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.

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.

Effect of morphine use on oral P2Y12 platelet inhibitors in acute myocardial infarction: Meta-analysis

Background Morphine is the recommended analgesic in acute myocardial infarction (AMI). This recommendation has come under scrutiny because of possible slow uptake of oral antiplatelet agents. Objective We performed a meta-analysis of all available studies in AMI patients treated with prasugrel or ticagrelor (P2Y12 inhibitors) that reported use of morphine prior to loading the antiplatelet agents to critically assess the safety of co-administration of morphine and the newer P2Y12 inhibitors. Methods Several sources were searched from inception to December 2017 with inclusion of eight studies, largely observational. Mean difference (MD) was calculated for continuous variables, and standardized mean difference (SMD) for platelet function was assessed by the various platelet assays, 2 h after the loading dose of oral P2Y12 inhibitors. Results Higher platelet activity was noted among morphine group [SMD = 0.8, 95% confidence interval (CI) = 0.4–1.1, p < 0.01]. Morphine use caused higher odds of “high residual platelet reactivity” at 2 h (odds = 3.3, 95 %CI = 2.2–5.1, p < 0.01). Ticagrelor reached a lower plasma concentration in morphine group (MD = −481.8 ng/ml, 95% CI = −841.2 to −122.4 ng/ml, p < 0.01) with a higher vomiting rate (odds = 5.3, 95% CI = 2.5–11.1, p < 0.01). However, the composite of in-hospital mortality, stroke, and re-infarction was not significantly different between the groups (p = 0.83). Conclusion Co-administration of morphine with P2Y12 inhibitors possibly decreases their efficacy in platelet inhibition. However, this did not translate into higher adverse outcomes because of low event rates, inadequate for analysis. A large randomized study is needed to evaluate the narcotic-P2Y12 interaction.

Low-Dose Prasugrel in Patients with Resistance to Clopidogrel for the Treatment of Cerebral Aneurysms / 신경중재치료의학

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.

Effect of morphine on pharmacokinetics and pharmacodynamics of P2Y12 receptor antagonists / 中国药理学通报

P2Y12 receptor antagonists and morphine are often recommended in patients with acute myocardial infarction.P2Y12 receptor antagonists can rapidly and potently reduce the platelet activity and prevent future thrombotic events.Meanwhile,combined morphine is used to relieve symptoms of angina.A number of studies have confirmed that morphine can decrease plasma concentrations of clopidogrel and impair its anti-platelet activity,which may lead to poor response in clopidogrel-treated patients with acute coronary syndrome.The randomized trials in healthy volunteers and patients with acute myocardial infarction also confirmed the similar drug-drug interaction between morphine and ticagrelor or prasugrel.Although the P2Y12 receptor antagonists combined with morphine are still used for myocardial infarction patients,there are few report on the objective evaluation of this drug interaction.This review,based on the findings of experimental as well as observational and randomized clinical studies,summarizes completely the drug interactions between oral P2Y12 receptor antagonists and morphine.

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)

The Use Pattern and Clinical Impact of New Antiplatelet Agents Including Prasugrel and Ticagrelor on 30-day Outcomes after Acute Myocardial Infarction in Korea: Korean Health Insurance Review and Assessment Data

BACKGROUND AND OBJECTIVES: Despite the favorable efficacy of new antiplatelet agents demonstrated in randomized controlled trials, their clinical implications in Korea are unclear. The purpose of this study was to investigate trends in antiplatelet agent use for acute myocardial infarction (AMI) and their impact on 30-day clinical outcomes. METHODS: AMI patients undergoing percutaneous coronary intervention between 2010 and 2015 were assessed using claim data from the Health Insurance Review and Assessment Service. RESULTS: The use of new antiplatelet agents has rapidly increased since 2013 and has been preferred over clopidogrel (Plavix; Bristol-Myers Squibb/Sanofi Pharmaceuticals) since 2015. Both prasugrel (Effient; Eli Lilly and Company) (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.31–0.67; p < 0.001) and ticagrelor (Brilinta; AstraZeneca Pharmaceuticals LP) (OR, 0.84; 95% CI, 0.71–0.98; p=0.032) had an independent effect on lowering 30-day mortality in a weighted multivariable logistic regression model. However, new antiplatelet agents had no significant effect on other clinical outcomes including myocardial infarction, stroke, bleeding, and readmission within 30 days. CONCLUSION: The use of new antiplatelet agents is rapidly increasing, and they have been used more commonly than clopidogrel since 2015. We demonstrated that new antiplatelet agents have a favorable effect on reducing 30-day mortality in AMI patients in Korea.

Effect of Ticagrelor versus Prasugrel on Platelet Reactivity:A Meta-analysis / 中国药房

OBJECTIVE:To systematically review the effect of ticagrelor versus prasugrel on platelet reactivity,and provide evi-dence-based reference for clinical treatment. METHODS:Retrieved from PubMed,CJFD and Wanfang Database,randomized con-trolled trials(RCT)about the effect of ticagrelor versus prasugrel on platelet reactivity were collected. Meta-analysis was performed by using Rev Man software after data extract and quality evaluation by Cochrane 5.1.0. RESULTS:Totally 17 RCTs were enrolled,involv-ing 2 757 patients. Results of Meta-analysis showed,regardless of Verity Now(VN)detection method [MD=15.43,95%CI(-0.39, 31.25),P=0.06] or vasodilator stimulus phosphoprotein(VASP)detection method [MD=-3.04,95%CI(-8.98,2.90),P=0.32], ticagrelor and prasugrel had the same effects on platelet reactivity under loading dose,the differences were not statistically significant;regardless of VN detection method [MD=-48.94,95%CI(-58.04,-39.84),P<0.001] or VASP detection method [MD=-14.32, 95%CI(-20.45,-8.20),P<0.001],the effects of ticagrelor were better than prasugrel on platelet reactivity under maintenance dose,the differences were statistically significant. CONCLUSIONS:At the loading dose,there was no difference between ticagrelor and prasugrel,but ticagrelor has more benefits than prasugrel under maintenance dose.

An Intra-procedural Stent Thrombosis in a Prasugrel Resistant Patient Treated with Ticagrelor / 계명의대학술지

Stent thromboses due to multifactorial causes including hypercoagulable conditions and high on treatment platelet reactivity (HTPR), which means a low response to anti-platelet therapy, especially clopidogrel. Prasugrel is a third generation thienopyridine and inactive pro-drug requiring metabolic activation in vivo, which improves the rate of HTPR with clopidogrel. This drug is mostly effective, with a potent, fast, and consistent anti-platelet action, but rare cases of inadequate platelet inhibition with prasugrel have been reported. Here we describe the case of a 47-year-old man who presented with a recurrent acute myocardial infarction and ST during an intravascular ultrasound pullback and was resistant to prasugrel, was successfully treated with ticagrelor.

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).

Evaluation of the relative efficacy and safety of prasugrel and clopidogrel in medically managed high risk UA / NSTEMI ACS population.

Background: The term “acute coronary syndrome” encompasses unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Antiplatelet therapy is one of the cornerstones of therapy in UA/NSTEMI. Objective: To compare efficacy and safety of Prasugrel and clopidogrel both theinopyridines antiplatelet drugs in high risk (TIMI Score 3 or more) medically managed UA/NSTEMI. Materials and Methods: A prospective, randomized study was conducted in GNDH, Amritsar. 100 patients were included, 50 patients received Prasugrel and 50 received clopidogrel. Outcomes like angina episodes, bleeding, stroke, ischemic ECG changes, and arrhythmia were compared during hospital stay and follow-up for 3 months. Results: Prasugrel was associated with significant lower incidence of major adverse cardiac event (MACE) 9 compared to 19 with clopidogrel during hospital stay. During follow up for 3 months 2 events occurred with Prasugrel and 3 with clopidogrel which were non-significant. Conclusion: Use of Prasugrel was associated with less number of MACE than the patients who were on clopidogrel. Although for the individual adverse coronary events, except for angina there was no statically significant difference, but when the total MACE observed during the study was compared, it was significantly less in the patient on Prasugrel therapy. Safety of the Prasugrel in present study was identical to clopidogrel.

A pharmacodynamic study of the optimal P2Y12 inhibitor regimen for East Asian patients with acute coronary syndrome

BACKGROUND/AIMS: Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have greater antiplatelet efficacy but may increase the risk of bleeding. In this study, we compared the pharmacodynamic efficacy of prasugrel and ticagrelor in East Asian patients with acute coronary syndrome (ACS). METHODS: We selected 83 ACS patients undergoing percutaneous coronary intervention who were discharged with 90 mg ticagrelor twice daily (n = 24), 10 mg prasugrel daily (n = 39) or 5 mg prasugrel daily (n = 20). After 2 to 4 weeks, on-treatment platelet reactivity (OPR) was assessed in terms of P2Y12 reaction units (PRUs) using the VerifyNow P2Y12 assay (Accumetrics). We compared East Asian (85 < PRU < or = 275) and Caucasian (85 < PRU < or = 208) criteria for assessing the therapeutic window of OPR. RESULTS: OPR was lowest in the ticagrelor group, followed by the 10 mg prasugrel and 5 mg prasugrel groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, respectively; p < 0.001). The 5 mg prasugrel group had the highest proportion of patients with OPR values within the therapeutic window, followed by the 10 mg prasugrel and ticagrelor groups (90.0% vs. 46.2% vs. 12.5%, respectively; p < 0.001 for East Asian criteria; 60.0% vs. 43.6% vs. 12.5%, respectively; p < 0.001 for Caucasian criteria). CONCLUSIONS: Short-term administration of 5 mg prasugrel facilitated maintenance within the therapeutic window of OPR compared with the 10 mg prasugrel and ticagrelor groups. Thus, 5 mg prasugrel daily may be the optimal antiplatelet regimen for stabilized East Asian ACS patients.

Solubilization effect of SBE-β-CD and HP-β-CD on prasugrel / 中国药学杂志

OBJECTIVE: To improve the solubility of prasugrel in aqueous solution, the solubilization effect of SBE-β-CD and HP-β-CD research on prasugrel.

Prasugrel-Induced Hypersensitivity Skin Reaction

We report a case of hypersensitivity skin reaction to prasugrel. The patient exhibited a generalized skin rash after treatment with prasugrel, which was resolved after discontinuation of prasugrel and substitution to clopidogrel. Clopidogrel was successfully administered as an alternative to prasugrel without any signs of further hypersensitivity.

Lower Loading Dose of Prasugrel Compared with Conventional Loading Doses of Clopidogrel and Prasugrel in Korean Patients Undergoing Elective Coronary Angiography: A Randomized Controlled Study Evaluating Pharmacodynamic Efficacy

BACKGROUND AND OBJECTIVES: Although prasugrel allows for rapid and potent platelet inhibition, the efficacy and safety of lower doses of prasugrel for patients of East Asian ethnicity has not yet been investigated. We compared the effect of a lower loading dose (LD) of prasugrel with conventional LDs of clopidogrel and prasugrel in Korean patients. SUBJECTS AND METHODS: Forty-three Korean patients undergoing coronary angiography were enrolled in the study. Participants were randomly administered LDs of clopidogrel 600 mg, prasugrel 30 mg or prasugrel 60 mg prior to coronary angiography. Platelet reactivity was assessed at baseline and at the time of peak platelet inhibition using light transmission aggregometry (LTA), the VerifyNow assay, and multiple electrode aggregometry. RESULTS: Although baseline platelet reactivity between the groups showed no significant differences, at the time of peak platelet inhibition, the prasugrel 30 mg (18.9+/-10.0%) and 60 mg groups (13.8+/-10.8%) showed significantly more potent platelet inhibition than the clopidogrel 600 mg group (52.9+/-15.8%; p<0.001) by LTA. However, there were no significant differences between the prasugrel 30 mg and 60 mg groups (p=0.549). CONCLUSION: The loading effect of prasugrel 30 mg was more potent than clopidogrel 600 mg and was not significantly different from prasugrel 60 mg.

Successful Prasugrel Rescue Therapy in Clopidogrel Resistant Patients Who Had Recurrent Stent Thrombosis of Drug-Eluting-Stent: The Role of Prasugrel in Clopidogrel Nonresponders

Stent thrombosis is a very serious problem after drug-eluting stent (DES) implantation even though its incidence is about or less than 1%. As the clopidogrel resistance is expected to play an important role in the occurrence of stent thrombosis, new anti-platelet agents overcoming this issue can give us another choice. We experienced a case of a 58-year-old male with successful prasugrel rescue therapy in a patient with clopidogrel resistance who had recurrent stent thrombosis following DES implantation.

New Oral Antiplatelet Agents / 대한내과학회지

Antiplatelet agents play an essential role in the treatment of acute coronary syndrome (ACS). Aspirin and thienopyridines comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS. Thienopyridines are a class of drugs that function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet receptors. While clopidogrel remains in extensive use in clinical practice, it cannot meet the needs in many clinical conditions because of its pharmacological limitations. In recent years, newly developed P2Y12 antagonists, such as prasugrel and ticagrelor, have proven to be of higher efficacy and less resistance. As a third generation thienopyridine, prasugrel exerts a much more rapid and consistent inhibitory effect on platelet aggregation than clopidogrel. Treatment with ticagrelor, nonthienopyridine oral antiplatelet drug, significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding as compared with clopidogrel. The present review aims to discuss the current knowledge on the safety and efficacy of new oral antiplatelet agents including prasugrel and ticagrelor.

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.