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Background and Objectives: Dual antiplatelet therapy (DAPT) is essential in the treatment of patients with acute coronary syndrome (ACS). The objective of this study was to evaluate the effectiveness of antiplatelet medication in our practice and to investigate the factors that influence it. Materials and Methods: A prospective cohort observational study was conducted, in which 193 patients with ACS were enrolled. The patients were stented in the catheterization laboratory between May 2019 and October 2020, before and during the COVID-19 pandemic, and were receiving DAPT. Their platelet functions were tested using a Multiplate Analyzer. In addition to this, clinical data, demographics, laboratory tests, and cardiovascular risk factors were also analyzed. Results: 43.46% of the patients treated with aspirin were found to be resistant to it. This phenomenon was more common in men (48.17% vs. 31.48%, p = 0.036), and it was associated with being under the age of 50 (OR: 2.08; 95% CI: 1.11-3.90) and weighing over 70 kg (OR: 3.00; 95% CI: 1.21-7.40). Most of the patients treated with clopidogrel were in the optimal treatment window, while about half of the patients treated with ticagrelor had an exaggerated pharmacological response. Among the laboratory parameters, leukocytosis and platelet count were found to be determinants of platelet reactivity for both the aspirin and ticagrelor treatments. Conclusions: Many patients treated with antiplatelet agents are outside of the treatment window. The results obtained showed that low doses of gastro-resistant aspirin tablets are ineffective, and their efficacy can be influenced by various clinical and laboratory factors. Patients receiving ticagrelor have significantly reduced platelet reactivity, influenced only by certain laboratory indicators. The pandemic significantly influenced the results of the platelet aggregation tests only in patients treated with clopidogrel.
Assuntos
Síndrome Coronariana Aguda , COVID-19 , Intervenção Coronária Percutânea , Masculino , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Clopidogrel/uso terapêutico , Ticagrelor/uso terapêutico , Ticagrelor/farmacologia , Pandemias , Ticlopidina/uso terapêutico , Ticlopidina/farmacologia , Estudos Prospectivos , Síndrome Coronariana Aguda/tratamento farmacológico , Agregação Plaquetária , Adenosina/efeitos adversos , Quimioterapia Combinada , Aspirina/uso terapêutico , Intervenção Coronária Percutânea/efeitos adversos , Resultado do TratamentoRESUMO
AIM: The aim of the present study was to investigate the patterns of platelet reactivity and discriminators of therapeutic response to dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel in patients with acute coronary syndrome (ACS). DESIGN: In this multicentre prospective observational study, 492 patients with ACS were enrolled. Platelet aggregation was determined by multiple electrode aggregometry after stimulation with adenosine diphosphate (ADP) or arachidonic acid (AA) as agonists in the maintenance phase of treatment with prasugrel or ticagrelor. RESULTS: Age emerged as the strongest variable influencing aspirin response status: The mean AA-induced platelet aggregation in patients <49 years of age was 49% higher than in those >49 years (13.1 U vs 8.8 U; P = 0.011). The second strongest discriminator of aspirin response was sex: Male patients had a 40% higher AA-induced platelet aggregation values than female patients (9.5 U vs 6.8 U; P = 0.026). Platelet count emerged as the only variable influencing ADP antagonists response status showing that patients with platelet count >320 g/L displayed higher ADP-induced platelet aggregation. About 12% of patients had high on-treatment platelet reactivity (HTPR) to aspirin, 3% and 4% a HTPR to prasugrel and ticagrelor, respectively, and only 2% displayed HTPR to dual antiplatelet therapy. CONCLUSION: When potent platelet inhibitors as prasugrel and ticagrelor are administered with aspirin, HTPR to DAPT plays only a marginal role.
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Multi-resistant microorganisms are a long-standing problem for public healthcare, as inactivating those resistant pathogens with conventional antibiotics or antiseptics often no longer achieves the expected clinical success. The aim of this in vitro study was to investigate the antibacterial efficacy of binary combinations of conventional antibacterial agents with cold atmospheric plasma (CAP), when both are applied in non-lethal concentrations. In this study, Enterococcus faecalis biofilms were treated with CAP in binary combinations with benzalkonium chloride (BAC), chlorhexidine (CHX), or ciprofloxacin (CIP), respectively, which were applied in different sequences. In order to evaluate effects of binary use of two different antibacterial approaches, the so-called latest time point of retreatment (LTPR) was defined. For this purpose, regrowth curves of the bacteria were measured following the respective treatment combinations. LTPR is defined as the time component of the inflection point of a normalized regrowth curve and allows the rating and interpretation of single or binary treatments with different agents or approaches. Furthermore, LTPR designates the latest time point where a retreatment appears to be appropriate for preventing regrowth of the bacteria in case the first treatment was not lethal. Here in our study, the binary combination of 10 min CAP with BAC, CHX, or CIP leads to higher LTPRs as compared to single treatments for both sequences of application. Overall, the combination of two antimicrobial approaches is an effective alternative for inactivating bacteria in biofilms instead of a single treatment. Thus, LTPR provides a novel promising way to determine antibacterial effects for single or binary use of given antimicrobial approaches.
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Neuroendovascular techniques for treating cerebral aneurysms and other cerebrovascular pathology are increasingly becoming the standard of care. Intraluminal stents, aneurysm coils, and other flow diversion devices typically require concomitant antiplatelet therapy to reduce thromboembolic complications. The variability inherent with the pharmacodynamic response to common antiplatelet agents such as aspirin and clopidogrel complicates optimal selection of antiplatelet agents by clinicians. This review serves to discuss the literature related to antiplatelet use in neuroendovascular procedures and provides recommendations for clinicians on how to approach patients with variable response to antiplatelet agents, particularly clopidogrel.
Assuntos
Transtornos Cerebrovasculares/terapia , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/terapia , Complicações Intraoperatórias/prevenção & controle , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Tromboembolia/prevenção & controle , Disponibilidade Biológica , Clopidogrel/efeitos adversos , Clopidogrel/farmacocinética , Clopidogrel/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina/farmacocinética , Humanos , Complicações Intraoperatórias/sangue , Taxa de Depuração Metabólica/fisiologia , Inibidores da Agregação Plaquetária/farmacocinética , Testes de Função Plaquetária , Stents , Tromboembolia/sangueRESUMO
BACKGROUND: The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS). OBJECTIVE: We aimed to evaluate the level of PR inhibition achieved by a 180 mg LD of ticagrelor and the rate of high on-treatment platelet reactivity (HTPR) in ACS patients undergoing PCI. METHODS: We performed a multicentre prospective observational study enrolling ACS patients undergoing PCI. Patients were included if they were admitted for ST-elevation myocardial infarction or non ST-elevation ACS. To assess PR, a VASP index was measured at least 6 and within 24 hours following a 180 mg LD of ticagrelor. HTPR was defined as a VASP index ≥50%. RESULTS: One hundred and fifteen patients were included: 31.3% of STEMI, 49.6% of NSTEMI and 19.1% of unstable angina. Following ticagrelor LD the mean VASP index was 17±14%. However the response to ticagrelor was not uniform with a small inter-individual variability: inter quartile range: 7.6-22.8% and a rate of HTPR of 3.5%. A high number of patients, 65.6%, had a VASP index <16%. None of the baseline characteristics of the study population was associated with PR. In addition, PR was similar in STEMI, NSTEMI and unstable angina (p=0.9). CONCLUSION: In ACS patients the level of PR inhibition achieved by a 180 mg loading dose of ticagrelor is not uniform and the rate of HTPR is 3.5%. A high proportion of patients exhibited a VASP index <16%.