Impact of Levosimendan and Its Metabolites on Platelet Activation Mechanisms in Patients during Antiplatelet Therapy-Pilot Study.

Levosimendan is used for the short-term treatment of severe heart failure or other cardiac conditions. The area of existing clinical applications for levosimendan has increased significantly. This study aimed to assess whether levosimendan and its metabolites impact the mechanisms related to platelet activation. In this study, we included patients with coronary artery disease receiving antiplatelet therapy. We analyzed the pharmacodynamic profile using three independent methods to assess platelet activity. The results of the conducted studies indicate a mechanism of levosimendan that affects the function of platelets, causing higher inhibition of platelet receptors and, thus, their aggregation. It is essential to clarify whether levosimendan may affect platelets due to the need to maintain a balance between bleeding and thrombosis in patients treated with levosimendan. This is especially important in the case of perioperative bleeding. This study was conducted in vitro; the research should be continued and carried out in patients to check the complete pharmacokinetic and pharmacodynamic profile.

Platelet Reactivity in the Exacerbation of Psoriasis.

Background: Psoriasis is a chronic, inflammatory, immune-mediated disease with a specific cutaneous presentation. Increased platelet aggregation has been observed in patients with extensive psoriatic lesions. The aim of this study was to evaluate the clinical factors affecting platelet reactivity in patients with an exacerbation of psoriasis. Methods: This was a prospective, single-center, observational study, enrolling patients hospitalized for an aggravation of psoriasis. Enrolled patients underwent single platelet function testing with light transmission aggregometry on the first morning of hospitalization. Results: 120 patients were enrolled in the study. Of the compared subgroups, women had higher maximal platelet aggregation (MPA) than men (77% vs. 72%; p = 0.03), and those with BMIs < 25 kg/m2 showed higher platelet reactivity compared to subjects with BMIs ≥ 25 kg/m2 (75% vs. 73%; p = 0.02). There was a positive correlation between MPA and platelet count (r = 0.27; p < 0.01), as well as C-reactive protein concentration (r = 0.20; p = 0.03), while a negative correlation was observed with total cholesterol (r = -0.24; p = 0.01) and triglycerides (r = -0.30; p < 0.01). A two-step analysis based on multidimensional models with random effects revealed that every increase in the platelet count by 103/µL led to an increase in MPA by 0.07% (R2 = 0.07; p < 0.01), and an increase in triglycerides' concentration by 1 mg/dL was related to a reduction in MPA by 0.05% (R2 = 0.07; p < 0.01). Conclusions: The increased platelet reactivity observed in patients with psoriasis appears to be multifactorial and related to several clinical and laboratory features. Further research is warranted to put these findings into a clinical perspective.

Correction: Kujawski et al. Autonomic and Cognitive Function Response to Normobaric Hyperoxia Exposure in Healthy Subjects. Preliminary Study. Medicina 2020, 56, 172.

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Vascular density and macular sensitivity in eyes after scleral buckling surgery for macula-on rhegmatogenous retinal detachment.

PURPOSE: To investigate the structure and function of the retina after scleral buckling (SB) surgery due to macula-on rhegmatogenous retinal detachment (RRD). METHODS: Twenty eyes with repaired macula-on RRD and 20 fellow eyes were included. All patients within 6-12 months of the procedure, were examined to evaluate retinal structure using spectral domain optical coherence tomography (SD-OCT) and vessel density (VD) by OCT angiography (OCTA). Best corrected visual acuity (BCVA) and microperimetry (MP) tests were used to assess retinal function. RESULTS: Analysis of the microvascular network using OCTA between the operated and healthy fellow eyes showed a significant reduction on VD in superficial vascular plexus (SVP), deep vascular plexus (DVP) and radial peripapillary capillaries (RPC) (p< 0.001, p = 0.019 and p = 0.008, respectively). Comparison of retinal structure in SD-OCT showed no significant differences on thickness in ganglion cell complex (GCC) and peripaillary retinal nerve fiber layer (pRNFL) (p> 0.05) between examined eyes. Retinal function analysis by MP examination showed a decrease of retinal sensitivity (p = 0.0013) whereas postoperative BCVA showed no differences (p = 0.62) in the operated eyes. Significant Pearson's correlations were observed between retinal sensitivity and VD in SVP, RPC (p< 0.05). CONCLUSION: In the eyes after SB surgery due to macula-on RRD, changes in retinal sensitivity were accompanied by impairment of the microvascular network assessed by the OCTA.

Assessment of the influence of selected stress factors on the growth and survival of Listeria monocytogenes.

BACKGROUND: Listeria monocytogenes are Gram-positive rods, which are the etiological factor of listeriosis. L. monocytogenes quickly adapts to changing environmental conditions. Since the main source of rods is food, its elimination from the production line is a priority. The study aimed to evaluate the influence of selected stress factors on the growth and survival of L. monocytogenes strains isolated from food products and clinical material. RESULTS: We distinguished fifty genetically different strains of L. monocytogenes (PFGE method). Sixty-two percent of the tested strains represented 1/2a-3a serogroup. Sixty percent of the rods possessed ten examined virulence genes (fbpA, plcA, hlyA, plcB, inlB, actA, iap, inlA, mpl, prfA). Listeria Pathogenicity Island 1 (LIPI-1) was demonstrated among 38 (76.0%) strains. Majority (92.0%) of strains (46) were sensitive to all examined antibiotics. The most effective concentration of bacteriophage (inhibiting the growth of 22 strains; 44.0%) was 5 × 108 PFU. In turn, the concentration of 8% of NaCl was enough to inhibit the growth of 31 strains (62.0%). The clinical strain tolerated the broadest pH range (3 to 10). Five strains survived the 60-min exposure to 70˚C, whereas all were alive at each time stage of the cold stress experiment. During the stress of cyclic freezing-defrosting, an increase in the number of bacteria was shown after the first cycle, and a decrease was only observed after cycle 3. The least sensitive to low nutrients content were strains isolated from frozen food. The high BHI concentration promoted the growth of all groups. CONCLUSIONS: Data on survival in stress conditions can form the basis for one of the hypotheses explaining the formation of persistent strains. Such studies are also helpful for planning appropriate hygiene strategies within the food industry.

Cardiovascular Response to Intravenous Glucose Injection during Hemodialysis with Assessment of Entropy Alterations.

BACKGROUND: The quality of autonomic blood pressure (BP) control can be assessed by the entropy of serial BP data. The aim of this study was to evaluate the effect of hemodialysis (HD) and glucose infusion (GI) on amplitude aware permutation entropy (AAPE) of hemodynamic variables during HD in chronic kidney disease patients with and without type-2 diabetes mellitus (DM). METHODS: Twenty-one patients without DM (NDO) and ten with DM were studied. Thirty minutes after the start of HD, a 40% glucose solution was administered. Hemodynamic data were extracted from continuous recordings using the Portapres® system. RESULTS: AAPE decreased during HD in all patients and all hemodynamic signals with the exception of AAPE of mean and diastolic BP in DM patients. GI led to an increase in AAPE for cardiac output in all patients, while AAPE for heart rate and ejection time increased only in DM studies, and AAPE for systolic, diastolic, and mean arterial pressure, as well as total peripheral resistance, increased only in NDO patients. CONCLUSIONS: The reduction in entropy during HD indicates impaired autonomic control in response to external perturbations. This state is partially reversed by the infusion of glucose with differences in central and peripheral responsiveness in DM and NDO patients.

Determinants of the Level of Anti-SARS-CoV-2 IgG ANTibodiEs after Vaccination (DANTE-SIRIO 7) Study in a Large Cohort of Healthcare Workers.

The aim of this study was to determine anti-SARS-CoV-2 IgG concentrations and their major determinants in healthcare workers (HCWs) after full vaccination with the BNT162b2 vaccine. We recruited 847 individuals vaccinated with two doses of the BNT162b2 vaccine, who completed the questionnaire, and whose antibody concentrations were tested after 3 and 6 months after full vaccination. Anti-SARS-CoV-2 IgG levels were measured on the routinely employed Siemens Atellica system. The cutoff for positivity was ≥21.8 BAU/mL. Three and 6 months after vaccination, the majority of participants were seropositive. Median concentrations of anti-SARS-CoV-2 IgG significantly decreased from 1145 BAU/mL (IQR: 543-2095) to 225 BAU/mL (IQR: 100-510). Major positive determinants of antibody levels were fever after both doses of vaccine, prior-COVID-19 exposure, and muscle pain after the first dose. Lack of symptoms after the second dose and time since vaccination were significant negative determinants of anti-SARS-CoV-2 IgG concentrations. No other factors, including age and gender, or underlying comorbidities had a significant effect on antibody levels in HCWs. The anti-SARS-CoV-2 response after two doses of BNT162b2 vaccine was independently associated with prior-COVID-19 exposure, time since vaccination, and the occurrence of symptoms after either dose of vaccine. Easily reportable adverse reactions may facilitate the identification of immune response in HCWs.

The impact of mild therapeutic hypothermia on platelet reactivity in comatose survivors of cardiac arrest with acute myocardial infarction treated with ticagrelor.

BACKGROUND: The aim of the study was to assess the antiplatelet effect of ticagrelor in patients with myocardial infarction (MI) after out-of-hospital cardiac arrest (OHCA) treated with percutaneous coronary intervention (PCI) and mild therapeutic hypothermia (MTH) vs. MI patients without OHCA treated with PCI. METHODS: The study was designed and performed as a phase IV, single-center, investigator-initiated, prospective, observational study assessing the early pharmacodynamic effect (within first 24 h) of a ticagrelor loading dose (180 mg) in both groups of patients (MTH group vs. MI group). For assessment of ticagrelor pharmacodynamics Multiple Electrode Aggregometry (MEA) was applied. RESULTS: Compared with the MTH group, platelet inhibition was persistently stronger in the MI group over the entire observation period (up to 24 h), with the highest difference at 4 hours after loading with ticagrelor (25.8 ± 26.4 vs. 75.8 ± 40.9 U, p = 0.002). As a consequence, there was a higher prevalence of high platelet reactivity in the MTH group, with the most explicit difference at 6 hours after the loading dose of ticagrelor (78% vs. 7%, p < 0.001). CONCLUSIONS: In comparison with patients treated with primary PCI for uncomplicated MI, the antiplatelet effect of ticagrelor in patients with MI complicated with OHCA, undergoing MTH and primary PCI, is attenuated and delayed.

Alterations in Fixation Indices in Primary Open-Angle Glaucoma by Microperimetry.

The aim of this study was to determine whether primary open-angle glaucoma (POAG) is associated with changes in fixation stability parameters assessed by microperimetry (MP) and whether the severity of glaucoma is related to a deterioration in these indicators. This study analyzed fixation stability using MP macular analyzer integrity assessment (MAIA) in patients with mild and moderate/severe POAG and healthy controls. The resulting fixation indices were correlated with parameters used to assess retinal function with MP and standard automated perimetry (SAP) and retinal structure with optical coherence tomography (OCT) and OCT angiography (OCTA). We enrolled 54 eyes in the POAG groups (32 eyes with mild POAG and 22 eyes with moderate/severe POAG) and 24 eyes in the healthy group. It was shown that fixation stability in POAG eyes deteriorated with increasing disease severity, and significant differences in bivariate contour ellipse area (BCEA) including 95% of fixation points were observed among groups (p = 0.042). Quantitative analysis of structural and functional retinal parameters also showed significant deterioration with the progression of glaucoma (p < 0.001). Correlations among fixation parameters and abnormalities in the retinal structure and function were confirmed. We concluded that POAG is associated with disturbances in the fixation pattern, which worsen as the disease progresses and can be effectively assessed by performing a MP test.

Diurnal Variability of Platelet Aggregation in Patients with Myocardial Infarction Treated with Prasugrel and Ticagrelor.

BACKGROUND: Contemporary antiplatelet treatment in acute myocardial infarction (AMI) is based on one of two P2Y12 receptor inhibitors, prasugrel or ticagrelor. The aim of this study was to compare diurnal variability of platelet reactivity between patients receiving prasugrel and ticagrelor during the initial phase of maintenance treatment after AMI. METHODS: It was a prospective, two-center, pharmacodynamic, observational study. Blood for platelet testing was sampled at four time points on day four after AMI (8:00, 12:00, 16:00, 20:00). Diurnal variability of platelet reactivity was expressed as a coefficient of variation (CV) of the above-mentioned measurements. RESULTS: 73 invasively-treated patients were enrolled (ticagrelor: n = 47, prasugrel: n = 26). CV was greater in patients treated with ticagrelor compared with prasugrel according to a VASP assay (47.8 [31.6-64.6]% vs. 21.3 [12.9-25.5]%, p < 0.001), while no statistical differences were detected when the CVs of platelet aggregation according to Multiplate were compared between ticagrelor- and prasugrel-treated patients. Ticagrelor-treated patients showed more pronounced platelet inhibition than prasugrel at 16:00 and 20:00 (VASP16:00: 20.6 ± 15.0 vs. 24.9 ± 12.8 PRI, p = 0.049; VASP20:00: 18.6 ± 17.7 vs. 26.0 ± 11.7 PRI, p = 0.002). CONCLUSIONS: Ticagrelor shows greater diurnal variability in platelet aggregation than prasugrel during the initial maintenance phase of AMI treatment, and this is due to the continuous increase of platelet inhibition after the morning maintenance dose. Both drugs provide an adequate antiplatelet effect early after AMI. Evaluation of the clinical significance of these findings warrants further investigation.

An assessment of heart rate and blood pressure asymmetry in the diagnosis of vasovagal syncope in females.

Introduction: Heart Rate Asymmetry (HRA) describes a phenomenon of differences between accelerations and decelerations in human heart rate. Methods used for HRA assessment can be further implemented in the evaluation of asymmetry in blood pressure variations (Blood Pressure Asymmetry-BPA). Methods: We have analyzed retrospectively the series of heartbeat intervals extracted from ECG and beat-to-beat blood pressure signals from 16 vasovagal patients (age: 32.1 ± 13.3; BMI: 21.6 ± 3.8; all female) and 19 healthy subjects (age: 34.6 ± 7.6; BMI: 22.1 ± 3.4; all female) who have undergone tilt test (70°). Asymmetry was evaluated with Poincaré plot-based methods for 5 min recordings from supine and tilt stages of the test. The analyzed biosignals were heart rate (RR), diastolic (dBP) and systolic Blood Pressure (sBP) and Pulse Pressure (PP). In the paper we explored the differences between healthy and vasovagal women. Results: The changes of HRA indicators between supine and tilt were observed only in the control group (Porta Index p = 0.026 and Guzik Index p = 0.005). No significant differences in beat-to-beat variability (i.e. spread of points across the line of identity in Poincaré plot-SD1) of dBP was noted between supine and tilt in the vasovagal group (p = 0.433 in comparison to p = 0.014 in healthy females). Moreover, in vasovagal patients the PP was significantly different (supine: 41.47; tilt: 39.27 mmHg) comparing to healthy subjects (supine: 35.87; tilt: 33.50 mmHg) in supine (p = 0.019) and in tilt (p = 0.014). Discussion: Analysis of HRA and BPA represents a promising method for the evaluation of cardiovascular response to orthostatic stressors, however currently it is difficult to determine a subject's underlying health condition based only on these parameters.

Oral NAloxone to overcome the moRphine effect in acute COronary syndrome patients treated with TICagrelor - NARCOTIC trial.

BACKGROUND: Numerous worldwide clinical trials have proven the indisputably negative influence of morphine on the pharmacokinetics and pharmacodynamics of P2Y12 receptor inhibitors in patients presenting with acute coronary syndromes. The aim of this trial was to evaluate whether oral coadministration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome 'the morphine effect'. METHODS: Consecutive unstable angina patients receiving ticagrelor and morphine with or without orally administered naloxone underwent assessment of platelet reactivity using Multiplate analyzer as well as evaluation of the pharmacokinetic profile of ticagrelor and its active metabolite, AR-C124910XX, at 9 pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose. RESULTS: The trial shows no significant differences regarding the pharmacokinetics of ticagrelor between both study arms throughout the study period. AR-C124910XX plasma concentration was significantly higher 120 min after the ticagrelor loading dose administration (p = 0.0417). However, the evaluation of pharmacodynamics did not show any statistically significant differences between the study arms. CONCLUSIONS: To conclude, this trial shows that naloxone co-administration in ticagrelor-treated acute coronary syndrome patients on concomitant treatment with morphine shows no definite superiority in terms of ticagrelor pharmacokinetic and pharmacodynamic profile.

Prevalence and antimicrobial susceptibility of Listeria monocytogenes strains isolated from a meat processing plant.

INTRODUCTION AND OBJECTIVE: The ability of L. monocytogenes to create biofilm results in the higher resistance to disinfectants and determines the need to search for effective methods of eradication. The aim of the study was to assess the level of L. monocytogenes contamination in the environment of a meat processing plant. The sensitivity of tested isolates to various antimicrobials used for disinfection purposes was also estimated. MATERIAL AND METHODS: The samples were taken from raw materials, semi-finished and final products, as well as food contact surfaces inthe production hall and deli meat packaging department. The number of L. monocytogenes and the effect of eight different biocides on bacteria planktonic forms and biofilm formed on stainless steel and polypropylene was investigated. The effect of blood and albumin on L. monocytogenes resistance to disinfectants was also analysed. RESULTS: The prevalence of L. monocytogenes on food contact surfaces was estimated at 2.93% (10 of 340 swabs taken). The samples of raw and processed products were not contaminated. Various disinfectants reduced the growth of planktonic L. monocytogenes forms at both tested concentrations 0.5% and 0.1% (irrespective of time exposure). The highest efficacy against L. monocytogenes biofilm was reported for agents containing hydrogen peroxide. The reduction of bacteria number ranged from 6.93-7.21 log CFU × cm-2, and was dependent on the surface type and time of agent application. CONCLUSIONS: In this study, the effectiveness of various disinfectants against planktonic bacteria and Listeria biofilm was observed. For the majority of disinfectants, the extension of time exposure increased bacteria elimination from the biofilm. The presence of blood resulted in reduction of the antilisterial action of most of the disinfectants applied at low concentrations.

Pharmacokinetic Modeling of Morphine's Effect on Plasma Concentrations of Ticagrelor and Its Metabolite in Healthy Volunteers.

This study aimed to build a mathematical model describing the pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) in a stable setting with concomitant administration of morphine. The model consists of a set of four differential equations prepared upon the available knowledge regarding the biological processes in the pharmacokinetics of ticagrelor. The set of equations was solved numerically using the Runge-Kutta method. The data were obtained in a double-blind, randomized, placebo-controlled, crossover trial. Twenty-four healthy volunteers received a 180-mg ticagrelor loading dose together with either 5-mg morphine or placebo. Blood samples were analyzed with liquid chromatography-tandem mass spectrometry to assess plasma concentrations of ticagrelor and AR-C124910XX before ticagrelor loading dose and after that 1, 2, 3, 4, and 6 h. The model allowed us to reproduce the experimental results accurately and led us to conclusions consistent with clinical observations that morphine delays the time of maximum drug concentration and that the morphine effect occurs due to decreased gastrointestinal motility. Based on the model, we were able to predict the effect of drug dose on receptor blocking efficacy.

SARS-CoV-2-Morphology, Transmission and Diagnosis during Pandemic, Review with Element of Meta-Analysis.

The outbreak of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2). Thus far, the virus has killed over 2,782,112 people and infected over 126,842,694 in the world (state 27 March 2021), resulting in a pandemic for humans. Based on the present data, SARS-CoV-2 transmission from animals to humans cannot be excluded. If mutations allowing breaking of the species barrier and enhancing transmissibility occurred, next changes in the SARS-CoV-2 genome, leading to easier spreading and greater pathogenicity, could happen. The environment and saliva might play an important role in virus transmission. Therefore, there is a need for strict regimes in terms of personal hygiene, including hand washing and surface disinfection. The presence of viral RNA is not an equivalent of active viral infection. The positive result of the RT-PCR method may represent either viral residues or infectious virus particles. RNA-based tests should not be used in patients after the decline of disease symptoms to confirm convalescence. It has been proposed to use the test based on viral, sub-genomic mRNA, or serological methods to find the immune response to infection. Vertical transmission of SARS-CoV-2 is still a little-known issue. In our review, we have prepared a meta-analysis of the transmission of SARS-CoV-2 from mother to child depending on the type of delivery. Our study indicated that the transmission of the virus from mother to child is rare, and the infection rate is not higher in the case of natural childbirth, breastfeeding, or contact with the mother. We hope that this review and meta-analysis will help to systemize knowledge about SARS-CoV-2 with an emphasis on diagnostic implications and transmission routes, in particular, mother-to-child transmission.

Heart Rate Asymmetry Analysis During Head-Up Tilt Test in Healthy Men.

The purpose of this study is to assess the cardiovascular system response to orthostatic stress in a group of 133 healthy men using heart rate asymmetry (HRA) methods. HRA is a feature of variability in human heart rate which is dependent upon external and internal body conditions. The initial phases of head-up tilt test (HUTT), namely, supine and tilt, were chosen as the external body affecting factors. Various calculation methods of HRA, such as Porta's index (PI), Guzik's index (GI), and its variance based components, were used to assess the heart rate variability (HRV) and its asymmetry. We compared 5-min ECG recordings from both supine and tilt phases of HUT test. Short-term HRA was observed in 54.1% of men in supine phase and 65.4% of men in tilt phase. The study revealed significant increase of GI (from 0.50 to 0.52, p < 0.001) in the tilt phase as well as significant changes in HRV descriptors between HUTT phases. Our results showed that the variability of human heart rate and its asymmetry are sensitive to orthostatic stress. The study of short-term HRA is a potential additional tool to increase sensitivity in conditions where HUTT is a diagnostic tool, such as vasovagal syncope.

Relationship between Cardiopulmonary, Mitochondrial and Autonomic Nervous System Function Improvement after an Individualised Activity Programme upon Chronic Fatigue Syndrome Patients.

BACKGROUND: The therapeutic effects of exercise from structured activity programmes have recently been questioned; as a result, this study examines the impact of an Individualised Activity Program (IAP) on the relationship with cardiovascular, mitochondrial and fatigue parameters. METHODS: Chronic fatigue syndrome (CFS) patients were assessed using Chalder Fatigue Questionnaire (CFQ), Fatigue Severity Score (FSS) and the Fatigue Impact Scale (FIS). VO2peak, VO2submax and heart rate (HR) were assessed using cardiopulmonary exercise testing. Mfn1 and Mfn2 levels in plasma were assessed. A Task Force Monitor was used to assess ANS functioning in supine rest and in response to the Head-Up Tilt Test (HUTT). RESULTS: Thirty-four patients completed 16 weeks of the IAP. The CFQ, FSS and FIS scores decreased significantly along with a significant increase in Mfn1 and Mfn2 levels (p = 0.002 and p = 0.00005, respectively). The relationships between VO2 peak and Mfn1 increase in response to IAP (p = 0.03) and between VO2 at anaerobic threshold and ANS response to the HUTT (p = 0.03) were noted. CONCLUSIONS: It is concluded that IAP reduces fatigue and improves functional performance along with changes in autonomic and mitochondrial function. However, caution must be applied as exercise was not well tolerated by 51% of patients.

ANalgesic Efficacy and safety of MOrphiNe versus methoxyflurane in patients with acute myocardial infarction: the rationale and design of the ANEMON-SIRIO 3 study: a multicentre, open-label, phase II, randomised clinical trial.

INTRODUCTION: The unfavourable influence of morphine on the pharmacokinetics of ticagrelor resulting in weaker and retarded antiplatelet effect in patients with acute coronary syndrome (ACS) has been previously shown. Replacing morphine with methoxyflurane, a potent, non-opioid analgesic agent, that does not weaken or delay the effect of antiplatelet agents may improve the clinical efficacy of treatment of patients with ACS. METHODS: The ANEMON-SIRIO 3 study was designed as a multicentre, open-label, phase II, randomised clinical trial aimed to test the analgesic efficacy and safety of methoxyflurane in patients with ACS. The study population will comprise patients with ST-elevation myocardial infarction or non-ST-elevation ACS admitted to the study centres with typical chest pain requiring analgesic treatment. Before percutaneous coronary intervention (PCI) for the patients with index ACS will be randomly assigned in 1:1 ratio to receive methoxyflurane administered by inhalation, or to obtain morphine administered intravenously. Analgesic treatment will be followed by 300 mg loading dose of aspirin and 180 mg loading dose of ticagrelor. Patients will be assessed with regard to pain intensity according to the Numeric Pain Rating Scale at baseline, 3 min after study drug administration and immediately after PCI. Moreover, patients will be actively monitored with regard to the occurrence of side effects of evaluated therapies, as well as adverse events that may be related to insufficient platelet inhibition (no-reflow phenomenon assessed immediately after PCI, administration of GPIIb/IIIa inhibitors during PCI, acute stent thrombosis). ETHICS AND DISSEMINATION: The study will be conducted in six Polish clinical centres from the beginning of in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov, NCT04476173.

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines.

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.