CardioSource WorldNews Interventions | It’s certainly time: about 8.5 million Americans have lower extremity PAD and, globally, that number swells to more than 200 million people with PAD symptoms ranging from none to severe.¹ This represents a sharp increase from the beginning of the century: In 2000 it was estimated that “only” 164 million individuals worldwide had PAD.

The American College of Cardiology (ACC) and American Heart Association (AHA) have just published new PAD guidelines incorporating updated data and answering 3 systematic review questions on antiplatelet therapy and revascularization to sharpen the focus on this highly prevalent but potentially modifiable and readily treatable condition.² There is also an important trial ongoing that should serve to answer some of the questions about best treatment strategies or at least provide a larger evidence base for practitioners to consult. And, as per usual, industry is doing its part by inventing and iterating its way to better tools to treat PAD in the operating room and the cath lab.

Good guidance is desperately needed. As reported recently in JACC: Cardiovascular Interventions, PAD therapies may perform differently in practice than in randomized trials.³ Manesh R. Patel, MD, FACC, and W. Schuyler Jones, MD, FACC, argue the need for learning health systems, thus complicating an already challenging situation.

CSWN: Interventions spoke to the chair of the writing committee responsible for the new PAD guidelines from the ACC/AHA,⁴ Marie Denise Gerhard-Herman, MD,  MMSc, FACC, (Harvard Medical School, Boston), as well as other PAD experts to provide an update on a condition that’s gaining a lot more respect as it proves to be so difficult to manage in its advanced stages.

Guidelines Highlight Screening

A primary motive behind releasing new guidelines, said Dr. Gerhard-Herman, is to help clinicians better understand how to detect and diagnose PAD and, frankly, to motivate them to just do it. Unfortunately, while vascular expertise is now taught in all training programs, it is not a longstanding component of cardiology general practice, she said, and as such, many physicians are still not screening for the disease appropriately.

“All leg pain isn’t the same and this guideline is really good at helping clinicians sort out someone who has stable PAD or CLI, or even acute limb ischemia,” she said. “These all have different management strategies so people need to be really aware.”

PAD’s most common symptom, intermittent claudication (IC), which is defined as leg pain associated with walking and relieved by rest, is generally indicative of insufficient blood supply to the legs caused by occlusive artery disease. Annual IC estimates at ~60 years of age range from a low of 0.2% in Iceland to a high of 1.0% in Israel.⁵ Smoking ranks high as a particularly significant risk factor for PAD, but several other risk factors, including diabetes, hypertension, and dyslipidemia, are also important.

All patients at increased risk for PAD should undergo a comprehensive medical history and a review of symptoms and signs to assess for PAD-specific symptoms (IC, but also other walking impairment, ischemic rest pain, and nonhealing wounds). They also need to undergo a vascular examination, where the presence of abnormal physical findings, such as a pulse abnormality, will require confirmation with the ankle brachial index (ABI) to establish or rule-out PAD. A resting ABI should also be “considered” in those at increased risk but without history or physical examination findings suggestive of PAD.

“We emphasized that you can use the ankle brachial index, but also the toe brachial index when the ABI is greater than 1.4,” said Dr. Gerhard-Herman. Both are inexpensive and noninvasive tests that can be administered physicians, but also by a variety of trained allied health personnel.

“Cancer” of the Leg

A subset of patients with PAD—estimates range from 1% to 10%—will develop critical limb ischemia (CLI), which is characterized by varying degrees of foot or ankle ischemic rest pain, tissue loss, or gangrene in the presence of PAD and hypoperfusion to the lower extremity.

“CLI is probably one of or even the worst presentation of cardiovascular disease nowadays,” said Victor Aboyans, MD, PhD, from the Dupuytren University Hospital, Limoges, France, during the recent European Society of Cardiology (ESC) meeting. Only 1 in 3 to 4 patients diagnosed with CLI are alive and fully recovered at 1 year. Dr. Aboyans has played a prominent role in establishing guidelines and practice standards for the treatment of PAD in Europe.

In his recent ESC presentation entitled “Critical Limb Ischemia, the Acute Coronary Syndrome of the Leg: Saving the Patient,” Dr. Aboyans cited a 2010 Japanese study showing the “dismal” prognosis in patients with CLI. The researchers found that the survival rate in those with CLI at 5 years was 27.2% compared to 70.4% in those with intermittent claudication and 87.4% in the general population of Japanese men and women with a mean age of 71 years.⁶

“So, we [are calling] CLI an acute coronary syndrome of the leg but if you had a center with this kind of survival after acute coronary syndrome, this center should be shut down,” said Dr. Aboyans. He suggested that the survival curves for CLI look more like those seen in metastatic breast and lung cancer and suggested that it might be more appropriate to call CLI a “cancer” of the leg.

CLI patients have a high prevalence of CV risk factors that require careful management beyond revascularization, said Dr. Aboyans. Just taking smoking cessation as an example, the survival differences between those who quit and those who don’t are marked.

In a 2014 study, only 30% of patients successfully quit smoking in the year after lower extremity angiography and PAD diagnosis.⁷ During follow-up to 5 years, however, those who stopped smoking had an all-cause mortality rate of 14% compared to 31% for those who did not quit (hazard ratio: 0.40; p < 0.05). Their amputation-free survival was 81% versus 60% for patients who continued to smoke.

Too Much Care…or Too Little?

PAD may well be one of the most crowded diseases in all of medicine. The catalog of specialists who provide treatment for PAD includes general practitioners and internists, cardiologists, interventional cardiologists, vascular medicine specialists, interventional radiologists, and vascular surgeons.

Ironically, it also seems to languish as one of the most neglected areas of medicine. Patients who should be screened for PAD are not screened and some, unfortunately, are progressing to CLI or even acute limb ischemia and undergoing disabling limb amputations that may be unnecessary.

“If you look around the country at the amputation rates, there is huge variability and that shouldn’t be the case,” said Kenneth Rosenfield, MD, FACC, in an interview with CSWN:I. “There are many institutions where patients are admitted and they are cared for by someone who is not savvy with all the different options and they just end up going to amputation.”

Dr. Rosenfield is a cardiologist and section head of Vascular Medicine and Intervention at Massachusetts General Hospital in Boston, as well as the chair of the STEMI and Acute MI Quality Improvement Committee at MGH.

Recent data on PAD treatment offer some interesting contradictions. There has been concern expressed in the popular media that with endovascular procedures on the rise, perhaps some are being done unnecessarily or inappropriately. On the flip side, however, competing data show that folks aren’t getting revascularized enough and that too many are progressing to CLI and amputation.

“I think the field has been concerned that maybe the public has been getting the wrong impression as to why there has been a rise in endovascular procedures and what the impact of this rise has been on the care of patients with PAD,” said Mehdi Shishehbor, DO, MPH, PhD, FACC, in an interview with CSWN: Interventions Executive Editor Rick McGuire.

Dr. Shishehbor is the director of Endovascular Services in the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at the Cleveland Clinic and a recognized expert in endovascular technique. He is also the senior author on a JACC state-of-the-art review and expert statement on CLI that comprehensively examines the epidemiology of CLI, current diagnosis, and treatment techniques, as well as after care.⁸

“CLI is a real challenge and we want to engage it and overcome it,” Dr. Shishehbor said in a recent interview with CSWN: Interventions. “Unlike claudication, where we have a lot of tools that have been evaluated and indicated for the superficial femoral artery…for below the knee and for CLI, we really have not made a lot of advances…So part of our thought process is to try to impact other aspects of disease, such as having a multidisciplinary team to take care of the wound, and diagnosing these patients at earlier stages so we can catch them early before they undergo major amputation…”

In an earlier study that sought to characterize trends in hospitalization of U.S. patients with CLI from 2003 to 2011 using the Nationwide Inpatient Sample, his group found that while CLI admissions have remained fairly constant, the rates of surgical revascularization have dropped and the rates of endovascular procedures have increased.⁹ This increase in endovascular care was—even after multiple adjustments—associated with decreases in in-hospital death and major amputation in the United States. Of note, the study was quite robust, including a total of 642,433 CLI admissions.

The endovascular approach was also associated with a short length of stay and greater cost effectiveness. “So, overall it appeared that the endovascular approach was superior to the surgical approach in these 650,000 patients,” said Dr. Shishehbor.

Not all the data appear to be quite so magnanimous or equitable: studies also can be found demonstrating that a surprisingly large number of patients may be having inappropriate lower limb amputations, and there seem to be some clear racial, sex, socioeconomic, and geographic disparities in this regard.

“There’s been data for the last 2 or 3 years showing that a lot of these [CLI] patients—actually between 40% and 70%—undergo amputation without any revascularization,” said Dr. Shishehbor as just one example of the failings of current CLI care. One study found that 54% of patients with CLI who underwent major lower extremity amputation had no vascular procedures performed in the year before amputation.¹⁰

“If you’re in the middle of the Ozarks it can be pretty dicey what the evidence is warranting an amputation, which is why we really wanted to emphasize the basics in the new guidelines, really identify the disease and its various manifestations and make sure cardiologists, but other doctors too, are focused on this disease,” said Dr. Gerhard-Hermann in an interview.

The BEST is Yet to Come

As might be expected when so many disciplines contribute their experience and expertise, the decision to recommend a medical, surgical, or endovascular approach for patients with CLI varies significantly depending on who is doing the recommending, as well as on access to an appropriate procedural environment. There is also a lack of consensus that has stemmed from the lack of an evidence-based standard of care for patients with CLI.

There is evidence that points both ways and in between: The BASIL trial is the only prospective randomized trial comparing surgical and endovascular options for limb ischemia and it was published back in 2005.¹¹ The trial showed that surgery and balloon angioplasty offered similar rates of amputation-free survival and mortality. Similarly, a recent review by the Agency for Healthcare Research and Quality found no differences in all-cause mortality, amputation, and amputation-free survival between the 2 strategies.¹² However, other data, such as that by Shishehbor and colleagues mentioned earlier, has clearly favored the endovascular approach.

Many of the unanswered questions regarding the optimal approach to CLI are being addressed by the National Heart, Lung, and Blood Institute–sponsored, multicenter, randomized BEST-CLI (Best Endovascular vs. Best Surgical Therapy in Patients with Critical Limb Ischemia) trial. This ongoing trial—which saw its Boston-based trio of principal investigators awarded a $25 million NIH grant to conduct it—will provide first results in 2017 and promises to rigorously compare “best endovascular” and “best surgical” options in 2,100 CLI patients.

One of the PIs is Dr. Kenneth Rosenfield, who explained the reasoning behind the trial and what they hope to accomplish with it.

“We are hoping that BEST-CLI gives us a lot of answers about which patients do better with open bypass and which patients do better with an endovascular approach using any number of devices,” said Dr. Rosenfield. “Essentially, surgeons can use all techniques and conduits and interventionalists can use every device that is available commercially, whether it’s approved or not for revascularization, so it’s a real world trial.” The trial will submit a proof-of-concept investigational device exemption application to the U.S. Food and Drug Administration to cover all devices.

Another way in which BEST-CLI is hoping to stay real is by allowing hybrid procedures. Although initially prohibited, the protocol was later amended to combine surgical endarterectomy of the common femoral artery with post-randomization endovascular treatment of more distal disease.¹³

“In BEST-CLI we tried to promote the CLI team approach. In fact, it’s written into the policies and procedures of the trial to encourage a team-based CLI approach and everybody brings different expertise to the table or to the management of the patients and that’s the way it should be,” said Dr. Rosenfield.

BEST CLI will also provide contemporary cost­effectiveness data about surgical and endovascular approaches to treating CLI, and the impact of those treatments on quality of life and overall functioning.

CLI and Affordable Care

The Affordable Care Act is designed to provide the American consumer with value-based health care, meaning quality care at the lowest cost. While there are quality measures defined for things like heart failure and transcatheter aortic valve replacement, CLI has so far been left off the list. One Centers for Medicare & Medicaid Service (CMS) quality and cost improvement effort is the Bundled Payments for Care Improvement Initiative, which is testing how bundled payments from CMS or a third-party payer for “clinical episodes” can result in better care and smarter spending. This initiative is likely to have a strong impact on CLI care, said Dr. Shishehbor et al. in their JACC review on the topic, but maybe not for the better.

“Unfortunately, patients with CLI have many comorbidities, are typically high risk for surgery or endovascular intervention, require multiple treatment devices, and post significant risk for readmission and wound complications,” they wrote. As such, Dr. Shishehbor and his colleagues fear that bundled payments will serve to dissuade physicians and hospitals from treating these complex and challenging patients.

“A more appropriate reimbursement algorithm should take all of these complexities into account and should encourage treating such patients,” they said, echoing similar concerns that have been voiced about bundled payments for complex cardiac care.

“Doctors want to have the flexibility to select the devices they use to achieve the optimal result for the patients,” explained Dr. Rosenfield (who is an author on the JACC CLI review). “The concern is that bundled payments will set a rate that will not allow for the use of multiple expensive devices, which is often what’s required to restore the most blood flow to the leg.”

That said, he thinks that as long as the bundles are not “too draconian,” they will actually help interventionists think carefully about how they practice and become better stewards of the health care dollar.

In good news, Dr. Rosenfield said there are signs that CMS might soon approve reimbursement for supervised exercise training for patients with symptomatic PAD. “This would be a really great thing for US claudicants,” he said, since the “vast majority of patients” do not adhere to exercise recommendations and supervision would help ensure they do. A final decision is expected in March 2017.

Multiple trials have shown the short- and long-term benefit of supervised exercise for patients with PAD and the new guidelines recommend such supervised training as an initial treatment for claudication to improve functional status and quality of life as well as to reduce leg symptoms (Class I, Level of Evidence A).

Encouraging Progress

Even in an environment of increasing prevalence of PAD and its risk factors, there is evidence that patients are benefitting from improved interventional devices and techniques, with declining mortality and major amputation rates. That said, CLI remains associated with very high morbidity and mortality, especially in those who lose limbs. And just getting people screened and treated early continues to be a problem.

“PAD hasn’t really hit the recognition stage with a lot of cardiologists, in particular, and with a lot of doctors, in general,” said Dr. Gerhard-Herman, who added that while it’s great to get better information on the best treatments, first providers need to get better at detecting PAD and CLI. Hopefully these new guidelines, reviews, and trial findings will inspire more clinicians to take a close look at their patient’s legs.

References

1. Fowkes FG, et al. Lancet. 2013; 382: 1329-40.
2. Gerhard-Herman MD, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.11.007
3. Patel MR, Jones W. J Am Coll Cardiol Intv. 2016;9(7):725-727.
4. Gerhard-Herman MD, Gornik HL, et al. J Am Coll Cardiol. 2016;():. doi:10.1016/j.jacc.2016.11.007.
5. Criqui MH, Aboyans V. Circ Research. 2015; 116: 1509-26.
6. Kumakura H, et al. J Vasc Surg. 2010;52:110-7.
7. Armstrong EJ, et al. J Vasc Surg. 2014;60:1565-71.
8. Shishehbor MH, et al. J Am Coll Cardiol. 2016;68:2002-15.
9. Agarwal S, et al. J Am Coll Cardiol. 2016;67:1901-13.
10. Goodney PP, et al. Circ Cardiovasc Qual Outcomes. 2012;5:94-102.
11. Adams DJ, et al. Lancet. 2005;366:1925-34.
12. Jones WS, et al. Am Heart J. 2014:167:489-98.e7.
13. Menard MT, et al. J Am Heart Assoc. 2016;5:e003219.

Read the full November/December issue of CardioSource WorldNews Interventions at ACC.org/CSWNI

Keywords: CardioSource WorldNews Interventions, American Heart Association, Edema, Lower Extremity, Referral and Consultation

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