De-escalation strategies in patients with acute coronary syndrome: a step towards precision medicine.

INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a cornerstone in the treatment of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Current international guidelines recommend the use of 12 months of DAPT with newer P2Y12 inhibitors (i.e. ticagrelor or prasugrel) as first-line therapy in this setting. However, intense and prolonged DAPT regimens are associated with an increased risk of bleeding, with relevant prognostic implications. Recently, a strategy of de-escalation of P2Y12 inhibitors has been proposed as an alternative to conventional DAPT to mitigate the risk of bleeding while preserving ischemic protection after ACS. AREAS COVERED: In this review, we summarize the available evidence on guided and unguided strategies for P2Y12 inhibitor de-escalation in patients with ACS undergoing PCI. EXPERT OPINION: Among patients with ACS, guided and unguided de-escalation strategies are safe and effective for secondary cardiovascular prevention. Although the implementation of genetic and platelet function tests is of interest for treatment personalization, the routine use of guided de-escalation strategies seems impractical. In this context, unguided de-escalation approaches appear more attractive, convenient, and suitable for contemporary practice.

[New frontiers in antiplatelet therapy: guided therapy and de-escalation after acute coronary syndrome or percutaneous coronary intervention]. / Le nuove frontiere della terapia antiaggregante: terapia guidata e de-escalation dopo sindrome coronarica acuta o rivascolarizzazione coronarica percutanea.

Dual antiplatelet therapy (DAPT) is a cornerstone in the management of patients with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). The use of intensified or prolonged antithrombotic regimens is invariably associated with a reduction in ischemic risk yet an increase in the risk of bleeding complications. The selection of the optimal antiplatelet therapy in each individual patient remains therefore crucial. In recent years, novel approaches alternative to the conventional DAPT and based on the escalation or de-escalation of P2Y12 antagonists have been proposed. These strategies, chosen according to clinical features, genetic factors, and platelet function, have been developed to optimize and individualize the treatment of patients with coronary artery disease and improve their prognosis. In this review, we summarize recent evidence about escalation and de-escalation strategies (guided and unguided), and discuss the utility of genetic and platelet function tests in patients with ACS and/or undergoing PCI.

Antithrombotic Therapy Optimization in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

The antithrombotic management of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) poses numerous challenges. Triple antithrombotic therapy (TAT), which combines dual antiplatelet therapy (DAPT) with oral anticoagulation (OAC), provides anti-ischemic protection but increases the risk of bleeding. Therefore, TAT is generally limited to a short phase (1 week) after PCI, followed by aspirin withdrawal and continuation of 6-12 months of dual antithrombotic therapy (DAT), comprising OAC plus clopidogrel, followed by OAC alone. This pharmacological approach has been shown to mitigate bleeding risk while preserving adequate anti-ischemic efficacy. However, the decision-making process remains complex in elderly patients and those with co-morbidities, significantly influencing ischemic and bleeding risk. In this review, we discuss the available evidence in this area from randomized clinical trials and meta-analyses for post-procedural antithrombotic therapies in patients with non-valvular AF undergoing PCI.

[Anti-inflammatory therapies for cardiovascular diseases: novel evidence, clinical implications, and future perspectives]. / Terapie antinfiammatorie in pazienti con malattie cardiovascolari: nuove evidenze, implicazioni cliniche e prospettive.

Inflammation plays an important role in cardiovascular disease. Growing evidence suggests a profound involvement of the inflammatory response in the development and progression of atherosclerosis and its complications. In patients with atherosclerotic cardiovascular disease (ASCVD), residual cardiovascular risk often remains high despite optimal medical therapy and the achievement of the therapeutic targets recommended by current guidelines. Among the multiple components of residual risk, residual inflammatory risk, assessed by plasma levels of high-sensitivity C-reactive protein, has shown a strong association with the incidence of cardiovascular events. Recent studies suggest that therapeutic modulation of inflammation, particularly the interleukin (IL)-1/IL-6 pathway, is a promising strategy for the prevention and treatment of cardiovascular and kidney diseases. This review aims to discuss pragmatically the interaction between inflammation and ASCVD, describe current evidence on anti-inflammatory therapies in patients with cardiovascular and renal diseases, and outline the potential implications of these new therapeutic approaches in contemporary and future practice.

Escalation and De-Escalation of Antiplatelet Therapy after Acute Coronary Syndrome or PCI: Available Evidence and Implications for Practice.

Dual antiplatelet therapy (DAPT) is the gold standard for the antithrombotic management of patients with an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Implementation of intensified or prolonged DAPT regimens has proven to lower the risk of ischemic events but at the expense of increased bleeding. Importantly, bleeding is a predictor of poor prognosis. Risk stratification and selection of tailored antiplatelet strategies to maximize the net clinical benefit in individual patients with ACS or undergoing PCI is therefore potentially beneficial. Recently, novel approaches including DAPT de-escalation or escalation have been proposed as possible alternatives to standard DAPT. These strategies, which are generally based on patient's risk profile, genetics, and/or platelet function have been proposed to offer more tailored treatments in patients with ACS or PCI, with the ultimate goal of providing adequate ischemic protection while mitigating the risk of bleeding. This review summarizes the available evidence on DAPT de-escalation or escalation (both guided and unguided) and discusses the practical implications of these strategies in the contemporary management of patients with ACS and/or undergoing PCI.

Chiral sulfoxides as activators of allyl trichlorosilanes in the stereoselective allylation of aldehydes.

Chiral aryl methyl sulfoxides proved to be efficient activators in the asymmetric allylation of aldehydes with allyl trichlorosilanes. High enantioselectivity was found in the case of electron-poor aldehydes. The high levels of diastereoselectivity and the detection of nonlinear effects have allowed the elucidation of some mechanistic aspects of the reaction.