Implications of Early Failure of Superficial Femoral Artery Endoluminal Interventions

Implications of Early Failure of Superficial Femoral Artery Endoluminal Interventions Irfan I. Galaria, MD, MBA, Scott M. Surowiec, MD, Jeffrey M. Rhodes, MD, Cynthia K. Shortell, MD, Karl A. Illig, MD, and Mark G. Davies, MD, PhD, Rochester, New York

Although the long-term (>30 days) effects of endoluminal treatment of superficial femoral artery (SFA) disease have been well studied, the implications of early ( £ 30 days) failure are still unclear. We examined the consequences of early failure after endovascular treatment of the SFA. We anticipate that early failure will not be associated with significant morbidity and mortality and will not interfere with surgical bypass options. A prospective database of patients undergoing endovascular treatment of the SFA between 1986 and 2004 was maintained. Intention-to-treat analysis was performed. Angiograms were reviewed in all cases to assess lesion characteristics and pre- and post procedure runoff. Results were standardized to current Transatlantic Intersociety Consensus (TASC) and Society for Vascular Surgery (SVS) criteria. There were 441 limbs in 360 patients (70% male, average age 65 years) that underwent endovascular treatment. There was early failure in 39 procedures (8%). Twenty-nine cases (74%) failed immediately (<24 hr), and 10 cases (26%) failed within the first 30 days following intervention. Factors that predicted failure were TASC category D and preprocedural SVS symptom grade ‡5. The 90-day mortality in the group was 0%, and major morbidity was 4%. No emergent endovascular intervention, bypass, or unplanned amputation occurred within 30 days of these failures. There was no change in the level of amputation or the level of distal anastomosis of a bypass graft as a result of an early failure. Early failure of endoluminal therapy for SFA disease is not associated with significant morbidity and mortality. Options for surgical bypass are not compromised, and the amputation level is not altered. Aggressive endoluminal approaches to SFA disease should be considered as a first-line therapy in all patients.

INTRODUCTION Significant narrowing of the superficial femoral artery (SFA) can lead to claudication and can evolve to chronic critical ischemia. Patients with claudication receive aggressive risk factor modification and are placed on exercise programs; interventions are reserved for failures of this therapy. For critical ischemia, revascularization, if possible, is the standard of care. In the last few years, Division of Vascular Surgery, Department of Surgery, Center for Vascular Disease, University of Rochester, Rochester, NY, USA. Presented at the Fifteenth Annual Winter Meeting of the Peripheral Vascular Surgery Society, Steamboat Springs, CO, January 28-30, 2005. Correspondence to: Mark G. Davies, MD, PhD, Division of Vascular Surgery, Center for Vascular Disease, University of Rochester, 601 Elmwood Avenue, Box 652, Rochester, NY 14642, USA, E-mail: [email protected] Ann Vasc Surg 2005; 19: 787-792 DOI: 10.1007/s10016-005-7972-4  Annals of Vascular Surgery Inc. Published online: October 10, 2005

treatment of SFA occlusive disease has undergone a shift in management. Endoluminal therapy for symptomatic SFA occlusive disease is increasingly being performed as first-line therapy. We have recently reported our long-term experience with endoluminal therapy for SFA occlusive disease and showed that percutaneous angioplasty and stenting of the SFA can be performed safely with excellent procedural success rates. However, the patency rates were strongly dependent on lesion type; the results of endoluminal therapy compared favorably with surgical bypass for Transatlantic Intersociety Consensus (TASC) A and B lesions, while patients who were treated for TASC C and D lesions had much lower patency rates.1 In an era where more aggressive endoluminal therapy is becoming more acceptable, the implications of early ( £ 30 days) endoluminal failure remain unclear. We examined the consequences of early failure after endovascular treatment of the SFA. We anticipate that early failure will not be associated with significant mor787

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bidity and mortality and will not interfere with surgical bypass options.

Annals of Vascular Surgery

3, and every 6 months following their procedure. During follow-up, angiograms were performed only if noninvasive studies suggested restenosis/ occlusion.

METHODS Experimental Design/Setting This is a retrospective review. A database of patients undergoing percutaneous transluminal angioplasty (PTA) and/or stenting of the SFA between 1986 and 2004 was prospectively maintained at the University of Rochester as previously described.1 For each patient, demographics, symptoms, existing comorbid conditions, and risk factors for atherosclerosis were identified. All patients with claudication were encouraged to exercise daily, and their risk factors were identified and corrected through their primary-care providers. Those patients who developed tissue loss or deteriorating symptoms on these regimens were offered endoluminal intervention. Patients with critical ischemia were treated within the same hospitalization. Therapy for individual patients was dictated by individual attending physician preference and was not regulated by unit guidelines. All patients received aspirin daily (81 or 325 mg) as a general cardiovascular protection agent. At the time of the intervention, 2% of patients were on coumadin, and this was continued after the procedure. Noninvasive studies were performed initially; however, patients with serious symptoms or signs of severe stenosis/occlusion based on initial noninvasive tests received angiograms. Angiograms and angiographic reports were reviewed; lesions were categorized under the TASC system, and the distal runoff was scored. Angioplasty was performed under systemic heparin administration (40–60 U/kg), and completion angiography was performed to assess the technical result. Stents were utilized (at the discretion of the operator) for flow-limiting dissections, intimal flaps, or poor technical results (‡50% residual stenosis). In general, for TASC C and D lesions, primary stenting was utilized. No procedures or interventions were performed that could have potentially jeopardized the outflow vessel. A glycoprotein IIb/IIIa inhibitor (abciximab 3.75 mcg/kg hourly for 12 hr) was used at the discretion of the primary operator when thought to provide benefit. Patients who had a successful endoluminal intervention received 75 mg of clopidogrel (Plavix); while a patient was on clopidogrel, the dose of aspirin was maintained at 81 mg/day. Patients who were already on clopidogrel prior to the intervention were left on the drug after the intervention. Patients underwent routine duplex follow-up at 1,

Definitions Early failure was defined as an inability to cross the lesion at the time of the primary procedure or by the presence of an occlusion or ‡50% restenosis within the first 30 days after the initial procedure. Coronary artery disease was defined as a history of angina pectoris, myocardial infarction, congestive heart disease, or prior coronary artery revascularizations. A patient with chronic renal insufficiency had a serum creatinine level of 1.5 mg/dL (132.6 lmol/ L) or greater or was on peritoneal dialysis or hemodialysis. Cerebrovascular disease included a history of stroke, transient ischemic attack, or carotid artery revascularization. Hypertension was defined as systolic blood pressure >150 mm Hg or diastolic blood pressure >90 mm Hg on three occasions during a 6-month period. Hypercholesterolemia was defined as fasting cholesterol >200 mg/dL, lowdensity lipoprotein (LDL) >130 mg/dL, or triglycerides > 200 mg/dL. Diabetes was defined as a fasting plasma glucose >110 mg/dL or HbA1c >7%. TASC classification of disease severity for femoral lesions was used to define the categories of the lesions.2 TASC A lesions denote a single stenosis up to 3 cm in length. TASC B lesions denote a single stenosis or occlusions 3-5 cm in length, heavily calcified lesions up to 3 cm in length, multiple lesions each <3 cm, or lesions in the absence of continuous tibial runoff. TASC C lesions denote single stenosis or occlusion >5 cm or multiple lesions, each 3-5 cm, with or without calcium. TASC D lesions denote complete common femoral or SFA occlusions and complete popliteal or proximal trifurcation occlusions. A death within 30 days of the procedure was considered procedure-related. A major complication was defined as any event, regardless of how minimal, not routinely observed after endoluminal therapy that required treatment with a therapeutic intervention or rehospitalization within 30 days of the procedure. Runoff at the tibial level was determined by the number of patent vessels present, with a maximum of 3 (scored as 0, 1, 2, or 3). Statistical Analysis All statistical analyses were performed on an intention-to-treat basis. Measured values are reported as percentages or means ± 1 standard deviation. Limb-salvage rates were calculated using

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Kaplan-Meier analysis and reported using current Society for Vascular Surgery (SVS) criteria.2 Standard errors are reported in Kaplan-Meier analyses. The log rank test was used to determine differences between life tables. Analyses were performed using SAS software, version 8.2 (SAS Institute, Cary, NC). Multivariate stepwise regression analysis was used to determine the influence of preprocedural and periprocedural factors on outcomes. The significance level p £ 0.10 was used to include or eliminate a covariate from the model. Covariates were considered to be significantly associated with the outcome if they were included in the final model and their significance level was p £ 0.05. Interactions between statistically significant covariates were checked. Logistic regression models were used for outcomes that were measured shortly after the procedure (complications, shortterm clinical benefits). The dependence of each covariate on the outcome was first checked separately using the chi-squared test. Covariates with the significance level of p £ 0.10 were included in the multivariate stepwise analysis.

RESULTS There were 441 limbs in 360 patients (70% male, average age 65 years) that underwent endovascular treatment. Median patient follow-up was 1.8 years (range 0–11). Follow-up within 3 months was available in 88% of cases. All patients received heparin during the procedure, and 8% also received a GPIIb/GPIIIa inhibitor for 12 hr after the procedure. Five percent required thrombolysis for in situ thrombosis or distal embolization during the primary procedure, and 37% of limbs were treated with a concomitant stent. Procedures in 39 patients (8%) failed early (£ 30 days): 21 procedures failed between 2001 and 2004, six procedures failed between 1996 and 2000, nine procedures failed between 1991 and 1995, and three procedures failed between 1986 and 1990. All of these early failures were due to stenosis or occlusion at the site of primary intervention; none of these early failures was due to distal embolization of thrombus. No TASC A patients, 11% of TASC B patients, 15% of TASC C patients, and 33% of TASC D patients had procedures that failed early. Indications for intervention in these patients were tissue loss in 46%, claudication in 39%, and rest pain in 15%. Mean SVS ischemia grade was 4 (range 1-5). TASC lesion grades in patients with early failure were A (0%), B (28%), C (31%), and D (41%). Average runoff at the tibial level was fewer than two patent vessels. A

Outcomes of early SFA PTA failure 789

Table I. Characteristics of and indications for intervention for all patients and for patients who had an early failure of the SFA procedure Characteristic

Total patients (n) Male Female Mean age (years) History of previous myocardial infarction Congestive heart failure Hypertension IDDM NIDDM Hyperlipidemia Statin use Cerebrovascular disease Chronic renal insufficiency (Cr >1.5 mg/dL) Hemodialysis Indication for intervention Claudication Rest pain Tissue loss

Early All patients failure (%) (%)

39 74 26 69 56

360 70 30 65 50

30 71 24 27 48 51 23 28

26 78 25 33 56 48 18 28

8

9

39 15 46

66 16 18a

IDDM, insulin-dependent diabetes mellitus; NIDDM, noninsulin-dependent diabetes mellitus. a p > 0.001, significant difference between the two groups.

comparison of patient characteristics, indications for intervention, and disease characteristics between patients with early SFA intervention failure and all 360 patients who received SFA endoluminal intervention are delineated in Tables I and II. Of the 39 procedures that failed early, 29 cases (74%) failed immediately (<24 hr) and 10 cases (26%) failed within the first 30 days following intervention. The only factors that predicted failure were TASC category D (p < 0.001) and preprocedural SVS grade ‡ 5 (p < 0.001). No other specific lesion characteristics or procedural events were identified that predicted early failure. In the early failure group, 34 (87%) patients received a stent. The 90-day mortality was 0%, and major morbidity (intimal flap, 1%; uncontrolled dissection, 2%; perforation, 1%) was 4%. Patient survival rates by life table analysis (Fig. 1) for early failure versus non-early failure patients were similar; 89% and 85% of early failure patients were still alive at 1 and 3 years, respectively. The limb-salvage rate at 3 years for all secondary procedures performed on the early failure patients was 84 ± 9%, which was similar to the 3-year limb-salvage rate for all other primary endoluminally treated patients (88 ± 8%, Fig. 2).

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Table II. Disease characteristics and procedural data Early failure (%)

Characteristic

TASC lesion category Aa B C Da Presenting SVS limb ischemia grade 1 (Mild claudication) 2 (Moderate claudication) 3 (Severe claudication) 4 (Rest pain) 5-6 (Tissue loss)a Mean no. of preprocedural patent tibial vessels a

All patients (%)

0 28 31 41

48 22 19 11

3 13 31 17 36 1.8

6 27 32 16 19 2.2

DISCUSSION

p > 0.001, significant difference between the two groups.

Early PTA Failures

All PTA Patients

100 95 90 85 80 75 70 0

3

1

5

Years

Years

0

1

3

5

34

24

12

6

211

94

76

Early failures

All patients 360

(below or above the knee), and closer review suggested that in these patients SFA intervention had been performed in an attempt to decrease the level of amputation. Patients with above- or below-knee amputation had a presenting SVS limb ischemia score of 4.5, tibial runoff of 1.75 vessels on average, and TASC D grade lesions. Three of these major amputations were a result of failed bypass procedures that were attempted salvage procedures for failed endoluminal therapy. The remainder of patients were treated conservatively and have not suffered major amputations.

Fig. 1. Patient survival. Error bars are omitted for clarity. The number of patients at risk at each time interval is shown below the figure. Standard error did not exceed 10% at all time intervals that were analyzed.

No emergent endovascular intervention, bypass, or unplanned amputation occurred within 30 days of these failures. There was no change in the level of amputation or the level of distal anastomosis of a bypass graft as a result of an early failure. Eight percent of patients underwent a second successful SFA endoluminal intervention using the retrograde popliteal approach, and 49% of patients underwent an ipsilateral femoral-popliteal bypass. Four patients (10%) did require a major amputation

Despite the rising incidence of endoluminal interventions for TASC A-D grade SFA lesions, few studies have examined the consequences of early failure. Because of the perceived higher failure rates in patients with more severe lesions, as supported in this study, many surgeons have avoided attempting percutaneous repair in these patients for fear of, primarily, precluding or interfering with the success of a bypass procedure.1,3-5 Our results do not support such a contention as we did not see a difference in clinical outcome as defined by a change in level of anastomosis or amputation level in the event of early failure of the intervention. Our results suggest that early failure does not increase a patient’s risk of mortality. There were no periprocedural deaths due to any cause; mortality following an initial early failed endoluminal intervention paralleled results seen for patients in other studies who received only a single, successful primary intervention — endoluminal or bypass surgery alone.6,7 In our study, the presence of TASC D lesions and high initial SVS grade (‡5) were the only characteristics associated with early failure. One-third of patients with TASC D lesions that were treated failed early; in contrast, none of the patients treated for TASC A lesions had an early failure. To our knowledge, no other study has specifically attempted to correlate procedural risk factors with early failure only. Diabetes, renal failure, lesions >10 cm, poor distal runoff, and occlusion have all previously been shown to adversely effect longterm patency.6,8,9 Although there were no set guidelines to direct the placement of a stent, patients with more severe lesions (TASC grade C and/ or D) were more likely to have received a stent than patients with less severe lesions. As a result, 87% of patients in the early failure group received a stent because, in general, patients who had early failure were more likely to have presented with a

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Outcomes of early SFA PTA failure 791

% Saved Limbs

Early PTA Failures

All PTA Procedures

100 95 90 85 80 75 70 65 60 0

6

12

18

24

30

36

42

48

Months Post-Intervention

12

24

36

48

Early failures 34

Months

0

24

12

12

7

All procedures 421

237

151

106

98

Fig. 2. Limb salvage. Error bars are omitted for clarity. The number of procedures at risk at each time interval is shown below the figure. Standard error did not exceed 10% at all time intervals that were analyzed.

seriously threatened limb, based on presenting SVS score and TASC lesion grade. Four randomized trials have shown that primary stenting has no added benefit and does not lead to significantly worse outcomes compared to angioplasty alone.6,10-12 Therefore, in this study, patients most probably failed early due to the greater severity of their lesions as opposed to the presence of a stent. Although patients in the early failure group had more severe lesions based on preprocedural TASC grade and SVS limb ischemia score, their limb-salvage rates at 1 and 3 years were essentially identical to the group of patients who did not experience early failure. For patients with early failure, these rates included results for both types of secondary intervention – endoluminal and open bypass – and may explain, in part, why limb-salvage rates in these patients were better than predicted based on published reports for patients with severe SFA lesions that were treated with endoluminal intervention alone.3-5 No emergent endovascular intervention, bypass, or unplanned amputation occurred within 30 days of these failures; and although there were too few cases to perform a statistical comparison, our results suggest that there was no change in the level of amputation or the level of distal anastomosis of a bypass graft as a result of early failure. Of the patients initially reviewed for this study, there were 35 of 321 patients (excluding the 39 in the early failure group) who ultimately received above- or below-knee amputations. Of these 35 patients, the

presenting SVS score (4.1 ± 1.2) and tibial runoff (1.5 ± 0.8) were similar to those of patients in the early failure group who also required an amputation.1 The percentage of patients in the early failure group who received a major amputation (10%) is similar to the percentage in the non-early failure group who also required an amputation (11%). Based on our observations of preprocedural and postocclusion angiograms, there seemed to be no significant change or reduction in collateral circulation; however, we could not objectively quantify or describe the similarity in the preprocedural and postfailure films. We could not identify a study that effectively addressed this concern in patients who had early failure following angioplasty; but such an observation is supported by Lipsitz et al.,13 who noted that the number of postoccluded collateral vessels following subintimal angioplasty of the SFA did not differ significantly from the preprocedural number of collateral vessels. Better measures are needed to document the clinical and/or anatomic affects of a failed endoluminal intervention aside from simple observations or counting collateral vessels. More data are needed before a policy of primary endoluminal intervention may be adopted for all SFA lesions. Nonetheless, our results suggest that early failure of endoluminal therapy for SFA disease is not associated with significant morbidity and mortality, and options for surgical bypass are not compromised.

REFERENCES 1. Surowiec SM, Davies MG, Lee D, et al. Percutaneous angioplasty and stenting of the superficial femoral artery. J Vasc Surg 2005;41:269–278. 2. TASC Working Group. Management of peripheral arterial disease (PAD): Transatlantic Inter-Society Consensus (TASC). Eur J Vasc Endovasc Surg 2000;19:S1-S244. 3. Cheng SW, Ting AC, Ho P. Angioplasty and primary stenting of high-grade, long-segment superficial femoral artery disease: is it worthwhile. Ann Vasc Surg 2003;17:430-437. 4. Tefera G, Turnipseed W, Tanke T. Limb salvage angioplasty in poor surgical candidates. Vasc Endovasc Surg 2003;37:99104. 5. Van der Zaag ES, Legemate DA, Prins MH, Reekers JA, Jacobs MJ. Angioplasty or bypass for superficial femoral artery disease? A randomized controlled trial. Eur J Vasc Endovasc Surg 2004;28:132-137. 6. Becquemin JP, Favre JP, Marzelle J, Nemoz C, Corsin C, Leizorovicz A. Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: a multicenter prospective randomized study. J Vasc Surg 2003;37:487-494. 7. Ballotta E, Renon L, Toffano M, Da Giau G. Prospective randomized study on bilateral above-knee femoropopliteal revascularization: polytetrafluoroethylene graft versus

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reversed saphenous vein. J Vasc Surg 2003;38:10511055. 8. Clark TW, Groffsky JL, Soulen MC. Predictors of long-term patency after femoropopliteal angioplasty: results from the STAR registry. J Vasc Interv Radiol 2001;12:923-933. 9. Kroger K, Buss C, Goyen M, Santosa F, Rudofsky G. Diameter of occluded superficial femoral arteries limits percutaneous recanalization: preliminary results. J Endovasc Ther 2002;9:369-374. 10. Cejna M, Schoder M, Lammer J. PTA vs. stent in femoropopliteal obstruction [in German]. Radiologe 1999;39:144150.

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11. Vroegindeweij D, Vos LD, Tielbeek AV, Buth J, van de Bosch H. Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: a comparative randomized study. Cardiovasc Intervent Radiol 1997;20:420-425. 12. Zdanowski Z, Albrechtsson U, Lundin A, et al. Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions? A randomized controlled study. Int Angiol 1999;18:251-255. 13. Lipsitz EC, Ohki T, Veith FJ, et al. Fate of collateral vessels following subintimal angioplasty. J Endovasc Ther 2004;11. 269-273.