P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS.

P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial.

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).

Safety and effectiveness of introducing a robotic-assisted percutaneous coronary intervention program in a tertiary center: a prospective study.

Background: Robotic-assisted percutaneous coronary intervention (PCI) is a novel technology that permits remote operation of interventional devices. However, little is known about the safety and effectiveness of introducing a robotic PCI program in a hospital already experienced in traditional coronary angioplasty. Methods: Prospective single-arm survey to assess the safety and effectiveness of robotic-assisted PCI in comparison to pre-defined performance goals. The study cohort comprised all consecutive cases treated with robotic PCI since its introduction. The safety primary endpoint was a composite of (I) overall death or (II) non-fatal adverse events related to target vessel complications (stent thrombosis, myocardial infarction, vessel perforation or cardiac tamponade, or repeat invasive treatment) during the index hospitalization. The efficacy primary endpoint was robotic-assisted procedural success, a composite of (I) successful dilatation of the target lesion and (II) successful robotic assistance, defined as absent non-planned manual conversion. Results: A total of 83 patients and 112 lesions were prospectively enrolled. The rate of angiographic success was 99.1%. From these, 97 lesions (86.6%) were treated with only robotic PCI or with hybrid according to the pre-interventional plan. The rates of efficacy and safety primary endpoints were 85.7% and 2.4% respectively (P<0.01 for non-inferior to the pre-defined performance threshold). Conclusions: Introduction of robotic-assisted PCI in a tertiary center was associated with safe and effective results, comparable to pre-defined goals of optimal performance.

Use of robotic assistance to reduce proximity and air-sharing during percutaneous cardiovascular intervention.

Aim: Traditional percutaneous cardiovascular interventions require close physical proximity between the patients and the healthcare team, posing occupational hazards that range from radiation exposure to interpersonal air contamination. Materials & methods: Prospective single-arm pilot study (n = 10) to investigate robotic-assisted intervention as a strategy to reduce proximity during the procedure. Primary end point: composite of angiographic success, intervention performed with the team positioned >2 meters from the patient for ≥50% procedure duration, and absence of in-hospital death or acute target lesion occlusion. Results: The composite primary end point was achieved in 100% of cases. Conclusion: Robotic-assisted percutaneous intervention provided successful invasive treatment while reducing proximity and shared air space between the care-delivery team and the patient during the procedure. Trial registration number: NCT04379453 (Clinicaltrials.gov).

Lay abstract Minimally invasive therapies for cardiovascular diseases are techniques that limit the size of incisions needed and so lessen wound healing time, but traditionally require close contact between the patients and the healthcare team. This fact poses hazards that range from radiation exposure to the spread of airborne diseases. We developed a small study of ten patients to investigate whether a new method of robotic-assisted stent implantation for the treatment of a heart attack would reduce proximity between the patient and medical staff during the procedure. To evaluate the effectiveness of that strategy, we assessed the success of the procedure (by analyzing the images of the operation), the amount of time the team was positioned more than 2 meters from the patient and the occurrence of complications during the hospitalization. We concluded that this method of robotic-assisted stent implantation after a heart attack provided successful treatment while reducing proximity and shared air space between the care-delivery team and the patient.

Robotic-assisted intervention strategy to minimize air exposure during the procedure: a case report of myocardial infarction and COVID-19.

Percutaneous coronary interventions (PCI) is traditionally a manual procedure executed by one or more operators positioned at a close distance from the patient. The ongoing pandemic of coronavirus disease 2019 (COVID-19) has imposed severe restrictions to such an interventional environment. The novel SARS-CoV-2 virus that causes COVID-19 is transmitted mainly through expelled respiratory particles, which are known to travel approximately 3-6 feet away from infected persons. During PCI, that contamination range obligatorily poses the team and the patient to direct air exposure. We herein present a case report with the description of a minimum-contact strategy to reduce interpersonal air exposure during PCI. The approach designed to minimize proximity between the patient and the healthcare team included the performance of robotic-assisted PCI, operated by unscrubbed cardiac interventionalists from a control cockpit located outside the catheterization suite. Also included, was the delineation of the potential zone of respiratory particle spread; a circle measuring 4 meters (13.1 feet) in diameter was traced on the floor of the cath lab with red tape, centered on the patient's mouth and nose. The team was rigorously trained and advised to minimize time spent within the 4-meter perimeter as much as possible during the procedure. Following this strategy, a 60-year-old male with non-ST-elevation myocardial infarction and COVID-19 was treated with successful coronary implantation of two stents in the obtuse marginal branch and one stent in the circumflex artery. The total duration of the procedure was 103 minutes and 22 seconds. During most of the procedure, the 4-meter spread zone was not entered by any personnel. For each individual team member, the proposed strategy was effective in ensuring that they stayed outside of the 4-meter area for the majority of their work time, ranging from 96.9% to 59.7% of their respective participation. This case report illustrates the potential of robotic-assisted percutaneous coronary intervention in reducing physical proximity between the team and the patient during the procedure.

Association between Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios and Coronary Artery Calcification Score among Asymptomatic Patients: Data from a Cross-Sectional Study.

INTRODUCTION: Atherosclerosis is a low-grade inflammatory disease. Among markers of inflammation, importance has been given to the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). The objective of this study was to examine the association between these hematological indices of inflammation and coronary atherosclerotic calcification in clinically asymptomatic patients. METHODS: This study had clinical and laboratorial data collected from consecutive asymptomatic patients that underwent computed tomography coronary artery calcium (CAC) scoring. Risk factors, NLR, and PLR were evaluated at different categories of CAC scoring. Statistical tests included chi-square, linear regression, and logistic regression. Patients (N = 247; age 60.4 ± 8.0 years and 60.7% men) were allocated into four categories according to the CAC score. RESULTS: Respective age, sex (male), NLR, and PLR distribution within groups were as follows: CAC = 0 (n = 98; 52.5 ± 13.6 years, 55%, 2.0 ± 1.0, and 121.5 ± 41.5), CAC 1-100 (N = 64; 61.3 ± 11.0 years, 60%, 2.2 ± 1.2, and 125.6 ± 45.6), CAC 101-400 (N = 37; 64.2 ± 11.6 years, 67%, 2.6 ± 1.3, and 125.4 ± 55.9), and CAC > 400 (N = 48; 69.3 ± 11.1 years, 66%, 3.3 ± 2.0, and 430.1 ± 1787.4). The association between risk factors and CAC score was assessed. Hypertension status and smoking status were similar within groups, while the presence of diabetes (P = 0.02) and older age (P ≤ 0.001) was more prevalent in the CAC > 400 group. LDL cholesterol was greater in the higher CAC score groups (P = 0.002). Multivariate logistic regression of the quartile analysis showed that age and NLR were independently associated with CAC > 100 (OR (CI), P value): 2.06 (1.55-2.73, P = 0.00001) and 1.82 (1.33-2.49, P = 0.0002), respectively. CONCLUSION: Within asymptomatic patients, NLR provides additional risk stratification, as an independent association between NLR extent and CAD extent was identified. Moreover, PLR was not an inflammation marker for CAD severity.

Regression of Atherosclerotic Plaques of Cholesterol-Fed Rabbits by Combined Chemotherapy With Paclitaxel and Methotrexate Carried in Lipid Core Nanoparticles.

In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once/week: LDE-PTX (n = 10; 4 mg/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: -49% in LDE-PTX and -59% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in -57%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor α gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions.

Effectiveness and safety of iodopovidone in an experimental pleurodesis model.

OBJECTIVES: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model. METHODS: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine) and immunological (Interleukin-8 [IL-8], VEGF and TGFß) parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura) and microscopic (pleura and retina) analyses were performed. RESULTS: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10%) correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits. CONCLUSION: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated.

Effectiveness and safety of iodopovidone in an experimental pleurodesis model

OBJECTIVES: Chemical pleurodesis is an important therapeutic tool to control recurrent malignant pleural effusion. Among the various sclerosing agents, iodopovidone is considered effective and safe. However, in a recent study, ocular changes were described after iodopovidone was used in recurrent pneumothorax. The aim of the study was to evaluate the efficacy and morbidity of iodopovidone pleurodesis in an experimental model. METHODS: New Zealand rabbits were submitted to intrapleural injection of iodopovidone at concentrations of 2%, 4% and 10%. Biochemical (lactic dehydrogenase, proteins, triiodothyronine, free thyroxine, urea and creatinine) and immunological (Interleukin-8 [IL-8], VEGF and TGFβ) parameters were measured in the pleural fluid and blood. After 1, 3, 7, 14 and 28 days, groups of animals were euthanized, and macro- (pleura) and microscopic (pleura and retina) analyses were performed. RESULTS: An early pleural inflammatory response with low systemic repercussion was observed without corresponding changes in thyroid or renal function. The higher concentrations (4% and 10%) correlated with greater initial exudation, and maximum pleural thickening was observed after 28 days. No changes were observed in the retinal pigment epithelium of the rabbits. CONCLUSION: Iodopovidone is considered to be an effective and safe sclerosing agent in this animal model. However, its efficacy, tolerance and safety in humans should be further evaluated. .