Management of Femoropopliteal Occlusive Disease in the Endovascular Era

Introduction

Chronic lower-extremity ischemia affects approximately 10% of patients over the age of 70, with the total number of affected patients exceeding 10 million. Within this group, only a fraction of patients have symptoms consistent with intermittent claudication, and even fewer of these ultimately present to a physician with complaints related to their arterial disease. In addition to the functional limitations caused by pain with walking, many patients fear limb loss as an ultimate complication and outcome. However, it is imperative that physicians emphasize how unlikely an amputation is given the natural history of this disease, as well as reassure patients that there are a variety of measures available to improve their functional status. In fact, multiple studies show amputation rates of 1–7% at 5 to 10 years after a diagnosis is made, and rates of only 10% after 10 years or more.¹ While relief of symptoms is a primary objective when treating patients with claudication, truly effective care requires simultaneous risk factor modification for these patients as well. The goals of this article are the following: 1) to provide a brief review of the natural history and diagnosis of intermittent claudication; 2) to review the data on surgical bypass and endovascular intervention for femoropopliteal lesions (based on the Transatlantic Inter-Society Consensus Working Group [TASC] classification scheme); and 3) to utilize these data to formulate recommendations for patient management.

Clinical History

Claudication is derived from the Latin word “claudicare”, meaning “to limp”. In current medical practice, patients are given a diagnosis of intermittent claudication when they report symptoms of leg pain that are reproducibly brought on by exercise and relieved within a few minutes of rest. This pain is typically described as cramping, or a feeling of fatigue in the buttocks, thighs and/or calves, depending on the location(s) of arterial disease. More important is the differentiation of intermittent claudication, which has become “lifestyle-limiting” for a patient. There are unfortunately no strict definitions to determine this phenomenon, thus they must instead be tailored for individual patients. Questioning of patients should be focused on the distances they can walk before stopping to rest, as well as activities they can and cannot perform due to their symptoms. It is imperative to remember that a one-block walking distance in a patient who is house-bound due to other medical comorbidities is vastly different from a similar distance in an active patient who is very mobile.

Pathophysiology

Similar to angina pectoris, the pathophysiology of extremity claudication is muscle ischemia resulting from diminished oxygen delivery. During exercise, an existing stenosis or occlusion in an artery does not allow enough blood flow to meet the increased metabolic demands of the supplied muscle groups.

Physical Exam

A comoplete vascular exam is imperative in any patient reporting symptoms consistent with claudication, the findings of which may correlate with the reported location of the patient’s symptoms. Femoral pulses may be absent with aortoiliac disease, popliteal pulses absent with superficial femoral artery disease, and distal foot pulses absent in diabetic patients with tibioperoneal disease. Additionally, these patients usually do not have physical findings of ulcers or gangrene, as this would signify more advanced disease and limb-threatening ischemia.

Noninvasive Studies

Because patients are frequently unreliable when judging the distance they can walk, objective measurements are usually required before deciding on the appropriate therapy. An ankle-brachial index (ABI) of 0.5–0.9 usually accompanies the diagnosis of claudication, although patients with a normal resting ABI may experience a decrease after treadmill exercise.² Moreover, these exercise studies should be undertaken by patients with classic symptoms of claudication in the setting of palpable pulses on physical examination.

Treatment

Noninterventional. Risk-factor modification, while beneficial for all aspects of cardiovascular and peripheral vascular disease, is specifically imperative in the treatment of claudication. Cessation of smoking alone is critical to halting the progression of symptoms, with the ability to decrease a patient’s ultimate amputation rate by a factor of three to four.³ Next, although exercise therapy is difficult for many patients, this constitutes the mainstay of conservative therapy for claudication, with its benefits shown in numerous randomized trials.⁴ The most effective programs consist of supervised walking on treadmills for 60 minutes or more at least 3 times a week. Besides increasing the actual distance traveled by a patient before stopping, exercise rehabilitation improves the quality of life and functional status.⁵

Pharmacologic. Pharmacologic therapy has been a welcomed adjunct to the treatment of claudication. In 1984, pentoxyfylline (Trental) was the first drug approved by the Food and Drug Administration, and its mechanism was to increase red blood cell flexibility and ultimately decrease blood viscosity. Recent meta-analyses, however, failed to support the proposed benefits for walking distance and functional status.⁶ The second drug for claudication, cilostazol (Pletal), did not gain approval until 1999. This phosphodiesterase inhibitor increases cyclic adenosine monophosphate (cAMP), causes vasodilatation, has antiplatelet effects and modifies plasma lipoproteins. Cilostazol has been shown to improve maximal walking distance by 50% as well as significantly enhancing quality of life.⁷ The main contraindication to the use of cilostazol is congestive heart failure due to the reported increased risk of death in this subgroup of patients. Although other medications are currently in use in Europe, they have not yet been approved for use in the United States.

Interventional. When patients report no symptomatic improvement with conservative measures or medication, the next decision process involves either persistent medical management without intervention, or the use of endovascular and traditional vascular surgical approaches to treat the disease. Inflow procedures (which will not be discussed in this article) include aorto-iliac-femoral bypass, extra-anatomic bypass or aorto-iliac angioplasty with stenting. Traditional infrainguinal surgical therapy for femoropopliteal lesions involves femoral-to-popliteal bypass (either above-knee or below-knee) using either a vein or a prosthetic as conduit. Current infrainguinal endovascular options include balloon angioplasty, subintimal angioplasty, angioplasty with selective stenting and primary stenting. TASC initially stratified femoropopliteal lesions in 2000 (Figure 1) and made recommendations for therapy based on lesion type (stenosis versus occlusion), location and length.⁸ Based on this original classification scheme, lesions most amenable to percutaneous transluminal angioplasty (PTA) were short (< 3 cm) stenoses in patients who had claudication and good runoff. Longer lesions and occlusions could be treated by angioplasty, but the initial and long-term patency rates were lower. Extensive post-PTA dissection or significant residual stenosis could be treated with stent placement to avoid acute occlusion and its attendant morbidity.

Results

Surgical bypass. The most frequently quoted randomized, prospective, multicenter study evaluated 845 bypasses over a 6-year period.⁹ An in-depth evaluation of this study reveals vein to be the optimal conduit. Four-year patency above-knee was 61 ± 12% vein versus 38 ± 13% polytetrafluoroethylene prosthetic (PTFE) (p > 0.25), while patency below-knee was 76 ± 9% vein versus 54 ± 11% PTFE (p < 0.05). Even after a successful bypass, however, many patients with peripheral vascular disease are still plagued by concomitant cardiac and cerebrovascular disease. Studies examining the patency of infrainguinal bypass have identified that nearly 50% of patients have died by 5 years postprocedure, and this information is crucial to determining the optimal therapy for each patient. Moreover, the morbidity of bypass surgery can be quite significant and not simply limited to local wound complications or myocardial infarction. Readmissions to the hospital, reoperations, slow time to healing and time spent in rehabilitation must be factored into the risk-benefit analysis.¹⁰ In fact, the ideal outcome (patent graft, healed wound, no additional operations in a fully-ambulatory patient who can sustain independent living) may only be obtainable 14–22% of the time,¹⁰ thus functional outcomes must be considered in this patient population as well.

Endovascular therapy. Before the incorporation of stents and balloons into the treatment of vascular surgical disorders, there would have been no debate about which modality to employ first, but the current technological avalanche in this field has fueled numerous such debates. When factoring in all of the potential pitfalls accompanying traditional surgical approaches to claudication, as well as the overall health and life-expectancy of patients with peripheral vascular disease, less invasive endovascular therapy begins to appear preferable. In a summary of series that included 1469 limbs (with claudicants comprising 72% of these), the averages for results of femoropopliteal PTA included 90% technical success and patencies of 61% at 1 year, 51% at 3 years and 48% at 5 years.⁸ Additionally, 5-year patency of PTA for stenoses in claudicants was 68% versus 35% for PTA of occlusions.¹¹ This compares to 80% patency rates of vein bypasses, 75% patency of above-knee PTFEs and 65% patency of below-knee PTFEs.

Patients treated for claudication had significantly better outcomes than those requiring treatment for limb salvage. In a meta-analysis that included 923 balloon dilatations and 473 stent implantations, combined 3-year patency rates after balloon dilatation were 61% for stenoses and claudication, 48% for occlusions and claudication, 43% for stenoses and critical ischemia and 30% for occlusions and critical ischemia. Three-year patency rates after stent implantation were 63–66% and were independent of clinical indication and lesion type.¹² In another study, the 3-year patency rates were 68% for single, short stenoses and 20% for long, multifocal stenoses.¹³ Dilatation of long (> 5 cm) occlusions (TASC-D) had dismal results: 22 of 23 initially successful PTA procedures had failed within 6 months.¹⁴ Surowiec et al put the TASC 2000 guidelines to the test with their retrospective review of 380 angioplasty/stenting procedures of the superficial femoral artery from 1986–2004.¹⁵ Mean follow up was 1.8 years from initial intervention and claudication was the indication in 66% of the treated limbs. Limbs were standardized to the newly-created TASC 2000 grading system, which showed grades of A (48%), B (18%), C (22%) and D (12%). The authors further compared these interventions to groups of similar patients undergoing prosthetic or venous femoropopliteal bypass. Technical success (defined by < 30% residual stenosis) was achieved in 93% of vessels. Primary patency for all lesions was 75%, 66%, 60% and 50% at 1, 2, 3 and 6 years, respectively. Limb salvage rates at 5 years were 90% for claudicants and 67% for critical limb ischemia. The patency of prosthetic bypasses over 5 years mirrored TASC-B lesions, while venous bypasses mirrored TASC-A lesions. Furthermore, failure of an intervention was associated with a TASC-C or D lesion. Overall, the authors concluded that endovascular intervention was favorable for TASC-A/B lesions, while open-surgical bypass was superior for TASC-C/D lesions.

In a more contemporary series evaluated completely after the formation of the TASC 2000 guidelines, Conrad et al assessed femoropopliteal angioplasty/stenting in 238 limbs from January 2002 to July 2004, with a mean follow up period of 24 months.¹⁶ TASC classifications were as follows: A (11%), B (43%), C (41%) and D (5%). The indication was claudication in 54% of patients, with 35% of patients undergoing concurrent interventions in more distal anatomic locations. Technical success (< 20% residual stenosis) was achieved in 97% of vessels. Actuarial primary patency at 36 months was 65.6% for claudicants and 42.4% for critical limb ischemia (p = 0.004). Assisted primary patency was 93% at 36 months, irrespective of the indication for the intervention. Limb salvage was 100% for claudicants and 90% for critical ischemia. Although TASC-C/D lesions were predictive of primary and assisted primary failures, assisted patency was still 89.7%, with a limb salvage rate of 94.2% at 36 months. Overall, the authors concluded that although reintervention is frequently necessary, acceptable outcomes with minimal morbidity could still be achieved with these more advanced lesions. Therefore, this group adopted their conclusions to justify an “intervention-first” approach in all patients with significant femoropopliteal disease.

While numerous single-center studies exist documenting an apparently high success rate with a minimal morbidity for angioplasty in claudicants, Vogel et al explored this phenomenon from a different and intriguing angle.¹⁷ By examining the Washington State Hospital discharge database (CHARS) between 1997 and 2004, the authors compared cohorts of patients (n = 1718) undergoing angioplasty for claudication versus other diagnoses to evaluate readmissions, reinterventions and other such outcomes. Yearly angioplasty procedures doubled over the course of the study period. Furthermore, claudicants undergoing angioplasty were younger (68 vs. 72 years of age), more likely male (52%) and had a lower comorbidity index compared to other patients. Additionally, these patients were more likely to receive a stent (67% vs. 55%; p < .01), be discharged home, and to have private insurance (32% vs. 20%; p < .01). The 30-day readmission rate was much higher than expected (10% claudicants, 23% all other diagnoses), and the reintervention rate in readmitted claudicants was 28%. The authors concluded that the results of femoropopliteal angioplasty for claudication in the community at large differ from the reported findings in small case series published in the literature; moreover, their population-based study raises significant concerns about the aggressive and increasing use of angioplasty for what was once considered a “noninterventional disease process”.

Enough controversy exists regarding the use of angioplasty for femoropopliteal disease, and the situation becomes even more complicated when trying to analyze the data for stenting. There is general agreement that for acute failure of angioplasty of an SFA lesion, stent placement is indicated. Technology for infrainguinal stents has continued to improve and may be added to a femoropopliteal angioplasty procedure when necessary. There have been conflicting reports in the literature about the routine use of stents for infrainguinal disease.^18,19 A recent randomized trial demonstrated significantly higher primary patency rates of initial stenting versus PTA of femoropopliteal artery lesions TASC-A and B at 1-year and, subsequently, 2-year follow up.^20,21 Unfortunately, the 104 patients (90% claudicants) were not compared to a similar group of patients undergoing optimal conservative therapy with medication, smoking cessation programs and exercise regimens. Moreover, although walking distances increased compared to baseline in both treatment groups, the relative clinical benefit cannot be defined in the absence of a medically-treated group (who frequently experience similar improvements in walking distances without intervention). Such a question was staged to be addressed with the EXACT Trial (EXercise versus Angioplasty in Claudication Trial), a multicenter, randomized, controlled trial in the United Kingdom, but recruitment failed to attract enough patients and the trial was closed prematurely in 2004.²²

In October 2004, this journal posed the following poignant question for a discussion forum: “percutaneous revascularization for SFA/popliteal arterial disease: how and when will endovascular techniques and devices become truly competitive with bypass surgery?” Seven distinguished authors in the field shared their viewpoints on this pressing and timely issue, and they predominantly agreed that the time for intervention was already upon the vascular community; however, most also agreed that despite the enthusiasm for the available techniques, true success had yet to be determined with rigorous experiments and statistical analysis. Now 3 years later, the vascular community is still no closer to answering this question. More interventionalists (radiologists, cardiologists and vascular surgeons) are familiar with the techniques of endovascular procedures, but the exact role of endovascular options on the treatment spectrum are still fluctuating with time.

TASC revisited. As a result of evolving technologies and advances in endovascular therapy, the TASC group met again recently to establish new criteria to stratify lesions into the A–D groupings, with the accompanying new recommendations for treatment.²³ So was this paradigm shift justified based on results, or was it the natural response to justify the past 7 years of therapy? Unfortunately, this question will remain unanswered until one of two scenarios occurs: either new studies are performed using the 2007 TASC guidelines, or researchers from prior studies retrospectively reclassify their treated lesions and then recalculate their results using this new classification system. To illustrate the dilemma that arises with reclassification, what was formerly a TASC-C lesion in 2000 is now a TASC-B lesion in 2007, and many Bs have become As. More specifically, a C lesion (TASC 2000) that may previously have been treated with surgical bypass may now be treated as a B lesion (TASC 2007) using endovascular means. Unfortunately, the patency rate for this intervention should more closely approximate that of a C lesion, and thus be lower than expected based on the only available studies to date. A true clinical dilemma therefore arises when quoting studies published before the 2007 TASC guidelines to justify therapeutic actions in current, modern-day practice.

Conclusion

It is imperative for physicians to emphasize to their patients that claudication follows a benign course and is rarely limb-threatening, thus conservative options (i.e., exercise regimens, smoking cessation programs) and pharmacologic therapy may be all that is required. If more invasive therapy is required, however, the mainstays of treatment are surgical bypass and endovascular therapy. Although endovascular therapy has assumed a more prominent role in recent years and has seen a dramatic increase in its utilization, the long-term results still remain less than optimal for TASC-C and D lesions. When taking into account the multiple factors inherent in vascular surgical decision making, we adhere to the following principles when conservative options have failed and the claudication is “lifestyle-limiting”: 1) endovascular approaches should be employed for all TASC-A and B lesions as well as TASC-C and D lesions in certain situations (medically high-risk patients for surgical bypass, absence of suitable conduit for bypass, elderly patients); and 2) surgical bypass is the preferred option for TASC-C and D lesions in low-risk patients with available conduit, as well as in patients who have failed 2 prior endovascular interventions. Although adopting an “endovascular-first” protocol is not unreasonable, physicians must acknowledge that many of their interventions will fail, the costs will be higher due to reinterventions and many patients may ultimately still require surgical bypass. Overall, we believe that a multimodality approach tailored to the individual patient’s clinical situation is critical to not only achieve technical success, but also to foster population-based guidelines that optimize the efficiency and use of the healthcare system.