2021 Volume 85 Issue 12 Pages 2146-2148
Recently, endovascular treatment devices for peripheral artery disease (PAD) have been developed. In addition to bare-metal stents, drug-eluting stents and drug-coated balloons are currently approved for use in patients with PAD as well as in those with coronary artery disease. Although medical treatment and exercise are recommended first in guidelines in Europe and the United States,1,2 peripheral revascularization therapy using these catheter devices has increased and has become a common procedure.3 Several studies have revealed that endovascular approaches for femoropopliteal disease reduce symptoms, improve quality of life (QOL), and have a lower incidence of periprocedural complications,4 indicating that endovascular approaches may be effective and safe for treatment of symptomatic PAD.
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Effects of Paclitaxel-Containing Devices on Mortality in Previous StudiesBased on the results of trials using paclitaxel-containing devices (PTXDs),5–9 endovascular treatment with PTXD has often been performed as the first-line approach in patients with symptomatic PAD.1,2 However, several reports and a meta-analysis have indicated that PTXD use was significantly associated with a higher incidence of all-cause mortality.10,11 In contrast, there are several reports of opposite results, according to which PTXD use does not increase the mortality risk in product-specific, patient-level analyses.12–14 Therefore, it remains uncertain whether PTXD use has a favorable or negative effect on mortality in patients with PAD who undergo endovascular treatment with PTXDs, especially among Japanese patients.
Effects of PTXDs on Mortality in Japanese Patients With PADRecently, Nakamura et al focused on this important unsolved query in a manuscript published in the Circulation Journal.15 In this study, the authors analyzed the effect of PTXDs on 5-year all-cause mortality in 2,581 Japanese patients with PAD using the data from 12 pivotal studies conducted in Japan: 6 single-arm studies, including 5 post-marketing surveillance studies, and 6 randomized controlled trials. The endovascular treatment devices for PAD used in this study are listed in Table. They demonstrated that the mortality in patients with PAD treated with PTXDs was significantly lower than in those not treated with PTXDs in the crude data analysis (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.67–0.97; P=0.023), whereas it was no longer significantly different between the groups after adjusting for several confounding factors (HR, 1.01; 95% CI, 0.39–2.58; P=0.987) (Figure). The challenges in clarifying the unsolved question in Japanese patients with PAD appears extremely valuable, even though the resulting effect on mortality was not shown to be favorable when PTXDs are used.
Devices | Vendor |
---|---|
Paclitaxel-containing device (PTXD) | |
Drug-eluting stent | |
Zilver PTX Drug-Eluting Peripheral Stent | Cook Medical, Bloomington, IN, USA |
Eluvia Drug-Eluting Vascular Stent System | Boston Scientific, Marlborough, MA, USA |
Drug-coated balloon | |
IN.PACT Admiral | Medtronic, Santa Rosa, CA, USA |
Lutonix Paclitaxel-Coated Balloon | Bard/Becton Dickinson, Covington, GA, USA |
Non-PTXD | |
Bare-metal stent | |
Misago | Terumo, Tokyo, Japan |
Smart Vascular Stent System | Cordis, Cardinal Health, Santa Clara, CA, USA |
Life Stent | Bard/Becton Dickinson, Covington, GA, USA |
Zilver Flex Vascular Self-Expanding Stent | Cook Medical, Bloomington, IN, USA |
Compiled from information in the study by Nakamura et al.15
Effect of paclitaxel-containing devices on mortality. HR, hazard ratio; CI, confidence interval; PTXD, paclitaxel-containing device. *Adjusted for study, age, sex, hypertension, hyperlipidemia, diabetes mellitus, smoking, hemodialysis, and Rutherford category >3. **Adjusted for age, sex, hypertension, hyperlipidemia, diabetes mellitus, and Rutherford category >3. (Reproduced from Nakamura et al.15)
In the study by Nakamura et al, the authors also searched for risk factors for all-cause mortality using the multivariate Cox proportional hazards model.15 Consequently, age ≥75 and 65–74 years (vs. <65 years), male sex, hyperlipidemia, type 2 diabetes, hemodialysis, and the clinical stage of PAD evaluated based on the Rutherford category of >3 were significantly associated with 5-year mortality. However, PTXD use was not found to be an independent risk factor for all-cause mortality (HR, 1.01; 95% CI, 0.39–2.58; P=0.987). In other words, the use of PTXD did not have a negative effect on 5-year mortality.
Should We Use PTXDs for Endovascular Treatment in Patients With PAD?Since the study by Nakamura et al,15 could not reveal a favorable effect of PTXD use on mortality; the results may warn physicians to avoid the use of PTXDs unquestioningly. However, the purpose of endovascular approaches using catheter devices for the treatment of PAD is generally to increase local vascular flow, relieve patient symptoms, and reduce restenosis and the target lesion revascularization (TLR) rate, resulting in improved patient activities of daily living and QOL, rather than to reduce mortality. According to the results of this study,15 novel questions might have been raised regarding the usefulness of the PTXDs in an actual clinical setting and whether PTXDs should be used for endovascular treatment in patients with PAD. The authors clearly elaborated on these questions in the clinical implications section of the manuscript;15 that is, this study will alleviate the concerns of patients and physicians about the long-term safety of PTXDs in daily practice. Given the apparent clinical benefit of PTXDs in reducing restenosis and the TLR after endovascular treatment, PTXDs should be offered to patients with intermittent claudication and chronic limb-threatening ischemia to improve their symptoms and QOL.
Conclusive RemarksAlthough PTXDs are not a useful tool to reduce mortality in patients with PAD, they may be considered useful when patient symptoms and QOL will be expected to improve. PTXD use does not affect mortality in Japanese patients with PAD.
E.K. has received remuneration from Daiichi-Sankyo and Ono Pharmaceutical.