Among the latest data and developments for treating critical limb ischemia (CLI) are options with clinical results worthy of consideration as potential therapies for advanced peripheral artery disease (PAD) patients. Recent data analyses from studies and clinical trials, as well as new stent procedures and products, evidenced results that suggest more optimistic patient outcomes.

Recommendations and Research Highlight Benefits for Patients

The latest guidelines for treating PAD include recommendations on the use of antiplatelet therapy to reduce the risk of blood clots as well as the use of statin drugs to lower cholesterol. The recommendations also include advising patients to participate in an exercise program as part of their medical therapy. These new guidelines, published in Circulation and the Journal of the American College of Cardiology, are intended to replace guidelines last updated in 2011.

In addition, the new guidelines offered recommendations for when vascular procedures such as angioplasty and stent placement should be considered for patients who have less severe PAD, but who continue to have limitations in walking despite treatment with medication and exercise. However, in a separate study, researchers found that restoration of leg blood flow is better than exercise for PAD patients, and may stop the progression of scarring in their leg muscles. For the study, researchers looked at the levels of transforming growth factor-beta and the amount of collagen in calf muscle biopsies from patients with PAD severe enough to be considered for surgery.

After 6 months, researchers compared changes in biopsy results, which showed that scarring factors increased in the exercise and control groups, but not in the patients who underwent revascularization. Additional findings showed that while patients in both the revascularization and exercise groups increased their walking on a treadmill, only the revascularization group improved the distance they could walk for a set period of time.

Also focused on blood flow restoration, the Akesys PRAVA scaffold system from Akesys Medical is designed for the treatment of blockage in the superficial femoral artery (SFA). The product, which recently had its first clinical trial and successful implant, restores blood flow to the leg and is then resorbed into the body, leaving no permanent implant behind.

Along with monitoring the blood flow and exercise regimen of PAD patients, one company is advancing treatment of PAD by way of measuring oxygen. Profusa has received a $1.75 million grant from the National Institutes of Health (NIH), which will allow for the support of fast-tracked phase I and II studies of the company’s Lumee tissue-integrated biosensors for continuous oxygen monitoring. The results of the studies are intended to improve the clinical outcomes of patients suffering with PAD.

Procedure Safety and Efficacy Detailed in Clinical Trial Data

In an attempt to reduce the risk of stroke, a new surveillance project will evaluate the safety and efficacy of transcarotid artery revascularization (TCAR) in a comparison with carotid endarterectomy (CEA). Launched by the Society for Vascular Surgery Patient Safety Organization (SVS-PSO), the project is designed to obtain additional data about real-world outcomes of TCAR vs CEA, as performed by centers participating in the Vascular Quality Initiative (VQI).

Another study recently introduced was the ECLIPSE clinical trial, which will compare the Diamondback 360 Coronary Orbital Atherectomy System (Cardiovascular Systems, Inc. [CSI]) against conventional angioplasty – including specialty balloons, for vessel preparation prior to drug-eluting stent (DES) implantation. The randomized trial will include up to 2000 subjects in up to 60 sites in the United States. The trial is expected to begin recruiting in the spring of 2017.

One study that has already completed its enrollment is LIBERTY 360°, which will evaluate acute and long-term clinical and economic outcomes of endovascular device interventions, including CSI’s orbital atherectomy system, in treating PAD. The study enrolled over 1200 patients at 53 sites across the United States, with patients followed for 5 years and a risk score developed as a clinical predictor of outcomes to provide guidance for interventions.

Shockwave Medical announced positive clinical results from DISRUPT PAD, a multicenter study that evaluated the safety and performance of lithoplasty to treat PAD. Results from 95 patients with calcified vascular stenosis of the superficial femoral and popliteal artery enrolled at 8 sites demonstrated that lithoplasty technology provides a safe and successful treatment option.

Also announcing positive results of its Tack Optimized Balloon Angioplasty – Below-the-Knee 12-month clinical study was Intact Vascular. The study indicated that of 35 subjects enrolled at 6 sites in Europe and New Zealand, 87.1% had freedom from major amputation. All subjects suffered from CLI in one or both legs, and 32 patients were treated with the 4 Fr Tack Endovascular System following standard balloon angioplasty in the tibial and peroneal arteries. Patients in the study demonstrated an improvement after the procedure, and results suggest an increasing number of patients continue to improve as more time passes.

Product-Specific Clinical Studies Offer Global Importance

Along with clinical studies that seek to validate the safety and efficacy of an emerging vascular procedure based on patient outcomes, the same is often true with new products introduced to the medical industry that are also seeking to validate their usage in patients with PAD and CLI. One such product is the Stellarex drug-coated balloon (DCB), an angioplasty balloon that was the subject of the ILLUMENATE multicenter, single-arm study designed to assess its clinical performance in the superficial femoral and popliteal arteries. Twelve-month interim data showed that the first 153 of 371 patients enrolled demonstrated a primary patency rate at 12 months of 84.7%.

In the HEROES-DCB clinical trial, the Lutonix (Bard Peripheral Vascular) and IN.PACT (Medtronic) DCB technologies will be evaluated for their efficacy with respect to patient outcomes. The multicenter, randomized trial will enroll 275 patients, and is intended to determine if there is any difference in patient outcomes between the two similar Food and Drug Administration (FDA)-approved DCBs to treat PAD.
Also from Medtronic, new data from two studies involving the company’s IN.PACT Admiral DCB found that it maintains durable, consistent, and safe outcomes in trials involving chronic total occlusion when studying gender and diabetes subgroups. Data included 1-year results from the chronic total occlusion imaging cohort from the IN.PACT global study, and the 2-year gender and diabetic subgroup analyses was from the IN.PACT SFA trial.

On a larger scale, enrollment has been completed on the BIOFLOW-V clinical trial, with 1334 patients enrolled at 91 sites in the United States, Canada, Europe, Israel, and the Asia-Pacific region in less than a year. The study is designed to determine the safety and efficacy of Biotronik’s Orsiro hybrid DES system. Patients with coronary artery disease were assigned to receive either the Orsiro or another currently available DES, with the primary endpoint as target-lesion failure at 12 months post index procedure.

Product Launches Look to Advance CLI Treatment

New product introductions are often viewed as either an immediate asset for the medical industry, or as an immediate liability until it’s proven indispensable by the industry. One company looking to prove the import of its products is Asahi Intecc, whose new peripheral guidewires feature diameters of 0.014˝ and 0.018˝, along with precision braiding Act One dual-coil technology, which improves torque transmission and durability. The wires also offer tapered microtips to better cross complex lesions, and hydrophilic coating in the spring coil with uncoated distal tips for better tactile feedback.

Looking to expand treatment options for patients with end-stage CLI, LimFlow has received the CE mark for its LimFlow System, designed for venous arterialization of the lower limbs in end-stage patients at risk of limb amputation for CLI. The system is for patients who have exhausted all current revascularization options, and is intended to bypass diseased arteries and divert blood flow into the tibial vein to successfully vascularize the ischemic foot, thus promoting chronic wound healing and avoid major amputation.

For as much research that is completed in a lab, and as many new products that are born of necessity, there will never be a substitute for clinical trials with real patients to evidence the results. It’s this method that allows physicians and surgeons to see first-hand the kind of treatment that can become a life and limb saver for patients with CLI.