De-escalação de inibidores dos receptores P2Y12 após intervenção coronária percutânea / P2Y12 inhibitor de-escalation after percutaneous coronary interventions

Em pacientes que apresentam síndromes coronárias agudas e são tratados com intervenção coronária percutânea, a prescrição do esquema antiplaquetário duplo, composto de ácido acetilsalicílico e um inibidor dos receptores P2Y12, é mandatória, contribuindo para a redução de eventos cardíacos maiores. No entanto, ao mesmo tempo em que previne eventos isquêmicos, essa associação pode precipitar complicações hemorrágicas maiores, o que é mais comumente observado quando são prescritos os medicamentos mais potentes, como o prasugrel ou o ticagrelor. Essas constatações levaram à procura de alternativas terapêuticas capazes de manter a proteção contra eventos isquêmicos e, ao mesmo tempo, prevenir a ocorrência de hemorragias. Uma das estratégias que está em estudo é a de-escalação dos inibidores P2Y12, que consiste no uso dos medicamentos mais potentes numa fase precoce após o procedimento, com substituição deles pelo clopidogrel, após um período de, em geral, 30 dias de evolução; outra possibilidade seria a simples redução da dose do fármaco de maior potência, algo que, até o momento, só pode ser cogitado com o prasugrel. A de-escalação pode ser feita de forma guiada, utilizando testes de mensuração objetiva da agregação plaquetária ou exames para avaliar o perfil genético dos pacientes, ou não guiada, na qual o cardiologista simplesmente faz a substituição ou redução da dose ao fim do período estipulado, sem o auxílio de exames complementares. A literatura contempla ensaios clínicos com essas duas opções de estratégia, os quais são discutidos nesta revisão. Até o momento, nenhuma diretriz médica recomenda de forma explícita o uso regular dessa alternativa terapêutica.

In patients who have acute coronary syndromes and are treated with percutaneous coronary intervention, the prescription of a dual antiplatelet regimen, consisting of acetylsalicylic acid and a P2Y12 receptor inhibitor, is mandatory, contributing to the reduction of major cardiac events. However, while preventing ischemic events, this association may precipitate major bleeding complications, which is more commonly seen when more potent drugs, such as prasugrel or ticagrelor, are prescribed. These findings led to the search for therapeutic alternatives that could maintain the protection against ischemic events and, at the same time, prevent the occurrence of hemorrhages. One of the strategies being studied is de-escalation of P2Y12 inhibitors, which consists of the use of more potent drugs in an early phase after the procedure, replacing them with clopidogrel, after a period of, in general, 30 days of clinical course. Another possibility would be to simply reduce the dose of the most potent drug, which so far can only be considered with prasugrel. De-escalation can be done in a guided way, using objective measuring tests of platelet aggregation or exams to assess the genetic profile of patients, or unguided, in which the cardiologist simply replaces or reduces the dose at the end of the stipulated period, with no ancillary tests. The literature includes clinical trials with these two strategy options, which are discussed in this review. So far, no medical guideline explicitly recommends the regular use of this therapeutic alternative.

The clinical profile of patients with intracerebral hemorrhage after receiving acute coronary syndrome regimen in a tertiary hospital: A case series

@#Coronary heart disease, which includes acute coronary syndromes (ACS) is a major cause of death and morbidity. Treatment for this condition includes dual anti-platelet treatment combined with an anti-coagulant and an anti-dyslipidemic. Bleeding complications may occur and one fatal adverse event is intracerebral hemorrhage (ICH). ACS cases in a tertiary hospital for the years 2014-2018 showed that there were 7 patients who presented with symptomatic ICH after treatment administration that accounts for 0.01% of a total of 1,097 patients. These patients were over the age of 50, but with no sex predilection. Common comorbidities were hypertension and malignancy. All patients presented with acute onset neurologic deficits within 1-4 days after administration of ACS regimen, with ICH scores of 3-4 signifying a high mortality rate of 72-90%. 6 out 7 patients had significant volume of ICH with mass effects, and 1 with subarachnoid hemorrhage. This lead to poor outcome in all patients with 6 out of 7 mortalities and 1 left with substantial disability. It was found that given the total number of patients administered with the said treatment, there is a low incidence of ICH.

Dual antiplatelet therapy for mild stroke and transient ischemic attack / 国际脑血管病杂志

Patients with mild stroke and transient ischemic attack (TIA) have a high risk of early recurrence or deterioration. Antiplatelet therapy has been recognized to reduce the risk of ischemic vascular events. All guidelines recommend antiplatelet therapy for patients with ischemic stroke. Dual antiplatelet therapy (DAPT) refers to the application of two drugs with different mechanisms to block platelet aggregation and prevent thrombosis. There are many combinations of DAPT, and its safety and effectiveness are still uncertain. This article reviews the efficacy and safety of DAPT in patients with mild stroke and TIA.

Uso de terapia antiagregante dual luego de angioplastía coronaria: duración, frecuencia de sangramientos y validación de scores de riesgo de hemorragia en una cohorte chilena / Dual anti platelet therapy post PTCA: duration, bleeding risk and validation of scores for predicting risk of bleeding in a Chilean population

Resumen: Introducción: La terapia antiagregante dual (TAD) con aspirina más clopidogrel o ticagrelor es fundamental para prevenir trombosis de stent y nuevos eventos cardiovasculares (CV) en pacientes sometidos a angioplastía coronaria (AC). Sin embargo, TAD se asocia a un riesgo aumentado de hemorragias, en particular cuando su uso se prolonga. Recientemente se han creado puntajes (DAPT, PRECISE-DAPT) que buscan estimar el riesgo de sangrado en pacientes con TAD por tiempo prolongado, los que quisimos evaluar en nuestra población. Métodos: Se utilizó la base de datos prospectiva de Prevención Cardiovascular del Hospital Clínico U. Católica, seleccionando pacientes sometidos a AC el año 2015. Se realizó una encuesta telefónica estandarizada para identificar episodios de sangrado definidos según clasificación ISTH, tiempo de uso de TAD y nuevos eventos CV. Se calcularon los puntajes DAPT y PRECISE-DAPT. Se usó pruebas de t de Student, test exacto de Fisher y curva ROC, según correspondiese, considerando significativa una p<0,05. Resultados: Se incluyeron 227 pacientes (edad 64,2±12,3 años, 22,5% mujeres), de los cuales el 69,6% eran hipertensos, 28,6% diabéticos, 26,9% fumadores y 5,3% insuficientes renales crónicos. En el 63% de los pacientes la AC fue por síndrome coronario agudo, se implantaron 1,4±0,7 stents/paciente y el 37% de los pacientes recibió sólo stents metálicos. Al momento de la encuesta, el seguimiento fue de 26±3 meses. Se registró un tiempo promedio de duración de TAD de 12,6±7,4 meses, con 99,1% de los pacientes recibiendo aspirina, 93,4% clopidogrel, 6,6% ticagrelor y 9,3% anticoagulantes orales. Hubo 35 (15,4%) nuevos eventos CV (revascularización 14, infarto 12, accidente cerebrovascular 2 y muerte 7) y 31 (13,6%) episodios de sangrados (criterio ISTH). De acuerdo con el criterio TIMI de sangrado se registraron 5 (2,2%) episodios graves, 9 (3,9%) leves y 17 (7,4%) menores. En 10 (4,4%) pacientes se modificó la TAD debido al sangrado. PRECISE-DAPT se asoció de manera significativa a los episodios de sangrado (p<0,01); tener un puntaje de alto riesgo (>25) aumentó más de 3 veces el riesgo de sangrado (OR 3,1 IC 1,4-7,1, p<0,01) y una curva ROC estableció que en la población estudiada el mejor punto de corte fue de 18 puntos (C-statistic 0,69) (Figuras 1A y B). El uso de TACO aumentó el riesgo (OR 3,4 IC 1,2-9,5, p=0,02). Si bien miden distintos parámetros, los puntajes de riesgo DAPT y PRECISE-DAPT se correlacionaron significativamente en nuestra cohorte (p<0,01). Conclusiones: En esta cohorte de la vida real se demuestra que la ocurrencia de sangramientos es un evento frecuente en pacientes con TAD, similar a la tasa de nuevos eventos CV, y por tanto debe ser un factor relevante a considerar al momento de la AC y la selección de la TAD. El puntaje PRECISE-DAPT es una herramienta útil para predecir sangrados, aunque nuestros resultados sugieren que en población chilena los valores de corte pueden ser algo menores que lo previamente publicado .

Abstracts: Background: Dual antiplatelet therapy (DAT) with aspirin plus clopidogrel or ticagrelor is essential for the prevention of stent thrombosis and new cardiovascular events in patients undergoing PCI. However, DAT is associated with an increased risk of bleeding, more so when it is used for prolonged time periods. Scores (DAPT, PRECISE-DAPT) developed to predict bleeding risk were evaluated in this study. Method: The prospective Cardiovascular Prevention database at Catholic University Hospital was used to select patients who underwent PCI followed by DAT during 2015. By phone contact information on bleeding episodes - according to the ISTH classification -, new cardiovascular events and DAT duration were collected. DAPT and PRECISE- DAPT scores were calculated. Student's t test, Fisher exact test and ROC analysis were used. Significance was established at p< 0.05. Results: 277 patients were included (age 64.2±12.3 y-o, 22.5% women). Hypertension was present in 66.9%, diabetes in 28.6%, smoking habit in 26.9% and renal failure in 5.3%. The indication for PCI was acute coronary syndrome in 63%, 1.4±0.7 stents per patient were implanted and 37% of patients received bare metal stents exclusively. Follow-up extended for 26±3 months. DAT was active for 12.6±7.4 months and 9.3% of patients received oral anticoagulant therapy. There were 35 (15.4%) new cardiovascular events (14 revascularizations, 12 myocardial infarctions, 2 CVA and 7 deaths). Conversely, there were 31 (13.6%) bleeding episodes. According to the TIMI classification, bleeding episodes were severe in 2.2%, mild in 3.9% and minor in 7.4%. In 4% of patients DAT was modified due to bleeding. PRECISE-DAPT score was significantly associated to bleeding episodes (p<0.01). A high score (>25) was associated with a 3-fold risk of bleeding (OR 3.1, CI 1.4-7.1 (p<0.01). Through ROC analysis the best PRECISE-DAPT cutting point in this cohort was 18 (C=0.69). The use of oral anticoagulation increased bleeding risk (OR 3.4 CI 1.2 - 9.5, p=0.02). DAPT and PRECISE-DAPT were significantly correlated (p<0.01). Conclusion: Bleeding is a frequent complication of DAT, similar to the risk of new cardiovascular events. PRECISE-DAPT score is useful to estimate the risk of bleeding, although this study suggests that in the studied population the cutting point may be somewhat lower than previously published.

Operative outcomes of aTAAD patients with antiplatelet agents misdiagnosed as ACS / 中华胸心血管外科杂志

Objective Acute Stanford type A aortic dissection(aTAAD) is often misdiagnosed as acute coronary syndrome(ACS), anti-platelet therapy for ACS will influence the timing and outcome of aTAAD.We reviewed the surgical outcome of these misdiagnosed aTAAD patients.Methods From January 2011 to October 2015, 309 aTAAD patients have received surgical therapy in our department, among them 15 patients had misdiagnosed as ACS and taken oral anti-platelet therapy, 9 male and 6 female, the average age was(60.6±8.7) years.Retrospectively reviewed the data of perioperative and follow-up period.Results 5 patients took orally aspirin, 10 took aspirin and clopidogrel.2 patients had received operation 7 days after stopping the agents, 3 days for 3 patients, 1 day for 1 patient, and the other 5 patients received emergency operation without stopping the agents.The cardiopulmonary bypass time was(259.7±64.8) minutes, aortic cross-clamp time was(181.0±51.7) minutes, and selective cerebral perfusion and lower body arrest time was(34.9±8.1) minutes.There were 2 in-hospital deaths due to circulation failure(mortality 13.3%).The average drainage volume in the first 24 hours after operation was(800.7±598.8)ml.During a mean follow-up period of(20.6±17.4) months, one patient had suddenly death.Conclusion aTAAD misdiagnosed as ACS was not rare, anti-platelet therapy will increase the risk of bleeding.The decision of operation time rely on considering balance between the rupture risk of aortic dissection and the hemorrhage risk of anti-platelet therapy.Emergency operation for these patients will increase the bleeding and transfusion.

Different durations of dual anti-platelet therapy after percutaneous coronary intervention with drug-eluting stents in patients with coronary disease: A systematic review / 中国药学杂志

OBJECTIVE: To evaluate the benefits and risks of different durations of dual anti-platelet therapy after percutaneous coronary intervention with drug-eluting stent in patients with coronary disease. METHODS: PubMed, Embase, Cochrane Library, CBM, CNKI, VIP, Wanfang Data, Clinical Trials and ICTRP were searched for randomized controlled trials(RCTs) comparing different DAPT durations after PCI with DES in patients with coronary disease. Risk of bias was assessed with the tool recommended by Cochrane Collaboration. Network Meta-analysis was performed with WinBUGS 1.4.3 and ST ATA 12.0. RESULTS: A total of 3 230 articles were found and 10 RCTs including 31 643 patients were systematically reviewed. Network Meta-analysis showed there was no significantly difference among the 6 different durations in the rates of stent thrombosis, myocardial infarction, all-cause mortality and major bleeding, except that the durations of 6 months [OR 10.56, 95% CI(1.62, 9.17)] and 12 months [OR 4.05, 95% CI(1.01, 11.46)] were different with 30 months in the rate of stent thrombosis. Ranking of cumulative probabilities showed that 30 months and 36 months of DAPT had the lowest risk of stent thrombosis and myocardial infarction, meanwhile duration of 3 months and 6 months had the lowest risk of all-cause mortality and major bleeding. CONCLUSION: Clinicians should assess the risks of stent thrombosis and bleeding according to patient's individual condition and determine the optimal duration of DAPT. It is considered feasible to appropriately extend the duration of DAPT in patients at lower bleeding risk.

The role of point-of-care assessment of platelet function in predicting postoperative bleeding and transfusion requirements after coronary artery bypass grafting.

Objective: Objective platelet function assessment after cardiac surgery can predict postoperative blood loss, guide transfusion requirements and discriminate the need for surgical re‑exploration. We conducted this study to assess the predictive value of point‑of‑care testing platelet function using the Multiplate® device. Methods: Patients undergoing isolated coronary artery bypass grafting were prospectively recruited (n = 84). Group A (n = 42) patients were on anti‑platelet therapy until surgery; patients in Group B (n = 42) stopped anti‑platelet treatment at least 5 days preoperatively. Multiplate® and thromboelastography (TEG) tests were performed in the perioperative period. Primary end‑point was excessive bleeding (>2.5 ml/kg/h) within first 3 h postoperative. Secondary end‑points included transfusion requirements, re‑exploration rates, intensive care unit and in‑hospital stays. Results: Patients in Group A had excessive bleeding (59% vs. 33%, P = 0.02), higher re‑exploration rates (14% vs. 0%, P < 0.01) and higher rate of blood (41% vs. 14%, P < 0.01) and platelet (14% vs. 2%, P = 0.05) transfusions. On multivariate analysis, preoperative platelet function testing was the most significant predictor of excessive bleeding (odds ratio [OR]: 2.3, P = 0.08), need for blood (OR: 5.5, P < 0.01) and platelet transfusion (OR: 15.1, P < 0.01). Postoperative “ASPI test” best predicted the need for transfusion (sensitivity ‑ 0.86) and excessive blood loss (sensitivity ‑ 0.81). TEG results did not correlate well with any of these outcome measures. Conclusions: Peri‑operative platelet functional assessment with Multiplate® was the strongest predictor for bleeding and transfusion requirements in patients on anti‑platelet therapy until the time of surgery. Study registration: ISRCTN43298975 (http:// www.controlled‑trials.com/ISRCTN43298975/).

Manejo odontológico en pacientes con terapia antiagregante plaquetaria / Dental treatment in patients with anti-platelet (anti-aggregating) therapy

La terapia antiagregante plaquetaria se considera hoy en día esencial en aquellos pacientes que poseen riesgo de presentar accidentes cerebrovasculares, formación de trombos y en la colocación de prótesis valvular o stents coronarios, ésta permite la profilaxis ante cualquier evento tromboembólico que se pueda presentar; indiscutiblemente uno de sus efectos secundarios es la tendencia al sangrado, por lo tanto esto hace relevante conocer las consecuencias en la práctica odontológica habitual para evitar accidentes y prevenir hemorragias postoperatorias. El objetivo de este trabajo es presentar los fármacos más usados dentro de esta terapia, su mecanismo de acción y la elaboración de un protocolo definido para la atención adecuada de este tipo de pacientes.

Anti-platelet therapy is nowadays considered essential for those patients who are at risk to sustain strokes (cerebro-vascular events), thrombus formation, as well as in cases of coronary valvular prostheses (stents). This therapy allows prophylaxis before any possible thrombo-embolic event. Tendency to bleeding is doubtlessly one of its secondary effects. It therefore becomes relevant to be knowledgeable with consequences that might be encountered in common dental practice so as to avoid accidents and prevent post-operative bleeding (hemorrhage). The aim of the present study was to present drugs most used in this therapy, discuss their mechanism of action and to develop a defined protocol for the proper care of these patients.

Triple anti-platelet therapy protecting acute coronary syndrome patients from complication within 30 days after PCI / 中华急诊医学杂志

Objective To investigate the efficacy and safety of triple anti-platelet therapy (low-dose tirofiban plus aspirin and clopidogrel) comparing to dual anti-platelet therapy (aspirin and clopidogrel) in preventing stent thrombosis (ST) and major adverse cardiac events (MACE) within 30 days after implantation of drug-eluting stent (DES) in ACS patients.Methods A total of 2904 ACS patients treated with DES from March 2004 to November 2010 were enrolled for retrospective study.Of them,1145 patients were treated with dual anti-platelet therapy (DAT) and 1759 patients with triple anti-platelet therapy (TAT).The incidences of ST,MACE (cardiac death,urgent target vessel revasculanization and myocardial infarction) and side effects occurred within 30 days after PCI were compared between two groups by Fisher' s exact test.Results (1)Although there were significant differences in age,the degree of coronary stenosis,the number of smokers,diabetes,hyperlipidemia and coronary diffuse lesion between two groups,but these differences did not impact on the end point events showed by Cox analysis.The rest of the general condition of patients between two groups was no difference.(2) The incidence of ST as primary end point was lower in TAT group than that in DAT group (0.11％ vs.1.05％,P =0.0036),reducing the relative risk by 89.52％.In addition,the incidence of MACT as secondary end point was also lower in TAT group than that in DAT group (0.17％ vs.1.48％,P =0.0005),reducing the relative risk by 88.51％.Among the total,the incidences of cardiac death and urgent target vessel re-vascularization in TAT group were lower than those in DAT group with significant differences.However,there was no difference in the incidence of myocardial infarction between two groups.(3) Both two groups had no severe hemorrhage complication,the incidence of mild hemorrhage was similar in two groups (0.45％ vs.0.35％,P =0.6720).Nesides,the incidence of acute thrombocytopenia between two groups was also similar (0.45％ vs.0.09％,P =0.083).Conclusions The patients with ACS in the TAT group have significant lower incidence of ST and MACE than those in the DAT group within 30 days after PCI.While the risk of bleeding and the incidence of acute thrombocytopenia do not increase.

Proposal for Pretreatment of Patients in Antiplatelet Therapy Requiring Minor Oral Surgery

PURPOSE: Many patients in anti-platelet therapy have been consulted for bleeding risks before minor oral surgery. However, there has not been an established pretreatment protocol for treating these patients. The purpose of this study is to make a protocol for the preoperative management for patients in anti-platelet therapy. PATIENTS AND METHODS: The existed consultation pattern of patients was examined in the Department of Oral and Maxillofacial Surgery, Yonsei Dental Hospital. Based on the observation, a protocol including classification of medical status of patients and the type of oral surgery in need was introduced. This protocol had been performed for 6 months. RESULT: Following this protocol, the frequency of consultation for bleeding risk was decreased. The number of minor oral surgeries with concurrent anti-platelet therapy was increased. There was no severe bleeding event observed among minor oral surgeries that were performed while maintaining anti-platelet therapy. CONCLUSION: This protocol can be used as a guideline for clinical practice of patients in anti-platelet therapy requiring minor oral surgery.