Rationale and design of a randomized study comparing the agent drug coated balloon to plain old balloon angioplasty in patients with In-stent restenosis.

BACKGROUND: Drug-coated balloon (DCB) technology was developed as an alternative treatment for obstructive coronary artery disease (CAD) and in-stent restenosis (ISR). Management of coronary ISR is clinically challenging and frequently encountered in practice. The Agent DCB uses an inactive excipient to effectively deliver a targeted, therapeutic dose of paclitaxel to the vessel wall. STUDY DESIGN: AGENT IDE is a prospective, multicenter, randomized controlled trial to evaluate superiority of the Agent DCB to balloon angioplasty in treating patients with ISR. A total of 480 patients with ISR of a previously treated lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm will be initially randomized. Subjects presenting with recent myocardial infarction (MI), complex lesions, or thrombus in the target vessel will be excluded. An adaptive group sequential design with one formal interim analysis for sample size re-estimation will be conducted, and the sample size may be increased to a maximum of 600 subjects. The primary endpoint is the rate of 12-month target lesion failure (TLF; composite of any ischemia-driven revascularization of the target lesion (TLR), target vessel related MI, or cardiac death) and will be tested for superiority in the test arm against the control. Functional status and general health-related quality of life will be measured by changes in the EQ-5D scores. Subjects will be followed for 5 years following the index procedure. CONCLUSION: This study will prospectively evaluate the safety and efficacy of Agent DCB in patients treated for coronary ISR.

Safety and efficacy metrics for primary nitinol stenting in femoropopliteal occlusive disease: a meta-analysis and critical examination of current methodologies.

BACKGROUND: The efficacy and safety of primary stenting for superficial femoral artery (SFA) disease have been benchmarked against historically derived performance goals. However, contemporary evidence evaluating SFA stenting is accumulating. The objective of this systematic review and meta-analysis was to quantitatively assess outcomes after primary SFA stenting with nitinol stents in contemporary practice, to compare these rates with commonly used efficacy and safety goals, and to discuss the clinical and regulatory implications of these findings. METHODS AND RESULTS: We searched MEDLINE, the US Food and Drug Administration (FDA) website, reference lists of qualifying articles, and conference proceedings until October 2012. Studies prospectively assessing primary nitinol stenting for diseased SFA were sought. Data from 11 prospective clinical trials were included. The twelve-month primary patency (PP) rate was reported in five trials. The meta-analytic 12-month PP rate was 71.6% (95% confidence interval [CI] 66.4-76.7%). The meta-analytic rate of 30-day freedom from a composite of death, target limb amputation, and reintervention was 99.9% (95% CI 100.0-90.0%). CONCLUSION: Contemporary nitinol-based bare-metal stents performed well in controlled settings. Occurrence of the 1-month composite safety endpoint was extremely uncommon.

Drug-Coated Balloons in the Management of Coronary Artery Disease.

Drug-coated balloons (DCBs) are specialized coronary devices comprised of a semicompliant balloon catheter with an engineered coating that allows the delivery of antiproliferative agents locally to the vessel wall during percutaneous coronary intervention. Although DCBs were initially developed more than a decade ago, their potential in coronary interventions has recently sparked renewed interest, especially in the United States. Originally designed to overcome the limitations of conventional balloon angioplasty and stenting, they aim to match or even improve upon the outcomes of drug-eluting stents without leaving a permanent implant. Presently, in-stent restenosis is the condition with the most robust evidence supporting the use of DCBs. DCBs provide improved long-term vessel patency compared with conventional balloon angioplasty and may be comparable to drug-eluting stents without the need for an additional stent layer, supporting their use as a first-line therapy for in-stent restenosis. Beyond the treatment of in-stent restenosis, DCBs provide an additional tool for de novo lesions for a strategy that avoids a permanent metal scaffold, which may be especially useful for the management of technically challenging anatomies such as small vessels and bifurcations. DCBs might also be advantageous for patients with high bleeding risk due to the decreased necessity for extended antiplatelet therapy, and in patients with diabetes and patients with diffuse disease to minimize long-stented segments. Further studies are crucial to confirm these broader applications for DCBs and to further validate safety and efficacy.

Rationale and Design of the SAFE-PAD Study.

BACKGROUND: Recent evidence from randomized controlled trials has raised concerns about the long-term safety of paclitaxel-coated peripheral devices used for femoropopliteal artery revascularization. In response to a call for more real-world data on the safety of these devices, the SAFE-PAD study (Safety Assessment of Femoropopliteal Endovascular treatment with Paclitaxel-coated Devices) was designed with input from the Food and Drug Administration to provide a long-term, comprehensive evaluation of the mortality risk associated with paclitaxel-coated devices among Medicare beneficiaries. METHODS AND RESULTS: SAFE-PAD is an observational cohort study of fee-for-service Medicare beneficiaries that underwent femoropopliteal artery revascularization with either a drug-coated device or nondrug-coated device from 2015 through 2018. All patients age 66 years or older who underwent revascularization will be identified using a combination of International Classification of Diseases, Tenth Revision procedural codes, Current Procedural Terminology codes, and Healthcare Common Procedure Coding System C-codes. The safety end point of all-cause death will be updated semiannually and continued until the median duration of follow-up surpasses 5 years. Sub-group analyses will be conducted by device type, patient characteristics, and procedural setting. Registration: The SAFE-PAD study has been registered on URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496544. CONCLUSIONS: The SAFE-PAD study will evaluate the long-term safety of drug-coated devices compared with nondrug-coated devices for femoropopliteal artery revascularization among a broad, real-world population of patients with peripheral artery disease.

Long-term safety of drug-coated devices for peripheral revascularisation.

BACKGROUND: Meta-analyses of randomised trials of paclitaxel-coated peripheral devices found an association with worse long-term survival. AIMS: We aimed to assess long-term mortality in patients treated with drug-coated versus non-drug-coated devices who are insured by Medicare Advantage (MA), an alternative to traditional Medicare that represents >30% of the Medicare eligible population. We analysed data from an MA administrative claims data source that includes both inpatient and outpatient femoropopliteal artery revascularisation procedures. METHODS: Patients treated with or without drug-coated devices for femoropopliteal artery revascularisation from 4/2015-12/2017 were studied using Optum's De-identified Clinformatics Datamart Database. Mortality was assessed up to December 2019 using Kaplan-Meier cumulative mortality curves and Cox proportional hazard models. Inverse probability of treatment weighting was used to adjust for differences between groups. RESULTS: Of 16,796 patients revascularised, 4,427 (26.4%) were treated with drug-coated devices: 3,600 (81.3%) balloons and 827 (18.7%) stents. The median follow-up was 2.66 years (IQR 2.02-3.52). Treatment with drug-coated devices was associated with similar long-term mortality to non-drug-coated devices (adjusted HR 1.03, 95% CI: 0.96-1.10; p=0.39). Results were comparable for patients treated with balloons alone (adjusted HR 1.00, 95% CI: 0.92-1.08; p=0.96) or stents (adjusted HR 1.02, 95% CI: 0.88-1.18; p=0.78). These findings did not differ based on treatment setting, disease severity, age, sex or comorbidity burden (interaction p>0.05 for all). CONCLUSIONS: In this large cohort, there was no evidence of increased long-term mortality following treatment with drug-coated devices.

Primary Results of the EVOLVE Short DAPT Study: Evaluation of 3-Month Dual Antiplatelet Therapy in High Bleeding Risk Patients Treated With a Bioabsorbable Polymer-Coated Everolimus-Eluting Stent.

[Figure: see text].

Weighing the potential late benefits versus early hazard associated with bioresorbable vascular scaffolds in percutaneous coronary interventions: a Markov decision analytic model.

OBJECTIVE: Use of poly-L-lactic acid-based bioresorbable scaffolds (BRS) has been associated with increased risk of device thrombosis during the first 3 years after implantation as compared to metallic everolimus-eluting stents (EES). The long-term performance of BRS relative to EES remains unknown. METHODS: We used a Markov decision analysis model to evaluate the effectiveness of BRS vs. EES over a lifetime horizon. In addition to one-way sensitivity analyses of key variables, we evaluated the impact of optimal implantation technique and limiting procedures to larger vessels (>2.6 mm in diameter) on model results. RESULTS: Assuming no risk of target lesion revascularization for BRS after 3 years, we found a small increment in quality-adjusted life expectancy (QALE) of 0.02 with the use of BRS relative to EES, with benefit being observed after 21.8 years. Optimal implantation technique and limiting to larger vessels resulted in larger gains in QALE (0.08 and 0.06, respectively) with BRS and shorter times to equipoise (6.7 and 8.3 years, respectively). Model results were highly sensitive to variations in the relative risk of stent thrombosis (BRS vs. EES). CONCLUSIONS: Based on currently available data, it would take approximately 21.8 years for the presumed late benefits of current BRS relative to EES to overcome the early hazard associated with their use under favorable assumptions. Optimal implantation technique and limiting procedures to larger vessels improved BRS performance and reduced time to equipoise. Eliminating the higher BRS thrombosis risk is necessary in developing future generations of BRS as an acceptable alternative to EES.