On October 14, 2014, the US Food and Drug Administration (FDA) granted approval for the Lutonix® Drug Coated Balloon (DCB) Catheter (CR Bard, Inc.) for percutaneous transluminal angioplasty (PTA), after predilatation, of de novo or restenotic lesions up to 150 mm in length in native vascular disease of the superficial femoral or popliteal arteries with reference vessel diameters of 4 to 6 mm. This approval was announced 122 days following a unanimously favorable recommendation from the FDA’s Circulatory System Devices Panel. A detailed review of this circulatory panel deliberation and recommendation is in this issue .

This approval is the first for the DCB technology for clinical commercial use in the United States. It comes 6 years after the first clinical proof of concept (for a different DCB technology) in a small randomized clinical trial reported by Tepe et al. and 2 years after the Lutonix DCB became commercially available in Europe. Given the requirements of the FDA for a rigorous randomized controlled trial adequately powered for a novel combination device, this is a reasonable amount of time to give assurances of safety and effectiveness of this technology prior to marketing release in the United States.

The American Heart Association (AHA) estimates that peripheral arterial disease (PAD), a life-threatening condition, affects more than 8 million Americans by narrowing arteries and reducing blood flow to the limbs . Patients with PAD in the femoropopliteal arteries are at risk for lower-extremity amputation, particularly in people over the age of 50 . Successful treatment of PAD in the femoropopliteal arteries requires improved blood flow (patency) for longer periods of time. Although there are pharmacologic, noninvasive, and invasive treatment options, each has associated limitations and higher recurrence rates, especially in the diffuse and long lesions. PTA is currently the first-line, standard-of-care treatment for PAD, according to the American College of Cardiology and AHA 2011 guidelines.

DCB has emerged as a combination device successfully reducing the restenosis rate and the need for repeat revascularization when compared with PTA alone. This was demonstrated in small randomized clinical trials that were conducted outside of the United States. LEVANT 2 was the first large randomized trial that demonstrated the safety and effectiveness of the Lutonix DCB technology when compared to PTA. This trial was designed in consultation with the FDA and was fast to enroll subjects in the United States and Europe.

PAD is not limited to the superficial femoral artery (SFA). It also includes lesions below the knee and is associated with higher rates of limb ischemia and amputation. These cases are much more challenging to treat, and a technology that works for the SFA may not be as effective and safe for popliteal and tibial narrowing, as was shown in the IN.PACT DEEP study .

For more than three decades, numerous technologies and devices were tested and used for the treatment of SFA lesions. Among these devices were improved balloons, including scoring balloons, atherectomy and laser devices, vascular brachytherapy, newly designed metallic stents, and drug-eluting and covered stents. All of these were suboptimal to obtain long-term patency rates, in part, because the characteristics of the disease often were diffused with high burden of atherosclerotic plaque and, in part, because of suboptimal trial design issues.

One exception was the Zilver® PTX® drug-eluting peripheral stent that demonstrated superiority over PTA alone. Although the Zilver PTX is approved both in Europe and in the United States, its use is somewhat limited when physicians avoid placing stents in the SFA territory.

Designing clinical trials in the SFA is challenging probably because of the complexity of the disease (multiple and diffuse lesions); reluctant patients to participate in invasive follow-up testing; and duplex ultrasound, which is not that accurate. Furthermore, patients have multiple lesions left untreated proximal and distal to the SFA lesions or lesions in contralateral limb, which makes evaluating the clinical utility of the device used difficult.

Most of the studies so far suffered from inadequate inclusion and exclusion criteria or were underpowered and lacked systematic follow-up imaging. Until now, the ultimate control group to test any new technology in the SFA was plain old balloon angioplasty (POBA). Most of the studies included only short lesions, and the endpoints included secondary patency. But with the approval of the DCB and drug-eluting stent (DES) technologies in the SFA, a head-to-head trial would be the best way to evaluate these devices. For example, trials could include the Lutonix DCB versus the Zilver PTX DES and a new DCB coated with sirolimus versus an approved DCB coated with paclitaxel.

The Lutonix DCB labeling for use reflects the LEVANT studies but does not address other important conditions, such as in-stent restenosis in the SFA, longer lesions > 150 mm, and below-the-knee lesions. These other indications are subject to ongoing investigations, and if they mimic the results of the most-recent studies for de-novo lesions in the SFA, the scope of the DCB technology for PAD will be enormous.

Nevertheless, there are currently limitations to the technology for the approved indication. The rate of dissection following POBA that required stenting is significant. The combination of stent and DCB did demonstrate an increase of restenosis and thrombosis probably because of a lack of healing. Perhaps these patients would benefit from DES alone without DCB. Lesions > 150 mm will require multiple balloons, which will increase the cost of the procedure and result in higher concentrations of the drug in the periphery and higher concentrations of particulates that can deteriorate the microvasculature. Finally, it is not clear what the durability of this technology would be over a period of 5 years and beyond.

Although short lesions may do well with POBA or stenting alone and some may argue that the use of DCB can be deferred only for secondary patency, remember that this argument failed for coronary lesions when DES launched for the treatment of de-novo lesions and that we should target the best available therapy for our patients if possible.

It is important to note that the Lutonix is the first DCB to be introduced to the US market, but there will be followers. By 2015, it is likely that there will be a second DCB approved for marketing in the United States. The technology will continue to be refined with a focus on safety and effectiveness, which will offer opportunity for even better outcome with the combined use of atheroablative technology, such as laser and atherectomy devices to obtain and maintain larger lumen.

The approval of DCB for marketing in the United States opens the opportunity to expand the treatment for PAD and for improved quality of life to many patients. It also offers the potential for broadening the indications over time. The sponsor, the investigators, and the FDA should be congratulated for finding a safe and effective landing zone for the technology for the benefit of US patients.