Patient-level Pooled Meta-analysis of Patients With Chronic Limb-threatening Ischemia and Complex Femoropopliteal Lesions Treated With the BioMimics 3D Stent

The pooled analysis demonstrated good and durable results through 2 years across all subgroups, despite those subgroups typically being associated with poorer clinical outcomes. Patients with CLTI in this study had higher rates of TLR and target limb amputation, which is to be expected considering that these patients had more diabetes, nonhealing wounds, and complex lesions with a higher rate of CTO and degree of calcification compared with patients with IC, a phenomenon well-known in the literature.^7,20 Similarly, patients with CTO and TASC C/D lesions had more TLRs but no difference in major amputations. There was no difference in outcomes between PACSS 3,4 and PACSS 0-2 lesions. 

CLTI represents an advanced stage of atherosclerosis and is in itself a predictor of poor outcomes, particularly with higher Rutherford classes.^20,22-24 Systemic arterial calcification contributes to arterial stiffening, hypertension, heart failure, and pulse-pressure-related organ damage,²⁵ and other vascular beds are nearly always affected.^22,25 Similarly, diabetes mellitus, renal failure, CTO, calcification, and lack of patent outflow vessels are predictors for poor outcomes.^{6,18,23,25-28}

Mimetic stents have a higher flexibility with a higher resistance to compression and resistance to fracture, which is particularly useful in the femoropopliteal bed with its high mechanical stresses of compression and twisting.²¹ The BioMimics 3D stent is unique in this category in that the helical centerline design is intended to promote swirling flow, thereby increasing wall shear stress to ultimately reduce intimal hyperplasia.^12,18,21 In addition, it has a transition zone with reduced outward radial force at both ends of the stent to avoid flow disturbances between the stented and not-stented regions to minimize the risk of edge restenosis.¹² These features could be especially relevant in complex lesions such as CTOs, severe calcification, and long TASC C/D lesions, and in patients with CLTI.

In the current analysis, patients with CLTI had more severe calcification, a higher rate of CTO, and longer lesions; as expected, these more complex lesions were more frequently associated with CLTI compared with IC. Thus, while the lower freedom from TLR in patients with CLTI or with CTO or TASC C/D lesions is expected, the outcomes are still good, ie, the 12-month data in the CLTI group are in alignment with the Superficial Femoral Artery-Popliteal EvidencE Development (SPEED) objective performance goals (OPG) of 79% for superficial femoral artery lesions, which is based on the Society for Vascular Surgery Vascular Quality Initiative (VQI) Peripheral Vascular Intervention registry data.²⁹ It is surprising that there was no difference in outcomes related to lesion calcification severity. From 12 to 24 months, the TLR curves start to flatten, possibly attributable to the 3-dimensional helical centerline design of the stent with its enhanced swirling flow and wall shear stress.^12-14 Pooled 3-year data are not available as the MIMICS RCT was followed for 2 years only, but the 3-year outcomes from MIMICS-3D report a 3-year freedom from TLR of 73.8% in patients with CLTI, which was not significantly different to patients with IC, offsetting the differences in baseline characteristics.¹⁵ Notably, Rutherford class 5 and 6 patients were excluded in the MIMICS RCT and MIMICS-2 studies, which could have introduced a bias in the pooled analysis.

Data of stent usage in complex femoropopliteal lesions in similar populations are scarce, but the outcomes of the subgroups compare well across a variety of devices to the data in the available literature (Supplemental Table 7). Twelve- and 24-month freedom from TLR in CTO lesions were 82.6% and 80.6% vs 83.5% and 81.8% in a population treated with the Supera stent (Abbott Vascular),5 however, this study excluded lesions with severe PACSS 2 and 4 calcification and calcification of 270 degrees or more in vessel circumference; 81% freedom from TLR at 12 months was described in a series of patients with CTO treated with bare metal stents (BMS), drug-eluting stents (DES), and covered stents.³⁰ In patients with PACSS 3,4 lesions, the 24-month freedom from TLR in this analysis was 81.5% compared with 59.8% for PACSS 3 and 62.3% for PACSS 4 patients treated with either BMS or DES.²⁸ For patients with TASC C/D lesions, in our meta-analysis we observed a freedom from TLR of 85.7% at 12 months compared with 64% to 85.4% for the Zilver PTX DES (Cook Medical) in a subgroup analyses of the STELLA-PTX trial and the Zilver PTX single arm study,^31,32  and compared with 70.5% to 80.3% reported in trials with BMS.^33-35 At 24 months in our meta-analysis, freedom from TLR was 81.5% compared with 73% for conventional nitinol stents,³⁵ and 81.8% and 86.9% in 2 small series of 50 patients treated with the Supera stent.^5,36 The good outcomes in TASC C/D lesions are particularly relevant as there is an increased use of endovascular therapy in these lesions,³⁷ and patients with a high TASC class are more severely diseased and at increased risk when treated with surgery.¹ Furthermore, a recent study demonstrated cost-effectiveness through 3 years of percutaneous transluminal stenting with optional stenting over bypass surgery in TASC B and C lesions.³⁸

Freedom from major amputation through 24 months was 93.7% in patients with CLTI vs 100% in patients with IC. It is acknowledged that there should be no anticipated major amputation at 24 months for the IC group. No patient with IC had a major amputation, so the major amputations in the other subgroups were in patients with CLTI. The higher rate in patients with CLTI is not surprising considering that, of the 138 patients with CLTI, 61% were Rutherford 5 or 6, and these patients had more comorbidities and more complex lesions with fewer patent infrapopliteal vessels. 

Importantly, no major amputation occurred beyond 1 year. This rate compares favorably to published literature for femoropopliteal stents; it is well above the SPEED OPG of 90% at 12 months for stents in patients with CLTI with superficial femoral artery lesions,²⁹ or the VQI data of 89.2% for freedom from amputation for paclitaxel-coated devices at 12 months and 86.5% for non-paclitaxel-coated devices in patients with CLTI at 18 months.³⁹ For the remaining high-risk subgroups, freedom from major amputation at 24 months was close to 100%, ranging from 97.9% to 98.5%. 

As stated above, the helical centerline stent has high flexibility with a high resistance to compression and stent fractures. Accordingly, only 4 stent fractures in 828 patients were reported, of which only 3 were confirmed by the clinical events committee. While calcification is a predictor for stent fractures,²⁶ stent fractures were absent in PACSS 3,4 lesions. Importantly, while long and TASC C/D lesions are associated with a high risk of stent fractures,³⁷ in this pooled analysis with a substantial number of patients with x-ray analysis, the 24-month stent fracture rate in TASC C/D lesions was only 1.2%. This is significantly lower than the 9.0% to 17.8% fracture rate at 12 months for straight, slotted-tube nitinol BMS.^32,33,37 A study of the Supera stent reported 0% stent fracture at 24 months; however, it only included 52 patients with TASC C/D lesions, and calcification above 5 cm in vessel length or 270-degree circumference was excluded.⁵

Overall, treatment with the helical centerline stent across the 3 studies led to a sustained high clinical improvement across all subgroups with a minimum improvement of at least 1 Rutherford class in 85% of TASC C/D lesions and the highest clinical improvement (97.3%) in patients with CLTI.