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.

Disnea secundaria a ticagrelor posterior a arteriografía coronaria. Reporte de caso / Dyspnea secondary to ticagrelor posterior to coronary arteriography. Case report

Resumen Los antiagregantes plaquetarios son medicamentos ampliamente utilizados para la prevención y tratamiento de patologías aterotrombóticas, como lo es el síndrome coronario agudo. A pesar de tener un efecto benéfico, no están exentos de ocasionar múltiples alteraciones a nivel sistémico, como lo es la disnea en pacientes sometidos a manejo con ticagrelor. Se expone el caso de un paciente de 66 años con antecedente de cardiopatía isquémico-hipertensiva, tabaquismo pesado y alergia al ácido acetilsalicílico (ASA), con requerimiento de 2 arteriografías coronarias, quien presenta disnea en reposo en menos de 24 horas posterior al inicio de manejo antiagregante tromboprofiláctico con ticagrelor, que resuelve de forma satisfactoria tras la suspensión del medicamento. Al ser un efecto secundario relativamente frecuente en el marco del uso del ticagrelor, se hace relevante revisar los hallazgos en la literatura actual sobre la aparición de disnea en pacientes tratados con dicho fármaco, para así tener en cuenta posibles recomendaciones acerca del manejo de la disnea asociada a ticagrelor, basadas en el conocimiento actual. MÉD.UIS.2022;35(1): 9-15.

Abstract Antiplatelet agents are widely used drugs for the prevention and treatment of atherothrombotic pathologies such as acute coronary syndrome, however, despite having a beneficial effect, they're not exempt from causing multiple systemic alterations, such as dyspnea in patients undergoing management with ticagrelor. We will now present the case of a 66-year-old patient with a history of hypertensive ischemic heart disease requiring 2 cardiac catheterizations, heavy smoking and allergic to Acetyl Salicylic Acid (ASA) who presented dyspnea at rest in less than 24 hours after the start of thromboprophylaxis management with ticagrelor, that resolves satisfactorily after discontinuation of the drug. Because it is a frequent side effect in the framework of the use of ticagrelor, it's relevant to review the current literature on the appearance of dyspnea in patients treated with ticagrelor, to highlight recommendations for the management of dyspnea associated with ticagrelor based on current knowledge. MÉD.UIS.2022;35(1): 9-15.

Inhibidores del receptor plaquetario P2Y12. Parte 2 de 2: etiología, diagnóstico y manejo de la resistencia / Platelet P2Y12 receptor inhibitors. Part 2 of 2: Etiology, diagnosis and management of resistance

Resumen: las enfermedades cardiovasculares, que comprenden 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, de los cuales una tercera parte se debe a eventos trombóticos. La antiagregación plaquetaria con diferentes agentes, incluidos los inhibidores del receptor plaquetario P2Y12, se ha convertido en la piedra angular de la prevención primaria y secundaria y del tratamiento de las enfermedades cardiovasculares, entre ellas el infarto agudo de miocardio, la apoplejía y las enfermedades trombóticas. Sin embargo, varios estudios de investigación han demostrado que algunos individuos presentan disminución en la respuesta in vivo a estas sustancias, la cual se expresa como resistencia. En el primer módulo se abordó el papel de las plaquetas en la enfermedad aterotrombótica y se describieron los seis inhibidores del receptor plaquetario P2Y12, disponibles para su uso clínico actual o a futuro: la ticlopidina, el clopidogrel, el prasugrel, el ticagrelor, el cangrelor y el elinogrel. En este segundo módulo se tratará el concepto de la resistencia a los inhibidores del receptor plaquetario P2Y12, en particular al clopidogrel, la etiología de la resistencia y el monitoreo de la antiagregación con inhibidores del receptor plaquetario P2Y12 mediante pruebas de función plaquetaria, como una manera de hacer una antiagregación personalizada; finalmente, se darán las pautas básicas para el manejo de la resistencia a los inhibidores del receptor plaquetario P2Y12. (AU)

Abstract: Cardiovascular diseases, including in general affections of heart, brain, and blood vessels, are the leading worldwide cause of death with seventeen millions of deaths annually and a third part of them are due to thrombotic events. Platelet antiaggregation with different agents, like inhibitors of the platelet receptor P2Y12, has become the cornerstone of primary and secondary prevention and for the treatment of cardiovascular diseases, as acute myocardial infarction, stroke, and thrombotic diseases. However, several research studies have shown a decrease in the in vivo response to these substances in some individuals, which is expressed as resistance. The first module addressed the role of platelets in atherothrombotic disease and described the six P2Y12 platelet receptor inhibitors available for current or future clinical use: ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor and elinogrel. In this second module, it will discuss the concept of resistance to P2Y12 platelet receptor inhibitors, particularly clopidogrel, the resistance etiology, and antiplatelet monitoring with inhibitors of P2Y12 platelet receptor by platelet function tests, as a way to make a «personalized antiaggregation¼. Finally, it will give the basic guidelines for the management of resistance to P2Y12 platelet receptor inhibitors. (AU)

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)

Randomized Comparison of the Platelet Inhibitory Efficacy between Low Dose Prasugrel and Standard Dose Clopidogrel in Patients Who Underwent Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: Increased bleeding rates with standard dose prasugrel have led to increased questions about the effectiveness and safety of the lower maintenance dose. We compared platelet inhibitory efficacy between low dose prasugrel and standard dose clopidogrel in patients on maintenance dose dual antiplatelet therapy. SUBJECTS AND METHODS: Forty-three patients who underwent percutaneous coronary intervention were randomized to receive 75 mg clopidogrel (n=23) or 5 mg prasugrel (n=20). Another 20 patients were allocated to 10 mg prasugrel as a reference comparison group. All patients (weight, > or =60 kg; age, 235) was significant lower in the 5 mg prasugrel group than that in the 75 mg clopidogrel group (15.0% vs. 56.5%, p=0.010). CONCLUSION: Prasugrel (5 mg) is more potent antiplatelet therapy than 75 mg clopidogrel in non-low body weight and non-elderly patients on a maintenance dose dual antiplatelet therapy.