Treatment of distal unruptured intracranial aneurysms using a surface-modified flow diverter under prasugrel monotherapy: a pilot safety trial.

BACKGROUND: Flow diverters (FDs) are effective in the treatment of carotid aneurysms. Compared with carotid aneurysms, the treatment of distal intracranial aneurysms with FDs has been associated with a relatively high incidence of complications. Low thrombogenic modified-surface FDs may reduce ischemic complications and allow for the use of a single antiplatelet medication. The aim of this study was to assess the safety and efficacy of the p48 MW HPC Flow Modulation Device (Phenox GmbH, Bochum, Germany) to treat distal intracranial aneurysms used in combination with prasugrel monotherapy. METHODS: This was a single-center, prospective, pivotal, open, single-arm study. Patients were included in this study from December 2019 to September 2020. The primary endpoints were the incidence of any neurologic deficit after treatment until 1 month of follow-up, defined as National Institutes of Health Stroke Scale (NIHSS) ≥1, and the incidence of acute ischemic lesions in magnetic resonance imagin (MRI) images 48 hours after treatment. The secondary endpoint was the rate of complete occlusion of the aneurysms at the 1-month follow-up. RESULTS: Twenty-one patients harboring 27 distal aneurysms of the anterior circulation were included. Mean age was 57.8 (SD 9.7) years, and 16 patients were female (80%). No patient had neurologic symptoms at the 1-month follow-up. Four patients (20%) had asymptomatic acute brain ischemic lesions on MRI. Complete aneurysm occlusion occurred in 9/27 (33.3%) aneurysms at the 1-month follow-up. CONCLUSION: In this pilot safety trial, treatment of distal intracranial aneurysms with p48 MW HPC under monotherapy with prasugrel appeared to be safe.

Tratamento da sca no paciente diabético: o que mostram as evidências / Treatment of acs in the diabetic patient: what the evidence shows

O diabete mellitus (DM) é uma comorbidade muito frequente entre os pacientes com síndrome coronariana aguda (SCA), acometendo, aproximadamente, 20 a 37% desses. Além de ser um preditor de risco independente, também está relacionado a uma maior prevalência de quadros atípicos de SCA. Apesar disso, é importante ressaltar que no caso da SCA, a maioria dos pacientes com DM apresenta o mesmo quadro clínico que os pacientes sem a doença. Assim como para os pacientes não diabéticos, os scores de risco devem ser aplicados. Entretanto, essa comorbidade por si própria já prediz uma maior gravidade. Inclusive é mais aconselhável utilizar para esses pacientes uma estratégia invasiva precoce. Em relação ao tratamento medicamentoso da SCA, não há alterações significativas no tratamento dos pacientes com DM para os pacientes sem DM. Já no que diz respeito à terapia de reperfusão, muito se extrapola dos conhecimentos em angina estável, em que há uma superioridade do tratamento cirúrgico sobre o percutâneo para os pacientes com DM, ainda que haja falta de evidências no contexto agudo. Finalmente, o conjunto de evidências não é definitivo para indicar a melhor estratégia para o controle da hiperglicemia, entretanto, sabe-se que tanto a hiperglicemia quanto à hipoglicemia durante a internação está relacionada aos piores desfechos. Portanto, é importante evitar valores de glicemia superiores a 180 mg/dL e inferiores a 90 mg/dL, ficando a estratégia de controle rigoroso de glicemia com insulina intravenosa restrita aos pacientes selecionados.

Diabetes mellitus (DM) is a frequent comorbidity among patients with acute coronary syndrome (ACS), affecting about 20% to 37% of these patients. Besides being an independent risk predictor, it is also related to a higher prevalence of atypical presentations of ACS. Despite this, it is important to emphasize that in the case of ACS the majority of patients with DM have the same clinical presentation as patients without the disease. Just as for non-diabetic patients, risk scores should be applied. However, this comorbidity per se predicts a greater severity. Also, it is preferable to use an early invasive strategy for these patients. Regarding the medicinal treatment of ACS, there are no significant differences between the treatment of patients with DM and those without DM. In relation to reperfusion therapy, much of it is extrapolated from knowledge of stable angina, in which surgical treatment takes precedence over percutaneous treatment for patients with DM, despite the lack of evidence in the acute context. Finally, there is no definitive body of evidence to indicate the best strategy to control hyperglycemia, but it is known that both hyperglycemia and hypoglycemia during hospitalization are associated with worse outcomes. Thus, it is important to avoid glycemia values above 180 mg/dL and below 90 mg/dL, restricting the strategy of strict glycemic control with intravenous insulin to selected patients.

Antiplaquetários nas Síndromes Coronarianas Agudas / Antiplatelet Agents in Acute Coronary Syndromes

Em condições de equilíbrio, a hemostasia é mantida através de uma complexa interação entre endotélio, plaquetas e fatores de coagulação. Situações que cursam com injúria e descontinuidade do revestimento endotelial estimulam a adesão, ativação e agregação de plaquetas, culminando com a formação de trombos arteriais ou venosos. Neste contexto, a terapia antiplaquetária ocupa um papel de destaque no manejo das patologias advindas deste processo, notadamente as síndromes coronarianas agudas.O maior domínio conceitual dos receptores, agonistas e antagonistas das cascatas fisiopatológicas envolvidasneste processo possibilitou o desenvolvimento de novos fármacos e o refinamento da terapêutica atual, tornando necessário o pleno conhecimento do arsenal antiplaquetário no que tange à sua indicação, posologia, momento de administração e duração do tratamento. O objetivo desta revisão é definir o papel dos fármacos antiplaquetários no manuseio da síndrome coronariana aguda, revisitando aspectos já consolidados e abordando tópicos atuais e ainda controversos acerca do tema

P2Y12 receptor inhibition with prasugrel and ticagrelor in STEMI patients after fibrinolytic therapy: Analysis from the SAMPA randomized trial.

BACKGROUND: A pharmacodynamic comparison between ticagrelor and prasugrel after fibrinolytic therapy has not yet been performed. METHODS: In the single-center SAMPA trial, 50 consecutive STEMI patients previously treated with clopidogrel and undergoing a pharmacoinvasive strategy were randomized to either a ticagrelor (n=25) 180mg loading dose followed by 90mg bid, or a prasugrel (n=25) 60mg loading dose followed by 10mg/day, initiated after fibrinolytic therapy but before angiography. Platelet reactivity was assessed with the VerifyNow P2Y12 assay at 0, 2, 6, and 24h after randomization. RESULTS: Mean times from fibrinolysis to prasugrel or ticagrelor administration were 11.1±6.9 and 13.3±6.3h, respectively (p=0.24). The values of PRU decreased significantly from baseline to 2h (all p<0.001) and from 2h to 6h (all p<0.001) in both groups. There was no difference in PRU values between 6h and 24h. The mean PRU values at 0, 2, 6, and 24h were 234.9, 127.8, 45.4, and 48.0 in the prasugrel group and 233.1, 135.1, 67.7, and 56.9 in the ticagrelor group, respectively. PRU values did not significantly differ between groups at any time period of the study. CONCLUSIONS: In patients with STEMI treated with fibrinolytic therapy, platelet inhibition after clopidogrel is suboptimal and can be further increased with more potent agents. Ticagrelor and prasugrel demonstrated a similar extent of P2Y12 receptor inhibition within 24h, although maximal platelet inhibition after these potent agents was not achieved for 6h.

Estratégias antiplaquetárias orais nas fases aguda e crônica das síndromes coronarianas aguda / Oral antiplatelet strategies in the acute and chronic of acute coronary syndromes

Desde os primeiros estudos com ácido acetilsalicílico (AAS), até publicações mais recentes com novos bloqueadores de ADP e bloqueadores do receptor de trombina, pode-se afirmar que o conhecimento sobre o tratamento antiplaquetário nas síndromes coronarianas agudas (SCA) evoluiu de forma exponencial. Atualmente, a dupla antiagregação (DAP) é parte essencial do tratamento das SCA em todas as suas formas de apresentação, sendorecomendada por no mínimo um ano em todos os pacientes, independentemente da estratégia de revascularização utilizada, desde que não haja contraindicações ao seu uso. Ao mesmo tempo que se demonstrava eficácia crescente com o uso de antitrombóticosde forma geral (incluindo-se os antiplaquetários), cada vez mais a comunidade científica se conscientizava da importância do sangramento que ocorria com o uso desses medicamentos e negava, ao menos parcialmente, os benefícios obtidos. Assim sendo, os maiores desafios nos tempos atuais em termos de terapêutica antitrombótica nas SCA voltam-se para o desenvolvimento de estratégias terapêuticas personalizadas individualmente, que possam ter o máximo possível de benefício emtermos de eventos isquêmicos, com o mínimo possível de sangramento. Isso inclui não apenas uma análise cuidadosa dos medicamentos a serem associados, mas também do tempo de sua utilização. Tais estratégias constituem o foco principal da presente revisão...

Since the first studies with acetylsalicylic acid (ASA) up to more recent publications with new blockers of ADP and anti-thrombin receptor blockers, it is fair to say that knowledge about antiplatelet therapy in acute coronary syndromes (ACS) has grown exponentially. Currently, dual antiplatelet (DAP) therapy is an essential part of the treatment in all presentation forms of ACS, and it is recommended for at least one year for all patients, regardless of the revascularization strategy used, provided there are no contraindications to its use. Alongside the demonstration of increased efficacy of antithrombotics in general (including antiplatelet drugs), the scientific community became increasingly aware of the impactof bleeding that occurred with the use of these drugs, and that were undermining, at least partially, the benefits obtained.Thus, the main challenge today regarding anti-thrombotic treatment in ACS is the development of tailored therapeutic strategies that can produce the greatest possible benefit in terms of ischemic events, with minimal bleeding. This includes not only a careful analysisof the drugs to be associated, but also the duration of their use. Such strategies are the focus of the present review...

Upstream clopidogrel, prasugrel, or ticagrelor for patients treated with primary angioplasty: Results of an angiographic randomized pilot study.

OBJETIVES: The main objective of the present randomized pilot study was to explore the effects of upstream prasugrel or ticagrelor or clopidogrel for patients with ST-segment-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: Administration of clopidogrel "as soon as possible" has been advocated for STEMI. Pretreatment with prasugrel and ticagrelor may improve reperfusion. Currently, the angiographic effects of upstream administration of these agents are poorly understood. METHODS: A total of 132 patients with STEMI within the first 12 hr of chest pain referred to primary angioplasty were randomized to upstream clopidogrel (600 mg), prasugrel (60 mg), or ticagrelor (180 mg) while still in the emergency room. All patients underwent protocol-mandated thrombus aspiration. RESULTS: Macroscopic thrombus material was retrieved in 79.5% of the clopidogrel group, 65.9% of the prasugrel group, and 54.3% of the ticagrelor group (P = 0.041). At baseline angiography, large thrombus burden was 97.7% vs. 87.8% vs. 80.4% in the clopidogrel, prasugrel, and ticagrelor groups, respectively (P = 0.036). Also, at baseline, 97.7% presented with an occluded target vessel in the clopidogrel group, 87.8% in the prasugrel group and 78.3% in the ticagrelor group (P = 0.019). At the end of the procedure, the percentages of patients with combined TIMI grade III flow and myocardial blush grade III were 52.3% for clopidogrel, 80.5% for prasugrel, and 67.4% for ticagrelor (P = 0.022). CONCLUSIONS: In patients with STEMI undergoing primary PCI within 12 hr, upstream clopidogrel, prasugrel or ticagrelor have varying angiographic findings, with a trend toward better results for the latter two agents. © 2015 Wiley Periodicals, Inc.

Efficacy of Change to New P2Y12 Receptor Antagonists in Patients High on Treatment Platelet Reactivity Undergoing Percutaneous Coronary Intervention.

Selective intensification of platelet inhibition may improve high on treatment platelet reactivity (HPR). We evaluated the efficacy of dual-antiplatelet therapy, including clopidogrel (CPG), compared to new P2Y12-receptor antagonists in patients with HPR undergoing percutaneous coronary intervention, regarding the outcome of composite major adverse cardiac events (MACEs, including death, acute coronary syndrome [ACS], and stent restenosis). The presence of HPR (71 of 181 patients) almost doubled the risk of MACEs. The new antiplatelet agent reduced MACEs (45.8%, 26%, and 16.7% for CPG, prasugrel, and ticagrelor [TGL]; RR 0.36; 0.13-0.98, P = .03, TGL), specifically in patients with ACS. Failure to reduce HPR after the antiplatelet change and diabetes were independent predictors for MACEs. The HPR was early and effectively reduced after changing the antiplatelet therapy, but the intensity of this reduction did not significantly decrease the risk of MACEs. These findings support the benefit of HPR-guided intensification of platelet inhibition. Whether the intensity of this reduction improves the patient's clinical outcomes deserves further investigation.

Efectividad y seguridad del prasugrel, comparado con el clopidogrel, para el tratamiento de Síndrome Coronario Agudo ( SCA ) en adultos / Effectiveness and safety of prasugrel compared to clopidogrel for the treatment of acute coronary syndrome (ACS) in adults

INTRODUCCIÓN: Prasugrel es un inhibidor de la agregación y activación plaquetario, se emplea para la prevención de eventos aterotrombóticos con síndrome coronario agudo que hayan sido manejados con intervención coronaria percutánea. Se utiliza asociado a ácido acetil-salicílico (aspirina). La tecnología cuenta con registro sanitario para la indicación. POBLACIÓN: Pacientes mayores de 18 años con síndrome coronario agudo. INTERVENCIÓN: Prasugrel más a spirina. COMPARACIÓN: Clopidogrel más aspirina. RESULTADOS: Infarto no fatal, muerte, evento cerebrovascular, sangrado mayor. CONCLUSIONES: -Efectividad: prasugrel es una intervención más efectiva comparada con clopidogrel, para el tratamiento de pacientes con síndrome coronario agudo. -Seguridad: los pacientes que reciben prasugrel en comparación con clopidogrel, presentan un incremento en el sangrado mayor y en el sangrado que amenaza la vida. No hay diferencias en el sangrado intracraneal con prasugrel en comparación con clopidogrel. Costo-efectividad: el uso de prasugrel comparado con clopidogrel genera un costo adicional en Colombia de $79.987.695 por cada año de vida ganado ajustado por calidad..