Vessel Patency and Associated Factors of Drug-Coated Balloon for Femoropopliteal Lesion

Background Although clinical trials have reported favorable outcomes after drug-coated balloon (DCB) therapy for femoropopliteal lesions, their real-world performance and predictors have not been well evaluated. This study aimed to elucidate 1-year freedom from restenosis and to explore the associated factors after a DCB for femoropopliteal lesions in clinical settings. Methods and Results This multicenter, prospective cohort registered 3165 de novo or restenotic femoropopliteallesions (mean lesion length, 13.5±9.3 cm; chronic total occlusion, 25.9%; severe calcification, 14.6%) that underwent successful DCB (Lutonix [24.2%] and IN.PACT Admiral [75.8%]) treatment between March 2018 and December 2019. Patency was assessed at 12±2 months. The primary outcome measure was 1-year freedom from restenosis and its associated factors. Bailout stenting was performed in 3.5% of patients. The postprocedural slow flow phenomenon was observed in 3.9% of patients. During a median follow-up of 14.2 months, 811 patients experienced restenosis. The Kaplan-Meier estimate of freedom from restenosis was 84.5% at 12 months (79.7% at 14 months). Focal, tandem, diffuse, and occlusive restenosis accounted for 37.4%, 9.8%, 18.9%, and 33.9%, respectively. Freedom from target lesion revascularization was 91.5% at 12 months. Risk factors independently associated with 1-year restenosis were a history of revascularization, smaller distal reference vessel diameter, severe calcification, chronic total occlusion, low-dose DCB, and residual stenosis. Conclusions The 1-year clinical outcomes after DCB use for femoropopliteal lesions in real-world practice was favorable. The additive risk factors were associated with a lower rate of freedom from restenosis

1-Year Results of the ZEPHYR Registry (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery) Predictors of Restenosis

AbstractObjectivesThis study sought to assess the rate and predictors of 1-year restenosis after drug-eluting stent implantation for femoropopliteal (FP) lesions in patients with peripheral arterial disease.BackgroundZilver PTX, a paclitaxel-eluting stent for FP lesions, provides superior outcomes to angioplasty and bare-metal stents in clinical trials. However, its real-world outcomes and the associated features remain unclear.MethodsThis was a prospective multicenter study enrolling 831 FP lesions (797 limbs, 690 patients) treated by Zilver PTX implantation. The primary endpoint was 1-year restenosis. Secondary endpoints included major adverse limb event and stent thrombosis.ResultsMean lesion length was 17 ± 10 cm. One-year restenosis, major adverse limb event, and stent thrombosis rates were 37%, 22%, and 2%, respectively. The generalized linear mixed model showed that lesion length ≥16 cm assessed by angiography and distal external elastic membrane area ≤27 mm2 and minimum stent area ≤12 mm2 assessed by intravascular ultrasound were independent risk factors for restenosis. One-year restenosis rates were 15% in cases with none of these risk factors and 50% in those with ≥2 risk factors.ConclusionsThe current study demonstrated 1-year real-world outcomes after drug-eluting stent treatment for FP lesions, including challenging ones in clinical practice. Lesion length, external elastic membrane area, and minimum stent area were independent predictors for restenosis. (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery—Prospective Multicenter Registry [ZEPHYR]; UMIN000008433

Polymer-Based Drug-Eluting Stent Treatment Extends the Time to Reintervention for Patients With Symptomatic Femoropopliteal Artery Disease: Clinical Evidence and Potential Economic Value

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were performed through 5 years. Mean time to first reintervention was calculated in post-hoc analysis for patients who underwent a clinically driven target lesion revascularization (CD-TLR) through 3 or 5 years following the index procedure. To simulate potential cost savings associated with differential CD-TLR burden over time, a cost-avoidance analysis using input parameters from IMPERIAL and US 100% Medicare standard analytical files was developed. Results: Among patients with a first CD-TLR through 3 years of follow-up, mean time to reintervention was 5.5 months longer (difference 166 days, 95% CI: 51, 282 days; p = 0.0058) for patients treated with Eluvia (n = 56) than for those treated with Zilver PTX (n = 30). Through the 5-year study follow-up period, CD-TLR rates were 29.3% (68/232) for Eluvia and 34.2% (39/114) for Zilver PTX (p = 0.3540) and mean time to first reintervention exceeded 2 years for patients treated with Eluvia at 737 days versus 645 days for the Zilver PTX group (difference 92 days, 95% CI: -85, 269 days; p = 0.3099). Simulated savings considering reinterventions occurring over 1 and 5 years following initial use of Eluvia over Zilver PTX were US $1,395,635 and US$1,531,795, respectively, when IMPERIAL CD-TLR rates were extrapolated to 1000 patients. Conclusion: IMPERIAL data suggest initial treatment with Eluvia extends the time patients spend without undergoing reintervention. This extension may be associated with cost savings in relevant time frames

TUFT1 interacts with RABGAP1 and regulates mTORC1 signaling

The mammalian target of rapamycin (mTOR) pathway is commonly activated in human cancers. The activity of mTOR complex 1 (mTORC1) signaling is supported by the intracellular positioning of cellular compartments and vesicle trafficking, regulated by Rab GTPases. Here we showed that tuftelin 1 (TUFT1) was involved in the activation of mTORC1 through modulating the Rab GTPase-regulated process. TUFT1 promoted tumor growth and metastasis. Consistently, the expression of TUFT1 correlated with poor prognosis in lung, breast and gastric cancers. Mechanistically, TUFT1 physically interacted with RABGAP1, thereby modulating intracellular lysosomal positioning and vesicular trafficking, and promoted mTORC1 signaling. In addition, expression of TUFT1 predicted sensitivity to perifosine, an alkylphospholipid that alters the composition of lipid rafts. Perifosine treatment altered the positioning and trafficking of cellular compartments to inhibit mTORC1. Our observations indicate that TUFT1 is a key regulator of the mTORC1 pathway and suggest that it is a promising therapeutic target or a biomarker for tumor progression.UTokyo FOCUS Articles掲載「がんの増殖・転移を促進する新規因子の同定 小胞輸送を標的とする新しいがん治療戦略への可能性」 https://www.u-tokyo.ac.jp/focus/ja/articles/z0508_00119.htmlUTokyo FOCUS Articles "Possible target for future cancer treatment : Deregulation of system to move molecules in the cell may promote tumor growth, metastasis" https://www.u-tokyo.ac.jp/focus/en/articles/z0508_00120.htm

Sodium-glucose co-transporter 2 inhibitor use in patients with diabetes mellitus undergoing endovascular therapy for symptomatic peripheral artery disease

Abstract Background This study aimed to reveal the prevalence of sodium-glucose co-transporter 2 (SGLT2) inhibitor treatment and its association with restenosis risk in patients with diabetes mellitus undergoing endovascular therapy for symptomatic peripheral artery disease. Methods We used the database of a multicenter prospective study registering patients with symptomatic peripheral artery disease undergoing femoropopliteal drug-coated balloon treatment in Japan. The current analysis included 1058 patients with diabetes mellitus free from end-stage renal disease. The association of clinical characteristics with SGLT2 inhibitor use was investigated using the logistic regression model. The propensity score matching was adopted to compare the primary patency, i.e., freedom from restenosis, after endovascular therapy between patients treated with and without a SGLT2 inhibitor. Results The proportion of SGLT2 inhibitor treatment at revascularization was 14.8% (95% confidence interval, 12.8–17.1%). Younger age, increased body mass index, and increased hemoglobin A1c levels were independently associated with SGLT2 inhibitor use (all P < 0.05). The proportion of SGLT2 inhibitor reached 38.2% (95% confidence interval, 25.4–52.3%) in patients with the three associated factors. The propensity score-matching analysis demonstrated that primary patency was not different between patients treated with a SGLT2 inhibitor and those without it (72.0% [95% confidence interval, 64.1–80.9%] versus 67.8% [62.7–73.3%] at 2 years; P = 0.45). Conclusions SGLT2 inhibitors were not rarely used in patients with diabetes mellitus who underwent femoropopliteal endovascular therapy using a drug coated balloon for symptomatic peripheral artery disease in real-world settings. SGLT2 inhibitor treatment was not associated with an increased risk of restenosis