RESUMO
Myocardial fibrosis is a feature found in most cardiac diseases and a key element contributing to heart failure and its progression. It has therefore become a subject of particular interest in cardiac research. Mechanisms leading to pathological cardiac remodeling and heart failure are diverse, including effects on cardiac fibroblasts, the main players in cardiac extracellular matrix synthesis, but also on cardiomyocytes, immune cells, endothelial cells, and more recently, platelets. Although transforming growth factor-ß (TGF-ß) is a primary regulator of fibrosis development, the cellular and molecular mechanisms that trigger its activation after cardiac injury remain poorly understood. Different types of anti-TGF-ß drugs have been tested for the treatment of cardiac fibrosis and have been associated with side effects. Therefore, a better understanding of these mechanisms is of great clinical relevance and could allow us to identify new therapeutic targets. Interestingly, it has been shown that platelets infiltrate the myocardium at an early stage after cardiac injury, producing large amounts of cytokines and growth factors. These molecules can directly or indirectly regulate cells involved in the fibrotic response, including cardiac fibroblasts and immune cells. In particular, platelets are known to be a major source of TGF-ß1. In this review, we have provided an overview of the classical cellular effectors involved in the pathogenesis of cardiac fibrosis, focusing on the emergent role of platelets, while discussing opportunities for novel therapeutic interventions.
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Células Endoteliais , Insuficiência Cardíaca , Humanos , Células Endoteliais/metabolismo , Miocárdio/metabolismo , Fibroblastos/metabolismo , Fibrose , Insuficiência Cardíaca/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Miócitos Cardíacos/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.
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Urticária Crônica , Cilostazol , Dipiridamol , Quimioterapia Combinada , Produtos de Degradação da Fibrina e do Fibrinogênio , Loratadina , Inibidores da Agregação Plaquetária , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Urticária Crônica/tratamento farmacológico , Cilostazol/administração & dosagem , Cilostazol/uso terapêutico , Dipiridamol/administração & dosagem , Dipiridamol/uso terapêutico , Método Duplo-Cego , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/uso terapêutico , Loratadina/administração & dosagem , Loratadina/uso terapêutico , Loratadina/análogos & derivados , Inibidores da Agregação Plaquetária/administração & dosagem , Qualidade de Vida , Tetrazóis/administração & dosagem , Tetrazóis/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: The increased life expectancy of patients with haemophilia A (HA) has led to a growing prevalence of cardiovascular risk factors and events. There is still scarce evidence on the safety and appropriate duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) in HA patients. AIM: We describe our experience on the clinical management of Italian HA patients after ACS. METHODS: Nine patients with congenital HA treated with DAPT after a revascularization procedure performed for ACS have been enrolled and followed at the Angelo Bianchi Bonomi Haemophilia and Thrombosis Center in Milan between 2005 and September 2022. The safety and efficacy of DAPT with or without FVIII prophylaxis were assessed. RESULTS: Ten ACS events occurred in the nine HA patients (four mild and five severe). All events were treated with percutaneous transluminal coronary angioplasty with deployment of 1 to 3 drug-eluting stents followed by DAPT for 1-12 months. All patients except one were treated with FVIII prophylaxis during DAPT aimed at achieving FVIII trough levels ≥20-30 IU/dL. DAPT was effective in all cases in preventing early ACS recurrence, with only a late recurrence. We observed two clinically relevant non-major bleeds (one in a patient without FVIII prophylaxis) and three minor bleeds. No venous thrombosis occurred. CONCLUSION: The long-term secondary antithrombotic prevention consisting of DAPT and FVIII prophylaxis achieving a trough level of 20-30 IU/dL can be effective and safe in HA patients.
Assuntos
Síndrome Coronariana Aguda , Hemofilia A , Hemostáticos , Intervenção Coronária Percutânea , Trombose , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Hemofilia A/tratamento farmacológico , Fator VIII , Trombose/etiologia , Hemostáticos/uso terapêutico , Quimioterapia Combinada , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Resultado do TratamentoRESUMO
Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs. Bacterial and viral pathogens constitute an increasing threat to global public health, especially for patients with ongoing antithrombotic treatment who have a high risk of thrombotic recurrences and high susceptibility to severe infections with increased morbidity and mortality. Similarly, sepsis survivors are at increased risk for major vascular events. Coagulopathy, which often complicates severe infections, is associated with a high mortality and obligates clinicians to adjust antithrombotic drug type and dosing to avoid bleeding while preventing thrombotic complications. This clinical consensus statement reviews the best available evidence to provide expert opinion and statements on the management of patients hospitalized for severe bacterial or viral infections with a pre-existing indication for antithrombotic therapy (single or combined), in whom sepsis-induced coagulopathy is often observed. Balancing the risk of thrombosis and bleeding in these patients and preventing infections with vaccines, if available, are crucial to prevent events or improve outcomes and prognosis.
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Aterosclerose , Sepse , Trombose , Humanos , Fibrinolíticos/uso terapêutico , Anticoagulantes/uso terapêutico , Trombose/tratamento farmacológico , Trombose/etiologia , Trombose/prevenção & controle , Hemorragia/induzido quimicamente , Aterosclerose/tratamento farmacológico , Hemostasia , Sepse/complicações , Sepse/tratamento farmacológico , BiologiaRESUMO
This retrospective study analyzed the efficacy of combined antiplatelet therapy with Argatroban in treating acute ischemic stroke (AIS) and its impact on patients' coagulation and neurological functions. Clinical data of 113 AIS patients admitted between January 2021 and January 2023 were retrospectively analyzed. Patients were divided into control (n = 56) and observation (n = 57) groups based on treatment interventions. The control group patients were treated with antiplatelet drugs, while the observation group patients received combination therapy with apatinib on the basis of the control group treatment. Compared to the control group, the observation group demonstrated higher clinical efficacy, improved coagulation parameters, reduced stroke severity (measured by NIHSS), enhanced daily living abilities (BI scores), and lowered inflammatory and neural injury markers post-treatment. Adverse reaction incidence was similar between groups. Combining Argatroban with antiplatelet drugs in AIS management showed superior efficacy without increasing adverse effects, suggesting its potential for clinical application.
RESUMO
Platelets play a significant role in hemostasis, forming plugs at sites of vascular injury to limit blood loss. However, if platelet activation is not controlled, it can lead to thrombotic events, such as myocardial infarction and stroke. To prevent this, antiplatelet agents are used in clinical settings to limit platelet activation in patients at risk of arterial thrombotic events. However, their use can be associated with a significant risk of bleeding. An enhanced comprehension of platelet signaling mechanisms should facilitate the identification of safer targets for antiplatelet therapy. Over the past decade, our comprehension of the breadth and intricacy of signaling pathways that orchestrate platelet activation has expanded exponentially. Several recent studies have provided further insight into the regulation of platelet signaling events and identified novel targets against which to develop novel antiplatelet agents. Antiplatelet drugs are essential in managing atherothrombotic vascular disease. The current antiplatelet therapy in clinical practice is limited in terms of safety and efficacy. Novel compounds have been developed in response to patient variability and resistance to aspirin and/or clopidogrel. Recent studies based on randomized controlled trials and systematic reviews have definitively demonstrated the role of antiplatelet therapy in reducing the risk of cardiovascular events. Antiplatelet therapy is the recommended course of action for patients with established atherosclerosis. These studies compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. However, in patients undergoing percutaneous coronary intervention, it is still unclear whether the efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy depends on the type of P2Y12 inhibitor. This paper focuses on the advanced-stage evaluation of several promising antiplatelet drugs.
Assuntos
Inibidores da Agregação Plaquetária , Antagonistas do Receptor Purinérgico P2Y , Humanos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/farmacologia , Receptores Purinérgicos P2Y12/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , AnimaisRESUMO
BACKGROUND: Sneddon syndrome is an occlusive vasculopathy that presents clinically with generalized livedo racemosa on the skin and transient ischemic attacks, strokes, and cognitive or motor deficits in the central nervous system. Antiplatelet or anticoagulant therapy is recommended. Due to the limited therapeutic efficacy and the resulting serious complications, we propose combination therapy with additional infusion cycles of alprostadil and captopril and report initial long-term results. PATIENTS AND METHODS: We performed a systematic retrospective analysis of all patients with primary Sneddon syndrome who received combination therapy in our clinic between 1995 and 2020. Therapeutic outcomes were evaluated using descriptive statistics compared to historical controls receiving monotherapy. We also analyzed the event rate of complications when combination therapy was discontinued. RESULTS: During the 99.7 patient-years of follow-up, there were no transient ischemic attacks and the stroke rate dropped to 0.02 per patient-year. In comparison, the rates of transient ischemic attacks and strokes in the historical controls ranged from 0.08 to 0.035 per patient-year. After discontinuation of alprostadil therapy, eight events occurred in three patients. CONCLUSIONS: Combination therapy reduces the long-term incidence of ischemic events in patients with primary Sneddon syndrome.
Assuntos
Alprostadil , Quimioterapia Combinada , Síndrome de Sneddon , Humanos , Feminino , Estudos Retrospectivos , Masculino , Síndrome de Sneddon/epidemiologia , Síndrome de Sneddon/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Incidência , Alprostadil/uso terapêutico , Alprostadil/administração & dosagem , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/prevenção & controle , Ataque Isquêmico Transitório/tratamento farmacológico , Resultado do Tratamento , Transtornos Cerebrovasculares/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Vasodilatadores/uso terapêutico , Vasodilatadores/administração & dosagem , IdosoRESUMO
The blood platelet plays an important role but often remains under-recognized in several vascular complications and associated diseases. Surprisingly, platelet hyperactivity and hyperaggregability have often been considered the critical risk factors for developing vascular dysfunctions in several neurodegenerative diseases (NDDs) like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, platelet structural and functional impairments promote prothrombotic and proinflammatory environment that can aggravate the progression of several NDDs. These findings provide the rationale for using antiplatelet agents not only to prevent morbidity but also to reduce mortality caused by NDDs. Therefore, we thoroughly review the evidence supporting the potential pleiotropic effects of several novel classes of synthetic antiplatelet drugs, that is, cyclooxygenase inhibitors, adenosine diphosphate receptor antagonists, protease-activated receptor blockers, and glycoprotein IIb/IIIa receptor inhibitors in NDDs. Apart from this, the review also emphasizes the recent developments of selected natural antiplatelet phytochemicals belonging to key classes of plant-based bioactive compounds, including polyphenols, alkaloids, terpenoids, and flavonoids as potential therapeutic candidates in NDDs. We believe that the broad analysis of contemporary strategies and specific approaches for plausible therapeutic treatment for NDDs presented in this review could be helpful for further successful research in this area.
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Doença de Alzheimer , Doença de Huntington , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêuticoRESUMO
Low-dose aspirin has been hypothesized to prevent cancer risk by inhibiting platelet aggregation. However, the anti-cancer effect of low-dose aspirin has recently been questioned and its effect on breast cancer development remains unclear. The impact of other antiplatelet drugs on breast cancer risk has rarely been evaluated. Thus, this study aimed to investigate the associations between breast cancer risk and antiplatelet drug use in a nationwide nested case-control study. From the Danish healthcare registries, we identified as cases all women with invasive breast cancer diagnosis between 2001 and 2018 (n = 68 852). The date of diagnosis corresponded to the index date. We matched cases to 10 population controls on age and calendar time, using risk set sampling. Controls were assigned the same index date as their matched case. We used the prescription registry to identify exposure to low-dose aspirin, clopidogrel and dipyridamole. We defined ever use of antiplatelet drugs as at least two prescriptions filled up to 1 year before the index date. We applied conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for breast cancer associated with the use of antiplatelet drugs, overall, by breast cancer subtype and by cumulative dose. Twelve percent of women had ever been exposed to low-dose aspirin, 2% to clopidogrel and 2% to dipyridamole. In multivariable models, breast cancer risk was not associated with ever use of low-dose aspirin (OR = 1.00 [0.97-1.03]), clopidogrel (OR = 0.93 [0.87-1.00]), and dipyridamole (OR = 1.02 [0.94-1.10]), compared with never use, and there was no evidence of a dose-response relation. However, we found an inverse association between dipyridamole use and breast cancer risk among women aged <55 years old, with suggestion of a dose-response relationship (OR per 1000 Defined Daily Doses = 0.72 [0.54-0.95]). Associations did not differ by breast cancer histological type, estrogen receptor status or clinical stage at diagnosis. Overall, the findings from this study do not support the use of antiplatelet drugs for breast cancer prevention.
Assuntos
Neoplasias da Mama , Inibidores da Agregação Plaquetária , Feminino , Humanos , Pessoa de Meia-Idade , Aspirina/uso terapêutico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Estudos de Casos e Controles , Clopidogrel , Dinamarca/epidemiologia , Dipiridamol/uso terapêutico , Modelos LogísticosRESUMO
BACKGROUND: For ischaemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs or reducing the dose of antiplatelet drugs was a conventional clinical therapy method. But not a study to prove which way was better. And the machinery learning methods could help to obtain which way more suit for some patients. METHODS: Data from consecutive ischaemic stroke patients with gastrointestinal haemorrhage were prospectively collected. The outcome was a recurrent stroke rate, haemorrhage events, mortality and favourable functional outcome (FFO). We analysed the data using conventional logistic regression methods and a supervised machine learning model. We used unsupervised machine learning to group and analyse data characters. RESULTS: The patients of stopping antiplatelet drugs had a lower rate of bleeding events (p = 0.125), mortality (p = 0.008), rate of recurrence of stroke (p = 0.161) and distribution of severe patients (mRS 3-6) (p = 0.056). For Logistic regression, stopping antiplatelet drugs (OR = 2.826, p = 0.030) was related to lower mortality. The stopping antiplatelet drugs in the supervised machine learning model related to mortality (AUC = 0.95) and FFO (AUC = 0.82). For group by unsupervised machine learning, the patients of better prognosis had more male (p < 0.001), younger (p < 0.001), had lower NIHSS score (p < 0.001); and had a higher value of serum lipid level (p < 0.001). CONCLUSIONS: For ischemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs had a better prognosis. Patients who were younger, male, with lesser NIHSS scores at admission, with the fewest history of a medical, higher value of diastolic blood pressure, platelet, blood lipid and lower INR could have a better prognosis.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/induzido quimicamente , AVC Isquêmico/tratamento farmacológico , Aprendizado de Máquina , Lipídeos/uso terapêuticoRESUMO
Metal complexes displaying antiplatelet properties is a promising research area. In our methodology, Platelet-Activating Factor (PAF), the most potent lipid pro-inflammatory mediator, serves as a biological probe. The antiplatelet activity is exerted by the inhibition of the PAF-induced aggregation in washed rabbit platelets (WRPs) and in rabbit plasma rich in platelets (rPRPs). Herein, the synthesis and biological investigation of a series of organometallic tin(II) and tin(IV) complexes, featuring the oxygen tripodal Kläui ligands [(η5-C5R5)Co{P(OEt)2O}3]-, {R = H, (LOEt-); Me (L*OEt-)}, are reported. Reaction of NaLOEt (1a) and NaL*OEt (1b) with SnCl2, yielded the rare four-coordinate LOEtSnCl (2a) and L*OEtSnCl (2b) complexes. Accordingly, LOEtSnPh3 (3a) and L*OEtSnPh3 (3b) were prepared, starting from Ph3SnCl. Characterization includes spectroscopy and X-ray diffraction studies for 2a, 2b and 3b. The antiplatelet activity of the lead complexes 2b and 3a (IC50 = 0.5 µΜ) is superior compared to that of 1a and 1b, while both complexes display a pronounced inhibitory activity against thrombin (IC50 = 1.8 µM and 0.6 µM). The in vitro cytotoxic activities of 3a and 2b on human Jurkat T lymphoblastic tumor cell line is higher than that of cisplatin.
Assuntos
Antineoplásicos , Trombina , Animais , Humanos , Coelhos , Ligantes , Estanho , Fator de Ativação de Plaquetas , Oxigênio/químicaRESUMO
Anticoagulant therapy is a cornerstone treatment for coronavirus disease 2019 (COVID-19) due to the high rates of thromboembolic complications associated with this disease. We hypothesized that chronic antithrombotic therapy could play a protective role in patients hospitalized for COVID-19. Retrospective, observational study of all patients admitted to our hospital for ≥ 24 h from March 1 to May 31, 2020 with SARS-CoV-2. The objective was to evaluate clinical outcomes and mortality in COVID-19 patients receiving chronic anticoagulation (AC) or antiplatelet therapy (AP) prior to hospital admission. A total of 1612 patients were evaluated. The mean (standard deviation; SD) age was 66.5 (17.1) years. Patients were divided into three groups according to the use of antithrombotic therapy prior to admission (AP, AC, or no-antithrombotic treatment). At admission, 9.6% of the patients were taking anticoagulants and 19.1% antiplatelet therapy. The overall mortality rate was 19.3%. On the multivariate analysis there were no significant differences in mortality between the antithrombotic groups (AC or AP) and the no-antithrombotic group (control group). Patients on AC had lower ICU admission rates than the control group (OR: 0.41, 95% CI, 0.18-0.93). Anticoagulation therapy prior to hospitalization for COVID-19 was associated with lower ICU admission rates. However, there were no significant differences in mortality between the patients receiving chronic antithrombotic therapy and patients not taking antithrombotic medications. These findings suggest that chronic anticoagulation therapy at the time of COVID-19 infection may reduce disease severity and thus the need for ICU admission.
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COVID-19 , Fibrinolíticos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Coronavirus disease 2019 (COVID-19) is a pandemic syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection induces a process of inflammation and thrombosis supported by an altered platelet activation state. This platelet activation is peculiar being characterized by the formation of platelet-leukocytes rather than platelet-platelet aggregates and by an increased procoagulant potential supported by elevated levels of TF positive platelets and microvesicles.Therapeutic strategies targeting, beyond systemic inflammation (i.e. with tocilizumab, an anti interleukin-6 receptor), this state of platelet activation might therefore be beneficial. Among the antithrombotic drugs proposed as candidates to treat patients with SARS-CoV-2 infection, antiplatelet drugs, such as aspirin are showing promising results.
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Plaquetas/metabolismo , COVID-19/sangue , Humanos , SARS-CoV-2RESUMO
OBJECTIVE: To analyze the efficacy and safety of antiplatelet drugs combined with new oral anticoagulants (noac) in the treatment of coronary atherosclerotic heart disease (CAD). METHODS: The randomized controlled trials of noac combined with antiplatelet therapy in Cochrane, CNKI, PubMed, EMBASE, Wanfang, Google Scholar, and Baidu library were searched using the literature database. Two researchers independently searched and screened to ensure the consistency of the results, and the literature was summarized and analyzed by Revman 5.3 software. RESULTS: Five research results were included. The results showed that the incidence of mace [95% CI 0.75-0.95, or = 0.84,p = .04], the incidence of major and minor bleeding [95% CI 1.25-5.16, or = 2.54,p = .01], the mortality of cardiovascular disease [95% CI 0.78-0.96, or = 0.86, p = .05], the total mortality [95% CI 0.79-0.95, or = 0.87, p = .003], and the incidence of myocardial infarction in patients with CAD treated with noac and antiplatelet drugs [95% CI 0.77-0.95, or = 0.85, p = .004] was lower than that treated with antiplatelet drugs alone, and the difference was statistically significant (p < .05); the incidence of fatal bleeding [95% CI 0.81-2.08, or = 1.30, p = .28], the incidence of stroke [95% CI 0.50-1.03, or = 0.71, p = .07], and the incidence of intracranial hemorrhage [95% CI 1.02-2.56, or = 1.61, p = .06]. There was no significant difference with antiplatelet drugs alone (p > .05). CONCLUSION: Noac combined with antiplatelet drugs can reduce mace, total mortality, the incidence of myocardial infarction, and cardiovascular mortality in patients with CAD, but may increase the risk of bleeding.
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Doença das Coronárias , Infarto do Miocárdio , Acidente Vascular Cerebral , Anticoagulantes/efeitos adversos , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Eletrocardiografia/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/complicações , Hemorragia/tratamento farmacológico , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/etiologiaRESUMO
Ischemic stroke is a disease related to abnormal blood flow that leads to brain dysfunction. The early and late phases of the disease are distinguished. A distinction is made between the early and late stages of the disease, and the best effect in treating an ischemic stroke is usually achieved within the first hours after the onset of symptoms. This review looked at studies platelet activity monitoring studies to determine the risks and benefits of various approaches including antiplatelet therapy. A study was conducted on recently published literature based on PRISMA. This review includes 32 research articles directly addressing the importance of monitoring platelet function during antiplatelet therapy (dual or monotherapy) after ischemic stroke. In patients with transient ischemic attack or ischemic stroke, antiplatelet therapy can reduce the risk of stroke by 11-15%, assuming that patients respond well. Secondary prevention results are dependent on platelet reactivity, meaning that patients do not respond equally to antiplatelet therapy. It is very important that aspirin-resistant patients can benefit from the use of dual antiplatelet therapy. The individualized approach to secondary stroke prevention is to administer the most appropriate drug at the correct dose and apply the optimal therapeutic procedure to the individual patient.
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Plaquetas/efeitos dos fármacos , AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Aspirina/farmacologia , Aspirina/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Humanos , AVC Isquêmico/sangue , Inibidores da Agregação Plaquetária/farmacologiaRESUMO
The PulseRider (Cerenovus, Johnson & Johnson Medical Devices, New Brunswick, NJ, USA) is a neck reconstruction device that is used for the treatment of unruptured wide-necked bifurcation aneurysms. Herein, we describe the case of a 51-year-old male patient with a basilar apex aneurysm who was treated with PulseRider but had post-procedural brainstem infarctions caused by one of the proximal markers covering the origin of a perforator. In such cases, repositioning of the PulseRider should be performed to avoid infarctions.
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Infartos do Tronco Encefálico , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Infartos do Tronco Encefálico/diagnóstico por imagem , Infartos do Tronco Encefálico/etiologia , Infartos do Tronco Encefálico/terapia , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Stents , Resultado do TratamentoRESUMO
BACKGROUND: Clopidogrel in combination with aspirin after acute coronary syndromes (ACS) reduces recurrent ischaemic events compared to aspirin alone. Further reductions in events have been demonstrated when clopidogrel is replaced by ticagrelor or prasugrel albeit with increases in bleeding. There are few studies documenting the patterns of use of P2Y12 inhibitors or their association with outcomes in the Australian population. AIMS: To describe the patterns of use of each P2Y12 inhibitor and to determine the associations between initial P2Y12 inhibitor use and outcomes. METHODS: Data were extracted from Cooperative National Registry of ACS, Guideline Adherence and Clinical Events (CONCORDANCE)-a prospective database of patients presenting to 43 sites across Australia with ACS. Patients were stratified based on first antiplatelet agent received. Baseline clinical characteristics were compared between these patient groups and hospital investigations, management as well as in-hospital and 12 months outcomes (death, a composite of cardiac-related death, myocardial infarction, and stroke, and major bleeding) were compared between the three treatment cohorts after adjustment for differences in baseline characteristics. RESULTS: Mean ages of the clopidogrel (n=7,537), ticagrelor (n=1,878), and prasugrel (n=347) cohorts were 65, 63, and 58 yrs respectively (p<0.0001), the mean Global Registry of Acute Coronary Events (GRACE) risk scores were 107, 104, and 102 (p=0.0016). The ticagrelor and prasugrel cohorts were more likely to receive percutaneous coronary intervention (PCI) (clopidogrel 52%, ticagrelor 66%, prasugrel 88%, p<0.0001), and evidence based medications (≥4 guideline indicated medications: clopidogrel 76%, ticagrelor 82%, prasugrel 93%, p<0.0001). Patients treated with ticagrelor and prasugrel were less likely to experience in-hospital death (clopidogrel 2.5%, ticagrelor 1.4%, prasugrel 1.2%, p=0.05), major adverse cardiac events (MACE) (clopidogrel 5.1%, ticagrelor 3.0%, prasugrel 3.5% [p=0.01]), or bleeding (clopidogrel 8.4%, ticagrelor 4.6%, prasugrel 7.5% [p<0.001]) compared to clopidogrel. These differences were no longer apparent after multivariable adjustment. There was no difference in outcomes between cohorts at 12 months. CONCLUSIONS: In Australia, ticagrelor and prasugrel are used in younger patients who are more likely to undergo percutaneous coronary intervention (PCI) and receive evidence based therapy. Patients receiving clopidogrel were more likely to experience in hospital ischaemic or bleeding events but this was explained by their higher baseline risk. Selection of therapy was not associated with any difference in outcomes at 12-month follow-up, but our findings suggest there is room for improvement towards guideline-driven usage of P2Y12 inhibitors.
Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina/uso terapêutico , Austrália/epidemiologia , Clopidogrel/uso terapêutico , Hemorragia/induzido quimicamente , Mortalidade Hospitalar , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Antiplatelet drugs may prevent recurrent ischemic events after ischemic stroke but their relative effectiveness and harms still need to be clarified. Within this network meta-analysis we aimed to summarize the current evidence for using antiplatelet drugs for secondary stroke prevention. METHODS: We searched MEDLINE, EMBASE and CENTRAL up to September 2020. Randomized controlled trials (RCTs) assessing antiplatelet drugs for secondary stroke prevention were included. We did pairwise meta-analyses and network meta-analyses using random-effects models. Primary outcomes were all strokes (ischemic or hemorrhagic) and all-cause mortality. RESULTS: The review included 57 RCTs, 50 (n = 165,533 participants) provided data for the meta-analyses. Compared to placebo/no treatment, moderate to high-confidence evidence indicated that cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day significantly reduced the risk of all strokes (odds ratios, ORs and absolute risk difference, ARD): cilostazol 0.51 (95 % confidence interval, CI, 0.37 to 0.71; 3.6 % fewer), clopidogrel 0.63 (95 % CI, 0.49 to 0.79; 2.7 % fewer), dipyridamole + aspirin 0.65 (95 % CI, 0.55 to 0.78; 2.5 % fewer), ticagrelor 0.68 (95 % CI, 0.50 to 0.93; 2.3 % fewer), ticlopidine 0.74 (95 % CI 0.59 to 0.93; 1.9 % fewer), aspirin ≤ 150 mg/day 0.79 (95 % CI, 0.66 to 0.95; 1.5 % fewer). Aspirin > 150 mg/day and the combinations clopidogrel/aspirin, ticagrelor/aspirin, also decrease all strokes but increase the risk of hemorrhagic events. Only aspirin > 150 mg/day significantly reduced all-cause mortality (OR 0.86, 95 % CI 0.76 to 0.97; ARD 0.9 %, 95 %CI 1.5-0.2 % fewer, moderate confidence). Compared to aspirin ≤ 150 mg/day, clopidogrel significantly reduced the risk of all strokes, cardiovascular events, and intracranial hemorrhage outcomes. Cilostazol also appeared to provide advantages but data are limited to the Asian population. CONCLUSIONS: Considering the benefits and harms ratio, cilostazol, clopidogrel, dipyridamole + aspirin, ticagrelor, ticlopidine, and aspirin ≤ 150 mg/day appear to be the best choices as antiplatelet drugs for secondary prevention of patients with ischemic stroke or TIA. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020159896 .
Assuntos
Ataque Isquêmico Transitório , AVC Isquêmico , Quimioterapia Combinada , Feminino , Humanos , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/prevenção & controle , AVC Isquêmico/prevenção & controle , Metanálise em Rede , Inibidores da Agregação Plaquetária/uso terapêutico , Prevenção SecundáriaRESUMO
BACKGROUND: Ticagrelor has a bactericidal effect in vitro, and clinical studies suggest a beneficial effect in infections. Our aim was to determine the incidence of infections in patients treated with 3 different P2Y12 receptor inhibitors. METHODS: Retrospective registry in a cardiology department. Patients with coronary artery disease discharged on ticagrelor, prasugrel, or clopidogrel from March 2017 to June 2019 were included. The risk of infection was analyzed during the period of P2Y12 inhibitor treatment (12.4 ± 6.7 months). RESULTS: A total of 250 patients were included (ticagrelor 91 [36.4%], prasugrel 89 [35.6%], clopidogrel 70 [28.0%]). Mean age was 61.0 ± 13.1 years, and 63 (25.2%) were women. The most common reason to use these drugs was ST-segment elevation acute myocardial infarction (STEMI) (152 patients - 60.8%). STEMI was the reason to use prasugrel in 84 patients (94.4%), ticagrelor in 44 (48.4%), and clopidogrel in 24 (34.3%), p < 0.001. An infection during follow-up was seen in 87 patients (34.8%), 23 treated with ticagrelor (25.3%), 30 with prasugrel (33.7%) and 34 with clopidogrel (48.6%), p = 0.009. Ticagrelor was independently associated with a lower likelihood of infection (Hazard Ratio [HR] 0.52, 95% confidence interval [CI] 0.28-0.95; p = 0.035) compared to prasugrel (HR 0.96, 95% CI 0.54-1.73; p = 0.909) and clopidogrel (HR = 1). CONCLUSIONS: In patients admitted with coronary artery disease patients treated with ticagrelor had a lower frequency of infections during follow-up than those treated with other P2Y12 inhibitors. Further studies are necessary to clarify the bactericidal effect of ticagrelor in this context.
Assuntos
Doença da Artéria Coronariana , Idoso , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Cloridrato de Prasugrel/uso terapêutico , Estudos Retrospectivos , Ticagrelor/uso terapêuticoRESUMO
Stroke is one of the main causes of mortality and permanent disability. Secondary prevention of stroke recurrence therefore has a high priority. Secondary prevention of ischemic stroke includes optimization of the lifestyle and diet, treatment of risk factors, such as hypertension, diabetes mellitus and hyperlipidemia, prophylaxis of recurrence with antiplatelet treatment in patients with high vascular risk and anticoagulation in atrial fibrillation. In addition, secondary prevention includes carotid surgery or stenting in selected symptomatic patients and closure of a patent foramen ovale after cryptogenic stroke.