Abstract
Predictors of provisional stenting in patients undergoing lower extremity arterial interventions remain unclear. We performed an ad hoc analysis on the predictors of provisional stenting during infrainguinal arterial percutaneous interventions using data from the Percutaneous Lower Extremity Arterial Interventions Using Primary Balloon Angioplasty versus Silverhawk Atherectomy (SA) and Adjunctive Balloon Angioplasty trial. In the above trial, SA of infrainguinal de novo arterial lesions was shown to reduce significantly provisional stenting compared with primary percutaneous transluminal angioplasty (PTA). In this ad hoc analysis, patients were divided into two groups based on whether provisional stenting has occurred. Univariate analysis was conducted between the stent versus the no-stent group. Logistic regression (LR) analysis was performed to model for the predictors of provisional stenting. Variables included were diabetes, presence of moderate calcification (versus none to little), age, gender, hypercholesterolemia, Transatlantic Intersociety Consensus (TASC) D lesion (vs. TASC A to C), and treatment method (primary PTA vs. SA with adjunctive PTA). By LR analysis, predictors of stenting were as follows: moderate calcification (odds ratio [OR] 6.56, 95% confidence interval [CI] 1.21 to 35.56, p = 0.029), primary PTA (vs. SA) (OR 0.19, 95% CI 0.04 to 0.93, p = 0.04), and TASC D lesions (vs. A to C) (OR 0.10, 95% CI 0.01 to 0.87, p = 0.037). Provisional stenting in infrainguinal interventions is predicted by the use of primary PTA, presence of moderate calcification, and TASC D lesions after controlling for gender, age, hypercholesterolemia, and diabetes.
Keywords: Peripheral angioplasty, predictors of stenting, atherectomy, vessel calcification, long occlusions
Predictors of stenting in lower extremity arterial interventions have not been well defined. Balloon angioplasty has been associated with a higher rate of provisional stenting ranging from 10 to 43%.1,2,3,4 Atherectomy with the SilverHawk device showed a stenting rate ranging from 0 to 6.3% in various studies.5,6,7 Although stenting has been shown to reduce restenosis when compared with percutaneous transluminal angioplasty (PTA),3 stenting carries its own set of problems including a continued high rate of restenosis, thrombotic occlusions, stent fractures, and may potentially limit future therapies in the femoropopliteal artery.8,9,10
In the Percutaneous Lower Extremity Arterial Interventions Using Primary Balloon Angioplasty versus Silverhawk Atherectomy and Adjunctive Balloon Angioplasty trial, Silverhawk atherectomy (SA) of infrainguinal de novo arterial lesions was shown to reduce significantly bailout stenting compared with primary PTA.11 Provisional stenting was a predefined end point in this study with prespecified conditions for stenting including a residual of >30% or type C dissection and higher. We present an ad hoc analysis of this trial analyzing the clinical, angiographic, and procedural predictors of provisional stenting.
METHODS
In this two-center, prospective randomized trial in treating infrainguinal de novo lesions using PTA versus SA with adjunctive balloon angioplasty, patients were included if they were referred for percutaneous lower extremity intervention because of claudication (Rutherford Becker I to III) or chronic limb ischemia (Rutherford Becker IV to V). They were excluded if they had one or more of the following: (1) heavily calcified vessels or total occlusions longer than 10 cm or any total occlusion with suspicion of subintimal wire recanalization, (2) inability to take antiplatelet drugs or a history of coagulopathy, (3) chronic renal failure with creatinine over 2.5 mg/dL, and (4) decompensated congestive heart failure or acute coronary syndrome. The study was approved by the institutional board of each institution where the study was conducted. Informed consent was obtained on all patients. Target lesion revascularization (TLR) at 1 year was the primary end point of the study. Provisional stenting because of suboptimal acute angiographic results defined as a residual stenosis of >30% or the presence of type C or higher dissection was a secondary end point.
Randomization was done after crossing total occlusions if the wire was intraluminal. For patients enrolled in the SA arm, the SilverHawk atherectomy device (ev3 Endovascular, Plymouth, MN) was used before adjunctive PTA. Procedural success was defined as residual stenosis of ≤30% and/or no higher than a type B dissection. The same balloon angioplasty protocol was used in both arms:
balloon inflation time was 90 seconds, with two inflations each for every lesion treated;
balloon inflation pressure was started at 2 atm and was increased gradually (1-atm increments) until no waist was seen on the balloon.
Provisional stenting was performed in patients with procedural failure with nitinol self-expanding stents (LifeStent, Bard Peripheral Vascular, Tempe, AZ; and Protégé, ev3 Endovascular, Plymouth, MN). Stents were sized at 1 to 2 mm above the estimated vessel diameter. Stenting was not permitted for procedural success.
Statistical Analysis
Patients were divided into those who underwent provisional stenting versus those who did not get a stent. Univariate analysis was conducted between the two groups. Continuous variables were analyzed with t-testing and dichotomous variables with chi-square or Fisher's exact test. Logistic regression (LR) analysis was performed to model for the predictors of provisional stenting. A p value of <0.05 was considered significant.
RESULTS
A total of 58 patients were included in the study. Of these, 29 patients (36 vessels) were included in the SA arm and 29 patients (48 vessels) in the PTA arm. Approximately 80% of patients were claudicants, and the rest had chronic limb ischemia. There were 46 of 58 (79.3%) patients with only femoropopliteal vessels treated. The mean number of tibial runoffs was 1.9 ± 0.9. Total occlusions were present in 12 of 84 (14.3%) vessels treated.
Table 1 shows the differences in the demographic, clinical, and angiographic variables between the provisional stent and no-stent groups.
Table 1.
Univariate Analysis Comparing Baseline Demographic, Clinical, and Angiographic Variables of Provisional Stent Group Versus the No-Stent Group
| Parameter | No Provisional Stent | Provisional Stent | p Value |
|---|---|---|---|
| Age (years) | 67.17 ± 10.38 | 72.23 ± 13.32 | NS |
| BMI | 29.26 ± 5.76 | 27.31 ± 5.64 | NS |
| Male (%) | 60 | 69.6 | NS |
| Smoking (current) | 31.4 | 27.3 | NS |
| ABI: treated leg at baseline | 0.76 ± 0.25 | 0.72 ± 0.19 | NS |
| hs-CRP at baseline (mg/L) | 9.48 ± 11.03 | 8.98 ± 20.86 | NS |
| Prestenosis (%) | 82.77 ± 12.86 | 86.03 ± 13.36 | NS |
| Poststenosis (%) | 12.22 ± 8.30 | 4.22 ± 7.52 | 0.001 |
| Post TIMI flow | 2.98 ± 0.14 | 2.91 ± 0.53 | NS |
| Runoff treated leg | 2.03 ± 0.98 | 1.68 ± 0.89 | NS |
| Lesion length (mm) | 81.63 ± 84.99 | 98.59 ± 84.95 | NS |
| Balloon pressure (atm) | 8.92 ± 2.37 | 10.19 ± 2.16 | 0.016 |
| Hypertension (%) | 80 | 81.8 | NS |
| Hypercholesterolemia (%) | 80 | 68.2 | NS |
| Diabetes (%) | 51.4 | 36.4 | NS |
| Presence of angiographic thrombus (%) | 5.7 | 4.3 | NS |
| hs-CRP at 48 hours posttreatment (mg/L) | 24.81 ± 23.05 | 37.02 ± 29.12 | NS |
| Rutherford class II to V (%) | 100 | 100 | NA |
| Segment treated | NS | ||
| Femoral | 65.4 | 78.1 | |
| Tibial | 34.6 | 21.9 | |
| TASC lesions (%) | NS | ||
| TASC D | 9.6 | 22.6 | |
| TASC A, B, C | 90.4 | 77.4 | |
| Calcium (%) | 0.008 | ||
| None to little | 86.5 | 59.4 | |
| Moderate | 13.5 | 40.6 |
ABI, ankle brachial index; BMI, body mass index; hs-CRP, high sensitivity C-reactive protein; NS, not significant; TASC, Transatlantic Intersociety Consensus 2002; TIMI, thrombolysis in myocardial infarction.
There was a higher prevalence of moderate calcification in the stent group and a lower residual narrowing poststenting. Also, stent deployment was performed at a statistically higher pressure than balloon angioplasty alone, although this difference is clinically small (delta 1.27 mm Hg).
At 1 month, both groups had the same TLR and target vessel revascularization (TVR) although TLR trended in favor of the no-stent group compared with the stent group (Table 2). There were no differences in death and amputation in either group. Approximately 40% of patients in both groups were in a Rutherford Becker class II to IV.
Table 2.
Outcomes of Patients with Provisional Stenting Versus No Provisional Stenting
| Parameter | No Provisional Stent | Provisional Stent | p Value |
|---|---|---|---|
| Follow-up duration (months) | 9.79 ± 3.59 | 10.02 ± 3.41 | NS |
| ABI: treated leg at 30 days | 0.98 ± 0.17 | 0.91 ± 0.14 | NS |
| ABI: treated leg at 1 year | 0.94 ± 0.16 | 0.78 ± 0.22 | 0.031 |
| Rutherford class II to IV at 30 days | 44.1 | 30 | NS |
| Rutherford class II to IV at 1 year | 41.4 | 38.9 | NS |
| Death at 1 year (%) | 12.1 | 10 | NS |
| Amputation at 1 year (%) | 0 | 5.3 | NS |
| TLR cumulative at 1 year (%) | 9.6 | 15.6 | NS |
| TVR cumulative at 1 year (%) | 13.5 | 15.6 | NS |
ABI, ankle brachial index; NS, not significant; TLR, target lesion revascularization; TVR, target vessel revascularization.
LR analysis (Table 3) was performed to model for the predictors of provisional stenting. Variables included were diabetes, presence of moderate calcification (versus none to little), age, gender, hypercholesterolemia, Transatlantic Intersociety Consensus (TASC) D lesion (vs. TASC A to C), and treatment method (primary PTA vs. SA with adjunctive PTA). By LR analysis, predictors of stenting were as follows: moderate calcification (odds ratio [OR] 6.56, 95% confidence interval [CI] 1.21 to 35.56, p = 0.029), primary PTA (vs. SA) (OR 0.19, 95% CI 0.04 to 0.93, p = 0.04), and TASC D lesions (vs. A to C) (OR 0.10, 95% CI 0.01 to 0.87, p = 0.037).
Table 3.
Predictors of Provisional Stenting by LR Analysis
| Parameter | p Value | Odds Ratio | 95% Confidence Interval | ||||
|---|---|---|---|---|---|---|---|
| Lower | Upper | ||||||
| Atherectomy versus PTA | 0.04 | 0.189 | 0.038 | 0.928 | |||
| Calcium | |||||||
| Moderate versus none to little | 0.029 | 6.562 | 1.211 | 35.561 | |||
| TASC A, B, C lesions versus TASC D | 0.037 | 0.104 | 0.012 | 0.872 | |||
| Control variables | |||||||
| Gender | 0.261 | 2.359 | 0.528 | 10.533 | |||
| Age | 0.437 | 1.024 | 0.964 | 1.088 | |||
| Hypercholesterolemia | 0.882 | 0.888 | 0.185 | 4.265 | |||
| Diabetes | 0.072 | 0.255 | 0.057 | 1.131 | |||
LR, logistic regression; PTA, percutaneous transluminal angioplasty; TASC, Transatlantic Intersociety Consensus.
DISCUSSION
In this ad hoc analysis of the Percutaneous Lower Extremity Arterial Interventions Using Primary Balloon Angioplasty versus Silverhawk Atherectomy and Adjunctive Balloon Angioplasty trial, provisional stenting was performed under strict predefined end points.11 Patients could get a stent only if they had a residual narrowing of more than 30% or a type C and higher dissection. In the initial trial, patients who received primary angioplasty had more provisional stenting than those who were treated with initial atherectomy (62.1 vs. 27.6%, p = 0.017). Clinical, angiographic, and procedural predictors of stenting in infrainguinal interventions remain, however, unclear. In this ad hoc analysis, moderate calcification was a strong predictor of stenting (OR 6.56, p = 0.029). In contrast, the use of atherectomy as a primary therapy and treating type A to C lesions were associated with reduced odds of stenting (OR 0.19, p = 0.04 and 0.10, p = 0.037 respectively).
Reducing provisional stenting has several advantages when treating femoropopliteal or tibial disease. Although stenting is promising to reduce restenosis compared with balloon angioplasty by reducing acute recoil, dissections, and negative remodeling, the rate of restenosis remains substantially high with stenting alone,1,2,3 and no randomized data are available on stenting versus atherectomy. Furthermore self-expanding nitinol stents continue to have a high rate of fractures that have been linked to an increase in restenosis rate.8,9,10,12 Finally, stents may limit future pharmacologic or surgical targets for peripheral bypass preventing a viable revascularization alternative to patients. Reducing stenting therefore might have its advantages when treating infrainguinal disease.
In this study, the rate of amputation and death were similar in both arms. Also, there were no statistical differences in the TLR and TVR in both groups. The study, however, was likely to be underpowered to determine the differences in TLR or TVR between stenting and no stenting.
Limitations of the Study
This study is an ad hoc analysis and therefore is not powered to compare the differences in the two groups. Also, the overall number of patients is small. However, provisional stenting was not random and was done under predefined conditions, reducing the bias in the analysis.
CONCLUSION
In summary, provisional stenting in infrainguinal interventions appears to be predicted by the use of primary PTA, presence of moderate calcification, and TASC D lesions after controlling for gender, age, hypercholesterolemia, and diabetes. A large prospective trial testing this hypothesis is warranted.
ACKNOWLEDGMENTS
This work was supported by research grants from Edwards and ev3 Endovascular and by the Nicolas and Gail Shammas Research Fund at the Midwest Cardiovascular Research Foundation, Davenport, Iowa.
References
- Kasapis C, Henke P K, Chetcuti S J, et al. Routine stent implantation vs. percutaneous transluminal angioplasty in femoropopliteal artery disease: a meta-analysis of randomized controlled trials. Eur Heart J. 2009;30:44–55. doi: 10.1093/eurheartj/ehn514. [DOI] [PubMed] [Google Scholar]
- Krankenberg H, Schlüter M, Steinkamp H J, et al. Nitinol stent implantation versus percutaneous transluminal angioplasty in superficial femoral artery lesions up to 10 cm in length: the femoral artery stenting trial (FAST) Circulation. 2007;116:285–292. doi: 10.1161/CIRCULATIONAHA.107.689141. [DOI] [PubMed] [Google Scholar]
- Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med. 2006;354:1879–1888. doi: 10.1056/NEJMoa051303. [DOI] [PubMed] [Google Scholar]
- Zorger N, Manke C, Lenhart M, et al. Peripheral arterial balloon angioplasty: effect of short versus long balloon inflation times on the morphologic results. J Vasc Interv Radiol. 2002;13:355–359. doi: 10.1016/s1051-0443(07)61736-9. [DOI] [PubMed] [Google Scholar]
- Ramaiah V, Gammon R, Kiesz S, et al. TALON Registry Midterm outcomes from the TALON Registry: treating peripherals with SilverHawk: outcomes collection. J Endovasc Ther. 2006;13:592–602. doi: 10.1583/05-1780MR.1. [DOI] [PubMed] [Google Scholar]
- Zeller T, Rastan A, Sixt S, et al. Long-term results after directional atherectomy of femoro-popliteal lesions. J Am Coll Cardiol. 2006;48:1573–1578. doi: 10.1016/j.jacc.2006.07.031. [DOI] [PubMed] [Google Scholar]
- Biskup N I, Ihnat D M, Leon L R, Gruessner A C, Mills J L. Infrainguinal atherectomy: a retrospective review of a single-center experience. Ann Vasc Surg. 2008;22:776–782. doi: 10.1016/j.avsg.2008.08.003. [DOI] [PubMed] [Google Scholar]
- Adlakha S, Sheikh M, Wu J, et al. Stent fracture in the coronary and peripheral arteries. J Interv Cardiol. 2010;23:411–419. doi: 10.1111/j.1540-8183.2010.00567.x. [DOI] [PubMed] [Google Scholar]
- Scheinert D, Scheinert S, Sax J, et al. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol. 2005;45:312–315. doi: 10.1016/j.jacc.2004.11.026. [DOI] [PubMed] [Google Scholar]
- Laird J R. Limitations of percutaneous transluminal angioplasty and stenting for the treatment of disease of the superficial femoral and popliteal arteries. J Endovasc Ther. 2006;13(Suppl 2):II30–II40. doi: 10.1177/15266028060130S207. [DOI] [PubMed] [Google Scholar]
- Shammas N W, Coiner D, Shammas G, Dippel E, Christensen L, Jerin M. Percutaneous Lower Extremity Arterial Interventions Using Balloon Angioplasty Versus Silverhawk Atherectomy: Results of the SMARTHAWK Randomized Trial. Presented at the Society for Cardiovascular Angiography & Interventions (SCAI) 32nd Annual Scientific Sessions in Las Vegas from May 6–9, 2009. Catheter Cardiovasc Interv. 2009;73:S42. [Google Scholar]
- Schlager O, Dick P, Sabeti S, et al. Long-segment SFA stenting—the dark sides: in-stent restenosis, clinical deterioration, and stent fractures. J Endovasc Ther. 2005;12:676–684. doi: 10.1583/05-1672.1. [DOI] [PubMed] [Google Scholar]