Paclitaxel-Coated Zilver PTX Drug-Eluting Stent Treatment Does Not Result in Increased Long-Term All-Cause Mortality Compared to Uncoated Devices

Abstract

Purpose Patient-level data from two large studies of the Zilver PTX drug-eluting stent (DES) with long-term follow-up and concurrent non-drug comparator groups were analyzed to determine whether there was an increased mortality risk due to paclitaxel. Methods Data from the Zilver PTX randomized controlled trial (RCT) and Zilver PTX and bare metal stent (BMS) Japan post-market surveillance studies were analyzed.Five-year follow-up is complete in both DES studies; follow-up for the BMS study was limited to 3 years and is complete. Kaplan-Meier analyses assessed mortality. A Cox proportional hazards model identified significant factors related to mortality. Results In the RCT, there were 336 patients treated with the DES and 143 patients treated with percutaneous transluminal angioplasty (PTA) or BMS. In Japan, there were 904 DES patients and 190 BMS patients. There was no difference in all-cause mortality for the DES compared to PTA/BMS in the RCT (19.1% DES versus 17.1% PTA/ BMS through 5 years, p = 0.60) or Japan (15.8% DES versus 15.3% BMS through 3 years, p = 0.89). Cox proportional hazard models revealed that age, tissue loss, and congestive heart failure were significantly associated with mortality in the RCT, and critical limb ischemia, age, renal failure, and gender were significantly associated with mortality in Japan (all p \ 0.05). Neither treatment with Zilver PTX (p = 0.46 RCT, p = 0.49 Japan) nor paclitaxel dose (p = 0.86 RCT, p = 0.07 Japan) was associated with mortality. Conclusion Analyses of the Zilver PTX patient-level data demonstrated no increase in long-term all-cause mortality. Level of Evidence Zilver PTX RCT: Level 1, randomized controlled trial; Japan PMS studies: Level 3, post-market surveillance study.

Position Paper on the Diagnosis and Treatment of Peripheral Arterial Disease (PAD) in People with Diabetes Mellitus

“…Even after repeated use of paclitaxel-coated devices in the course of the disease, there was no correlation between paclitaxel and mortality. Similar results have been obtained in further published studies [60,61]. In patients with recurrent restenosis, complex stenosis, critical limb ischemia or multiple concomitant diseases who are already at an increased mortality risk and for whom every reintervention increases this risk, the use of medication-coated balloons should be carefully considered.…”

Evaluation of mortality following paclitaxel drug‐coated stent angioplasty of femoropopliteal lesions in real world

“…The unique aspect of the present evaluation is that the follow-up interventions were taken into account and a total dose of paclitaxel was calculated In addition, a large US nationwide centers for medicare and medicaid Services (CMS) claims data analysis showed no increased all-cause mortality in a real world setting following femoropopliteal interventions with drug-coated devices. 22 The mortality rates in the IMPERIAL and MAJESTIC study 19,20 and the results of Dake et al 18 following DES angioplasty are comparable to the described mortality rates of medically treated symptomatic PAOD patients. 23 The -compared to the present real-world study lower mortality rates -in the meta-analysis 6 and the aforementioned studies can be explained by the patient selection bias, which is due to the study protocol.…”

“…In this analysis the all-cause mortality rates for the DES compared to PTA/BMS in the RCT (19.1% DES versus 17.1% PTA/BMS through 5 years, p = .60) or Japan (15.8% DES versus 15.3% BMS through 3 years, p = .89) do not differ. 18 T A B L E 1 Baseline characteristics entire cohort According to Katsanos et al, 6 there is a significant correlation between the paclitaxel dose and the absolute mortality risk. There was a 0.4 ± 0.1 increased risk of death for every milligram of paclitaxel per year.…”

Paclitaxel exposure: Long‐term safety and effectiveness of a drug‐coated balloon for claudication in pooled randomized trials

“…The strength of these analyses is the power to detect small differences as well as the completeness of an endpoint such as mortality in these types of datasets that do not rely on in person follow‐up. Similarly, patient‐level independent analyses have also demonstrated the safety of drug‐coated devices 28‐31 . Recent efforts from independent investigators, societies and regulatory bodies are crucial for resolving the mortality signal issue.…”