Current Strategies to Guide the Antiplatelet Therapy in Acute Coronary Syndromes.

The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological basis of the treatment depends on platelet biology and physiology, and the interplay between these aspects and clinical practice must guide the physician in determining the best therapeutic options for patients with acute coronary syndromes. In the present narrative review, we discuss the latest novelties in the antiplatelet therapy of patients with acute coronary syndromes. We start with a description of platelet biology and the role of the main platelet signal pathways involved in platelet aggregation during an acute coronary syndrome. Then, we present the latest evidence on the evaluation of platelet function, focusing on the strengths and weaknesses of each platelet's function test. We continue our review by describing the role of aspirin and P2Y12 inhibitors in the treatment of acute coronary syndromes, critically appraising the available evidence from clinical trials, and providing current international guidelines and recommendations. Finally, we describe alternative therapeutic regimens to standard dual antiplatelet therapy, in particular for patients at high bleeding risk. The aim of our review is to give a comprehensive representation of current data on antiplatelet therapy in patients with acute coronary syndromes that could be useful both for clinicians and basic science researchers to be up-to-date on this complex topic.

[The IN-HF Registry: the history and the scientific production for the Italian cardiology community]. / Il programma IN-HF: la storia e la produzione scientifica a favore della comunità cardiologica italiana.

The Italian Network on Congestive Heart Failure (IN-CHF) project, later known as IN-HF Online, was launched in 1995 to provide the Italian cardiology community with a digital tool, standardized across the country, for managing outpatients with heart failure (HF), that enabled the creation of a database for clinical, educational and scientific purposes. During its almost three decades of activity, this observational research program has achieved highly positive scientific results. Indeed, IN-HF fostered professional relationships among individuals working in different centers, established a cultural network for the care of HF patients, periodically updated on the scientific advances, and allowed the assessment of several clinical, epidemiological, and prognostic features. These findings have been published in numerous national and international journals, as summarized in the present overview.

Gender differences in the development of heart failure after acute coronary syndrome: Insight from the CORALYS registry.

BACKGROUND: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. METHODS: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. RESULTS: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. CONCLUSIONS: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.

Clinical Outcomes of Percutaneous Left-Atrial Appendage Occlusion with Conscious Sedation without an Anesthesiologist on Site: Results from a Multicenter Study.

Background and Objectives: Percutaneous left-atrial appendage (LAA) occlusion is an important therapeutic option for preventing cardioembolic stroke in patients with non-valvular atrial fibrillation (AF) at high risk of thromboembolic events and with contraindications for oral anticoagulation (OAC). It is usually performed with transesophageal echocardiography (TOE) guidance under general anesthesia (GA). In this retrospective study, we present a multicenter experience of LAA occlusion performed with conscious sedation (CS) without an anesthesiologist on site. Materials and Methods: All the patients on the waiting list for LAA occlusion procedure at Infermi Hospital, Rivoli, and San Luigi Gonzaga University Hospital, Orbassano, from October 2018 to October 2022 were analyzed. All the procedures were performed with a Watchman/FLX LAA closure device under TOE and fluoroscopic guidance without an anesthesiologist on site. CS was performed with a combination of midazolam and fentanyl as needed. Results: One-hundred fifteen patients were included (age 76.4 ± 7.6 years, median CHA2DS2Vasc 4.4 ± 1.4). CS was performed using midazolam (mean dose 5.9 ± 2.1 mg), adding fentanyl for thirty-nine (33.9%) patients in case of poor tolerance for the procedure despite midazolam. The acute procedural success rate was 99.1%. We observed seven acute severe complications. No patients needed anesthesiological assistance during the procedure, and no cases of respiratory failure necessitating ventilation were reported. In a follow-up after 10 ± 9 months, one case of stroke (0.9%) and one case (0.9%) of transient ischemic attack (TIA) occurred. Conclusions: LAA occlusion performed under CS and without the presence of an anesthesiologist on site appears to be safe and effective. It can be an attractive alternative to general anesthesia (GA), as fewer resources are required.

Forecasting the Risk of Heart Failure Hospitalization After Acute Coronary Syndromes: the CORALYS HF Score.

The present study aimed to identify patients at a higher risk of hospitalization for heart failure (HF) in a population of patients with acute coronary syndrome (ACS) treated with percutaneous coronary revascularization without a history of HF or reduced left ventricular (LV) ejection fraction before the index admission. We performed a Cox regression multivariable analysis with competitive risk and machine learning models on the incideNce and predictOrs of heaRt fAiLure After Acute coronarY Syndrome (CORALYS) registry (NCT04895176), an international and multicenter study including consecutive patients admitted for ACS in 16 European Centers from 2015 to 2020. Of 14,699 patients, 593 (4.0%) were admitted for the development of HF up to 1 year after the index ACS presentation. A total of 2 different data sets were randomly created, 1 for the derivative cohort including 11,626 patients (80%) and 1 for the validation cohort including 3,073 patients (20%). On the Cox regression multivariable analysis, several variables were associated with the risk of HF hospitalization, with reduced renal function, complete revascularization, and LV ejection fraction as the most relevant ones. The area under the curve at 1 year was 0.75 (0.72 to 0.78) in the derivative cohort, whereas on validation, it was 0.72 (0.67 to 0.77). The machine learning analysis showed a slightly inferior performance. In conclusion, in a large cohort of patients with ACS without a history of HF or LV dysfunction before the index event, the CORALYS HF score identified patients at a higher risk of hospitalization for HF using variables easily accessible at discharge. Further approaches to tackle HF development in this high-risk subset of patients are needed.

Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry.

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.

Acute coronary syndrome in very elderly patients-a real-world experience.

Very elderly population constitutes an increasingly larger proportion of patients admitted for acute coronary syndromes (ACS). Notably, age represents both a proxy of frailty and an exclusion criterion in clinical randomized trials, which probably contributes to lack of data and undertreatment of real-world elderly patients. The aim of the study is to describe patterns of treatment and outcome of very elderly patients with ACS. All consecutive patients aged ≥ 80 years old (yo) admitted between January 2017 and December 2019 with ACS were included. The primary endpoint was in-hospital occurrence of major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, new onset cardiogenic shock, definite/probable stent thrombosis, and ischemic stroke. The secondary endpoints were in-hospital incidence of Thrombolysis in Myocardial Infarction (TIMI) major/minor bleedings, contrast-induced nephropathy (CIN), six-month all-cause mortality, and unplanned readmission. One hundred ninety-three patients (mean age 84.1 ± 3.5 yo, 46% females) were included, of whom 86 (44.6%), 79 (40.9%), and 28 (14.5%) presented with ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA), respectively. The vast majority of patients received an invasive strategy, with 92.7% undergoing coronary angiography and 84.4% to percutaneous coronary intervention (PCI). Aspirin was administered to 180 (93.3%) patients, clopidogrel to 89 (46.1%) patients, and ticagrelor to 85 (44%) patients. In-hospital MACE occurred in 29 patients (15.0%), whereas 3 (1.6%) and 12 patients (7.2%) experienced in-hospital TIMI major and TIMI minor bleeding, respectively. Of the overall population, 177 (91.7%) were discharged alive. After discharge, 11 patients (6.2%) died of all-cause death, whereas 42 patients (23.7%) required a new hospitalization within six months. Invasive strategy of ACS in elderly patients seems safe and effective. Six-month new hospitalization appears inevitably related to age.

Asociación entre el tratamiento hormonal y los eventos clínicos tempranos en mujeres con disección coronaria espontánea / Association between hormone therapy and short-term cardiovascular events in women with spontaneous coronary artery dissection

Introducción y objetivos Los cambios hormonales se reconocen como un factor desencadenante de la disección coronaria espontánea (DCE). Sin embargo, se desconoce si la exposición al tratamiento con hormonas exógenas (TH) en el momento del diagnóstico tiene algún impacto clínico. Se estudió en mujeres con DCE la asociación entre la TH y los eventos clínicos a corto plazo. Método Se incluyó a mujeres con DCE del registro DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish). Se identificó a las mujeres en TH (estrógenos, progestágenos o gonadotropinas) al momento del diagnóstico y se comparó sus resultados a corto plazo con aquellas sin TH activa. El evento compuesto medido fue infarto de miocardio no fatal o intervención coronaria percutánea no planificada durante los primeros 28 días después del cateterismo índice. Resultados De 224 mujeres que sufrieron una DCE (media de edad, 52,0±10,0 años), 39 (17,4%) estaban en TH y 185 (82,6%) no. No se observaron diferencias significativas entre ambos grupos en la demografía, la presentación clínica, las características angiográficas o el tratamiento inicial. Todas las pacientes en TH sistémico (n=36, 92%) lo suspendieron al diagnóstico. El evento compuesto se produjo en 7 pacientes (17,9%) con TH en comparación con 14 (7,6%) sin TH (p=0,039). Tras un ajuste multivariable, el TH se mantuvo asociado con el evento compuesto registrado en los primeros 28 días de seguimiento (HR=3,53; IC95%, 1,30-9,61; p=0,013). Conclusiones En mujeres con DCE, la exposición al TH en el momento de la presentación clínica se asoció con eventos cardiovasculares recurrentes a corto plazo, como infarto de miocardio no fatal o revascularización percutánea no planificada (AU)

Introduction and objectives Changes in sex hormone levels are a known triggering factor for spontaneous coronary artery dissection (SCAD) in women. However, it is unknown whether exposure to exogenous hormone therapy (HT) at the time of SCAD presentation modifies the clinical course of this condition. We investigated the association between HT in female patients presenting with SCAD and short-term clinical outcomes. Methods We enrolled consecutive patients presenting with SCAD from the DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish) registry. Women on HT (estrogens, progestagens, or gonadotropins) at the time of presentation were identified, and their clinical characteristics and short-term outcomes were compared with those not receiving active HT. The outcome measure was nonfatal myocardial infarction and/or unplanned percutaneous coronary intervention during the first 28 days after the index catheterization. Results of 224 women presenting with SCAD (mean age 52.0±10.0 years), 39 (17.4%) were currently using HT while 185 (82.6%) were not. No significant differences were noted in the baseline demographics, clinical presentation, angiographic features, or initial treatment received between the 2 groups. All patients on systemic HT (n=36, 92%) discontinued it at the time of diagnosis. The composite outcome occurred in 7 (17.9%) patients with prior HT compared with 14 (7.6%) without (P=.039). After multivariable adjustment, HT remained associated with the composite outcome recorded in the first 28 days of follow-up (HR, 3.53; 95%CI, 1.30-9.61; P=.013). Conclusions In women with SCAD, exposure to HT at the time of clinical presentation was associated with short-term recurrent cardiovascular events such as nonfatal myocardial infarction and/or unplanned percutaneous revascularization (AU)

IncidenCe and predictOrs of heaRt fAiLure after acute coronarY Syndrome: The CORALYS registry.

BACKGROUND: Previous studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS. METHODS AND RESULTS: CORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39-0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5-2.39 and HR 1.85,95%CI 1.6-2.14, respectively). CONCLUSIONS: Incidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS.

Association between hormone therapy and short-term cardiovascular events in women with spontaneous coronary artery dissection.

INTRODUCTION AND OBJECTIVES: Changes in sex hormone levels are a known triggering factor for spontaneous coronary artery dissection (SCAD) in women. However, it is unknown whether exposure to exogenous hormone therapy (HT) at the time of SCAD presentation modifies the clinical course of this condition. We investigated the association between HT in female patients presenting with SCAD and short-term clinical outcomes. METHODS: We enrolled consecutive patients presenting with SCAD from the DISCO-IT/SPA (dissezioni spontanee coronariche Italian-Spanish) registry. Women on HT (estrogens, progestagens, or gonadotropins) at the time of presentation were identified, and their clinical characteristics and short-term outcomes were compared with those not receiving active HT. The outcome measure was nonfatal myocardial infarction and/or unplanned percutaneous coronary intervention during the first 28 days after the index catheterization. RESULTS: Of 224 women presenting with SCAD (mean age 52.0±10.0 years), 39 (17.4%) were currently using HT while 185 (82.6%) were not. No significant differences were noted in the baseline demographics, clinical presentation, angiographic features, or initial treatment received between the 2 groups. All patients on systemic HT (n=36, 92%) discontinued it at the time of diagnosis. The composite outcome occurred in 7 (17.9%) patients with prior HT compared with 14 (7.6%) without (P=.039). After multivariable adjustment, HT remained associated with the composite outcome recorded in the first 28 days of follow-up (HR, 3.53; 95%CI, 1.30-9.61; P=.013). CONCLUSIONS: In women with SCAD, exposure to HT at the time of clinical presentation was associated with short-term recurrent cardiovascular events such as nonfatal myocardial infarction and/or unplanned percutaneous revascularization.

Left Ventricular Thrombus Management After Acute Myocardial Infarction in Clinical Practice: Results from LEVITATION Survey and Narrative Review.

PURPOSE: Left ventricular thrombus (LVT) after ST-elevation myocardial infarction still presents diagnostic and therapeutic challenges. The LEVITATION survey was designed to take a picture of LVT management in current clinical practice. METHODS: The survey covered diagnostic, therapeutic, and prophylactic issues and was completed by 104 European cardiac centers. Most of them (59%) were university or tertiary centers. RESULTS: The survey showed anterior apical a-/dyskinesia, large MI, spontaneous echo-contrast, late presentation with delayed PCI, and TIMI flow 0-1 as the most important perceived risk factors for LVT formation. Serial ultrasound imaging is the most used tool to diagnose LVT (88% of the centers), with contrast-enhanced ultrasound and cardiac MR performed in case of poor apex visualization or spontaneous echo-contrast. One third (34%) of the centers uses prophylactic anticoagulation to prevent LVT formation. In the presence of LVT, low molecular weight heparin is the most used in-hospital therapy. At discharge, vitamin K antagonist and direct oral anticoagulants are used in 67 and 32% of the cases, respectively. Triple antithrombotic therapy with aspirin plus clopidogrel and VKA is the most used strategy at discharge (55%), whereas a single antiplatelet therapy is preferred only in the case of moderate-to-high risk of bleeding. To assess LVT total regression, half of the centers use contrast-enhanced ultrasound and/or cardiac-MR. The duration of anticoagulation is usually 3-6 months (55%), with long-term prolongation in case of LVT persistence or recurrence. CONCLUSION: The survey has depicted for the first time the current real-world management of this neglected topic and has highlighted several grey zones that are still present and not supported by evidence.

[ANMCO Position paper: Evidence and practical indications for the use of low-dose rivaroxaban in stable coronary artery disease and peripheral artery disease]. / Position paper ANMCO: Evidenze e indicazioni pratiche per l'impiego di rivaroxaban a bassa dose nella malattia coronarica stabile e nell'arteriopatia periferica.

In patients with atherosclerotic disease, the occurrence of atherothrombotic events is the main determinant of morbidity and mortality. Growing evidence suggests the involvement of the coagulation pathway in the atherosclerotic process and the benefit of antithrombotic agents, such as direct oral anticoagulants, which interfere with both platelet aggregation and the coagulation cascade. The COMPASS trial has shown that in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD), low-dose rivaroxaban (2.5 mg twice daily) added to acetylsalicylic acid (ASA) 100 mg reduces major vascular events and mortality, with an increase in major bleeding but not in fatal bleeding or involving a critical organ. The reduction in major cardiovascular events has been confirmed in the overall population with CAD and in both patients with and without a previous percutaneous coronary revascularization, and also in patients with previous coronary bypass surgery. In patients with PAD, the combination of rivaroxaban 2.5 mg twice daily and ASA was found to reduce both major adverse cardiovascular events and major adverse limb events, including major limb amputations. In clinical practice, the use of rivaroxaban 2.5 mg co-administered with ASA has been approved in both patients with CAD and symptomatic PAD at high risk of ischemic events. However, in Italy, the national health system reimbursement is provided only for patients with PAD. In patients treated with rivaroxaban 2.5 mg, assessment and monitoring of bleeding risk is crucial to achieve the maximum clinical benefit.

A Psychoanalytic-Derived Brief Psychotherapeutic Approach in the Treatment of Major Depression: Monotherapy Studies.

Over the years, short term psychodynamic therapy (STPP) has been broadly researched in order to evaluate its efficacy in the treatment of major psychiatric disorders. In particular, a consistent number of studies focused on assessing clinical outcomes of the principal psychodynamic techniques in treating depressive disorders. We conducted a narrative review in which we aimed to evaluate the efficacy of STPP in monotherapy in major depressive disorder and to assess possible features that may correlate with its clinical use. Databases searched were PubMed, Ovid, Scopus, PsycINFO and Cochrane Libraries from inception to July 2022. Our research underlined that STPP in monotherapy is particularly effective in moderately severe depression and in preventing depressive relapses. Moreover, a case-by-case evaluation of its efficacy should be performed when considering STPP for the treatment of major depression with other comorbid psychiatric conditions. Although such key points emerged from scientific evidence, STPP should be better studied in the long-term perspective; further research is needed to define the clinical scenarios in which STPP can be considered a first-line approach as monotherapy in major depressive disorder compared to medications or other types of psychotherapy.

[Spontaneous coronary artery dissection: update on treatment and strategies to improve the diagnostic and therapeutic pathway]. / La dissezione coronarica spontanea: update sul trattamento e sulle strategie per migliorare il percorso diagnostico-terapeutico.

Spontaneous coronary dissection is an infrequent cause of acute coronary syndrome, which has been understood only recently in terms of pathophysiology, presentation, diagnosis and treatment. In particular, new evidence has emerged on its treatment in the interventional and medical fields, especially on the management of antiplatelet therapy, which is presented in this review; moreover, the local experience of the registry of spontaneous coronary dissections DISCO and its role in improving the management of these patients are reported.

Epilepsy and syncope - A case report and narrative review of arrhythmias connected to temporal lobe epilepsy.

We present the case of a 28-years-old male presenting to the Emergency Department for relapsing episodes of "déjà vu" and syncope. After a diagnostic workup by a multidisciplinary team, the simultaneous EEG and ECG monitoring showed an asystole associated with EEG anomalies in right fronto-temporal region of the brain. The brain MRI revealed an ischemic lesion concordant with EEG anomalies. In the suspicion of an ictal asystole, we decided not to implant a permanent pacemaker as the first line therapy but started a targeted anti-epileptic therapy. No more syncopal episodes nor dysrhythmias occurred during recovery and almost two years follow-up.

Net clinical benefit of different strategies of dual antiplatelet therapy in elderly patients: Data from the praise registry.

BACKGROUND: The safety and efficacy of potent P2Y12 inhibitors (Ticagrelor and Prasugrel) in dual antiplatelet therapy (DAPT) with aspirin in elderly acute coronary syndrome (ACS) patients remains unclear. METHODS: All ACS patients aged 75 years and older treated with Percutaneous Coronary Intervention (PCI) from PRAISE dataset were included. The safety and efficacy of Ticagrelor vs Clopidogrel was evaluated with inverse probability of treatment weighting (IPTW). Sensitivity analysis was performed for patients older or equal than 85 years old. All-cause mortality was the primary endpoint, while myocardial infarction (MI), Bleeding Academic Research Consortium (BARC) 3-5 bleedings and Major and Net Adverse Clinical and Cardiac Events (MACE and NACE) were the secondary ones. RESULTS: 4287 patients were included, 3197 treated with Clopidogrel and 1090 with Ticagrelor. After 16 ± 3 months, Ticagrelor showed neutral effect on NACE and mortality (HR 0.98; 0.63-1.52, p = 0.94 and HR 0.38; 0.14-1.04, p = 0,06), reduced risk of MACE and MI (HR 0.82; 0.23-0.91, p = 0.03 and HR 0.43; 0.14-0.89, p = 0.04) and increased risk of BARC 3-5 bleeding (HR 2.14; 1.19-3.85, p = 0.001). In very elderly patients (≥85 years) Ticagrelor decreased risk of MI and increased risk of bleeding (HR 0.69; 0.22-0.95, p = 0.04 and HR 2.36; 1.02-5.52, p = 0.04, all 95%CI) with neutral effect on NACE and MACE. CONCLUSIONS: In elderly ACS patients treated with PCI, Ticagrelor was associated with neutral effect on all-cause mortality, lower risk MACE and MI compared with Clopidogrel. Such benefit was counterbalanced by increased risk of major bleedings. These results were consistent among patients aged 85 years and older.

[Management of ST-elevation myocardial infarction in a patient with aspirin hypersensitivity without oral P2Y12 inhibitors]. / Gestione dell'infarto miocardico con sopraslivellamento del tratto ST in un paziente con ipersensibilità all'aspirina senza l'uso di inibitori orali del recettore P2Y12.

Aspirin hypersensitivity is a neglected issue, especially in the setting of ST-elevation myocardial infarction (STEMI). Nevertheless, in such context a prompt platelet inhibition remains crucial. We report the case of a patient presenting with STEMI, aspirin hypersensitivity and emesis causing inadequate intake of P2Y12 inhibitors managed with intravenous cangrelor therapy and aspirin desensitization. Possible options in the management of aspirin hypersensitivity in the acute phase are discussed. In selected patients with STEMI and aspirin hypersensitivity, particularly in the suspect of suboptimal enteric absorption of P2Y12 inhibitors, the use of cangrelor until aspirin desensitization is completed can be considered; bridge therapy to desensitization with glycoprotein IIb/IIIa inhibitors can be considered on a case by case basis, despite the scarce supporting evidence - bridge therapy with indobufen is not recommended due to the limited literature data.

Antiplatelet therapy and outcome in COVID-19: the Health Outcome Predictive Evaluation Registry.

BACKGROUND: Standard therapy for COVID-19 is continuously evolving. Autopsy studies showed high prevalence of platelet-fibrin-rich microthrombi in several organs. The aim of the study was therefore to evaluate the safety and efficacy of antiplatelet therapy (APT) in hospitalised patients with COVID-19 and its impact on survival. METHODS: 7824 consecutive patients with COVID-19 were enrolled in a multicentre international prospective registry (Health Outcome Predictive Evaluation-COVID-19 Registry). Clinical data and in-hospital complications were recorded. Data on APT, including aspirin and other antiplatelet drugs, were obtained for each patient. RESULTS: During hospitalisation, 730 (9%) patients received single APT (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (74±12 years vs 63±17 years, p<0.01), more frequently male (68% vs 57%, p<0.01) and had higher prevalence of diabetes (39% vs 16%, p<0.01). Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64), need for invasive ventilation (8.7% vs 8.5%, p=0.88), embolic events (2.9% vs 2.5% p=0.34) and bleeding (2.1% vs 2.4%, p=0.43), but had shorter duration of mechanical ventilation (8±5 days vs 11±7 days, p=0.01); however, when comparing patients with APT versus no APT and no anticoagulation therapy, APT was associated with lower mortality rates (log-rank p<0.01, relative risk 0.79, 95% CI 0.70 to 0.94). On multivariable analysis, in-hospital APT was associated with lower mortality risk (relative risk 0.39, 95% CI 0.32 to 0.48, p<0.01). CONCLUSIONS: APT during hospitalisation for COVID-19 could be associated with lower mortality risk and shorter duration of mechanical ventilation, without increased risk of bleeding. TRIAL REGISTRATION NUMBER: NCT04334291.

Sepsis of Patients Infected by SARS-CoV-2: Real-World Experience From the International HOPE-COVID-19-Registry and Validation of HOPE Sepsis Score.

Background: Patients with sepsis with a concomitant coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of patients with sepsis with a concomitant COVID-19, and we developed a risk score for the estimation of sepsis risk in COVID-19. Methods: We conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry, NCT04334291). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus. Results: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), hemoptysis, peripheral oxygen saturation (SpO2) <92%, blood pressure (BP) (systolic BP <90 mmHg and diastolic BP <60 mmHg), Glasgow Coma Scale (GCS) <15, elevated procalcitonin (PCT), elevated troponin I (TnI), and elevated creatinine >1.5 mg/dl. By assigning odds ratio (OR) weighted points to these variables, the following three risk categories were defined to develop sepsis during admission: low-risk group (probability of sepsis 3.1-11.8%); intermediate-risk group (24.8-53.8%); and high-risk-group (58.3-100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO2, decreased BP, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to hemoptysis. Conclusions: The HOPE Sepsis Score including nine parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate.