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Percutaneous Below-The-Knee Stent Percutaneous Below-The-Knee Stent

Implantation Among 468 Patients With Implantation Among 468 Patients With

Critical Limb Ischemia: Pooled Analysis Critical Limb Ischemia: Pooled Analysis

And Comparison Of Drug-Eluting And Comparison Of Drug-Eluting

Versus Bare-Metal StentsVersus Bare-Metal Stents

G. Biondi-Zoccai1, G. Sangiorgi2, M. Fusaro3, C. Moretti1, F. Sciuto1,

P. Omede1, M. Lotrionte4, P. Agostoni5, A. Abbate6, I. Sheiban1

1University of Turin, Turin, Italy (gbiondizoccai@gmail.com); 2Emo Centro Cuore Columbus, Milano,Italy; 3San Pellegrino Hospital, Castiglione delle Stiviere, Italy;

4Catholic University, Rome, Italy; 5AZ Middelheim, Antwerp, Belgium; 6Virginia Commonwealth University, Virginia, USA;

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BACKGROUND

• Percutaneous transluminal angioplasty (PTA) of below-the-knee (BTK) arterial occlusive disease has been recently proved equivalent to bypass surgery in the management of patients with chronic critical limb ischemia (CLI).

• However, results of balloon-only PTA are suboptimal in many patients, with a rate of flow-limiting dissections, acute recoil or early restenosis reaching up to 40-50%.

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BACKGROUND AND AIM

• BTK stenting on top of PTA has been proposed as a potential improvement of percutaneous revascularization results, yet data are still inconclusive.

• We thus aimed to perform a systematic and quantitative review of clinical results of BTK stenting in patients with CLI.

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OBJECTIVES

• To perform a systematic review of the

outcomes of BTK stenting in patients with

CLI.

• To pool major outcomes with meta-

analytic techniques and compare indirectly

different devices.

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METHODS

• PubMed and other databases were systematically searched for pertinent clinical studies published up to December 2007.

• Studies reporting on at least 5 patients treated with BTK stenting for CLI and at least 1-month follow-up were included. acts).

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METHODS

• Data were abstracted and pooled to generate risk estimates (with 95% confidence intervals) by means of random-effect methods with generic inverse-variance weighting, with RevMan 4.2 (Cochrane Collaboration).

• Interaction tests were computed to compare different stent types, exploiting chi-squared tests for heterogeneity between subgroups.

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METHODS

• We focused on the following end-points:– binary angiographic restenosis (BAR),

defined as in-stent diameter stenosis exceeding 50%,

– primary patency, defined as patency of the treated segment or vessel irrespective of residual stenosis,

– limb salvage, defined as freedom from above-the-ankle (ie major) amputation.

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REVIEW PROFILE

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INCLUDED STUDIESStudy Pts with stents Design Test device Control device

Bosier et al (2005) 20 Registry Balloon-expandable bioabsorbable stent -

Bosiers et al (2006) 18 Registry Sirolimus-eluting stent -

Bosiers et al (2007) 47 Registry Self-expandable BMS -

Commeau et al (2006) 30 Registry Sirolimus-eluting stent -

Feiring et al (2004) 82 Registry Balloon-expandable BMS -

Feiring et al (2007) 5 Case series Sirolimus-eluting stent -

Kickuth et al (2007) 35 Registry Self-expandable BMS -

Morgan et al (2005) 6 Case series Balloon-expandable BMS -

Rand et al (2006) 24 RCT Balloon-expandable BMS PTA

Scheinert et al (2006) 60 Non-RCT Sirolimus-eluting stent Balloon-expandable BMS

Siablis et al (2005) 29 Non-RCT Sirolimus-eluting stent

Siablis et al (2007) 29 Registry Paclitaxel-eluting stent -

Tepe et al (2007) 18 Registry Self-expandable BMS -

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RESULTS• We retrieved 18 non-randomized studies including

468 patients: 197 treated with balloon-expandable bare-metal stents (BMS), 100 with self-expandable BMS, 151 with drug-eluting stents (DES), and 20 with absorbable metal stents.

• After a median of 11 months, risk of BAR in the whole cohort was 28.0% (95% confidence interval 12.0-44.1%), primary patency was obtained in 73.1% (58.0-88.3%) and limb salvage was achieved in 95.7% (93.4-98.1%).

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RESULTS

• Stratified analysis according to stent type showed that DES were significantly superior to balloon-expandable BMS in preventing BAR (6.3% [0-15.5%] vs 43.3% [20.8-65.8%], p<0.0001) and increasing primary patency (89.6% [81.2-88.3%] vs 59.6% [25.9-93.4%], p<0.001).

• Yet they yielded similar rates of limb salvage (95.9% [91.6-100%] vs 95.2% [91.7-98.7%], p=0.58).

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RESULTS

• DES also appeared associated with a lower risk of BAR in comparison to self-expandable BMS (6.3% [0-15.5%] vs 20.4% [8.8-32.0%], p=0.048).

• Conversely, DES yielded, in comparison to self-expandable BMS, similar rates of primary patency (89.6% [81.2-88.3%] vs 79.0% [71.1-87.0%]) and limb salvage (95.9% [91.6-100%] vs 96.8% [91.8-100%], both p>0.05).

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RISK OF BINARY RESTENOSISStudy risk estimate (%) (random)or sub-category risk estimate (%) (SE) 95% CI

01 Balloon-expandable bare-metal stentSiablis (2005) 55.3000 (9.2000)Rand (2006) 79.7000 (8.2000)Scheinert (2006) 30.0000 (8.4000)Cioppa (2007) 28.6000 (11.7000)

Subtotal (95% CI)Test for heterogeneity: Chi² = 22.38, df = 3 (P < 0.0001), I² = 86.6%Test for overall effect: Z = 3.88 (P = 0.0001)

02 Self-expandable bare-metal stentBosiers (2007) 20.4000 (5.9000)

Subtotal (95% CI)Test for heterogeneity: not applicableTest for overall effect: Z = 3.46 (P = 0.0005)

03 Absorbable metal stentSubtotal (95% CI)Test for heterogeneity: not applicableTest for overall effect: not applicable

04 Drug-eluting stentSiablis (2005) 4.0000 (4.3000)Scheinert (2006) 0.0000 (5.6000)Siablis (2007) 18.3000 (7.2000)

Subtotal (95% CI)Test for heterogeneity: Chi² = 4.25, df = 2 (P = 0.12), I² = 52.9%Test for overall effect: Z = 1.34 (P = 0.18)

Total (95% CI)Test for heterogeneity: Chi² = 96.34, df = 7 (P < 0.001), I² = 92.7%

Test for overall effect: Z = 3.20 (P = 0.001)

0 50 100

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RATE OF PRIMARY PATENCYStudy risk estimate (%) (random)or sub-category risk estimate (%) (SE) 95% CI

01 Balloon-expandable bare-metal stentMorgan (2005) 47.0000 (20.4000)Siablis (2005) 40.5000 (10.7000)Rand (2006) 83.7000 (7.5000)Scheinert (2006) 13.0000 (6.1000)Cioppa (2007) 71.4000 (11.7000)

Subtotal (95% CI)Test for heterogeneity: Chi² = 59.42, df = 4 (P < 0.00001), I² = 93.3%Test for overall effect: Z = 3.07 (P = 0.002)

02 Self-expandable bare-metal stentBosiers (2007) 76.3000 (6.2000)Kickuth (2007) 82.0000 (6.5000)Tepe (2007) 79.0000 (9.6000)

Subtotal (95% CI)Test for heterogeneity: Chi² = 0.40, df = 2 (P = 0.82), I² = 0%Test for overall effect: Z = 19.44 (P < 0.00001)

03 Absorbable metal stentBosiers (2005) 73.3000 (9.9000)

Subtotal (95% CI)Test for heterogeneity: not applicableTest for overall effect: Z = 7.40 (P < 0.00001)

04 Drug-eluting stentSiablis (2005) 86.4000 (6.4000)Siablis (2007) 90.0000 (5.6000)Grant (2008) 100.0000 (12.5000)

Subtotal (95% CI)Test for heterogeneity: Chi² = 0.95, df = 2 (P = 0.62), I² = 0%Test for overall effect: Z = 22.44 (P < 0.00001)

Total (95% CI)

Test for overall effect: Z = 8.80 (P < 0.00001)

0 50 100

Test for heterogeneity: Chi² = 129.81, df = 11 (P < 0.001), I² = 91.5%

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RATE OF LIMB SALVAGEStudy risk estimate (%) (random)or sub-category risk estimate (%) (SE) 95% CI

01 Balloon-expandable bare-metal stentFeiring (2004) 96.0000 (2.2000)Morgan (2005) 66.0000 (19.3000)Siablis (2005) 100.0000 (7.7000)Rand (2006) 92.0000 (5.5000)Scheinert (2006) 90.0000 (5.5000)Cioppa (2007) 100.0000 (10.3000)

Subtotal (95% CI)Test for heterogeneity: Chi² = 4.25, df = 5 (P = 0.51), I² = 0%Test for overall effect: Z = 52.17 (P < 0.00001)

02 Self-expandable bare-metal stentBosiers (2007) 95.9000 (2.9000)Kickuth (2007) 100.0000 (5.5000)

Subtotal (95% CI)Test for heterogeneity: Chi² = 0.43, df = 1 (P = 0.51), I² = 0%Test for overall effect: Z = 37.73 (P < 0.00001)

03 Absorbable metal stentBosiers (2005) 94.7000 (5.0000)

Subtotal (95% CI)Test for heterogeneity: not applicableTest for overall effect: Z = 18.94 (P < 0.00001)

04 Drug-eluting stentSiablis (2005) 96.0000 (3.6000)Commeau (2006) 100.0000 (5.6000)Scheinert (2006) 100.0000 (5.6000)Bosiers (2007) 94.1000 (5.6000)Feiring (2007) 100.0000 (22.1000)Siablis (2007) 88.5000 (5.9000)

Subtotal (95% CI)Test for heterogeneity: Chi² = 2.78, df = 5 (P = 0.73), I² = 0%Test for overall effect: Z = 43.29 (P < 0.00001)

Total (95% CI)Test for heterogeneity: Chi² = 7.85, df = 14 (P = 0.90), I² = 0%Test for overall effect: Z = 79.86 (P < 0.00001)

50 75 100

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CONCLUSIONS

• This updated and comprehensive quantitative

analysis shows that percutaneous BTK

stenting is associated with favorable clinical

results in patients with CLI.

• Notwithstanding the limitations of primary

studies, DES appear superior to both

balloon-expandable and self-expandable

BMS in reducing the risk of restenosis and/or

improving patency rates.