasc Med 2017;22:NP1-N43.
[3] Ibid.
[4] ELEGANCE Registry https://clinicaltrials.gov/ct2/show/NCT04674969
[5] Gray WA, Keirse K, Soga Y, Benko A, et al; IMPERIAL investigators. A polymer-coated, paclitaxel-eluting stent (Eluvia) versus a polymer-free, paclitaxel-coated stent (Zilver PTX) for endovascular femoropopliteal intervention (IMPERIAL): a randomised, non-inferiority trial. Lancet 2018;392:1541-51.
[6] Ibid.
[7] McKeown, LA. EMINENT: Better Patency With DES Over BMS for Fem-Pop Lesions. TCTMD Oct 2021. Available at https://www.tctmd.com/news/eminent-better-patency-des-over-bms-fem-pop-lesions. Last accessed 25/05/2022.
[8] In EMINENT, primary sustained clinical improvement was defined as an improvement (decrease) by at least 1 Rutherford category, without TLR.
[9] Kaplan-Meier Estimate: Primary patency defined as core-lab assessed duplex ultrasound peak systolic velocity ratio (PSVR) ≤ 2.4 at 1-year in the absence of clinically-driven TLR or bypass of the target lesion.
[10] Gray et al., IMPERIAL investigators.
[11] Speck U, Stolzenburg N, Peters D, et al. How does a drug-coated balloon work? Overview of coating techniques and their impact. J Cardiovasc Surg (Torino) 2016;57:3-11.
[12] Steiner S, Schmidt A, Zeller T, et al. COMPARE: prospective, randomized, non-inferiority trial of high vs. low-dose paclitaxel drug-coated balloons for femoropopliteal interventions. Eur Heart J 2020;41:2541-52.
[13] Ibid.
[14] RANGER™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty (RANGER II SFA) Study Record Detail, https://clinicaltrials.gov/ct2/show/NCT03064126. Last accessed 25/05/2022.
[15] RANGER II SFA RCT 2-Year Results presented by Ravish Sachar, MD. VIVA 2021.
[16] Ibid.
[17] Secemsky EA, Shen C, Schermerhorn M, et al. Longitudinal assessment of safety of femoropopliteal endovascular treatment with paclitaxel-coated devices among Medicare beneficiaries: The SAFE-PAD study. JAMA Intern Med 2021;181:1071-80.
[18] Katsanos K, Spilopoulos 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. Journal of the American Heart Association. 2018;7:e011245.
[19] Bonaca M, Bauersachs R, Anand S, et al. Rivaroxaban in Peripheral Artery Disease After Revascularization. N Engl J Med 2020; 382:1994-2004.
[20] Dinh K, Limmer A, Paravastu S, et al. J of Endovascular Therapy, Volume: 26 issue: 5, page(s): 600-612.
[21] Nordanstig J, James S, Andersson M, et al. Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease. N Engl J Med 2020; 383:2538-2546.
[22] Secemsky EA, et al.
Caution:
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