Clinical Gains of Target Lesion Preparation in Patients Underwent Plasmonic Photothermal Therapy of Atherosclerosis: Adjudicated Subanalysis of NANOM-FIM Trial

Background
The aim of the study was to examine the role of the lesion preparation for the long-term clinical outcomes and patterns of arterial remodelling in patients with plasmonic photothermal therapy (PPTT) of atherosclerosis.

Methods
This is a subanalysis of the 5-year long-term clinical outcomes in three subsets of the intention-to-treat population (n=180) of NANOM-FIM trial (NCT01270139). The first subset was pre-treated with stenting proximal to the site of nano-intervention (n=13). Subjects in the second subset have undergone drug-coated balloon pre-dilation (n=20). Lesions of the third subset were not prepared (n=147).

Results
A 5-year major adverse cardiovascular events (MACE)-free survival achieved 39/60 (65.0%), 32/60 (53.3%), and 34/60 (56.7%) in groups respectively (p<0.05). Non-inferiority of patient-oriented composite endpoint (POCE) with the certain clinical benefits of the lesion preparation with the proximal stenting was demonstrated if compared with no preparation (38.5% vs 77.0%; OR, 0.19, 95%CI: 0.05, 0.63, p=0.006). The similar trend of POCE was confirmed for proximal stenting and nanointervention vs conventional stenting (38.5% vs 83.3%; OR, 0.13, 95%CI: 0.03, 0.46, p=0.002), pre-dilation vs no preparation (50.0% vs 77.0%; OR, 0.3, 95%CI: 0.11, 0.82, p=0.01), pre-dilation vs conventional stenting (50.0% vs 83.3%; OR, 0.2, 95%CI: 0.07, 0.61, p=0.004). TLF achieved 30.8%, 45.0%, and 32.2% in subsets respectively (p>0.05) if compare with 43.3% in the group with conventional stenting (p>0.05). The polynomial regression analysis of a degree of six (R2=0.774) confirmed the existence of the Glagov threshold or a window of the external elastic membraneenlargement between 21% and 44% of per cent atheroma volume (PAV; plaque burden, PB) in patients with a 30.7% decrease of PAV at 12-month follow-up. The adjusted linear regression analysis (in patients with PB between 37.8% and 70.8%) revealed moderate direct positive correlation (R2=0.5868) between PB and MACE.

Conclusions
Strategy with the lesion preparation proves the optimal level of safety demonstrating acceptable survival profile at the long-term follow-up in patients who underwent PPTT.