Is There Long-Term Clinical Equipoise Between CABG and PCI for Isolated Left Anterior Descending Artery Disease?

© 2023 Society for Cardiovascular Angiography and Interventions Foundation. Published by Elsevier Inc. on behalf of the Society for Cardiovascular Angiography and Interventions Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Rationale and design of PREvalence of DyspneA in patients treated with TicagrelOR (PREDATOR) program

Background: Ticagrelor, a reversible P2Y12 inhibitor, is a mainstay of antiplatelet strategy in patients withacute coronary syndrome (ACS). However, a large number of ticagrelor-induced dyspnea decrease patients’adherence and reduce an overall efficacy of the therapy. Design: The PREDATOR program consists of phase III and IV, multicenter, randomized, double-blind,placebo-controlled clinical trials and preceding pilot studies that assesses the prevalence and treatmentof ticagrelor-induced dyspnea in coronary artery disease (CAD) and ACS patients. The PREDATOR LDis designed to evaluate the occurrence of dyspnea after 180 mg ticagrelor loading dose, and relief ofdyspnea by theophylline administration in low-to-high risk acute coronary syndromes without ST-segmentelevation (NSTE-ACS) and stable CAD designated to undergo invasive treatment. The PREDATOR MD isa cross-over trial in stable CAD patients 1 year after percutaneous coronary intervention for ACS. Enrolledpatients will be randomized to one of four antiplatelet treatment regimens (ticagrelor 2x90 mg, ticagrelor2x60 mg, ticagrelor 2x45 mg or clopidogrel 75 mg [morning]+placebo [evening]) or placebo and will beassessed for dyspnea at the day 7, then undergo a switch of treatment and reassessment at day 14. Thesample size will be estimated based on preceding pilot studies. Discussion: The PREDATOR LD is expected to prospectively assess dyspnea rate with a loading doseof ticagrelor, and analyze a potential of theophylline to elevate symptoms of ticagrelor-induced dyspnea,while the PREDATOR MD will prospectively assess dyspnea and adverse events rate with a maintenancedose of P2Y12 inhibitors prospectively assess. All evaluations will be conducted using standardizedmetrics for dyspnea quantification

Fractional flow reserve and intravascular scan as part of the coronary fistulas diagnostic process: Future perspectives

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When a meta-analysis equals a single large-scale trial with meaningful follow-up

© 2021 The Author(s). Published on behalf of the European Society of Cardiology. All rights reserved. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/eurheartj/ehab460This commentary refers to ‘Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis’, by E.P. Navarese et al. doi:10.1093/ eurheartj/ehab246 and the discussion piece ‘In the pool: dilution or drowning?’, by V. Dayan et al. doi:10.1093/ eurheartj/ehab443Peer reviewe

Diabetogenic effect of statins: a comprehensive review on the clinical relevance, underlying pathomechanisms and rationale for tailored statin therapy

Statins are potent hypolipidemic drugs effectively reducing low-density lipoprotein (LDL) cholesterol serum concentration, but also exerting a wide range of pleiotropic effects. In numerous clinical trials statins were proven to substantially decrease cardiovascular morbidity and mortality both in primary and secondary prevention. However, a growing body of evidence suggests that statins, although safe and generally well-tolerated, are associated with an increased occurrence of new-onset diabetes mellitus (DM). The aim of this review is to explore the relationship between statin therapy and new-onset DM, including its clinical relevance and underlying pathomechanisms, and to discuss the concept of tailored statin therapy. According to our recently published comprehensive network meta-analysis including 113,394 patients, the high-dose statin regimens were connected with an elevated risk of new-onset DM as compared with moderate-dose statin regimens and a gradient for the risk of new-onset DM across different types and doses of statins was demonstrated. There are multiple possible mechanisms explaining the diabetogenic effect of statins (e.g., decreased insulin secretion, induction of b-cell apoptosis, increased insulin resistance or compromised glucose transport into the cells). Statins are among the most widely used drugs worldwide and physicians should be aware of the fact that there is a risk of new-onset DM across different types and doses of statins. Selection of adequate statin that suits patient’s needs remains the challenge of hypolipidemic therapy. The identification of individuals who would benefit more from smaller doses and/or use of less diabetogenic compounds could help to optimize the treatment and reduce the number of patients developing DM. The non-pharmacological approach such as adequate physical activity, weight reduction and low fat diet should not be neglected either. These actions create a chance to decrease baseline LDL-cholesterol concentration and reduce the number of both cardiovascular and DM risk factors. All in all, statins with their exceptional cardiovascular benefits will undoubtedly defend their position of a cornerstone of cardiovascular prevention because profits derived from statin therapy far exceed the potential harms connected with statin-induced impairments of glucose metabolism

Intracoronary versus intravenous abciximab administration in STEMI patients: overview of current status and open questions

Objectives: To perform a systematic review to provide rationale for intracoronary (IC) abciximab administration in patients with ST-segment elevation myocardial infarction (STEMI), to summarize recent studies comparing IC vs. intravenous (IV) abciximab administration in this setting and to define questions that need to be answered in future trials determining the optimal abciximab regimen. Methods: A search covering the period from January 1993 to June 2011 was conducted by two independent investigators using MEDLINE, CENTRAL and Google Scholar databases. Proceedings from the scientific sessions of ACC, AHA, ESC, TCT and EuroPCR were also considered. Results: IC administration allows one to obtain a much higher concentration of abciximab than IV injection at the culprit lesion. Therefore it is hypothesized that IC abciximab administration provides more efficient GP IIb/IIIa receptor inhibition and more pronounced additional dose-dependent antiplatelet, antithrombotic, and antiinflammatory effects when compared to the IV route. Numerous observational and randomized studies comparing IC vs. IV abciximab in STEMI patients indicated improvement in different surrogate end points (infarct size, obstruction of coronary microcirculation, ST segment resolution, inflammatory mediators and markers of platelet activation) related to IC administration. The evidence supporting clinical benefits associated with IC injection of abciximab comes from one randomized and several non-randomized trials as most of the studies were underpowered to assess clinical outcomes. No difference in bleeding complications was observed between IC and IV regimens. Issues that need to be addressed in future studies include: the use of IC abciximab in combination with thrombectomy, the role of selective delivery systems, and the necessity of a prolonged IV infusion of abciximab after IC bolus administration. Conclusions: An accumulating body of evidence suggests the superiority of IC over IV abciximab administration in STEMI patients. However, further trials are warranted to establish the optimal strategy of abciximab treatment in this setting

Genetic determinants of platelet response to clopidogrel

Antiplatelet agents are the mainstay treatment in the prevention and management of atherothrombotic complications. However, a substantial interpatient variability in response to clopidogrel has been reported. Furthermore, patients with coronary artery disease and lesser platelet inhibition in response to clopidogrel are at increased risk for cardiovascular events. Clopidogrel after absorption requires two-step oxidation by the hepatic cytochrome P450 to generate its active metabolite. Polymorphisms of genes encoding the cytochrome enzymes and P-glycoprotein involved in clopidogrel absorption are regarded as major determinants of the interindividual variability in the clopidogrel-induced platelet inhibition. In our review we discuss the prevalence and clinical significance of various alleles of the genes: CYP2C19 and ABCB1 in the setting of coronary artery disease. Allele CYP2C19*2 is associated with excess of ischaemic events including myocardial infarction and stent thrombosis. On the other hand, CYP2C19*17 allele poses a serious threat of bleeding. Data concerning the prognostic value of genetic variant 3435C?T of ABCB1 remain inconclusive

Montessori's mediation of meaning: a social semiotic perspective

The distinctive objects designed by Dr Maria Montessori as the centrepiece of her approach to pedagogy are the topic of this study. The Montessori approach to pedagogy, celebrating its centenary in 2007, continues to be used in classrooms throughout the world. Despite such widespread and enduring use, there has been little analysis of the Montessori objects to evaluate or understand their pedagogic impact. This study begins by outlining the provenance of the Montessori objects, reaching the conclusion that the tendency to interpret them from the perspective of the progressive education movement of the early twentieth century fails to provide insights into the developmental potential embodied in the objects. In order to appreciate that potential more fully, the study explores the design of the objects, specifically, the way in which the semiotic qualities embodied in their design orient children to the meanings of educational knowledge. A meta-analytic framework comprising three components is used to analyse the semiotic potential of the Montessori objects as educational artefacts. First, Vygotsky’s model of development is used to analyse the objects as external mediational means and to recognise the objects as complexes of signs materialising educational knowledge. In order to understand how the objects capture, in the form of concrete analogues, the linguistic meanings which construe educational knowledge, systemic functional linguistics, the second component of the framework, is used to achieve a rich and detailed social semiotic analysis of these relations, in particular, material and linguistic representations of abstract educational meanings. Finally, the pedagogic device, a central feature of Bernstein’s sociology of pedagogy, is used to analyse how the Montessori objects re-contextualise educational knowledge as developmental pedagogy. Particular attention is paid to the Montessori literacy pedagogy, in which the study of grammar plays a central role. The study reveals a central design principle which distinguishes the Montessori objects. This principle is the redundant representation of educational knowledge across multiple semiotic modes. Each representation holds constant the underlying meaning relations which construe quanta of educational knowledge, giving children the freedom to engage with this knowledge playfully, independently and successfully. The conclusion drawn from this study is that the design of the Montessori objects represents valuable educational potential which deserves continued investigation, as well as wider recognition and application. To initiate this process, the findings in this study may provide insights which can be used to develop tools for evaluating and enhancing the implementation of Montessori pedagogy in Montessori schools. The findings may also be used to adapt Montessori design principles for the benefit of educators working in non-Montessori contexts, in particular, those educators concerned with developing pedagogies which promote equitable access to educational knowledge