Interventional cardiologists, vascular surgeons and others in the U.S. now have a cornucopia of treatments for patients with peripheral artery disease (PAD), thanks to recent FDA approvals for drug-eluting stents and drug-coated balloons. But using these devices is no slam-dunk. Questions about patients and payments make some physicians hesitant to incorporate them into practice.
PAD has proliferated over the years in both wealthy and lower-income countries. Globally, the prevalence of PAD increased 25 percent between 2000 and 2010, with an estimated 202 million people living with the disease. In the U.S., more than 8.5 million adults in their fourth decade or beyond have PAD, and the disease claimed more than 62,000 lives in 2011.
The marketplace has kept pace with the growing demand for treatments, particularly for lower-extremity PAD. Device-based approaches for patients with PAD have expanded beyond atherectomy, conventional percutaneous transluminal balloon angioplasty (PTA) and bare-metal stents to self-expanding stents, vascular memetic implants, stent grafts and more. Now add to that the ability to deliver therapeutic drugs in this vascular bed, either through drug-eluting stents or drug-coated balloons.
“Obviously, the first step with anybody with PAD and intermittent claudication who doesn’t have critical limb ischemia is exercise therapy and medications and risk-factor reduction,” says Kenneth Rosenfield, MD, the section head for vascular medicine and intervention at Massachusetts General Hospital in Boston. “But if that doesn’t work, or if the patient feels disabled, or isn’t tolerating the medications well, or is not able to exercise or walk, then intervention is the next consideration. Once you start thinking about intervention, there is a wide array of tools in our armamentarium.”
In 2012, the FDA approved Cook’s Zilver PTX drug-eluting stent for use in the femoropopliteal artery in patients with PAD, making it the first drug-eluting stent to become available in the U.S. for this indication. The beauty of the device is its ability to deliver a dose of paclitaxel directly to the arterial wall to help prevent restenosis.
Then in October 2014, the agency gave the all-clear to Bard’s Lutonix drug-coated balloon for use in the superficial femoral artery (SFA) and the popliteal artery. This, too, was a first. Like the Zilver PTX, the Lutonix drug-coated balloon provided a concentrated hit of paclitaxel to arteries during the balloon inflation process but it did not leave a permanent implant. Less than three months later, the FDA approved another paclitaxel-coated balloon, Medtronic’s Admiral device, as a therapy for patients with atherosclerosis in the SFA or proximal popliteal artery.
But having these newer options doesn’t necessarily make treatment decisions easier. “Deciding amongst those is very challenging,” acknowledges Rosenfield, who served as the co-principal investigator of Bard’s pivotal LEVANT 2 (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis) clinical trial. “We don’t have the comparative data to determine which therapy is better in many circumstances, so we do the best we can and people develop their preferences.”
Tested over time
Approval for the Zilver PTX was based in part on results of a randomized trial that compared the Zilver PTX with PTA, with provisional drug-eluting or bare-metal stenting in patients with acute PTA failure (Circ Cardiovasc Interv 2011;4:495-504). The 12-month event-free survival rate in the drug-eluting stent group was 90.4 percent vs. 82.6 percent with PTA, with a wide spread in patency rates, at 83.1 percent vs. 32.8 percent, respectively. The drug-eluting stent also edged out the bare-metal stent at 12 months for patency and clinical benefit in the provisional group.
But for many physicians, the real test was how the intervention held up over the long term. “There were concerns that perhaps the benefit we saw at one year would not be durable, that the curves of patency between standard of care or PTA or bare-metal stents might come back and merge on the curve of drug-eluting stents, which had a higher patency,” recalls Michael Dake, MD, medical director of the catheterization and angiography laboratories at Stanford University School of Medicine and principal investigator of the Zilver PTX trial.
At five years, the drug-eluting stent not only appears to be holding its own but adding to its lead over the other