ABSTRACT
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.
Subject(s)
Purinergic P2Y Receptor Agonists , Dual Anti-Platelet Therapy , Angina, Unstable , Myocardial Infarction , Prasugrel HydrochlorideABSTRACT
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.
ABSTRACT
Thromboembolism is one of the major complications of stent assisted coiling in treatment of cerebral aneurysm. Clopidogrel resistance is so common and prasugrel is more effective in its rapid and potent effect. We investigated changes in the value of P2Y12 resistance unit (PRU) when prasugrel was administered to patients with clopidogrel resistance. One hundred mg of aspirin and 75 mg of clopidogrel were administered for 5 days before the procedure, and PRU were examined. The resistance to clopidogrel was defined as the inhibition of PRU was less than 20%. PRU was re-examined after loading 20 mg of prasugrel. We treated 98 consecutive patients between January 2018 and July 2018, and 24 patients (24.5%) had resistance to clopidogrel. Nineteen patients were female. The mean PRU value at admission was 238.5±36.9 and the percentage inhibition value was 4.8±6.3%. After the use of prasugrel, the mean PRU and percentage inhibition values were measured as 124.9±49.9 and 48.0±19.24, respectively. All patients except one patient had a PRU inhibition value as a responder. There was no hemorrhage or thromboembolic complication during mean 1.5 months follow-up after embolization procedure. In conclusion, in patients resistant to clopidogrel, the low dose prasugrel seems to be effective in keeping the percentage inhibition value of PRU within the normal range in treatment of cerebral aneurysm. Further study will be needed to determine the optimal dose of prasugrel to enhance prevention effect of thromboembolism and to reduce hemorrhagic complications during stent assisted coiling.