Global Medical Device Clinical Trials Involving Both the United States and Japan: Key Considerations for Development, Regulatory Approval, and Conduct.

As medical device development becomes increasingly global, the opportunities and potential advantages offered by international clinical trial and regulatory approval strategies are also growing. In particular, medical device clinical trials involving sites in both the United States and Japan and intended to support marketing in both countries may warrant particular consideration, given the similarities in their regulatory systems, patients and clinical practice patterns, and market sizes. Since 2003, the US-Japan Harmonization By Doing (HBD) initiative has been focused on identifying and addressing clinical and regulatory barriers to medical devices access in both countries via collaboration between governmental, academic, and industry stakeholders. Through the efforts of HBD participants, US-Japanese clinical trials have been conducted and the resulting data have supported regulatory approval for marketing in both countries. Based on these experiences, this paper outlines some of the key factors to consider when developing a global clinical trial involving US and Japanese participation. These considerations include the mechanisms for consultation with regulatory authorities on clinical trial strategies, the regulatory framework for clinical trial notification and approval, recruitment and conduct of clinical sites, and lessons learned from specific US-Japanese clinical trial experiences. The goal of this paper is to promote global access to promising medical technologies by assisting potential clinical trial sponsors in understanding when an international strategy may be appropriate and successful.

First peripheral drug-eluting stent clinical results from China: 1-year outcomes of the Zilver PTX China study.

Purpose: The benefit of using the Zilver PTX drug-eluting stent (DES) in superficial femoral artery (SFA) lesions has been demonstrated in multiple clinical studies. This prospective, multicenter study evaluated the 1-year safety and effectiveness of the DES for the treatment of femoropopliteal lesions in a Chinese patient population. Methods: Patients with a single de novo or restenotic SFA lesion ≤140 mm and a Rutherford classification of 2 to 4 were treated with the DES. The primary endpoint was primary patency assessed by duplex ultrasound at 1-year. Secondary endpoints included adverse events, event-free survival (EFS), and freedom from target lesion revascularization (TLR). Clinical outcomes included Rutherford classification, ankle-brachial index (ABI), and the walking impairment questionnaire (WIQ). Results: In this study, 178 patients with symptomatic peripheral artery disease were enrolled at nine institutions in China. The average lesion length was 79.0 ± 48.6 mm (range 14.8-245.4 mm) and 50.0% of lesions were total occlusions. The 1-year primary patency rate was 81.9%. Covariate analysis revealed that lesion length (p < 0.01) was the only significant factor for patency. No paclitaxel-related adverse events or amputations were reported. The 1-year rate for EFS was 94.9% and freedom from TLR was 95.5%. Through 1-year, treatment with the DES resulted in statistically significant improvement in ABI and WIQ scores compared with pre-procedure (p < 0.001). Clinical improvement of at least 1 Rutherford class was achieved in 142 of 174 patients (81.6%). Conclusion: This study showed promising short-term results for the treatment of SFA lesions with Zilver PTX DES in Chinese patients. Unique identifier: ClinicalTrials.gov, identifier: NCT02171962.

Navigating the Regulatory Pathway for Medical Devices-a Conversation with the FDA, Clinicians, Researchers, and Industry Experts.

Successful translation of new and innovative medical products from concept to clinical use is a complex endeavor that requires understanding and overcoming a variety of challenges. In particular, regulatory pathways and processes are often unfamiliar to academic researchers and start-ups, and even larger companies. Growing evidence suggests that the successful translation of ideas to products requires collaboration and cooperation between clinicians, researchers, industry, and regulators. A multi-stakeholder group developed this review to enhance regulatory knowledge and thereby improve translational success for medical devices. Communication between and among stakeholders is identified as a critical factor. Current regulatory programs and processes to facilitate communication and translation of innovative devices are described and discussed. Case studies are used to highlight the importance of flexibility when considering evidence requirements. We provide a review of emerging strategies, opportunities, and best practices to increase the regulatory knowledge base and facilitate medical device translation by all stakeholders. Clinicians, regulators, industry, and researchers require regulatory knowledge and collaboration for successful translation of innovative medical devices.

Vascular Quality Initiative Surveillance of Femoropopliteal Artery Paclitaxel Devices.

OBJECTIVES: This study sought to determine the safety and efficacy of paclitaxel (PTX) devices in the treatment of peripheral artery disease involving the femoropopliteal artery. BACKGROUND: A meta-analysis of PTX devices for the treatment of femoropopliteal artery disease reported a mortality signal. METHODS: This was a multicenter cohort study using an integrated clinical data surveillance system to conduct a prospective, propensity score-matched survival analysis of 2,456 patients in the Society for Vascular Surgery Vascular Quality Initiative from January 2017 to May 2020. The study compared PTX drug-coated balloon angioplasty versus percutaneous transluminal balloon angioplasty, PTX drug-eluting stents versus bare-metal stents, and any PTX device versus any non-PTX device. The primary outcome was 2-year survival. Secondary endpoints were successful ambulation and interventional success. RESULTS: Treatment with any PTX device versus any non-PTX device was associated with increased 2-year survival (89.5% vs 86.7%; HR: 0.79; 95% CI: 0.72-0.87; P = 0.004), improved interventional success (81.6% vs 77.6%; HR: 0.82; 95% CI: 0.74-0.91; P < 0.001), and higher rates of independent ambulation at 1 year (86.0% vs 83.4%; HR: 0.85; 95% CI: 0.79-0.91; P = 0.008). Treatment with PTX drug-coated balloon angioplasty was associated with improved survival at 2 years (88.9% vs 85.7%; HR: 0.77; 95% CI: 0.70-0.86; P = 0.005), while PTX drug-eluting stent therapy was associated with similar survival compared with bare-metal stent therapy (91.3% vs 89.6%; HR: 0.84; 95% CI: 0.70-1.01; P = 0.36). CONCLUSIONS: In this prospective, active surveillance of a national clinical registry, PTX-containing devices were associated with increased survival at 2 years and improved clinical outcomes at 1 year. (VQI DELTA Paclitaxel Device Safety Analysis [VQI-PTX]; NCT04110288).

Erratum: Advancing medical technology innovation and clinical translation via a model of industry-enabled technical and educational support: Indiana Clinical and Translational Sciences Institute's Medical Technology Advance Program - ERRATUM.

[This corrects the article DOI: 10.1017/cts.2021.1.].

Advancing medical technology innovation and clinical translation via a model of industry-enabled technical and educational support: Indiana Clinical and Translational Sciences Institute's Medical Technology Advance Program.

The success rate for translation of newly engineered medical technologies into clinical practice is low. Traversing the "translational valleys of death" requires a high level of knowledge of the complex landscape of technical, ethical, regulatory, and commercialization challenges along a multi-agency path of approvals. The Indiana Clinical and Translational Sciences Institute developed a program targeted at increasing that success rate through comprehensive training, education, and resourcing. The Medical Technology Advance Program (MTAP) provides technical, educational, and consultative assistance to investigators that leverages partnerships with experts in the health products industry to speed progress toward clinical implementation. The training, resourcing, and guidance are integrated through the entire journey of medical technology translation. Investigators are supported through a set of courses that cover bioethics, ethical engineering, preclinical and clinical study design, regulatory submissions, entrepreneurship, and commercialization. In addition to the integrated technical and educational resources, program experts provide direct consultation for planning each phase along the life cycle of translation. Since 2008, nearly 200 investigators have gained assistance from MTAP resulting in over 100 publications and patents. This support via medicine-engineering-industry partnership provides a unique and novel opportunity to expedite new medical technologies into clinical and product implementation.

Prediction Model for Freedom from TLR from a Multi-study Analysis of Long-Term Results with the Zilver PTX Drug-Eluting Peripheral Stent.

PURPOSE: Develop a prediction model to determine the impact of patient and lesion factors on freedom from target lesion revascularization (ffTLR) for patients who are candidates for Zilver PTX drug-eluting stent (DES) treatment for femoropopliteal lesions. METHODS: Patient factors, lesion characteristics, and TLR results from five global studies were utilized for model development. Factors potentially associated with TLR (sex, age, diabetes, hypertension, hypercholesterolemia, renal disease, smoking status, Rutherford classification, lesion length, reference vessel diameter (RVD), popliteal involvement, total occlusion, calcification severity, prior interventions, and number of runoff vessels) were analyzed in a Cox proportional hazards model. Probability of ffTLR was generated for three example patient profiles via combinations of patient and lesion factors. TLR was defined as reintervention performed for ≥ 50% diameter stenosis after recurrent clinical symptoms. RESULTS: The model used records from 2227 patients. The median follow-up time was 23.9 months (range: 0.03-60.8). The Kaplan-Meier estimates for ffTLR were 90.5% through 1 year and 75.2% through 5 years. In a multivariate analysis, sex, age, Rutherford classification, lesion length, RVD, total occlusion, and prior interventions were significant factors. The example patient profiles have predicted 1-year ffTLRs of 97.4, 92.3, and 86.0% and 5-year predicted ffTLRs of 92.8, 79.5, and 64.8%. The prediction model is available as an interactive web-based tool ( https://cooksfa.z13.web.core.windows.net ). CONCLUSIONS: This is the first prediction model that uses an extensive dataset to determine the impact of patient and lesion factors on ffTLR through 5 years and provides an interactive web-based tool for expected patient outcomes with the Zilver PTX DES. CLINICAL TRIAL REGISTRATIONS: Zilver PTX RCT unique identifier: NCT00120406; Zilver PTX single-arm study unique identifier: NCT01094678; Zilver PTX China study unique identifier: NCT02171962; Zilver PTX US post-approval study unique identifier: NCT01901289; Zilver PTX Japan post-market surveillance study unique identifier: NCT02254837. LEVELS OF EVIDENCE: Zilver PTX RCT: Level 2, randomized controlled trial; Single-arm study: Level 4, large case series; China study: Level 4, case series; US post-approval study: Level 4, case series Japan PMS study: Level 4, large case series.

Important considerations for trials for peripheral arterial disease: Lessons learned from the paclitaxel mortality signal: A report on behalf of the registry assessment for peripheral interventional Devices (RAPID) Paclitaxel Pathways Program.

The Registry Assessment of Peripheral Devices (RAPID) convened a multidisciplinary group of stakeholders including clinicians, academicians, regulators and industry representatives to conduct an in-depth review of limitations associated with the data available to assess the paclitaxel mortality signal. Available studies were evaluated to identify strengths and limitations in the study design and data quality, which were translated to lessons learned to help guide the design, execution, and analyses of future studies. We suggest numerous actionable responses, such as the development and use of harmonized data points and outcomes in a consensus lean case report form. We advocate for reduction in missing data and efficient means for accrual of larger sample sizes in Peripheral arterial disease studies or use of supplemental datasets. Efforts to share lessons learned and working collaboratively to address such issues may improve future data in this device area and ultimately benefit patients. Condensed Abstract: Data sources evaluating paclitaxel-coated devices were evaluated to identify strengths and limitations in the study design and data quality, which were translated to lessons learned to help guide the design, execution, and analyses of future studies. We suggest numerous actionable responses, which we believe may improve future data in this device area and ultimately benefit patients.

Long-Term Effectiveness of a Drug-Eluting Stent for Femoropopliteal In-Stent Restenosis: Subanalysis of the Zilver PTX Japan Post-Market Surveillance Study.

PURPOSE: To present a subgroup analysis of patients from a large real-world study evaluating the safety and effectiveness of the Zilver PTX drug-eluting stent (DES) for treating femoropopliteal in-stent restenosis (ISR). MATERIALS AND METHODS: This study examined patients enrolled in the Zilver PTX Japan Post-Market Surveillance Study (ClinicalTrials.gov identifier NCT02254837), a prospective, multicenter registry of 904 symptomatic patients with 1082 femoropopliteal lesions treated with the DES at 95 institutions in Japan. Five-year outcomes, including mortality, stent radiography, freedom from target lesion revascularization (TLR), and clinical benefit, were evaluated for 177 patients (mean age 74.2±8.3 years; 118 men) with 204 ISR lesions treated with the Zilver DES. Over half of the patients (108, 61.0%) were diabetic. Mean lesion length was 17.8±10.4 cm, and a third (72, 35.3%) were total occlusions. Outcome measures were all-cause mortality, thrombosis, freedom from TLR, and clinical benefit, defined as freedom from persistent or deteriorating ischemic symptoms. RESULTS: No device-related or procedure-related deaths or paclitaxel-related adverse events were reported. All-cause mortality was 25.1% at 5 years. Stent fracture was observed in 5 stents through 5 years. The 5-year rate of freedom from clinically-driven TLR was 73.4%, and the rate of clinical benefit was 63.6%. Improvement in Rutherford category and ankle-brachial index was sustained through 5 years. CONCLUSION: The safety and effectiveness of the Zilver PTX stent for the treatment of femoropopliteal ISR lesions demonstrated that this device provides a favorable treatment option in this difficult-to-treat subgroup.

Registry Assessment of Peripheral Interventional Devices objective performance goals for superficial femoral and popliteal artery peripheral vascular interventions.

BACKGROUND: The Superficial Femoral Artery-Popliteal EvidencE Development Study Group developed contemporary objective performance goals (OPGs) for peripheral vascular interventions (PVI) for superficial femoral artery (SFA)-popliteal artery disease using the Registry Assessment of Peripheral Interventional Devices. METHODS: The Society for Vascular Surgery Vascular Quality Initiative PVI registry from January 2010 to October 2016 was used to develop OPGs based on SFA-popliteal procedures (n = 21,377) for intermittent claudication and critical limb ischemia (CLI). OPGs included 1-year rates for target lesion revascularization (TLR), major amputation, and 1 and 4-year survival rates. OPGs were calculated for the SFA and popliteal arteries and stratified by four treatments: angioplasty alone (percutaneous transluminal angioplasty [PTA]), self-expanding stenting, atherectomy, and any treatment type. Outcomes were illustrated by unadjusted Kaplan-Meier analyses. RESULTS: Cohorts included PTA (n = 7505), stenting (n = 9217), atherectomy (n = 2510) and any treatment (n = 21,377). The mean age was 69 years, 58% were male, 79% were White, and 52% had CLI. The freedom from TLR OPGs at 1 year in the SFA were 80.3% (PTA), 83.2% (stenting), 83.9% (atherectomy), and 81.9% (any treatments). The freedom from TLR OPGs at 1 year in the popliteal were 81.3% (PTA), 81.3% (stenting), 80.2% (atherectomy), and 81.1% (any treatments). The freedom from major amputation OPGs at 1 year after SFA PVI were 93.4% (PTA), 95.7% (stenting), 95.1% (atherectomy), and 94.8% (any treatments). The freedom from major amputation OPG at 1 year after popliteal PVI were 90.5% (PTA), 93.7% (stenting), 91.8% (atherectomy), and 91.8%, (any treatments). The 4-year survival OPGs after SFA PVI were 76% (PTA), 80% (stenting), 82% (atherectomy), and 79% (any treatments), and for the popliteal artery were 72% (PTA), 77% (stenting), 82% (atherectomy), and 75% (any treatment). On a multivariable analysis, which included patient-level, leg-level, and lesion-level covariates, CLI was the single independent factor associated with increased TLR, amputation, and mortality. CONCLUSIONS: The Superficial Femoral Artery-Popliteal EvidencE Development OPGs define a new, contemporary benchmark for SFA-popliteal interventions using a large subset of real-world evidence to inform more efficient peripheral device clinical trial designs to support regulatory and clinical decision-making. It is appropriate to discuss proposals intended for regulatory approval with the US Food and Drug Administration to refine the OPG to match the specific trial population. The OPGs may be updated using coordinated registry networks to assess long-term real-world device performance.

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

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.

Drug-Eluting Stent Versus Drug-Coated Balloon Revascularization in Patients With Femoropopliteal Arterial Disease.

BACKGROUND: Randomized trials of drug-eluting stents (DES) and drug-coated balloons (DCB) for femoropopliteal interventions reported superior patency rates for both strategies compared to standard balloon angioplasty. To date, head-to-head comparisons are missing. OBJECTIVES: The authors sought to compare DES versus DCB for femoropopliteal lesions through 36 months. METHODS: Within a multicenter, randomized trial, 150 patients with symptomatic femoropopliteal disease were randomly assigned to primary DES implantation or DCB angioplasty with bailout stenting after stratification for lesion length (≤10 cm, >10 cm to ≤20 cm, and >20 cm to ≤30 cm). The primary effectiveness endpoint was primary patency at 12 months assessed by Kaplan-Meier. Secondary endpoints comprised major adverse events including death, major amputations, and clinically driven target lesion revascularization, and clinical outcomes. RESULTS: More than one-half of lesions were total occlusions, and the stenting rate was 25.3% in the DCB group. Kaplan-Meier estimates of primary patency were 79% and 80% for DES and DCB at 12 months (p = 0.96) but decreased to 54% and 38% through 36 months (p = 0.17), respectively. Freedom from clinically driven target lesion revascularization was >90% at 12 months but dropped to around 70% at 36 months in both groups. Overall, the mortality rate through 36 months was 7.3%, with 1 procedure-related death in the DCB group. Improvement of clinical outcomes was sustained through 36 months. CONCLUSIONS: Patency rates at 12 months suggest comparable effectiveness and safety of DES versus DCB plus bailout stenting in femoropopliteal interventions; a trend in favor of the DES was observed up to 36 months. (Randomized Evaluation of the Zilver PTX Stent vs. Paclitaxel-Eluting Balloons for Treatment of Symptomatic Peripheral Artery Disease of the Femoropopliteal Artery [REAL PTX]; NCT01728441).

Zilver PTX Post-market Surveillance Study of Paclitaxel-Eluting Stents for Treating Femoropopliteal Artery Disease in Japan: 2-Year Results.

PURPOSE: A prospective, multicenter post-market surveillance study in Japan evaluated the 2-year safety and effectiveness of the DES in real-world patients with complex femoropopliteal artery lesions. METHODS: There were no exclusion criteria, and consecutive symptomatic patients with femoropopliteal lesions treated with the DES were enrolled in the study. Clinically driven target lesion revascularization (TLR) was defined as reintervention performed for > 50% diameter stenosis after recurrent clinical symptoms of peripheral arterial disease. Clinical benefit was defined as freedom from persistent or deteriorating ischemic symptoms. Patency was evaluated by duplex ultrasound where physicians considered this standard of care. RESULTS: In this study, 905 patients were enrolled at 95 institutions in Japan. There were numerous comorbidities including a high incidence of diabetes (58.8%) and chronic kidney disease (43.6%). Additionally, 21.4% of patients were classified with critical limb ischemia. Lesions were complex, with an average length of 14.6 ± 9.6 cm (range 0.5-40 cm), 41.5% total occlusions, and 18.7% in-stent restenosis. In total, 1861 DES were placed in 1080 lesions. Two-year follow-up was obtained for > 90% of eligible patients. Freedom from TLR was 83.7%, and clinical benefit was 80.0% through 2 years. The 2-year primary patency rate was 70.3%. Rutherford classification significantly improved (p < 0.01), with approximately 80% of patients classified as Rutherford class 0 or 1 at 2 years. CONCLUSION: Despite more challenging lesion characteristics, 2-year results from the current study are similar to outcomes from the previous Zilver PTX studies, confirming the efficacy of the Zilver PTX DES in a complicated femoropopliteal lesion (Zilver PTX Post-Market Study in Japan; NCT02254837). LEVEL OF EVIDENCE: Post-market surveillance study, Level III.

Long-Term Effectiveness of the Zilver PTX Drug-Eluting Stent for Femoropopliteal Peripheral Artery Disease in Patients with No Patent Tibial Runoff Vessels-Results from the Zilver PTX Japan Post-Market Surveillance Study.

PURPOSE: To evaluate 2-year results of the Zilver PTX (Cook Medical, Bloomington, Indiana) drug-eluting stent (DES) for femoropopliteal peripheral artery disease (PAD) in patients with no continuous patent infrapopliteal runoff arteries compared with patients with ≥ 1 continuous patent runoff vessels. MATERIALS AND METHODS: A retrospective analysis of patients with femoropopliteal PAD enrolled in the Zilver PTX Post-Market Surveillance Study in Japan was performed. There were no exclusion criteria. Outcomes, including freedom from target lesion revascularization (TLR), patency, and clinical benefit, for the no-runoff group (n = 54) were compared with the runoff group (n = 846). RESULTS: The 2 groups were similar in terms of demographics, lesion characteristics, and comorbidities (P > .05). There was a higher incidence of critical limb ischemia in the no-runoff group compared with the runoff group (44.8% vs 19.7%; P < .01). There were 3 amputations (5.6%) in the no-runoff group versus 7 amputations (0.8%) in the runoff group (P = .02). At 2 years, freedom from TLR rates were 81.3% versus 83.8% (P = .87), patency rates were 68.4% versus 70.7% (P = .95), and clinical benefit rates were 73.7% versus 80.0% (P = .16) in the no-runoff versus runoff group, respectively. CONCLUSIONS: Results in patients with no continuous patent tibial runoff were favorable through 2 years and similar to results for patients with ≥ 1 continuous patent runoff vessels, indicating that the Zilver PTX DES may be a valid treatment option for patients with these difficult-to-treat lesions.

Impact of Chronic Renal Failure on Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Artery Disease: Subgroup Analysis from Zilver PTX Post-Market Surveillance Study in Japan.

PURPOSE: Favorable long-term outcomes of the Zilver PTX drug-eluting stent (DES) in femoropopliteal lesions have been demonstrated. Chronic renal failure (CRF) has been shown to be a risk factor for restenosis and decreased limb salvage. The results of the DES in patients with CRF have not previously been reported. This study compares the results with the DES in patients with CRF and those without CRF. METHODS: This retrospective analysis from the Zilver PTX Japan Post-Market Surveillance Study included 321 patients with CRF and 584 patients without CRF. Outcomes included freedom from target lesion revascularization (TLR) and patency. RESULTS: Of the patients included in this subgroup analysis, 2-year data were available for 209 patients in the CRF group and 453 patients in the non-CRF group. The two groups were similar in terms of lesion length and the frequency of in-stent restenosis. Critical limb ischemia, severe calcification, and diabetes were more common in patients with CRF, whereas total occlusion was more common in patients without CRF. Freedom from TLR rates were 81.4 versus 84.9% (p = 0.24), and patency rates were 70.7 versus 70.3% (p = 0.95) in patients with and without CRF at 2 years, respectively. CONCLUSION: This is the first comparative study of the DES in femoropopliteal artery lesions in patients with and without CRF. These results indicate that the DES placed in femoropopliteal artery lesions of CRF patients is safe and effective with similar patency and TLR rates to patients without CRF. LEVEL OF EVIDENCE: Level 3, Post-Market Surveillance Study.

A Quantitative Angiographic Comparison of Restenotic Tissue Following Placement of Drug-Eluting Stents and Bare Metal Stents in Symptomatic Patients With Femoropopliteal Disease.

PURPOSE: To evaluate the patterns of in-stent restenosis (ISR) within femoropopliteal bare metal stents (BMS) and drug-eluting stents (DES) as determined by quantitative angiographic analysis. METHODS: Utilizing results from independent core laboratory angiographic imaging analysis, quantitative assessment of the restenotic tissue burden was evaluated in 33 patients with symptomatic femoropopliteal ISR, including 20 lesions in 19 patients (mean age 71.5±8.1 years; 11 men) treated with DES and 14 lesions in 14 patients (mean age 70.6±9.2 years; 9 men) treated with BMS. RESULTS: The average time to target lesion revascularization was similar (8.7 months) for the DES and BMS groups. The DES group had significantly less recurrent disease burden (17.1%) compared with the BMS group (27.8%, p=0.03), representing a 39% relative reduction. CONCLUSION: Reduced restenotic tissue after endovascular intervention is associated with improved hemodynamics and fewer clinical symptoms and may explain the reduced need for reintervention in restenotic lesions initially treated with DES as compared with BMS. Further study of treatment failure modes may lead to improved device selection criteria to treat patients with peripheral artery disease.

Zilver PTX Post-Market Surveillance Study of Paclitaxel-Eluting Stents for Treating Femoropopliteal Artery Disease in Japan: 12-Month Results.

OBJECTIVES: This multicenter, prospective, post-market surveillance study in Japan evaluates the paclitaxel-coated Zilver PTX stent in real-world patients with complex lesions. BACKGROUND: The Zilver PTX stent is the first drug-eluting stent (DES) approved for the superficial femoral artery. Previously, results from a large randomized study and a complementary, large single-arm study supported the safety and effectiveness of the DES. METHODS: There were no exclusion criteria, and consecutive patients with symptomatic peripheral artery disease (PAD) treated with the DES were enrolled in the study. Clinically driven target lesion revascularization (TLR) was defined as reintervention performed for ≥50% diameter stenosis after recurrent clinical symptoms of PAD. Clinical benefit was defined as freedom from persistent or worsening symptoms of ischemia. Patency was evaluated by duplex ultrasound where physicians considered this standard of care. RESULTS: In this study, 907 patients were enrolled at 95 institutions in Japan. There were numerous comorbidities including high incidences of diabetes (58.8%), chronic kidney disease (43.8%), and critical limb ischemia (21.5%). Lesions were also complex, with an average length of 14.7 cm, 41.6% total occlusions, and 18.6% in-stent restenosis. In total, 1,861 DES were placed in 1,075 lesions. Twelve-month follow-up was obtained for >95% of eligible patients. Freedom from TLR was 91.0%, and clinical benefit was 87.7% through 12 months. The 12-month primary patency rate was 86.4%. CONCLUSIONS: Despite more challenging lesions, results from the current study are similar to outcomes from the previous Zilver PTX studies, confirming the benefit of the Zilver PTX DES in a real-world patient population. (Zilver PTX Post-Market Study in Japan; NCT02254837).

Nitinol stents with polymer-free paclitaxel coating for lesions in the superficial femoral and popliteal arteries above the knee: twelve-month safety and effectiveness results from the Zilver PTX single-arm clinical study.

PURPOSE: To report a prospective, single-arm, multicenter clinical study evaluating the Zilver PTX drug-eluting stent for treating the above-the-knee femoropopliteal segment (NCT01094678; http://www.clinicaltrials.gov ). METHODS: The Zilver PTX drug-eluting stent is a self-expanding nitinol stent with a polymer-free paclitaxel coating. Patients with symptomatic (Rutherford category 2-6) de novo or restenotic lesions (including in-stent stenosis) of the above-the-knee femoropopliteal segment were eligible for enrollment. Between April 2006 and June 2008, 787 patients (578 men; mean age 66.6±9.5 years) were enrolled at 30 international sites. RESULTS: Nine hundred lesions (24.3% restenotic lesions of which 59.4% were in-stent stenoses) were treated with 1722 Zilver PTX stents; the mean lesion length was 99.5±82.1 mm. The 12-month Kaplan-Meier estimates included an 89.0% event-free survival rate, an 86.2% primary patency rate, and a 90.5% rate of freedom from target lesion revascularization. There were no paclitaxel-related adverse events reported. The 12-month stent fracture rate was 1.5%. The ankle-brachial index, Rutherford score, and walking distance/speed scores significantly improved (p<0.001) from baseline to 12 months. CONCLUSIONS: These results indicate that the Zilver PTX drug-eluting stent is safe for treatment of patients with de novo and restenotic lesions of the above-the-knee femoropopliteal segment. At 1 year, the overall anatomical and clinical effectiveness results suggest that this stent is a promising endovascular therapy.

A new cardiopulmonary resuscitation method using only rhythmic abdominal compression: a preliminary report.

This article introduces 2 new cardiopulmonary resuscitation (CPR) concepts: (1) the use of only rhythmic abdominal compression (OAC) to produce blood flow during CPR with ventricular fibrillation and (2) a new way of describing coronary perfusion effectiveness, namely, the area between the aortic and right atrial pressure curves, summed over 1 minute, the units being millimeters of mercury per second. We call this unit the coronary perfusion index (CPI). True mean coronary perfusion pressure is CPI/60. We also relate CPI during CPR with ventricular fibrillation to the CPI for the normally beating heart in the same animal, obtained before each experiment. This 11-pig (25-35 kg) study compares the CPI for standard chest-compression CPR and that obtained with OAC-CPR. The coronary perfusion ratio for OAC-CPR compared with standard chest-compression CPR was 1.6 +/- 0.73 (P = .024). In other words, OAC-CPR produced 60% more coronary perfusion than standard chest-compression CPR, with no damage to visceral organs.