Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: The AGENT IDE Randomized Clinical Trial.

Importance: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States. Objective: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention. Design, Setting, and Participants: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023. Interventions: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon. Main Outcomes and Measures: The primary end point of 1-year target lesion failure-defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death-was tested for superiority. Results: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P = .003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P = .001) and target vessel-related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P = .02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P = .38) in the coated vs uncoated balloon groups, respectively. Conclusions and Relevance: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04647253.

SUPERB final 3-year outcomes using interwoven nitinol biomimetic supera stent.

IMPORTANCE: Long-term outcomes of an interwoven nitinol stent design represent the best in class for treatment of lower limb arterial obstructive disease METHODS: The subjects were enrolled in an open single arm study comparing the outcomes to an FDA mandated objective performance goal (OPG). RESULTS: About 325 patients (264 intention-to-treat and 64 roll-in subjects) were enrolled. Mean follow-up period was 887+/- 352 days. Treated lesion lengths were 7.8 cm ± 4.3 cm in the trial with chronic total occlusions comprising 24.6% (65/264) of subjects. Freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months was 89%, at 24 and 36 months it was 84% and 82% respectively. The difference in the 12 month CD-TLR was 7% at 36 months. The difference of clinically driven-TLR at 36 months in those subjects who received their stents deployed nominally in length, compressed or elongated (between -10% and +10% nominal length) had an impact on the CD-TLR. At 2 and 3 years, freedom from CD-TLR in minimal compression was 86.7%, and was 90.0% for moderate compression. In those stents deployed with minimal, moderate, or severe elongation (10-20%, 20-40%, or >40%, respectively) freedom from CD-TLR of 84.1%, 87.4%, and 77.0% respectively at 12 months. At 2 and 3 years, freedom from CD-TLR for moderate elongation was 81.8% and 78.2%, and for severe elongation was 63.4% and 42.3%, respectively. Fractures were distinctly uncommon with this stent with a single facture event in the 36 month follow-up period. DISCUSSION: The interwoven nitinol design stent is a stent that achieves an excellent primary patency but further maintains the durability of the stent through 36 months. Optimal stent deployment remains critical to the performance of this stent device and requires optimal vessel preparation. © 2017 Wiley Periodicals, Inc.

Cross-Seal IDE Trial: Prospective, Multicenter, Single-Arm Study of the Cross-Seal Suture-Mediated Vascular Closure Device System.

BACKGROUND: An increasing number of interventional procedures require large-sheath technology (>12F) with a favorable outcome with endovascular rather than open surgical access. However, vascular complications are a limitation for the management of these patients. This trial aimed to determine the effectiveness and safety of the Cross-Seal suture-mediated vascular closure device in obtaining hemostasis at the target limb access site following interventional procedures using 8F to 18F procedural sheaths. METHODS: The Cross-Seal IDE trial (Investigational Device Exemption) was a prospective, single-arm, multicenter study in subjects undergoing percutaneous endovascular procedures utilizing 8F to 18F ID procedural sheaths. The primary efficacy end point was time to hemostasis at the target limb access site. The primary safety end point was freedom from major complications of the target limb access site within 30 days post procedure. RESULTS: A total of 147 subjects were enrolled between August 9, 2019, and March 12, 2020. Transcatheter aortic valve replacement was performed in 53.7% (79/147) and percutaneous endovascular abdominal/thoracic aortic aneurysm repair in 46.3% (68/147) of subjects. The mean sheath ID was 15.5±1.8 mm. The primary effectiveness end point of time to hemostasis was 0.4±1.4 minutes. An adjunctive intervention was required in 9.2% (13/142) of subjects, of which 2.1% (3/142) were surgical and 5.6% (8/142) endovascular. Technical success was achieved in 92.3% (131/142) of subjects. Freedom from major complications of the target limb access site was 94.3% (83/88). CONCLUSIONS: In selected patients undergoing percutaneous endovascular procedures utilizing 8F to 18F ID procedural sheath, Cross-Seal suture-mediated vascular closure device achieved favorable effectiveness and safety in the closure of the large-bore arteriotomy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03756558.

Safety and efficiency of percutaneous coronary intervention using a standardised optical coherence tomography workflow.

BACKGROUND: While intravascular imaging guidance during percutaneous coronary intervention (PCI) improves outcomes, routine intravascular imaging usage remains low, in part due to perceived inefficiency and safety concerns.  Aims: The LightLab (LL) Initiative was designed to evaluate whether implementing a standardised optical coherence tomography (OCT) workflow impacts PCI safety metrics and procedural efficiency. METHODS: In this multicentre, prospective, observational study, PCI procedural data were collected over 2 years from 45 physicians at 17 US centres. OCT-guided PCI incorporating the LL workflow (N=264), a structured algorithm using routine pre- and post-PCI OCT imaging, was compared with baseline angiography-only PCI (angio) (N=428). Propensity score analysis identified 207 matched procedures. Outcomes included procedure time, radiation exposure, contrast volume, device utilisation, and treatment strategy. RESULTS: Compared with angiography alone, LL workflow OCT-guided PCI increased the median procedural time by 9 minutes but reduced vessel preparation time (2 min LL workflow vs 3 min angio; p<0.001) and resulted in less unplanned additional treatment (4% LL workflow vs 10% angio; p=0.01). With LL workflow OCT guidance, fewer cineangiography views were needed compared to angiography guidance, leading to decreased radiation exposure (1,133 mGy LL workflow vs 1,269 mGy angio; p=0.02), with no difference in contrast utilisation between groups (p=0.28). Furthermore, LL workflow OCT guidance resulted in fewer predilatation balloons and stents being used, more direct stent placement, and greater stent post-dilatation than angiography-guided PCI. CONCLUSIONS: The incorporation of a standardised pre- and post-PCI OCT imaging workflow improves procedural efficiency and safety metrics, at a cost of a modestly longer procedure time.

Wire-Interwoven Nitinol Stent Outcome in the Superficial Femoral and Proximal Popliteal Arteries: Twelve-Month Results of the SUPERB Trial.

BACKGROUND: Stent-based therapy in the superficial femoral and popliteal arteries in patients with peripheral artery disease is compromised by restenosis and risk of stent fracture or distortion. A novel self-expanding nitinol stent was developed that incorporates an interwoven-wire design (Supera stent, IDEV Technologies, Inc, Webster, TX) to confer greater radial strength, flexibility, and fracture resistance. METHODS AND RESULTS: This prospective, multicenter, investigational device exemption, single-arm trial enrolled 264 patients with symptomatic peripheral artery disease undergoing percutaneous treatment of de novo or restenotic lesions of the superficial femoral or proximal popliteal (femoropopliteal) artery. Freedom from death, target lesion revascularization, or any amputation of the index limb at 30 days (+ 7 days) postprocedure was achieved in 99.2% (258/260) of patients (P < 0.001). Primary patency at 12 months (360 ± 30 days) was achieved in 78.9% (180/228) of the population (P < 0.001). Primary patency by Kaplan-Meier analysis at 12 months (360 days) was 86.3%. No stent fracture was observed by independent core laboratory analysis in the 243 stents (228 patients) evaluated at 12 months. Clinical assessment at 12 months demonstrated improvement by at least 1 Rutherford-Becker category in 88.7% of patients. CONCLUSIONS: The SUPERB Trial, an investigational device exemption study using an interwoven nitinol wire stent in the femoropopliteal artery, achieved the efficacy and safety performance goals predesignated by the Food and Drug Administration. On the basis of the high primary patency rate, absence of stent fracture, and significant improvements in functional and quality-of-life measures, the Supera stent provides safe and effective treatment of femoropopliteal lesions in symptomatic patients with peripheral artery disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00933270.

Effect of clopidogrel pretreatment on periprocedural rise in C-reactive protein after percutaneous coronary intervention.

This study sought to determine the effect of clopidogrel pretreatment on the increase in C-reactive protein (CRP) after percutaneous coronary intervention. Clopidogrel pretreatment attenuated the periprocedural increase in CRP by 65% and was independently associated with an attenuation in the CRP increase in a multivariate model.

Effect of clopidogrel pretreatment on inflammatory marker expression in patients undergoing percutaneous coronary intervention.

Platelets play an important role in the inflammatory response. In a nonrandomized comparison, we examined the effect of clopidogrel pretreatment on platelet inflammatory marker expression in patients undergoing percutaneous coronary intervention (PCI). Platelet expression of the inflammatory markers CD40 ligand (L) and CD62 P-selectin (P) and serum levels of interleukin-6 and CD40L were compared in patients pretreated (>24 hours before PCI) or not pretreated with clopidogrel. Blood samples were obtained before and after the procedure, and from 18 to 24 hours later. Marker expression in resting and adenosine diphosphate (ADP) (50 micromol/L) and thrombin receptor activating peptide (TRAP) (10 micromol/L) activated samples was quantified by flow cytometry. Serum CD40L and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay. Seventy-nine patients were recruited into the study. Forty-two percent were pretreated with clopidogrel for a median of 5 days (range 1 to 1,325). Clopidogrel pretreatment was associated with lower ADP-activated platelet CD40L expression in baseline and postprocedural samples. Similarly, platelet CD62P expression at all time points in ADP-activated and in baseline and postprocedural TRAP-activated samples was lower in patients pretreated with clopidogrel. These differences remained after multivariate adjustment between the groups. Serum CD40L levels increased from 2.13 +/- 2.37 ng/ml at baseline to 4.77 +/- 3.86 ng/ml at 18 to 24 hours after the procedure (p <0.0001). Similarly, serum IL-6 levels increased at 18 to 24 hours after the procedure (14.8 +/- 42.0 pg/ml before vs 25.5 +/- 36.0 pg/ml at 18 to 24 hours after the procedure, p <0.0001). Clopidogrel pretreatment did not affect serum IL-6 or CD40L levels. Thus, clopidogrel pretreatment reduces platelet inflammatory marker expression in patients undergoing PCI.

Molecular and functional differences induced in thrombospondin-1 by the single nucleotide polymorphism associated with the risk of premature, familial myocardial infarction.

A serine (Ser-700) amino acid rather than an asparagine (Asn-700) at residue 700 of thrombospondin-1 has been linked to an increased risk for development of premature, familial heart attacks. We now have identified both functional and structural differences between the Ser-700 and Asn-700 thrombospondin-1 variants. The Ser-700 variant increased the rate and extent of platelet aggregation and showed increased surface expression on platelets compared with the Asn-700 variant. These differences could be ascribed to an enhanced interaction of the Ser-700 variant with fibrinogen on the platelet surface and are consistent with a prothrombotic phenotype in Ser-700 individuals. The Ser-700 variant thrombospondin-1 was conformationally more labile than the Asn-700 variant as demonstrated by increased susceptibility to proteolytic digestion and enhanced susceptibility to unfolding by denaturants. These data suggest a potential molecular and cellular basis for a genetic risk factor associated with early onset myocardial infarction.