Ischaemic and haemorrhagic risk distribution in real-life patients with acute coronary syndromes.

BACKGROUND: Effective treatment of non-ST-segment elevation acute coronary syndromes (NSTEACS) requires careful assessment of both ischaemic and bleeding risks. We aimed to analyse risk distribution and evaluate antiplatelet prescription behaviours in real-life settings. METHODS: Data from 1100 NSTEACS patients in Buenos Aires, Argentina, from the Buenos Aires I Registry, with a 15-month follow-up, were analysed. In-hospital and 6-month GRACE scores, CRUSADE, and Precise DAPT scores were calculated. RESULTS: The mean age was 65.4 ± 11.5 years with a majority being male (77.2%). In-hospital mortality was 2.7%, primarily due to cardiovascular causes (1.8%). Bleeding events occurred in 20.9% of patients, with 4.9% classified as ≥ BARC 3. Predominance of low bleeding (71.3%) and ischaemic (55.8%) risks on admission was observed. At 6 months, the low-risk Precise category (70.9%) and GRACE (44.1%) categories prevailed. Linear correlation analysis showed a moderately positive correlation (r = 0.61, p < .05) between ischaemic-haemorrhagic risks. Regarding the prescription of antiplatelet agents, in the low ischaemic-haemorrhagic risk group, there was a predominance of aspirin + clopidogrel (41.2%) over other high-potency antiplatelet regimens (aspirin + ticagrelor or prasugrel). In the low ischaemic and high haemorrhagic risk group, aspirin and clopidogrel were also predominant (58%). CONCLUSIONS: Our analysis underscores the significant relationship between ischaemic and haemorrhagic risks during NSTEACS hospitalisation. Despite the majority of patients falling into the low-intermediate risk category, the prescription of P2Y12 inhibitors in real-life settings does not consistently align with these risks.

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.

Intervenção coronária percutânea no paciente com alto risco de hemorragia / Percutaneous coronary intervention in the patient at high risk of bleeding

Na atualidade, as intervenções coronárias percutâneas são responsáveis por mais de 80% dos procedimentos de revascularização miocárdica. Esse resultado é possível por dois grandes avanços: o desenvolvimento de stents farmacológicos eficazes e seguros, somado a uma farmacoterapia antitrombótica potente e efetiva na prevenção de eventos aterotrombóticos, a qual, em geral, deve ser mantida por cerca de 6 a 12 meses após a intervenção índice. No entanto, expressivo contingente de casos, que a literatura situa em até 20% dos pacientes tratados, apresenta risco para desenvolver hemorragias significantes, que podem ter grave impacto no prognóstico. Assim, essa população requer uma série de cuidados relacionados com a indicação, a realização e o acompanhamento tardio. O processo se inicia pela identificação dos casos mais predispostos, o que, na maior parte das situações, é simples, havendo inclusive escores de risco que auxiliam o car­ diologista. Na sequência, a indicação do procedimento deve ser feita com propriedade. Os cuidados são iniciados pela prescrição preferencial do clopidogrel ao invés dos demais inibidores da P2Y12; no momento do procedimento, sempre que viável, a opção pela via radial é vantajosa, em especial em síndromes coronárias agudas. O uso de um modelo de stent com liberação de medicamentos também é recomendado nesses casos, pois os stents contemporâneos são seguros a ponto de permitirem a abreviação com segurança do tempo de uso do esquema antiplaquetário duplo. Por fim, mais recentemente, tem sido discutida a monoterapia com inibidores do receptor P2Y12, na qual a suspensão precoce do ácido acetilsalicílico não comprometeria a segurança e, ao mesmo tempo, seria capaz de prevenir eventos hemorrágicos de vulto.

Currently, percutaneous coronary interventions account for more than 80% of myocardial revascularization procedures. This result was enabled by two major advances: the development of effective and safe drug­eluting stents, in addition to a potent and effective antithrombotic pharmacotherapy in the prevention of atherothrombotic events, which, in general, should be maintained for about 6 to 12 months after the index intervention. However, a significant number of cases (up to 20% of treated patients according to literature) are at risk for developing significant bleeding, which can have a serious impact on prognosis. Therefore, this population requires a series of care measures related to indication, performance of the procedure, and late follow­up. The process begins with the identification of the most predisposed cases, which, in most situations, is simple, and there are risk scores that help the cardiologist. Next, the indication of the procedure should be done appropriately. Care begins with the preferential prescription of clopidogrel instead of other P2Y12 inhibitors; at the time of the procedure, whenever feasible, the option for the radial access is advantageous, especially in acute coronary syndromes. The use of a drug­eluting stent is also recommended in these cases, since contemporary stents are safe enough to safely shorten the duration of use of the dual antiplatelet regimen. Finally, more recently, monotherapy with P2Y12 receptor inhibitors has been discussed, in which early withdrawal of acetylsalicylic acid would not compromise safety and, at the same time, it would be able to prevent major bleeding events.

Antiplatelet Therapy And Percutaneous Coronary Interventions.

Dual antiplatelet therapy is one of the cornerstones of modern percutaneous coronary interventions. The development of new therapeutic agents has significantly reduced ischemic events at the risk of increased bleeding complications. Therefore, efforts are currently focused on optimizing therapeutic algorithms to obtain the greatest anti-thrombotic benefit associated with the lowest risk of bleeding, that is, the greater net clinical benefit. A significant number of trials evaluating different drug combinations or adjustments in treatment duration have been completed. However, clinical translation of these results is often difficult due to the heterogeneity of the therapeutic approaches. The aim of this manuscript is to provide an updated review of the literature regarding the use of dual antiplatelet therapy in patients undergoing coronary angioplasty and stenting.

Lo mejor del Congreso 2019 de la Sociedad Europea de Cardiología / The best of the 2019 European Society of Cardiology Congress / O melhor do Congresso da Sociedade Europeia de Cardiologia 2019

Resumen: El Congreso Europeo de Cardiología constituye uno de los eventos más relevantes de la comunidad cardiológica mundial. Fue realizado entre el 31 de agosto y el 4 de setiembre en el corazón de París, siendo el tema central la salud cardiovascular global. Como es habitual, contó con la presencia de más de 30.000 profesionales y destacados invitados. Se presentaron actualizaciones de varias guías de práctica clínica e importantes trabajos científicos que sin duda impactarán en el tratamiento de los pacientes con patología cardiovascular. A continuación realizaremos un breve resumen de algunos de los trabajos presentados: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

Summary: The European Congress of Cardiology is one of the most relevant events of the world cardiology community. It was held from August 31 to September 4 in the heart of Paris, France, the central theme being global cardiovascular health. As usual, it was attended by more than 30,000 professionals and prominent guests. Updates of several clinical practice guides and important scientific papers were presented. These undoubtedly will impact in the treatment of patients with cardiovascular pathology. Below we present a brief summary of some of the trials presented: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

Sumário: O Congresso Europeu de Cardiologia é um dos eventos mais relevantes da comunidade mundial de cardiologia. Foi realizada de 31 de agosto ao 4 de setembro no coração de Paris, na França, o tema central foi a saúde cardiovascular global. Como sempre, participaram mais de 30.000 profissionais e convidados de destaque. Atualizações de vários guias de prática clínica e importantes artigos científicos foram apresentados que, sem dúvida, impactarão o tratamento de pacientes com patologia cardiovascular. Abaixo, faremos um breve resumo de alguns trials apresentados: - A trial to evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and reduced left ventricular ejection fraction: DAPA-HF - Complete revascularization with multivessel PCI for myocardial infarction: the COMPLETE Trial - Angiotensin-neprylysin inhibition in heart failure with preserved ejection fraction: the PARAGON-HF - Antithrombotic therapy for atrial fibrillation with stable coronary disease: the AFIRE Investigators - Ticagrelor or prasugrel in patients with acute coronary syndromes: the ISAR-REACT 5 Trial

Drogas antiplaquetarias de utilización en Síndrome Coronario Agudo / Antiplatelet drugs used in Acute Coronary Syndrome

Los medicamentos antiplaquetarios, representan el pilar del tratamiento farmacológico, en el síndrome coronario agudo. Su utilización pronta y precisa, permiten ganar minutos importantes en la toma de decisiones de estos pacientes, que permitan una resolución cabal y de optimo pronostico. Esta pequeña y práctica revisión pretende destacar las características más importantes de cada uno de ellos, que ofrezca al clínico optimizar la decisión del medicamento que representa la mejor estrategia terapéutica, en el contexto individual de cada paciente. Para esto se presentan de manera resumida los estudios más recientes que comparan los diferentes agentes, durante el síndrome coronario, que permitan un manejo más individualizado del paciente.

Antiplatelet drugs represent the main pharmacologic treatment on an acute coronary syndrome. Its fast, and precise utilization allow us gain important minutes on de decision making process of this patients, that allows a fast resolution with optimal prognosis. This practical small review pretends to pinpoint the most important characteristics of each one of this drugs that allows the clinician get the best decision on with drug offers the best therapeutic strategy on the individual context of the patient. So we present a summary of the latest trials that compare this agents on acute coronary syndrome that allows individualization o the patient management.

Did Prasugrel and Ticagrelor Offer the Same Benefit in Patients with Acute Coronary Syndromes after Percutaneous Coronary Interventions Compared to Clopidogrel? Insights from Randomized Clinical Trials, Registries and Meta-analysis.

BACKGROUND: According to ACC/ AHA guidelines, a minimum of 1 year of dual anti- platelet therapy (DAPT) consisting of aspirin and a platelet ADP-receptor antagonist (P2Y12 inhibitor) is recommended for patients presenting acute coronary syndromes (ACS), regardless of which type of revascularization is performed during the acute event. METHODS: The purpose of this presentation was to review the present data either from a direct randomized comparison among the three compounds and also large prospective observational registries and meta-analysis were analyzed in detail. With this aim, we performed an extensive large search from PubMed/Medline Journals identifying studies comparing fashion the new P2Y12 inhibitors in patients with ACS including ST elevation myocardial infarction (STEMI) in direct and indirect manner. RESULTS: Pivotal large randomized clinical trials (RCT) in patients with ACS including STEMI, comparing clopidogrel, a first generation P2Y12 inhibitor against the newer prasugrel and ticagrelor showed major efficacy advantages of the latters although both drugs had more bleeding risk than clopidogrel. Direct comparisons of prasugrel and ticagrelor from large RCT are not yet available, however, several observational registries and metaanalysis reported results from an indirect comparison between both compounds. Major findings and limitations of each of these studies were identified, highlighted and discussed. CONCLUSION: Prasugrel and ticagrelor are both more effective than clopidogrel to prevent adverse cardiac events in patients with ACS. Compared to ticagrelor, prasugrel appears to be more effective in patients with STEMI, although lack of randomized data didn't allow to draw definitive conclusions.

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.

Inhibidores del receptor plaquetario P2Y12. Parte 1 de 2: escenario de acción, farmacología, aplicación clínica y limitaciones de su uso / Platelet P2Y12 receptor inhibitors. Part 1 of 2: Scenario of action, pharmacology, clinical application, and limitations of its use

Resumen: las enfermedades cardiovasculares, incluidas las afecciones del corazón, del cerebro y de los vasos sanguíneos en general, representan la primera causa de muerte a nivel mundial, con diecisiete millones y medio de muertes cada año. La prevención primaria y secundaria de las enfermedades aterotrombóticas, como el infarto agudo de miocardio, el accidente cerebrovascular y las enfermedades trombóticas, además de las medidas generales para el control de los factores de riesgo tales como la obesidad, el sedentarismo, el tabaquismo, la hipertensión arterial y la diabetes, se han centrado en el control de la agregación plaquetaria. El antiagregante plaquetario por excelencia o universal, sobre todo en la prevención primaria, es la aspirina y la terapia dual con la combinación de aspirina y un inhibidor del receptor plaquetario P2Y12, principalmente el clopidogrel, es usada en la prevención secundaria y en los casos de resistencia a la aspirina. En el momento, se dispone para uso clínico de seis inhibidores del receptor plaquetario P2Y12: la ticlopidina, el clopidogrel, el prasugrel, el ticagrelor, el cangrelor y el elinogrel. En este primer módulo, de dos que serán presentados, se abordará el uso de los inhibidores del receptor plaquetario P2Y12 en la práctica del día a día en la prevención primaria y secundaria de las enfermedades aterotrombóticas, enfocado en el análisis del papel de las plaquetas en la fisiopatología de la enfermedad aterotrombótica y la descripción de los seis inhibidores del receptor plaquetario P2Y12 disponibles ahora y en el futuro. En un segundo módulo se hará una aproximación al concepto de la resistencia a los inhibidores del receptor plaquetario P2Y12, su diagnóstico desde el punto de vista del laboratorio y las diferentes alternativas de manejo cuando se presenta resistencia a uno de estos medicamentos. (AU)

Abstract: Cardiovascular diseases, including in general heart diseases, brain, and blood vessels are the leading cause of death worldwide with 17.000.000 of deaths each year. Primary and secondary prevention of atherothrombotic diseases, as acute myocardial infarction, stroke, and thrombotic disorders, besides to the general measures for risk factors control such as obesity, sedentary lifestyle, smoke, high blood pressure, and diabetes, have focused on platelet aggregation control. The antiplatelet agent par excellence or universal, especially in primary prevention, is aspirin, and dual therapy with the combination of aspirin and a platelet receptor inhibitor P2Y12, with clopidogrel as the most used, for secondary prevention and in cases of aspirin resistance. Currently, six P2Y12 platelet receptor inhibitors are available for clinical use: ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor, and elinogrel. In this first of two modules, the use of P2Y12 receptor inhibitors in daily practice in the primary and secondary prevention of atherothrombotic diseases will be addressed focused on the analysis of the platelets role in atherothrombotic disease pathophysiology and description of the six P2Y12 platelet receptor inhibitors available now and in the future. In a second module, we will approach the concept of resistance to platelet P2Y12 receptor inhibitors, its diagnosis from the laboratory point of view and the different management alternatives when resistance to one of these drugs is present. (AU)

Análisis de costo efectividad de prasugrel, comparado con clopidogrel para pacientes con síndrome coronario agudo sometidos a intervención coronaria percutánea en Colombia / Analysis of cost effectiveness of prasugrel compared with clopidogrel for patients with acute coronary syndrome undergoing percutaneous coronary intervention in Colombia

Objetivo: determinar, desde la perspectiva del sistema de salud colombiano, la relación de costo-efectividad del prasugrel comparado con clopidogrel, para el tratamiento de pacientes adultos con síndrome coronario agudo. Material y métodos: se construyó un modelo de Markov con ciclos anuales en el cual los pacientes pueden permanecer sin experimentar nuevos eventos cardiovasculares, sufrir un nuevo evento o morir. En el caso base se adoptó un horizonte temporal de 10 años y una tasa de descuento de 3%. Las probabilidades de transición se extrajeron del ensayo clínico TRITON-TIMI 38, de las estadísticas vitales del Departamento Nacional de Estadística y de la información de los pacientes colombianos del registro ACCESS. Para identificar y medir el uso de recursos se diseñó un caso típico a partir de la revisión de guías y protocolos; para la valoración se emplearon manuales tarifarios colombianos. Se realizaron análisis de sensibilidad determinísticos y probabilísticos. Resultados: en el caso base, el costo por año de vida ajustado por calidad ganado con prasugrel es $79 987 695 pesos colombianos. Los resultados son sensibles a cambios en el horizonte temporal y al costo del clopidogrel. Bajo un umbral de disposición a pagar de tres veces el PIB per cápita colombiano, la probabilidad de que el prasugrel sea costo efectivo es 7%. Conclusiones: la decisión respecto a la inclusión del prasugrel en el tratamiento de pacientes con síndrome coronario agudo, sometidos a intervención coronaria percutánea depende fundamentalmente del costo del clopidogrel que el decisor considere relevante para realizar la comparación. (Acta Med Colomb 2015; 40: 310-317).

Objective: to determine the cost-effectiveness relation of prasugrel compared with clopidogrel for the treatment of adult patients with acute coronary syndrome from the perspective of Colombian health system. Material and methods: a Markov model with annual cycles in which patients can remain without experiencing new cardiovascular events, have a new event or die, was built. In the base case a time horizon of 10 years and a discount rate of 3% was adopted. Transition probabilities were taken from the clinical trial TRITON-TIMI 38, of vital statistics from the National Department of Statistics and from the information of Colombian patients in ACCESS registry. To identify and measure the use of resources, a typical case was designed from the review of guidelines and protocols; Colombian tariff manuals were used for assessment. Deterministic and probabilistic sensitivity analyzes were performed. Results: in the base case, the cost per year of quality-adjusted life gained with prasugrel is $ 79,987,695 Colombian pesos. The results are sensitive to changes in the timeframe and cost of clopidogrel. Under a threshold willingness to pay three times the per capita GDP of Colombia, the probability that prasugrel may be cost-effective, is 7%. Conclusions: the decision on the inclusion of prasugrel in the treatment of patients with acute coronary syndrome undergoing percutaneous coronary intervention depends mainly on the cost of clopidogrel that the decision maker considers relevant to perform the comparison. (Acta Med Colomb 2015; 40: 310-317).

Antiplaquetarios / Antiplatelets

Con el advenimiento de los antiplaquetarios se dio un gran avance en el tratamiento del infarto y el Accidente Vascular Cerebral. Con la combinación de los antiplaquetarios se potencia el efecto antitrombótico, mejorando los resultados y la reversión de los eventos, sin embargo, aumenta los efectos secundarios como el sagrado. Aproximadamente, existe alrededor de 20 fármacos antiplaquetarios, algunos se administran oral o intravenosamente como el tirofiban, abciximab, y la eptifibatida. En la presente revisión hablaremos solamente de la terapia oral de los principales antiplaquetarios orales, sus efectos secundarios, sus indicaciones y precauciones. Aunque, muchas veces se administra los medicamentos plaquetarios en dosis correctas no siempre se puede ver la recanalización del vaso sanguíneo debido a un síndrome de resistencia a los antiplaquetarios.

The advent of antiplatelet agents was a major advance in the treatment of thrombotic events, so that are revolutionizingthe treatment of heart attack and stroke. The combination of antithrombotic antiplatelet gave better effect andimprovement results and reverse of events. However, increases the side effects such as bleeding. Approximately existsaround twenty antiplatelet drugs, some are administered orally or intravenously as Tirofiban, Abciximab and Eptifibatide.In this review we will talk only therapy of oral antiplatelet main, side effects, indications and precautions. Although oftenadministrated the correct dose antiplatelet drugs, those can not always obtain the blood vessel recanalization due toresistance: syndrome antiplatelets.