Vessel Calcification as a Risk Factor for In-Stent Restenosis in Complex Femoropopliteal Lesions After Zilver PTX Paclitaxel-Coated Stent Placement

Abstract

Purpose: To evaluate the effect of vessel calcification on in-stent restenosis (ISR) after drug-coated stent (DCS) placement in the femoropopliteal segment. Materials and Methods: A retrospective multicenter study was undertaken involving 220 consecutive symptomatic patients (mean age 73.1±8.3 years; 175 men) with femoropopliteal lesions in 230 limbs treated with the Zilver PTX DCS and having duplex surveillance after the endovascular procedures. Mean lesion length was 16.4±9.8 cm (range 2–40); there were 104 (45.2%) total occlusions and 68 (29.6%) in-stent restenoses (ISR). Twenty (8.7%) vessels had no runoff. The majority of lesions (148, 64.3%) were calcified according to the peripheral arterial calcium scoring system (PACSS). Primary patency was evaluated by duplex. Lesions were classified as either PACSS 0–2 (none or unilateral wall calcification) or PACSS 3 and 4 (bilateral wall calcification). Multivariate analysis was performed to identify variables associated with ISR; the results are given as the hazard ratio (HR) and 95% confidence interval (CI). Results: The 1-, 2-, and 5-year primary patency and freedom from clinically-driven target lesion revascularization estimates were 75.9%, 63.6%, and 45.0%, and 84.7%, 73.7%, and 54.2%, respectively. Major amputations were performed on 4 limbs during follow-up. In multivariate analysis, vessel calcification (adjusted HR 1.718, 95% CI 1.035 to 2.851, p=0.036) was significantly correlated with the occurrence of ISR, along with lesion length (adjusted HR 1.041, 95% CI 1.013 to 1.070, p=0.003), and cilostazol administration (adjusted HR 0.476, 95% CI 0.259 to 0.876, p=0.017). Conclusion: This study suggested that bilateral vessel wall calcification was an independent risk factor for ISR in complex femoropopliteal lesions after Zilver PTX DCS placement, along with lesion length; cilostazol administration had a protective effect.

Commentary: Is Calcification Still an Unsolved Issue in the Drug-Solution Era?

“…In the prospective, multicenter ZEPHYR registry, 2,3 we demonstrated that lesion length 2 and the lack of cilostazol administration 3 were important risk factors for 1-year restenosis. Ichihashi et al 1 confirmed in their study that these factors increased the longer-term risk of patency loss, externally validating the clinical importance of the Zilver PTX in a different cohort. On the other hand, the clinical impact of vessel diameter seemed somewhat different between the ZEPHYR study and theirs.…”

“…Our ZEPHYR study showed that vessel diameters <4.5 mm, but not 4.5–6.0 mm, increased the risk of restenosis when compared to ≥6.0 mm. Ichihashi et al 1 reported a trend in the inverse relationship between vessel diameter and risk of restenosis (hazard ratio 0.8 per 1-mm increment), but the relationship did not reach statistical significance (p=0.138). The failure to detect a statistically significant difference might have come from the assignment of vessel diameter as a continuous variable or a small sample size (230 limbs).…”

“…It remains a hot topic in the endovascular field whether the device will guarantee patency to all types of lesions or if some specifically challenging lesions will still be vulnerable to restenosis. In the October 2019 issue of the JEVT , Ichihashi and colleagues 1 reported long-term outcomes and factors associated with loss of patency after femoropopliteal implantation of Zilver PTX (Cook Medical, Bloomington, IN, USA), a classical and therefore clinically important drug-coated stent.…”

“…The ZEPHYR study demonstrated that the presence or absence of calcification was not associated with restenosis risk. However, the relationship of grades of calcification severity to the restenosis risk remained undiscovered until Ichihashi et al 1 conducted their study utilizing the peripheral arterial calcium scoring system (PACSS) classification 4 to allow more detailed assessment of calcification. They found that bilateral calcification was a risk factor for restenosis.…”

New Innovations and Devices in the Management of Chronic Limb-Threatening Ischemia

“…76 Additionally, calcification prevents the transfer of drugs to the arterial wall during DCB angioplasty and is a risk factor for worse outcomes. 77–79 Intravascular lithoplasty (IVL) is a novel method of managing vascular calcification using acoustic shock waves, similar to lithotripsy which has been used to treat nephrolithiasis. The Shockwave Medical Peripheral Lithoplasty System (Shockwave Medical, Fremont, CA, USA) generates pulsatile mechanical energy that disrupts calcium while minimizing vessel trauma and allows low-pressure balloon angioplasty.…”