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.

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.

Low-dose Prasugrel in Patients with Resistance to Clopidogrel for the Treatment of Cerebral Aneurysms: Follow-up of over 6 Months / 신경중재치료의학

No abstract available.

Tratamento da sca no paciente diabético: o que mostram as evidências / Treatment of acs in the diabetic patient: what the evidence shows

O diabete mellitus (DM) é uma comorbidade muito frequente entre os pacientes com síndrome coronariana aguda (SCA), acometendo, aproximadamente, 20 a 37% desses. Além de ser um preditor de risco independente, também está relacionado a uma maior prevalência de quadros atípicos de SCA. Apesar disso, é importante ressaltar que no caso da SCA, a maioria dos pacientes com DM apresenta o mesmo quadro clínico que os pacientes sem a doença. Assim como para os pacientes não diabéticos, os scores de risco devem ser aplicados. Entretanto, essa comorbidade por si própria já prediz uma maior gravidade. Inclusive é mais aconselhável utilizar para esses pacientes uma estratégia invasiva precoce. Em relação ao tratamento medicamentoso da SCA, não há alterações significativas no tratamento dos pacientes com DM para os pacientes sem DM. Já no que diz respeito à terapia de reperfusão, muito se extrapola dos conhecimentos em angina estável, em que há uma superioridade do tratamento cirúrgico sobre o percutâneo para os pacientes com DM, ainda que haja falta de evidências no contexto agudo. Finalmente, o conjunto de evidências não é definitivo para indicar a melhor estratégia para o controle da hiperglicemia, entretanto, sabe-se que tanto a hiperglicemia quanto à hipoglicemia durante a internação está relacionada aos piores desfechos. Portanto, é importante evitar valores de glicemia superiores a 180 mg/dL e inferiores a 90 mg/dL, ficando a estratégia de controle rigoroso de glicemia com insulina intravenosa restrita aos pacientes selecionados.

Diabetes mellitus (DM) is a frequent comorbidity among patients with acute coronary syndrome (ACS), affecting about 20% to 37% of these patients. Besides being an independent risk predictor, it is also related to a higher prevalence of atypical presentations of ACS. Despite this, it is important to emphasize that in the case of ACS the majority of patients with DM have the same clinical presentation as patients without the disease. Just as for non-diabetic patients, risk scores should be applied. However, this comorbidity per se predicts a greater severity. Also, it is preferable to use an early invasive strategy for these patients. Regarding the medicinal treatment of ACS, there are no significant differences between the treatment of patients with DM and those without DM. In relation to reperfusion therapy, much of it is extrapolated from knowledge of stable angina, in which surgical treatment takes precedence over percutaneous treatment for patients with DM, despite the lack of evidence in the acute context. Finally, there is no definitive body of evidence to indicate the best strategy to control hyperglycemia, but it is known that both hyperglycemia and hypoglycemia during hospitalization are associated with worse outcomes. Thus, it is important to avoid glycemia values above 180 mg/dL and below 90 mg/dL, restricting the strategy of strict glycemic control with intravenous insulin to selected patients.

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.

Low-Dose Prasugrel in Treatment of Cerebral Aneurysms / 신경중재치료의학

No abstract available.

De-Escalation of P2Y₁₂ Receptor Inhibitor Therapy after Acute Coronary Syndromes in Patients Undergoing Percutaneous Coronary Intervention

Dual antiplatelet therapy (DAPT) — a combination of a P2Y₁₂ receptor inhibitor and aspirin — has revolutionized antithrombotic treatment. Potent P2Y₁₂ inhibitors such as prasugrel and ticagrelor exhibit a strong and more consistent platelet inhibition when compared to clopidogrel. Therefore, ticagrelor and prasugrel significantly reduce ischemic events, but at an expense of an increased bleeding risk in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). These observations have engaged intensive clinical research in alternative DAPT regimens to achieve sufficient platelet inhibition with an acceptable bleeding risk. Our review focusses on P2Y₁₂ receptor therapy de-escalation defined as a switch from a potent antiplatelet agent (ticagrelor or prasugrel) to clopidogrel. Recently, both unguided (platelet function testing independent) and guided (platelet function testing dependent) DAPT de-escalation strategies have been investigated in different clinical studies and both switching strategies could be possible options to prevent bleeding complications without increasing ischemic risk. In light of the still limited data currently available, future large-scale trials should accumulate more data on various DAPT de-escalation regimens with both ticagrelor and prasugrel in unguided and guided de-escalation approaches. In the current review we aim at summarizing and discussing the current evidence on this still emerging topic in the field of antiplatelet treatment.

Antiplaquetários nas Síndromes Coronarianas Agudas / Antiplatelet Agents in Acute Coronary Syndromes

Em condições de equilíbrio, a hemostasia é mantida através de uma complexa interação entre endotélio, plaquetas e fatores de coagulação. Situações que cursam com injúria e descontinuidade do revestimento endotelial estimulam a adesão, ativação e agregação de plaquetas, culminando com a formação de trombos arteriais ou venosos. Neste contexto, a terapia antiplaquetária ocupa um papel de destaque no manejo das patologias advindas deste processo, notadamente as síndromes coronarianas agudas.O maior domínio conceitual dos receptores, agonistas e antagonistas das cascatas fisiopatológicas envolvidasneste processo possibilitou o desenvolvimento de novos fármacos e o refinamento da terapêutica atual, tornando necessário o pleno conhecimento do arsenal antiplaquetário no que tange à sua indicação, posologia, momento de administração e duração do tratamento. O objetivo desta revisão é definir o papel dos fármacos antiplaquetários no manuseio da síndrome coronariana aguda, revisitando aspectos já consolidados e abordando tópicos atuais e ainda controversos acerca do tema

Dual antiplatelet therapy and non-cardiac surgery: evolving issues and anesthetic implications / 대한마취과학회지

Dual antiplatelet therapy (DAPT) consisting of aspirin plus a P2Y₁₂ inhibitor (clopidogrel, prasugrel, or ticagrelor) is imperative for the treatment of acute coronary syndrome, particularly during the re-endothelialization period after percutaneous coronary intervention (PCI). When patients undergo surgery during this period, the consequences of stent thrombosis are far more serious than those of bleeding complications, except in cases of intracranial surgery. The recommendations for perioperative DAPT have changed with emerging evidence regarding the improved efficacy of non-first-generation drug (everolimus, zotarolimus)-eluting stents (DES). The mandatory interval of 1 year for elective surgery after DES implantation was shortened to 6 months (3 months if surgery cannot be further delayed). After this period, it is generally recommended that the P2Y₁₂ inhibitor be stopped for the amount of time necessary for platelet function recovery (clopidogrel 5–7 days, prasugrel 7–10 days, ticagrelor 3–5 days), and that aspirin be continued during the perioperative period. In emergent or urgent surgeries that cannot be delayed beyond the recommended period after PCI, proceeding to surgery with continued DAPT should be considered. For intracranial procedures or other selected surgeries in which increased bleeding risk may also be fatal, cessation of DAPT (possibly with continuation or minimized interruption [3–4 days] of aspirin) with bridge therapy using short-acting, reversible intravenous antiplatelet agents such as cangrelor (P2Y₁₂ inhibitor) or glycoprotein IIb/IIIa inhibitors (tirofiban, eptifibatide) may be contemplated. Such a critical decision should be individually tailored based on consensus among the anesthesiologist, cardiologist, surgeon, and patient to minimize both ischemic and bleeding risks.

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.

Estratégias antiplaquetárias orais nas fases aguda e crônica das síndromes coronarianas aguda / Oral antiplatelet strategies in the acute and chronic of acute coronary syndromes

Desde os primeiros estudos com ácido acetilsalicílico (AAS), até publicações mais recentes com novos bloqueadores de ADP e bloqueadores do receptor de trombina, pode-se afirmar que o conhecimento sobre o tratamento antiplaquetário nas síndromes coronarianas agudas (SCA) evoluiu de forma exponencial. Atualmente, a dupla antiagregação (DAP) é parte essencial do tratamento das SCA em todas as suas formas de apresentação, sendorecomendada por no mínimo um ano em todos os pacientes, independentemente da estratégia de revascularização utilizada, desde que não haja contraindicações ao seu uso. Ao mesmo tempo que se demonstrava eficácia crescente com o uso de antitrombóticosde forma geral (incluindo-se os antiplaquetários), cada vez mais a comunidade científica se conscientizava da importância do sangramento que ocorria com o uso desses medicamentos e negava, ao menos parcialmente, os benefícios obtidos. Assim sendo, os maiores desafios nos tempos atuais em termos de terapêutica antitrombótica nas SCA voltam-se para o desenvolvimento de estratégias terapêuticas personalizadas individualmente, que possam ter o máximo possível de benefício emtermos de eventos isquêmicos, com o mínimo possível de sangramento. Isso inclui não apenas uma análise cuidadosa dos medicamentos a serem associados, mas também do tempo de sua utilização. Tais estratégias constituem o foco principal da presente revisão...

Since the first studies with acetylsalicylic acid (ASA) up to more recent publications with new blockers of ADP and anti-thrombin receptor blockers, it is fair to say that knowledge about antiplatelet therapy in acute coronary syndromes (ACS) has grown exponentially. Currently, dual antiplatelet (DAP) therapy is an essential part of the treatment in all presentation forms of ACS, and it is recommended for at least one year for all patients, regardless of the revascularization strategy used, provided there are no contraindications to its use. Alongside the demonstration of increased efficacy of antithrombotics in general (including antiplatelet drugs), the scientific community became increasingly aware of the impactof bleeding that occurred with the use of these drugs, and that were undermining, at least partially, the benefits obtained.Thus, the main challenge today regarding anti-thrombotic treatment in ACS is the development of tailored therapeutic strategies that can produce the greatest possible benefit in terms of ischemic events, with minimal bleeding. This includes not only a careful analysisof the drugs to be associated, but also the duration of their use. Such strategies are the focus of the present review...

Impact of novel P2Y12 receptor inhibitors on platelet reactivity in acute coronary syndrome patients undergoing percutaneous coronary intervention / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the impact of novel P2Y(12) receptor inhibitors including prasugrel or ticagrelor on platelet reactivity in patients with acute coronary syndrome (ACS) receiving percutaneous coronary intervention (PCI), and provide clinical data for novel oral P2Y(12) receptor inhibitors use among Chinese patients.</p><p><b>METHODS</b>Between October 2011 to February 2014, 174 consecutive patients (135 males; (67.8±11.8) years old) with ACS undergoing PCI in Kiang Wu Hospital, Macau were prospectively enrolled in this study. Oral aspirin and one P2Y(12) receptor inhibitor were administered for 5 days or above after PCI, patients were divided into clopidogrel, prasugrel and ticagrelor groups in accordance with the agent administered. Platelet reactivity of the patients was detected by VerifyNow P2Y(12) reaction unit (PRU); and the high on-treatment platelet reactivity (HPR) and non-HPR were defined as PRU≥208 and PRU<208 respectively. Patients with HPR during clopidogrel therapy were switched either to prasugrel or ticagrelor, or continued the same treatment; and then the platelet reactivity was monitored again.</p><p><b>RESULTS</b>There were 113 clopidogrel cases (64.9%), 20 prasugrel cases (11.5%) and 41 ticagrelor cases (23.6%). Fifty-seven cases (32.8%) were defined as HPR post P2Y(12) receptor inhibitor use, in which 55 cases (55/113, 48.7%) were treated with clopidogrel. The degree of inhibition of platelet reactivity was significantly different in patients on clopidogrel, prasugrel and ticagrelor therapy, percent inhibition assayed by the VerifyNow P2Y(12) system was 28.2%±23.5%, 61.4%±26.7% and 81.3%±19.8% respectively (P<0.05). Different degree of platelet reactivity was achieved by the 3 P2Y(12) receptor inhibitors at multiple time points. The among-group differences in platelet reactivity became apparent at the early treatment stage (P<0.05). Platelet aggregation decreased significantly in patients switched from clopidogrel to prasugrel or ticagrelor (P<0.05).</p><p><b>CONCLUSION</b>Novel oral P2Y(12) receptor inhibitors are more effective in inhibiting platelet reactivity in ACS patients, and our results show that novel oral P2Y(12) receptor inhibitors provide a new option for ACS patients with HPR post clopidogrel or high-risk features of ischemic complications, including stent thrombosis and post-PCI ischemic events.</p>

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.

Simultaneous Multivessel Acute Stent Thrombosis in a Patient with Gastrointestinal Bleeding / 대한내과학회지

Stent thrombosis is a rare, but potentially catastrophic complication of stent implantation. Dual antiplatelet therapy with aspirin and a thienopyridine (clopidogrel, prasugrel, or ticagrelor) is essential to minimize the risk of stent thrombosis in patients receiving drug-eluting stents. However, there is an ongoing debate regarding antiplatelet therapy in patients presenting with acute coronary syndrome and bleeding. Here, we report a case of a 59-year-old man with acute stent thrombosis immediately after percutaneous coronary intervention combined with acute coronary syndrome and gastrointestinal bleeding.

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).

Clopidogrel versus prasugrel en síndrome coronario agudo tratado con angioplastia / Clopidogrel versus prasugrel in acute coronary syndrome treated with coronary angioplasty

Al uso del clopidogrel se han agregado nuevos antiagregantes como prasugrel y ticagrelor. El objetivo de este estudio fue comparar la incidencia de eventos isquémicos y hemorrágicos en pacientes que han recibido clopidogrel o prasugrel.Se incluyeron de manera consecutiva todos los pacientes con angioplastia durante la internación por síndrome coronario agudo entre diciembre 2011 y diciembre 2012.Fueron incluidos 398 pacientes. No se observaron diferencias en la mortalidad de causa cardiovascular (clopidogrel 2.5% vs. prasugrel 2.9%, p = 0.48). El grupo prasugrel presentó una reducción en la tasa de infarto (1.9% vs. 6.8%, p = 0.01) con sangrado totales (18.5% vs. 8.5%, p = 0.001) a expensas de sangrados menores (12.4% vs. 3.4%, p < 0.001), sin diferencia en sangrados mayores (p = 0.27) y sangrados con peligro de vida (p =.0.20). Por análisis multivariado los predictores independientes de mortalidad cardiovascular fueron edad (odds ratio 1.08, intervalo de confianza, IC, 95% 1.02-1.16, p = 0.02) insuficiencia renal (odds ratio 6.98, IC 95% 1.23-39.71, p < 0.0001). En cuanto al sangrado total se identificaron la edad (odds ratio 1.06, IC 95% 1.02-1.09, p = 0.002), elevación del segmento ST (odds ratio 1.99, IC 95% 1.05-3.79, p = 0.02), insuficiencia renal (odds ratio 3.32, IC 95% 1.62-6.78, p = 0.002) y utilización de prasugrel (odds ratio 3.97, IC 95% 1.87-8.41, p < 0.0001). La utilización de prasugrel se asocia a una menor tasa de infarto agudo de miocardio al año de seguimiento, con incremento de hemorragias menores. No se observaron diferencias significativas en la mortalidad cardiovascular entre ambos grupos.

Greater antithrombotic potency new antiplatelet agents have been added such as prasugrel (PR) and ticagrelor to the traditional use of clopidogrel (CL) in the treatment of acute coronary syndrome (ACS). This study was aimed at comparing the incidence of long term ischemic and hemorrhagic events in patients treated with CL or PR during hospitalization. Retrospective ACS data base analysis performed by our cardiology service was completed prospectively. There were consecutively included all patients with percutaneous coronary intervention (PCI) during hospitalization due to ACS from December 2011 thru December 2012. A total of 398 ACS patients who underwent PCI with stent implantation were recruited. No differences in cardiovascular related deaths were observed in both groups (PR 2.9% vs. CL 2.5%, p = 0.48). PR group showed less re-infraction (1.9% vs. 6.8%, p = 0.01) with more total bleedings (18.5% vs. 8.5%, p = 0.001) and minor bleedings (12.4% vs. 3.4%, p < 0.001) with no differences in major and life threatening bleedings (p = ns). Multivariate analysis showed that independent predictors of cardiovascular mortality were age (OR 1.08, CI 95% 1.02-1.16) and renal failure (OR 6.98, CI 95% 1.23-39.71). Independent predictors for total bleeding were age (OR 1.06, CI 95% 1.02-1.09),ST segment elevation myocardial infarction (OR 1.99, CI 95% 1.05-3.79), renal failure (OR 3.32, CI 95% 1.62-6.78) and prasugrel use (OR 3.97, CI 95% 1.87-8.41). Use of prasugrel, in the ACS that requires PCI with stent, is associated with a lower myocardial infarction a year after follow-up, and it also leads to an increase of milder hemorrhage. No significant differences were observed in the cardiovascular mortality of both groups.

A Comparative Study the USA, Europe and Korea Guidelines of Antiplatelet Therapy for Patients with Acute Coronary Syndrome

OBJECTIVE: Patients with acute coronary syndrome (ACS) are typically managed with dual antiplatelet therapy of acetylsalicylic acid (aspirin) and P2Y12 receptor inhibitor. In this study, we discussed current and previous antiplatelet therapy guidelines and compared with guidelines of the USA (ACC/AHA), Europe (ESC) and Korea (KSC). METHOD: This study investigated from ACC/AHA Joint Guidelines (the USA), ESC Clinical Practice Guidelines (Europe) and Korea Society of Interventional Cardiology (Korea) web site, respectively. RESULTS: It is significant that difference between the current and the previous guidelines was integration of terminology from clopidogrel to P2Y12 receptor inhibitors since prasugrel and ticagrelor, new antiplatelet drugs, has been added. The other difference was all three guidelines has differences in dose of aspirin. The most notable difference was class of recommendation (COR) in P2Y12 receptor inhibitors. ACC/AHA and Korean guidelines recommend clopidogrel, prasugrel, and ticagrelor with COR IB; whereas, ESC recommend prasugrel and ticagrelor with IB which is higher than clopidogrel with IC. CONCLUSION: This research addresses important movement to revise the Korean existing guideline recommendations. New Korean antiplatelet therapy guideline should be avoiding obvious differences in ACC/AHA and ESC guidelines and harmonizing international guidelines.

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.

Oral antiplatelet agent hypersensitivity and cross-reactivity managed by successful desensitisation

Oral platelet aggregation inhibitors are widely used for the treatment and prevention of cardiovascular diseases, including coronary stent thrombosis. Premature discontinuation following percutaneous coronary intervention would pose a grave risk of in-stent thrombosis, acute myocardial infarction and eventual death. Although they share the same mechanism of adenosine diphosphate P2Y12 platelet receptor inhibition, they belong to either the chemical class of thienopyridines (clopidogrel, prasugrel, and ticlopidine) or cyclopentyl-triazolo-pyrimidines (ticagrelor and cangrelor). This case describes the first documented cross-reactive hypersensitivity of clopidogrel towards both its fellow thienopyridine, prasugrel, as well as the structurally dissimilar ticagrelor, and its subsequent successful desensitisation.

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.