Ten-Year Clinical Outcomes of Late-Acquired Stent Malapposition After Coronary Stent Implantation.

OBJECTIVE: The goal of this study was to determine the impact of late-acquired stent malapposition (LASM) on long-term clinical outcomes in patients treated with coronary stent implantation. Approach and Results: We investigated major adverse cardiac event during 10 years after 6-month intravascular ultrasound examination using our previous studies database. A total of 732 patients treated with bare-metal stent (54 LASM versus 678 non-LASM) and 529 patients treated with first-generation drug-eluting stent (82 LASM versus 447 non-LASM), who did not have clinical event or censoring at the time of follow-up intravascular ultrasound, were included for the present analysis. major adverse cardiac event was defined as the composite of cardiac death, target vessel-related myocardial infarction, target lesion revascularization and stent thrombosis. Multivariable adjustment and inverse probability weight were performed to consider baseline differences. After multivariable adjustment, LASM was related to a greater risk of major adverse cardiac event (hazard ratio, 1.666 [95% CI, 1.041-2.665]; P=0.0333) and very-late stent thrombosis (hazard ratio, 3.529 [95% CI, 1.153-10.798]; P=0.0271) than non-LASM in patients treated with first-generation drug-eluting stent, but not in those treated with bare-metal stent. Results were consistent after inverse probability weight. Among patients with LASM of first-generation drug-eluting stent, no late stent thrombosis occurred in patients who continued to receive dual antiplatelet therapy. CONCLUSIONS: The relationship between LASM and major adverse cardiac event might depend on the type of implanted stents during the long-term follow-up, highlighting the clinical significance of polymers and drugs in drug-eluting stent system.

Comparison Between Beta-Blockers with Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers with Angiotensin II Type I Receptor Blockers in ST-Segment Elevation Myocardial Infarction After Successful Percutaneous Coronary Intervention with Drug-Eluting Stents.

BACKGROUND/AIMS: Limited comparative data concerning long-term clinical outcomes of combination therapy between beta-blockers (BB) with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) therapy in patients with ST-segment elevation myocardial infarction (STEMI) are available. We thought to compare 2-year major clinical outcomes between BB with ACEI and BB with ARB therapy in patients with STEMI after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: 13,873 STEMI patients who underwent successful PCI with DES were enrolled and divided into two groups as the BB with ACEI group (n = 10,393) and the BB with ARB group (n = 3480). The clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, cardiac death (CD), recurrent myocardial infarction (re-MI), total coronary revascularization (target lesion revascularization [TLR], target vessel revascularization [TVR], non-TVR) during the 2-year follow-up period. RESULTS: After propensity score-matched (PSM) analysis, two PSM groups (3296 pairs, n = 6592, C-statistic = 0.675) were generated. Although the incidences of re-MI, TLR, and TVR were similar, the incidences of MACE (8.3% vs. 6.8%, log-rank p = 0.038, hazard ratio [HR] 1.210, 95% confidence interval [CI] 1.010-1.451, p = 0.039), all-cause death, CD, total revascularization, and non-TVR of the BB with ARB group were significantly higher than the BB with ACEI group after PSM. In addition, diabetes and multivessel disease were significant predictors for non-TVR. CONCLUSIONS: The combination BB with ACEI may be beneficial for reducing MACE in STEMI patients after successful PCI with DES than the BB with ARB.

Clinical Implication of Optical Coherence Tomography-Based Neoatherosclerosis.

Recent research has indicated neoatherosclerosis (NA), the de novo development of atherosclerosis within the neointimal region of the stented segment after coronary stent implantation, as a mechanism of late/very late stent thrombosis (VLST) and restenosis. This research is based on histologic and intravascular imaging studies. Optical coherence tomography (OCT) is an imaging tool that is superior with regard to resolution capacity, and can be used to visualize detailed information about distinct morphological characteristics of the restenotic tissue. Thus, OCT is a valuable imaging tool for examining NA, such as macrophage infiltration, lipid accumulation, in-stent calcification, or neointimal rupture. This article discusses the prevalence, predictors, and clinical implications of NA that can be observed by OCT.

Nanoporous Transparent MOF Glasses with Accessible Internal Surface.

While glassy materials can be made from virtually every class of liquid (metallic, molecular, covalent, and ionic), to date, formation of glasses in which structural units impart porosity on the nanoscopic level remains undeveloped. In view of the well-established porosity of metal-organic frameworks (MOFs) and the flexibility of their design, we have sought to combine their formation principles with the general versatility of glassy materials. Although the preparation of glassy MOFs can be achieved by amorphization of crystalline frameworks, transparent glassy MOFs exhibiting permanent porosity accessible to gases are yet to be reported. Here, we present a generalizable chemical strategy for making such MOF glasses by assembly from viscous solutions of metal node and organic strut and subsequent evaporation of a plasticizer-modulator solvent. This process yields glasses with 300 m(2)/g internal surface area (obtained from N2 adsorption isotherms) and a 2 nm pore-pore separation. On a volumetric basis, this porosity (0.33 cm(3)/cm(3)) is 3 times that of the early MOFs (0.11 cm(3)/cm(3) for MOF-2) and within range of the most porous MOFs known (0.60 cm(3)/cm(3) for MOF-5). We believe the porosity originates from a 3D covalent network as evidenced by the disappearance of the glass transition signature as the solvent is removed and the highly cross-linked nanostructure builds up. Our work represents an important step forward in translating the versatility and porosity of MOFs to glassy materials.

Incidence, clinical presentation, and predictors of early neoatherosclerosis after drug-eluting stent implantation.

BACKGROUND: Compared with bare-metal stents, neoatherosclerosis reportedly develops earlier and more frequently after drug-eluting stent (DES) implantation. This study evaluated the incidence, clinical presentation, and predictors of early neoatherosclerosis after DES implantation. METHODS: Neointimal characteristics were evaluated in 449 patients (482 lesions) who underwent follow-up optical coherence tomography ≤12 months after DES implantation (median 9.1 months) and displayed a mean neointimal thickness >100 µm. Neoatherosclerosis was defined as neointima with the presence of lipid or calcification. RESULTS: Early neoatherosclerosis, defined as occurrence of neoatherosclerosis within 12 months after DES implantation, was observed in 31 lesions (6.4%). Compared with patients without early neoatherosclerosis, those with early neoatherosclerosis presented with a higher incidence of clinical symptoms (13% vs 57%, respectively; P < .001) and had undergone a higher frequency of target-lesion revascularization (9% vs 55%, respectively; P < .001) at the time of optical coherence tomography follow-up. Multivariate logistic regression analysis showed that independent predictors of early neoatherosclerosis were hypertension (odds ratio 3.20, 95% CI 1.32-7.78, P = .010) and pre-stent low-density lipoprotein cholesterol ≥130 mg/dL at the time of the index procedure (odds ratio 3.89, 95% CI, 1.62-9.36, P = .002). CONCLUSIONS: Early neoatherosclerosis was detected in 6.4% of DES-treated lesions with neointimal thickness >100 µm at a median of 9.1 months after DES implantation. The occurrence of early neoatherosclerosis was significantly associated with presentation of clinical symptoms. Independent predictors of early neoatherosclerosis were hypertension and high pre-stent low-density lipoprotein cholesterol at the time of the index procedure.

Optical coherence tomography-based predictors for creatine kinase-myocardial band elevation after elective percutaneous coronary intervention for in-stent restenosis.

OBJECTIVES: We evaluated whether morphological characteristics of neointimal tissue of in-stent restenosis (ISR) lesions assessed by optical coherence tomography (OCT) affect periprocedural elevation of creatine kinase-myocardial band (CK-MB). BACKGROUND: The impact of neointimal characteristics of ISR lesions on periprocedural myocardial injury has not been sufficiently investigated. METHODS: A total of 125 patients with ISR lesions underwent elective percutaneous coronary intervention (PCI) and pre-PCI OCT examination. Measurements of CK-MB were performed upon hospitalization, before PCI, and every 8 hr for 24 hr after PCI. CK-MB elevation was defined as levels above the 99th percentile of the upper reference limit. Neoatherosclerosis was defined as neointima with lipid or calcification. RESULTS: Post-PCI CK-MB elevation was observed in 20 (16.0%) patients. The maximum length of consecutive cross-sections with neoatherosclerosis on the longitudinal axis of the stent was significantly larger in patients with post-PCI CK-MB elevation than in those without [8.8 mm (1.5-10.4) vs. 0.0 mm (0.0-1.0), P < 0.001], and thin-cap fibroatheroma (TCFA) were more frequently observed at the site of minimal lumen cross-sectional area in patients with post-PCI CK-MB elevation (55.0% vs. 1.9%, P < 0.001). Multivariate analysis revealed that the maximum length of segments with neoatherosclerosis [odds ratio (OR), 1.463; 95% confidence interval (CI), 1.090-1.962; P = 0.011] and TCFA (OR, 14.328; 95% CI, 1.118-183.628; P = 0.041) were independent predictors for post-PCI CK-MB elevation. CONCLUSIONS: A greater axial length of neoatherosclerosis and the presence of TCFA at the most stenotic site were significantly associated with post-PCI CK-MB elevation in ISR lesions.

Spontaneous Extraperitoneal Hematoma Related to May-Thurner Syndrome.

In this report, we describe a rare case: deep vein thrombosis due to May-Thurner syndrome with a spontaneous pelvic extraperitoneal hematoma. This unique challenge highlights balancing thrombosis treatment and bleeding risk. Endovascular treatment with delayed anticoagulation may be an alternative to surgery for stable retroperitoneal hematoma in May-Thurner syndrome patients.

Inflammation and platelet reactivity during adjunctive colchicine versus aspirin in patients with acute coronary syndrome treated with potent P2Y12 inhibitor.

Background: In patients undergoing percutaneous coronary intervention (PCI), the use of anti-inflammatory therapy with colchicine is associated with a reduction of recurrent ischemic events. The mechanisms of such findings are not fully elucidated. Objectives: To investigate the effects of colchicine versus aspirin on inflammation and platelet reactivity in patients with acute coronary syndrome (ACS) undergoing PCI. Methods: This observational study compared laboratory measurements in ACS patients receiving single antiplatelet therapy with ticagrelor or prasugrel plus colchicine (MACT) (n = 185) versus conventional dual-antiplatelet therapy (DAPT) with aspirin plus ticagrelor or prasugrel (n = 497). The primary outcome was the frequency of high residual inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L at 1 month post-PCI. Multiple sensitivity analyses were performed for the primary outcome, including multivariable adjustment, propensity-score matching, and inverse-probability weighted methods. Results: One month after PCI, patients treated with MACT had significantly lower levels of hs-CRP compared to those treated with DAPT (0.6 [0.4-1.2] vs. 0.9 [0.6-2.3] mg/L, p < 0.001). The frequency of high residual inflammation was also lower in the MACT group (10.8% vs. 27.2%, p < 0.001) (odds ratio [95% confidence interval] = 0.33 [0.20-0.54], p < 0.001). This effect was consistent across sensitivity analyses. There was no difference in platelet reactivity between MACT and DAPT (49.6 ± 49.0 vs. 51.5 ± 66.4 P2Y12 reaction unit [PRU] measured by VerifyNow, p = 0.776). Conclusion: In ACS patients undergoing PCI, MACT was associated with a lower rate of high residual inflammation without increasing platelet reactivity compared to conventional DAPT. Clinical trial registration: NCT04949516 for MACT pilot trial and NCT04650529 for Gyeongsang National University Hospital registry.

Macrophage-mannose-receptor-targeted photoactivatable agent for in vivo imaging and treatment of atherosclerosis.

Previous studies have demonstrated the effects of theranostic agents on atherosclerotic plaques. However, there is limited information on targeted theranostics for photodynamic treatment of atherosclerosis. This study aimed to develop a macrophage-mannose-receptor-targeted photoactivatable nanoagent that regulates atherosclerosis and to evaluate its efficacy as well as safety in atherosclerotic mice. We synthesised and characterised D-mannosamine (MAN)-polyethylene glycol (PEG)-chlorin e6 (Ce6) for phototheranostic treatment of atherosclerosis. The diagnostic and therapeutic effects of MAN-PEG-Ce6 were investigated using the atherosclerotic mouse model. The hydrophobic Ce6 photosensitiser was surrounded by the hydrophilic MAN-PEG outer shell of the self-assembled nanostructure under aqueous conditions. The MAN-PEG-Ce6 was specifically internalised in macrophage-derived foam cells through receptor-mediated endocytosis. After laser irradiation, the MAN-PEG-Ce6 markedly increased singlet oxygen generation. Intravital imaging and immunohistochemistry analyses verified MAN-PEG-Ce6's specificity to plaque macrophages and its notable anti-inflammatory impact by effectively reducing mannose-receptor-positive macrophages. The toxicity assay showed that MAN-PEG-Ce6 had negligible effects on the biochemical profile and structural damage in the skin and organs. Targeted photoactivation with MAN-PEG-Ce6 thus has the potential to rapidly reduce macrophage-derived inflammatory responses in atheroma and present favourable toxicity profiles, making it a promising approach for both imaging and treatment of atherosclerosis.

Nine-month angiographic and intravascular ultrasound outcomes after resolute zotarolimus-eluting stent implantation for the treatment of in-stent restenosis.

OBJECTIVES: We aimed to evaluate the mid-term outcomes of resolute zotarolimus-eluting stent (R-ZES) implantation for in-stent restenosis (ISR). BACKGROUND: There has been a paucity of data regarding the effects of new-generation drug-eluting stent to treat ISR. METHODS: From 2009 to 2010, a total of 98 patients with 98 ISR lesions were prospectively enrolled after R-ZES implantation for the treatment of ISR. Among 98 patients, 73 patients underwent follow-up angiography at 9 months. Serial intravascular ultrasound (IVUS) at both postprocedure and 9 months was evaluated in 55 patients. The overlapped segment of R-ZES was defined as the portion of R-ZES superimposed on previous stent. RESULTS: Late loss and binary restenosis rate were 0.3 ± 0.5 mm and 5.5% at 9 months. On IVUS, the percentage of neointimal volume and maximum percentage of neointimal area were 3.9 ± 6.3% and 17.3 ± 15.5%, respectively. There was no significant change of vessel volume index between postprocedure and 9 months (16.9 ± 4.7 mm³ /mm vs. 17.1 ± 4.6 mm³ /mm, P = 0.251). Late-acquired incomplete stent apposition was observed in 5 (5/55, 9.1%) cases. Compared with nonoverlapped segments of R-ZES, the overlapped did not show larger neointimal volume index (0.3 ± 0.5 mm³ /mm vs. 0.2 ± 0.3 mm³ /mm, P = 0.187) on 9-month IVUS. During follow-up (median, 353 days), repeat target-lesion revascularization was performed in four cases, but there were no death or stent thrombosis. CONCLUSIONS: This study suggested that R-ZES implantation for the treatment of ISR was effective up to 9 months and showed favorable vascular responses on serial IVUS assessment.

P2Y12 Inhibitor Monotherapy Combined With Colchicine Following PCI in ACS Patients: The MACT Pilot Study.

BACKGROUND: After a brief period of dual antiplatelet therapy, P2Y12 inhibitor monotherapy in the absence of aspirin effectively reduces bleeding without increasing recurrent ischemia in patients undergoing percutaneous coronary intervention (PCI). In addition, early anti-inflammatory therapies may have clinical benefits in acute coronary syndrome (ACS) patients. OBJECTIVES: The aim of this study was to investigate the feasibility of ticagrelor or prasugrel P2Y12 inhibitor monotherapy combined with colchicine immediately after PCI in patients with ACS. METHODS: This was a proof-of-concept pilot trial. ACS patients treated with drug-eluting stents were included. On the day after PCI, low-dose colchicine (0.6 mg daily) was administered in addition to ticagrelor or prasugrel maintenance therapy, whereas aspirin therapy was discontinued. The primary outcome was any stent thrombosis at 3 months. The key secondary outcomes were platelet reactivity measured by the VerifyNow assay (Accriva) before discharge and a reduction in high-sensitivity C-reactive protein (hs-CRP) over 1 month. RESULTS: We enrolled 200 patients, 190 (95.0%) of whom completed the 3-month follow-up. The primary outcome occurred in 2 patients (1.0%): 1 definite and 1 probable stent thrombosis. The level of platelet reactivity overall was 27 ± 42 P2Y12 reaction units, and only 1 patient had high platelet reactivity (>208 P2Y12 reaction units). The hs-CRP levels decreased from 6.1 mg/L (IQR: 2.6-15.9 mg/L) at 24 hours after PCI to 0.6 mg/L (IQR: 0.4-1.2 mg/L) at 1 month (P < 0.001), and the prevalence of high-inflammation criteria (hs-CRP ≥2 mg/L) decreased from 81.8% to 11.8% (P < 0.001). CONCLUSIONS: In ACS patients undergoing PCI, it is feasible to discontinue aspirin therapy and administer low-dose colchicine on the day after PCI in addition to ticagrelor or prasugrel P2Y12 inhibitors. This approach is associated with favorable platelet function and inflammatory profiles. (Mono Antiplatelet and Colchicine Therapy [MACT]; NCT04949516).

Preparation of Surfactant-Free Nano Oil Particles in Water Using Ultrasonic System and the Mechanism of Emulsion Stability.

Emulsion technology is widely used in the preparation of cosmetics, pharmaceuticals, drug delivery, and other daily necessities, and surfactants are frequently used to prepare these emulsions because of the lack of reliable surfactant-free emulsification techniques. This is disadvantageous because some surfactants pose health hazards, cause environmental pollution, have costly components, and place limitations on process development. In this paper, an efficient method for surfactant-free nano-emulsification is presented. In addition, we discuss the effects of different operating parameters on the oil particle size, as well as the effect of the particle size on the emulsion stability. Specifically, we compared three surfactant-free ultrasonic emulsification technologies (horn, bath, and focused ultrasonic systems). The focused ultrasonic system, which concentrates sound energy at the center of the dispersion system, showed the best performance, producing emulsions with a particle size distribution of 60-400 nm at 400 kHz. In addition, phase separation did not occur despite the lack of surfactants and thickeners, and the emulsion remained stable for seven days. It is expected to be widely used in eco-friendly emulsification processes.

Procedural Characteristics of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention and Their Clinical Implications.

Background Despite the clinical benefits to intravascular ultrasound (IVUS) guidance for percutaneous coronary intervention (PCI), most patients with coronary artery disease undergo angiography-guided PCI alone in the real-world setting. We sought to investigate the procedural characteristics of IVUS-guided PCI and their clinical outcomes, as compared with angiography-guided PCI. Methods and Results This was a cohort study using patient-level data from the IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) and ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions) clinical trials. A total of 2848 patients with 3872 native coronary lesions were included and procedural characteristics assessed by quantitative coronary angiography (QCA) were compared between IVUS and angiography guidance. Stent-to-reference vessel diameter ratio (ie, QCA stent sizing) was greater (1.11±0.16 versus 1.07±0.14, P<0.001) and high-pressure postdilation was more frequently performed (83.7% versus 75.4%, P<0.001) with IVUS guidance, whereas residual stent edge dissections were more frequent in lesions treated with IVUS guidance (4.6% versus 0.7%, P<0.001). Given the dissection risk, optimal QCA stent sizing for IVUS guidance was a stent-to-QCA reference vessel diameter ratio ≥1.1 to <1.3. Among 1424 patients (1969 lesions) treated with angiography guidance, QCA stent sizing <1.0 was observed in 651 (33.1%) lesions, while QCA stent sizing ≥1.1 to <1.3 was observed in only 526 (26.7%) lesions. Under angiography guidance, patients with both QCA stent sizing ≥1.1 to <1.3 and high-pressure postdilation (235 of 1424, 16.5%) had a lower risk of 3-year target lesion failure compared with others (hazard ratio, 0.532; 95% CI, 0.293-0.966 [P=0.038]). Conclusions IVUS-guided PCI resulted in larger QCA-assessed stent sizing and more frequent postdilation with high-pressure inflations. These procedures may further improve long-term clinical outcomes in patients undergoing PCI without IVUS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01308281 (IVUS-XPL); NCT02215915 (ULTIMATE).

Platelet Reactivity Was Not Associated with Infarct Size after Primary Percutaneous Coronary Intervention.

Potent antiplatelet therapy after primary percutaneous coronary intervention (PCI) has the potential to reduce infarct size. This study analyzed the association between on-treatment platelet reactivity and myocardial infarct size in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. In this single-center, retrospective study, 253 patients who underwent primary PCI for STEMI were divided into two groups according to platelet reactivity measurements (53 patients in the high platelet reactivity [HPR] group and 200 in the non-HPR group). Technetium Tc-99m tetrofosmin single-photon emission computed tomography (SPECT) was performed before hospital discharge. We measured the infarct size using SPECT imaging and serial cardiac biomarker levels, and compared the infarct sizes of each group. The patients with HPR were older (65.5±13.2 vs. 60.6±12.1 years, p=0.011) than the patients with non-HPR. On the other hand, the non-HPR group had a higher incidence of smoking (26.4% vs. 51.0%, p=0.001) than the HPR group. Infarct size was similar between the two groups (22.6±17.3% vs. 24.8±17.7%, p=0.416). Multivariate analysis revealed that onset to balloon time >240 min (odds ratio [OR]=1.92; 95% confidence interval [CI]=1.08-3.40; p=0.025) and anterior infarction (OR=5.28; 95% CI=3.05-9.14; p<0.001) were independent predictors of large (>22%) infarct size. HPR was not a predictor of infarct size assessed by SPECT. The two groups also showed analogous cumulative creatinine kinase-myocardial band and troponin T levels. In conclusion, compared to non-HPR, HPR showed no significant association with myocardial infarct size measured by SPECT imaging in early phase of MI.

Successful Therapy With Ticagrelor in Three-Vessel Stent Thrombosis Related to Clopidogrel Resistance.

A 65-year-old man developed 3-vessel stent thrombosis after percutaneous coronary intervention with aspirin and clopidogrel. Platelet tests revealed clopidogrel resistance, which resolved after changing clopidogrel to ticagrelor. Although routine platelet tests after stenting are not recommended, these tests may be considered to identify the cause of stent thrombosis and modify antiplatelet therapy.

Macrophage targeted theranostic strategy for accurate detection and rapid stabilization of the inflamed high-risk plaque.

Rationale: Inflammation plays a pivotal role in the pathogenesis of the acute coronary syndrome. Detecting plaques with high inflammatory activity and specifically treating those lesions can be crucial to prevent life-threatening cardiovascular events. Methods: Here, we developed a macrophage mannose receptor (MMR)-targeted theranostic nanodrug (mannose-polyethylene glycol-glycol chitosan-deoxycholic acid-cyanine 7-lobeglitazone; MMR-Lobe-Cy) designed to identify inflammatory activity as well as to deliver peroxisome proliferator-activated gamma (PPARγ) agonist, lobeglitazone, specifically to high-risk plaques based on the high mannose receptor specificity. The MMR-Lobe-Cy was intravenously injected into balloon-injured atheromatous rabbits and serial in vivo optical coherence tomography (OCT)-near-infrared fluorescence (NIRF) structural-molecular imaging was performed. Results: One week after MMR-Lobe-Cy administration, the inflammatory NIRF signals in the plaques notably decreased compared to the baseline whereas the signals in saline controls even increased over time. In accordance with in vivo imaging findings, ex vivo NIRF signals on fluorescence reflectance imaging (FRI) and plaque inflammation by immunostainings significantly decreased compared to oral lobeglitazone group or saline controls. The anti-inflammatory effect of MMR-Lobe-Cy was mediated by inhibition of TLR4/NF-κB pathway. Furthermore, acute resolution of inflammation altered the inflamed plaque into a stable phenotype with less macrophages and collagen-rich matrix. Conclusion: Macrophage targeted PPARγ activator labeled with NIRF rapidly stabilized the inflamed plaques in coronary sized artery, which could be quantitatively assessed using intravascular OCT-NIRF imaging. This novel theranostic approach provides a promising theranostic strategy for high-risk coronary plaques.

Factors Related to Major Bleeding After Ticagrelor Therapy: Results from the TICO Trial.

Background There is a lack of data on factors that are related to clinically relevant bleeding after ticagrelor treatment. We investigated the clinical and procedural factors related to major bleeding in patients with acute coronary syndrome treated with ticagrelor after coronary stent implantation. Methods and Results From the TICO (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome) randomized trial, a total of 2660 patients were included for the present study. Patients with major bleeding, defined by TIMI (Thrombolysis in Myocardial Infarction) major or Bleeding Academic Research Consortium type 3 or 5, were compared with those without major bleeding. On the basis of multivariable and receiver operating characteristic curve analyses, weight ≤65 kg, hemoglobin ≤12 g/dL, and estimated glomerular filtration rate <60 mL/min per 1.73 m2 were associated with an increased risk of major bleeding. In contrast, 3-month aspirin therapy with continued ticagrelor (versus 12-month aspirin and ticagrelor) was associated with a decreased risk of major bleeding. The lower risk of a net adverse clinical event (a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients treated with 3-month aspirin therapy reported from the TICO trial remained valid in patients with any of these risk factors (hazard ratio, 0.59; 95% CI, 0.39-0.90; Pinteraction=0.74). Conclusions Low body weight, anemia, and chronic kidney disease were risk factors for major bleeding after ticagrelor therapy. Early aspirin discontinuation had a net clinical benefit among patients with a bleeding risk. Registration URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02494895.

1-Month Dual-Antiplatelet Therapy Followed by Aspirin Monotherapy After Polymer-Free Drug-Coated Stent Implantation: One-Month DAPT Trial.

OBJECTIVES: The aim of this study was to determine whether 1 month of dual-antiplatelet therapy (DAPT) followed by aspirin monotherapy after polymer-free drug-coated stent (PF-DCS) implantation is noninferior to 6 to 12 months of DAPT after biodegradable-polymer drug-eluting stent (BP-DES) implantation. BACKGROUND: It is necessary to determine the optimal minimal duration of DAPT followed by aspirin monotherapy after percutaneous coronary intervention (PCI). METHODS: In this trial, 3,020 patients with coronary artery disease considered for PCI for noncomplex lesions were randomized to 1-month DAPT after PF-DCS (n = 1,507) or 6- to 12-month DAPT after BP-DES (n = 1,513). The primary endpoint was the 1-year composite of cardiac death, nonfatal myocardial infarction, target vessel revascularization, stroke, or major bleeding (noninferiority hypothesis margin of 3%). RESULTS: The primary endpoint occurred in 88 patients (5.9%) in the 1-month DAPT after PF-DCS group and 98 patients (6.5%) in the 6- to 12-month DAPT after BP-DES group (absolute difference -0.7%; upper limit of 1-sided 97.5% confidence interval: 1.33%; P < 0.001 for noninferiority). The occurrence of major bleeding was not different (1.7% vs 2.5%; P = 0.136). There was no difference in the occurrence of stent thrombosis (0.7% vs 0.8%; P = 0.842). CONCLUSIONS: Among patients who underwent PCI for noncomplex lesions, 1-month DAPT followed by aspirin monotherapy after PF-DCS implantation was noninferior to 6- to 12-month DAPT after BP-DES implantation for the 1-year composite of cardiovascular events or major bleeding. The present findings need to be interpreted in the setting of different types of stents according to antiplatelet strategy. (A Randomized Controlled Comparison Between One Versus More Than Six Months of Dual Antiplatelet Therapy After Biolimus A9-Eluting Stent Implantation; NCT02513810).

Safety of 3-Month Dual Antiplatelet Therapy After Implantation of Ultrathin Sirolimus-Eluting Stents With Biodegradable Polymer (Orsiro): Results From the SMART-CHOICE Trial.

Background This study sought to investigate the safety of 3-month dual antiplatelet therapy (DAPT) in patients receiving ultrathin sirolimus-eluting stents with biodegradable polymer (Orsiro). Methods and Results The SMART-CHOICE (Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Anti- platelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents) randomized trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT in 2993 patients undergoing percutaneous coronary intervention. The present analysis was a prespecified subgroup analysis for patients receiving Orsiro stents. As a post hoc analysis, comparisons between Orsiro and everolimus-eluting stents were also done among patients receiving 3-month DAPT. Of 972 patients receiving Orsiro stents, 481 patients were randomly assigned to 3-month DAPT and 491 to 12-month DAPT. At 12 months, the target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization, occurred in 8 patients (1.7%) in the 3-month DAPT group and in 14 patients (2.9%) in the 12-month DAPT group (hazard ratio [HR], 0.58; 95% CI, 0.24-1.39; P=0.22). In whole population who were randomly assigned to receive 3-month DAPT (n=1495), there was no significant difference in the target vessel failure between the Orsiro group and the everolimus-eluting stent group (n=1014) (1.7% versus 1.8%; HR, 0.96; 95% CI, 0.41-2.22; P=0.92). Conclusions In patients receiving Orsiro stents, clinical outcomes at 1 year were similar between the 3-month DAPT followed by P2Y12 inhibitor monotherapy and 12-month DAPT strategies. With 3-month DAPT, there was no significant difference in target vessel failure between Orsiro and everolimus-eluting stents. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02079194.

Nonhumidified intermediate temperature fuel cells using protic ionic liquids.

In this paper, the characterization of a protic ionic liquid, diethylmethylammonium trifluoromethanesulfonate ([dema][TfO]), as a proton conductor for a fuel cell and the fabrication of a membrane-type fuel cell system using [dema][TfO] under nonhumidified conditions at intermediate temperatures are described in detail. In terms of physicochemical and electrochemical properties, [dema][TfO] exhibits high activity for fuel cell electrode reactions (i.e., the hydrogen oxidation reaction (HOR) and oxygen reduction reaction (ORR)) at a Pt electrode, and the open circuit voltage (OCV) of a liquid fuel cell is 1.03 V at 150 degrees C, as has reported in ref 27. However, diethylmethylammonium bis(trifluoromethane sulfonyl)amide ([dema][NTf(2)]) has relatively low HOR and ORR activity, and thus, the OCV is ca. 0.7 V, although [dema][NTf(2)] and [dema][TfO] have an identical cation ([dema]) and similar thermal and bulk-transport properties. Proton conduction occurs mainly via the vehicle mechanism in [dema][TfO] and the proton transference number (t(+)) is 0.5-0.6. This relatively low t(+) appears to be more disadvantageous for a proton conductor than for other electrolytes such as hydrated sulfonated polymer electrolyte membranes (t(+) = 1.0). However, fast proton-exchange reactions occur between ammonium cations and amines in a model compound. This indicates that the proton-exchange mechanism contributes to the fuel cell system under operation, where deprotonated amines are continuously generated by the cathodic reaction, and that polarization of the cell is avoided. Six-membered sulfonated polyimides in the diethylmethylammonium form exhibit excellent compatibility with [dema][TfO]. The composite membranes can be obtained up to a [dema][TfO] content of 80 wt % and exhibit good thermal stability, high ionic conductivity, and mechanical strength and gas permeation comparable to those of hydrated Nafion. H(2)/O(2) fuel cells prepared using the composite membranes can successfully operate at temperatures from 30 to 140 degrees C under nonhumidified conditions, and a current density of 250 mA cm(-2) is achieved at 120 degrees C. The protic ionic liquid and its composite membrane are a possible candidate for an electrolyte of a H(2)/O(2) fuel cell that operates under nonhumidified conditions.