Peripheral artery disease (PAD) has always been overshadowed by its high-profile cousin, coronary artery disease. Now, as the number of costly endovascular interventions has soared nationally, PAD treatment is being scrutinized. In a field where clinical evidence is sparse, a flurry of questions is being asked: When does endovascular therapy make more sense for patients than surgical bypass? When PAD progresses to its most severe form—critical limb ischemia (CLI)—how do the financial and societal costs of revascularization compare with amputating the limb? Could early detection and treatment of PAD save lives and limbs, and perhaps a bundle of healthcare dollars?

Evidence needed, across the PAD spectrum

A pert 80-year-old woman walked into the office of Darren Schneider, MD, chief of vascular and endovascular surgery at New York-Presbyterian Hospital/Weill Cornell Medical Center. She had been referred by another physician who thought the woman needed surgical bypass on the basis of an ultrasound showing popliteal artery occlusion and an abnormal ankle brachial index (ABI). But Schneider’s observations and the patient’s questions left him puzzled. No visible wounds, no real pain emanating from the leg or foot, no ill effects from having walked 20 city blocks to Schneider’s office. In short, nothing to indicate an advanced case of CLI requiring intervention. “Because this woman hadn’t seen her doctor in five years, she decided to go back for a visit, and was told after an ultrasound that she was lucky she did, because she might lose her leg,” recounts Schneider. “That wasn’t true at all. She just needed a doctor who would follow her medically and be there to help if she ever got into trouble.”

The incident is emblematic of the lack of information and the misinformation that impacts the decisions of physicians and hospitals when it comes to treating PAD, which may affect as many as 10 million individuals in the United States alone. Experts worry that patients with the milder forms of PAD are being treated with unnecessary interventions even as patients with CLI are undergoing preventable amputations. In the absence of high-level clinical evidence and universal practice guidelines, decisions tend to be individualized and at times suspect, as evidenced by significant disparities in amputation and revascularization rates by race, socioeconomic status and geographic region.

“It’s the luck of the draw for patients,” says Kenneth Rosenfield, MD, MHCDS, section head for vascular medicine and intervention at Massachusetts General Hospital in Boston and 2016-17 president of the Society for Cardiovascular Angiography and Interventions (SCAI). “They may end up in the hands of a doctor who is talented and aware of CLI and its implications and get aggressive treatment. But they could just as easily find themselves with someone who is not particularly knowledgeable or aggressive. I’m appalled at the number of patients in this country who end up with an amputation for CLI without revascularization even being considered.”

Cost and reimbursement often weigh heavily in the decision. A hospital might get a DRG of more than $11,000 for an above-the-knee amputation, making it more financially attractive than a lengthy and complex endovascular intervention for a CLI patient where the cost of equipment alone could be $10,000, points out Mark W. Burket, MD, chief of the cardiovascular division and director of vascular medicine at the University of Toledo Medical Center in Ohio. “Amputation is seen as the solution because it takes care of the immediate problem with the limb,” he says, “but it’s extremely short-sighted both in terms of patient outcome and finances. After an amputation, the majority of patients do not regain ambulatory status, and there will frequently be a need for revision of the stump. Rehab costs also are considerable, and complications related to both the limb and cardiovascular system are commonplace, driving costs up even more.”

Indeed, a cost–utility analysis of limb preservation in patients with end-stage renal disease (J Vasc Surg 2014;60[2]:369-374) found that a primary amputation strategy for a non-healing foot wound pursued over five years generated total costs of $152,426, while the initial endovascular cost (with repeated interventions as needed) was $121,478, and $124,696 for surgical bypass. Over the patient’s lifetime, the healthcare costs for a person with a limb loss is around $500,000—not including increased risk for cardiovascular disease, obesity, joint and bone issues, depression and emotional distress—and the five-year mortality rate is between 50 and 74 percent, according to a Limb Loss Task Force/Amputee Coalition report in 2012. For the entire U.S. healthcare system, the annual cost for limb amputation is more than $8.3 billion, exclusive of rehabilitation and prosthetic costs (the latter could run as high as $450,000 for an amputee over five years), according to the report.

“While the costs of revascularization are significant because they involve long procedures requiring a lot of resources, the costs of amputation—including societal costs—are staggering,” observes John Laird, MD, medical director at the University of California, Davis Vascular Center. “When all the data are weighed, I believe revascularization is a very cost-effective strategy. It’s successful in avoiding amputation.”

Explosion in catheter-based procedures

National trend data—as shown in the figure on page 9—support Laird’s assertion. With CLI admission rates remaining constant from 2003 to 2011, there was a significant reduction in surgical revascularizations, from 13.9 percent in 2003 to 8.8 percent in 2011 (J Am Coll Cardiol 2016;67[16]:1901-13). Over the same period, endovascular revascularizations more than doubled, from 5.1 percent to 11 percent. This growth was accompanied by a steady reduction in in-hospital mortality and major amputations. Compared with surgical revascularization, endovascular procedures were associated with reductions in mortality (2.34 percent vs. 2.73 percent), mean length of stay (8.7 days vs. 10.7 days) and mean cost of hospitalization ($31,679 vs. $32,485). Measured on the basis of Medicare claims between 1996 and 2011, the rate of lower limb amputations fell 45 percent while endovascular interventions—including angioplasty, stenting and atherectomy—soared from 138 to 584 per 100,000 patients (JAMA Surg 2015;150[1]:84-6).

That explosion in catheter-based procedures, performed increasingly in doctors’ offices, has invited scrutiny from the government and the industry itself. Fanning the fires have been media revelations of cardiologists, vascular surgeons and radiologists who have billed Medicare millions of dollars for procedures to relieve blockages in the arms and legs that, in the view of some experts, could have been better handled with drugs or exercise.

“I think that endovascular procedures are definitely being abused,” acknowledges Schneider from New York-Presbyterian Hospital. “Unindicated procedures are being performed, probably because they reimburse very well, especially in office-based settings. On the other hand, if you really have a patient with critical limb ischemia, then aggressive revascularization is absolutely necessary.”  

In July 2015, the Centers for Medicare & Medicaid Services (CMS) convened a MEDCAC (Medicare Evidence Development and Coverage Advisory Committee) panel for a day-long examination of the scientific evidence surrounding the treatment of Medicare patients with lower-extremity PAD, including asymptomatic, intermittent claudication and CLI. Following presentations from a coalition of seven medical societies whose members manage patients with PAD, the MEDCAC panel made it clear that interventions for PAD in Medicare-eligible patients have limited scientific support, and that this void is of interest to CMS. The subject of how to effectively address CLI also was front and center at the Vascular Leaders Forum hosted by Vascular InterVentional Advances (VIVA) in April 2016 in Washington, D.C. The session—which brought together clinical thought-leaders with regulatory and reimbursement policy experts—focused on the clinical, operational and research gaps that exist in the field, and developing a new reference standard for moving forward.

“It’s not really the fault of doctors, but the fault of the system,” emphasizes Rosenfield. “We haven’t done a good job of defining the levels of CLI and what are the best treatment options for them. If we could predict upfront, for example, which wound—given a certain amount of revascularization—will heal vs. which won’t, then it might help us determine if a patient should be amputated, and the specific level of amputation needed. We just don’t have a good knowledge base around that because of the huge gaps in our research.”

Vascular leaders are hopeful that the $25 million National Institutes of Health–supported BEST-CLI (Best Endovascular vs. Best Surgical Therapy in Patients with Critical Limb Ischemia) trial, will provide some critical answers. The randomized study, being led by Rosenfield and co-principal investigators Alik Farber, MD, and Matthew Menard, MD, will tackle endovascular vs. open surgical revascularization from the standpoints of efficacy, functional outcomes and cost-effectiveness. To date, the only randomized trial to address that issue was BASIL (Bypass vs. Angioplasty in Severe Ischemia of the Leg). Begun 17 years ago, BASIL reported after five years of patient follow-up that both surgical and endovascular interventions had similar rates of amputation-free survival and mortality, with surgery being more expensive in the short-run. BEST-CLI, which will enroll about 2,100 patients, is about three years from completion.    

The promise of early diagnosis & treatment

Beyond closing research gaps, many experts in the field are looking to early diagnosis and treatment of PAD before it progresses to CLI as a powerful strategy in the physician’s armamentarium. “Once you get to the more advanced stages of CLI, particularly where there’s major tissue loss, it’s very difficult to limit the damage and correct the problem,” explains Burket. “So the earlier we intervene—ideally at the rest-pain stage and a threat of tissue loss—the better the outcomes.”

In an April 2016 editorial, several of the medical societies that presented to the MEDCAC panel called for diagnosis of PAD at the earliest stage so that antiplatelet therapy, lipid-lowering drugs, blood pressure control, smoking cessation, exercise and diet modification could be actively pursued. For patients with intermittent claudication, the coalition recommended not just medical and life modification therapies, but also supervised exercise training, “which has been shown to result in significant improvement in maximum walking time, pain-free walking, and maximum walking distance” (Vasc Med online April 10, 2016).

Tethered to this early detection strategy is another concept embraced years ago by cardiovascular medicine that the PAD/CLI community seems to be warming to: multispecialty teams. Endorsed by the American College of Radiology, SCAI, Society of Interventional Radiology, Society for Vascular Medicine and VIVA, these collaborative teams are seen as a way to help ensure best practice in peripheral artery intervention by combining the knowledge and skills of endovascular and surgical specialists, podiatrists, orthotists, and wound care and infectious disease specialists.

“Any physician who is honest will admit there is a point where they reach the limit of their knowledge and experience,” allows Burket. “So the more people who are willing to put aside their differences and egos and work together, the better the outcomes for patients suffering from critical limb ischemia.”