Tibial Angioplasty for Limb Salvage in High-Risk Patients and Cost Analysis
Article Outline
Background
We examined the efficacy and cost of tibial angioplasty in patients with critical limb ischemia (CLI) at high operative risk.
Methods
A retrospective analysis of all consecutive patients who underwent tibial angioplasty with critical ischemia Rutherford class 4 and 5 from January 2001 to April 2007 was performed. Demographic information, presentation, and angiographic characteristics of the lesions were analyzed. The primary end point was freedom from major amputation. Secondary end points were overall survival and recurrence. Cost comparison was performed between the endovascular group and a matched group of high-risk patients submitted to femoral tibial bypass in the same period.
Results
Forty-five patients, with mean age of 69.6 years and a 2.5:1 (male:female) ratio, had 49 limbs treated. The mean follow-up was 7.7 months (range 1–61.5). Eighty percent of the patients were Rutherford class 5. Incidence rates were as follows: diabetes 90%, chronic renal failure 73%, end-stage renal disease (ESRD) on hemodialysis 45%, and coronary disease 69%. Single vessel run-off to the foot was present in 57% of patients and complete occlusion of all tibial vessels in 12%. Only the tibial vessels were angioplastied in 55% of patients. Angiographic success rate was 84%. Thirty-day mortality was 2% and major complications occurred in 6.1%. A poor angiographic result was a statistically significant predictor (p = 0.009) of symptomatic recurrence (43%) (worsening of preexisting symptoms and/or signs or new ones). Cardiac disease was the major cause of mortality beyond 30 days (12.5%). Freedom from major amputation in the entire group was 75.5%, with no difference between tibial and diffuse infrainguinal angioplasty (p = 0.61). Recurrence, especially early recurrence, was a significant predictor of amputation (p = 0.04 and p = 0.0008, respectively). There was a trend toward presence of ESRD and recurrence (p = 0.06). Both average hospital cost ($2,910.60 vs. $17,703.50) and length-of-stay (LOS) (<1 vs. 9 days) were significantly reduced in the angioplasty group (p < 0.0001).
Conclusion
Tibial angioplasty has acceptable rates of limb salvage in patients with CLI considered to be at high risk for surgery, despite high recurrence rates. The presence of diabetes or ESRD did not reduce the rate of success in this series, although ESRD seemed to predict recurrence. The procedure has low morbidity and mortality with lower cost and LOS compared with open revascularization. Aggressive angioplasty should be an option to patients who otherwise would face primary amputation.
Introduction
Successful functional limb salvage is the goal of therapy for patients with critical limb ischemia (CLI). Patients with end-stage renal disease (ESRD) who are dialysis-dependent with or without diabetes are at highest risk for poor surgical outcomes.1, 2 They tend to have more distal arterial occlusive disease involving the tibial vessels, frequently with severe calcification, which could impact medium- and longer-term success rates. Percutaneous transluminal angioplasty (PTA) of tibial arteries has been suggested to be an effective option in this subgroup of patients, with the advantage that the procedure does not preclude surgery in case of failure.3, 4
The purpose of this study was to evaluate the outcomes of tibial PTA in patients of Rutherford categories 4 and 5 considered to be at high risk for conventional surgery. In addition, a cost analysis was performed to compare angioplasty and bypass costs.
Methods
The study protocol was reviewed and approved by the Research Ethics Board of University Health Network.
A retrospective analysis was carried out through hospital and office charts of all vascular patients referred to Toronto General Hospital from January 1, 2001, to March 31, 2007, with the diagnosis of tibial disease all patients are added in the database after they have the vascular lab studies done according to their main level of disease. Patients were included if they had CLI (Rutherford category 4 or 5) and were considered to be at high risk for surgery based on their comorbidities using the American Society of Anesthesiologists Scoring Physical Status Classification System (ASA ≥3). Patients were excluded if they had any kind of revascularization prior to this procedure, were considered to be at low risk for open surgery (ASA <3), had any significant iliac lesions assessed by either vascular laboratory or contrast-enhanced computerized tomography, or did not have complete follow-up information. The ankle-brachial index (ABI) was not included in the analysis because it was inaccurate in almost 50% of the patients due to calcified vessels. In the follow-up period, clinical outcome including recurrence of symptoms (defined as any reopening or worsening of wounds or occurrence of new ones, recurrence or worsening of rest pain), need for further procedures, and level of amputation were observed.
Angioplasty was performed through ipsilateral antegrade puncture in all except two cases, in which the contralateral approach was used, using standard transluminal technique and low-profile guidewires and balloons (0.014- and 0.018-inch coronary systems).5 No subintimal angioplasty was intentionally performed. All patients received an average of 7,500 U of systemic unfractionated heparin during the procedure, and intra-arterial nitroglycerin was used to prevent and/or treat vasospasm (100–200 mg). Stents were not used routinely but only as a bailout procedure (one patient with dissection postdilatation and another with persistent elastic recoil). All patients were kept on antiplatelet therapy pre- and postintervention: aspirin (81–325 mg/day) or clopidogrel (75 mg/day) according to the physician's discretion. The lesions were classified according to the Trans-Atlantic Inter-Society Consensus (TASC) (Table I).3 Angiographic success was defined as a technically successful procedure with final residual stenosis <30% of the lumen of the vessel.
Table I. TASC classification for tibial lesions
| A | Stenosis <1 cm in length |
| B | Multiple focal stenosis <1 cm in length each, |
| one or two lesions at the trunk, | |
| short lesion distal in conjunction with femoropopliteal PTA | |
| C | Stenosis 1–4 cm in length, |
| occlusion 1–2 cm in length, | |
| extensive stenosis at trunk | |
| D | Occlusion >2 cm in length, |
| diffuse disease |
The primary end point was freedom from major amputation (above or below the knee). Secondary end points were overall survival and recurrence of symptoms.
A comparison between hospital costs of endovascular treatment and distal bypass procedures was performed using a control cohort of surgical patients, considered high-risk candidates (ASA ≥3) undergoing elective femoral tibial bypass for the same indications at the same period in our institution (Table II). Medical fees were excluded. The data were collected using the Eclipse Case Costing Software, AS 400 platform (Galatek, Upper Saddle River, NJ) in Canadian dollars and converted to US dollars according to the currency at the time (CAN$1.00 = U.S.$0.80). The length of stay (LOS) for each patient included all complications related to the initial procedure. In the endovascular group, whenever recurrence occurred, each procedure was considered separate for the purpose of analysis.
Table II. Demographic characteristics of patients undergoing open surgery and PTA
| Characteristics | Surgery | PTA |
|---|---|---|
| Age (years) | 68.8 (39–86) | 69.6 (43–92) |
| Male | 62.5% | 71.0% |
| Female | 37.5% | 29.0% |
| Rutherford class 4 | 37.5% | 20.0% |
| Rutherford class 5 | 62.5% | 80.0% |
| Hypertension | 90.6% | 88.0% |
| Diabetes | 71.9% | 90.0% |
| CRF | 43.7% | 73.0% |
| ESRD | 21.8% | 45.0% |
| CAD | 71.9% | 69.0% |
| Smoking | 46.9% | 20.0% |
| Hypercholesterolemia | 87.5% | 53.0% |
Fisher's exact test was used to determine the relationship between each of the risk factor and major amputation or recurrence (Table III). Any predictor variable that reached p ≤ 0.05 was considered statistically significant. Cox regression survival and Kaplan-Meier estimate survival analysis were used to evaluate the relation of freedom from major amputation, overall survival, and recurrence with each of the risk factors. The nonparametric Mann-Whitney U-test was used to analyze the costs. All analyses were conducted using SAS software (version 9.1; SAS Institute, Cary, NC).
Table III. Demographic characteristic of patients undergoing tibial angioplasty
| Characteristics | Patients, n (%) | Recurrence (%) | p | Amputation (%) | p |
|---|---|---|---|---|---|
| Males | 32 (71) | 16 (32) | 0.52 | 9 (18) | 1 |
| Females | 13 (29) | 5 (10) | 3 (6) | ||
| Diabetes | 44 (90) | 19 (39) | 1 | 10 (20) | 0.58 |
| Hypertension | 43 (88) | 19 (39) | 0.69 | 11 (22) | 1 |
| CRF | 36 (73) | 15 (31) | 0.78 | 8 (16) | 0.71 |
| ESRD | 22 (45) | 6(12) | 0.06 | 6 (12) | 0.68 |
| CAD | 34 (69) | 17 (35) | 0.13 | 9 (18) | 0.73 |
| Smoking | 10 (20) | 4 (8) | 1 | 1 (2) | 0.42 |
| Hypercholesterolemia | 26 (53) | 13 (26) | 0.29 | 6 (12) | 0.8 |
| Rutherford class 4 | 10 (20) | 6 (12) | 0.29 | 2 (4) | 1 |
| Rutherford class 5 | 39 (80) | 15 (31) | 10 (20) | ||
| Single-vessel runoff | 28 (57) | 11 (22) | 0.56 | 7 (14) | 0.92 |
| TASC C/D | 32 (65) | 12 (24) | 0.3 | 7 (14) | 0.73 |
Results
Forty-five patients with 49 affected limbs underwent tibial angioplasty for treatment of critical ischemia between January 1, 2001, and March 30, 2007 (Table III). The mean age was 69.6 years (±12.3 standard deviation [SD]), with a male/female ratio of 2.5:1. Those with tissue loss (Rutherford class 5) made up 80% of the patient population.
All patients were sent to angiography with the initial diagnosis of severe tibial disease, some of them associated with stenosis at the femoropopliteal segment. Fifty-seven percent of the limbs had single-vessel runoff, and in 12% there was complete occlusion of the tibial vessels with no in-line runoff to the foot. The majority of the lesions corresponded to TASC C, followed by TASC B and D. There were no TASC A lesions treated in this series. A total of 105 lesions varying from 2 to 5 cm in length were successfully angioplasted in 49 procedures (2.1 lesions treated/limb). In 45% of the limbs, the angiogram confirmed diffuse infrainguinal disease and the femoropopliteal segment was also angioplasted. The angioplasty was technically successful in all patients. Angiographic success (defined as <30% of residual stenosis) was obtained in 84% of the procedures with three major vascular complications (6.1%). One patient had a large hematoma with pseudoaneurysm, which required surgical treatment; one patient had popliteal dissection with distal embolization, requiring distal thrombolysis and repeated angioplasty; and a third patient had peroneal artery dissection, requiring secondary stenting with early distal occlusion in the postoperative period.
The mean follow-up was 7.7 months (range 1–61.5). Symptoms recurred in 43% (20 limbs), with a mean time of 5.3 months (range 1–36.7). The majority of recurrences (60%) occurred in the treated femoropopliteal territory (Fig. 1A), and angioplasty was repeated successfully in all but three (6.1%) patients who required subsequent elective bypass as a bailout procedure; in two the angioplasty could not be repeated due to progression of the disease, and a third patient refused endovascular treatment. Comorbidities and presentation did not predict recurrence (Table III). There was a trend toward the presence of ESRD and recurrence (p = 0.06). Patients with poor initial angiographic results (residual stenosis >30%) had significantly higher recurrence rates compared to those with initial angiographic success (Fig. 1B).
Fig. 1
Kaplan-Meier estimate survival curves. A Recurrence and territory angioplastied (diffuse, femoropopliteal + tibial territories; tibial, isolated tibial PTA). B Recurrence and residual stenosis after the initial angioplasty.
The 30-day mortality was 2%, corresponding to one patient with early failure requiring amputation and acute myocardial infarct in the early postoperative period. The late mortality was 12.5% (seven patients), mainly due to cardiac events (Fig. 2). In 83% of patients who died, the limb angioplasted was attached and viable at the time of death.
Fig. 2
Kaplan-Meier estimate overall survival.
Freedom from major amputation in the entire group was 75.5%. Limb salvage in patients who underwent treatment of both femoropopliteal and tibial arteries was 82% compared to 70% in those who had only tibial lesions treated, but this difference was not statistically significant (Fig. 3A). The recurrence and time for recurrence were statistically significant predictors of amputation (Fig. 3B).
Fig. 3
Kaplan-Meier estimate survival curves. A Amputation and territory angioplastied (diffuse, femoropopliteal + tibial territories; tibial, isolated tibial PTA). B Amputation and presence of recurrence.
The average of hospital cost, excluding medical reimbursement and including the costs directly related to all complications associated with the procedures, was US$2,910.60 among 26 subjects submitted to angioplasty and US$17,703.50 among 32 surgical patients. The average LOS for the angioplasty group was <1 day (≤3 days, 21 patients; >3 days, five patients) and that for the surgical group was 9 days (≤9 days, 17 patients; >9 days, 15 patients). Overall, both the average hospital cost and LOS were significantly reduced for patients submitted to angioplasty (p < 0.0001), even when the costs of repeated procedures were added in case of recurrence.
Discussion
Treatment of CLI can be challenging. Limb salvage rates are low, particularly in patients with ESRD and diabetes.6 Surgical procedures in this high-risk group are associated with high morbidity and mortality,7 especially in those who lack suitable venous conduit. Prosthetic and composite grafts have reduced long-term patency (35% in 5 years) and high reintervention rates, especially for distal bypasses.3, 6 PTA for infrainguinal lesions, introduced by Bolia more than 20 years ago, had initially poor results and was not widely accepted. However, small case series and retrospective reviews showed that with increased expertise and improvements in technique and technology PTA (particularly tibial) seems to be comparable to bypass surgery regarding limb salvage.1, 2, 5, 8, 9, 10, 11, 12 The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial, the only prospective randomized study comparing PTA with bypass surgery in patients with CLI, demonstrated that at 2 years of follow-up angioplasty had better results regarding limb salvage and overall mortality in patients with reduced life expectancy.13 This trial, however, included patients considered suitable for both procedures. The best short- and long-term treatment options for high surgical–risk patients await publication of longer-term randomized data. Large series and a meta-analysis of patients undergoing tibial bypass showed very good short- and long term results with good limb salvage at 5 and 10 years.14, 15, 16 However, the incidence of chronic renal failure among those patients was quite small (13–19.3%) despite the incidence of diabetes and that >50% of those procedures performed were short bypasses (popliteal tibial bypass). These excellent results were obtained in high-volume centers, which could represent bias and might not represent the average practice.
We demonstrated that critical ischemia in high surgical–risk patients can be successfully treated by endovascular means. The approach proved to be safe, with low morbidity, lower costs, and shorter LOS. Despite considerable recurrence rates, repeated procedures did not reflect higher complication rates and only three patients required surgery. This supports what other studies have demonstrated that previous PTA does not preclude surgery.13, 17, 18 Poor initial angiographic results predicted recurrence of symptoms, and early recurrence (<6 months) was significantly associated with a higher amputation rate. Interestingly, patients submitted to isolated tibial angioplasty had the same risk of amputation as patients submitted to diffuse infrainguinal angioplasty (p = 0.61).
The life expectancy in this subset of patients is reduced due to the severity of comorbidities and burden of atherosclerotic disease.2, 4, 13, 19 The main cause of death in our series was coronary artery disease. In such a high-risk population with limited life expectancy, less invasive procedures are desirable and long-term results are not the main priority.13 In fact, previous studies have shown that the primary patency rate in this population is very low at 1 year5, 10, 20, 21 and that angiographic reocclusion does not always result in recurrent symptoms.22 Follow-up angiographic patency is not known in our series because delayed angiography was performed only in patients with recurrent symptoms.
Considering the constant rise in the cost of health care, we compared the cost of angioplasty with a control cohort of patients submitted to open procedures. Despite the high incidence of recurrence and reintervention rates, hospital costs of angioplasty in this population were much lower when compared to surgery, even when the costs of reinterventions were added or procedural complications occurred. These costs excluded physician reimbursement. Same-day discharge in the PTA group resulted in significantly reduced LOS and costs. If the rate of reintervention in the angioplasty group increased with longer follow-up, this could mitigate the cost differences compared to open surgery. Further conclusions regarding the cost were not possible since the study is not a randomized comparison of contemporaneous equivalent groups.
The high incidence of diabetes and ESRD in the entire population, the small sample size, and the retrospective nature of the study are some of the limitations that restricted our conclusions. Further studies with long-term results are warranted. Despite these limitations, we were able to demonstrate good limb salvage at lower cost, supporting the use of a less invasive procedure in this high-risk population. Therefore, our algorithm for treatment of CLI has changed in favor of angioplasty first, especially in those with predominantly tibial artery occlusive disease, as an option for patients at high risk or unsuitable for bypass, who would otherwise face primary amputation.4, 20, 23
Conclusion
Angioplasty is a feasible, safe, and effective procedure for the treatment of CLI in patients considered to be at high risk for open revascularization. Initial success rates are acceptable, with low morbidity and mortality. LOS is shorter and costs are lower compared to open surgical procedures, even when reintervention is required. Limb salvage is higher in those treated for both superficial femoral artery and tibial disease compared to isolated tibial disease. Despite early high recurrence and reintervention rates, this initial aggressive endovascular approach is advised in these high-risk patients. Refinements in technique and technology will undoubtedly allow continued improvements in short- and long-term results.
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PII: S0890-5096(09)00108-3
doi:10.1016/j.avsg.2009.05.007
© 2009 Annals of Vascular Surgery Inc. Published by Elsevier Inc All rights reserved.
