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.

Tratamiento antiagregante guiado por pruebas de función plaquetaria en pacientes sometidos a angioplastia coronaria exitosa / Antiplatelet Therapy Guided by Platelet Function Testing after Successful Percutaneous Coronary Intervention / Antiplatelet Therapy Guided by Platelet Function testing after Successful Percutaneous Coronary Intervention Background

Introducción El tratamiento antiagregante dual con aspirina y clopidogrel constituye un tratamiento esencial para la prevención de eventos isquémicos en pacientes sometidos a angioplastia transluminal coronaria (ATC). Sin embargo, existe alta variabilidad interpaciente en la respuesta al clopidogrel, condicionando la falla en su efecto terapéutico, que se manifiesta como hiperreactividad plaquetaria residual (HPR). El prasugrel podría reducir este estado protrombótico. Objetivos 1) Estudiar la respuesta antiagregante en pacientes sometidos a ATC exitosa pretratados con clopidogrel o prasugrel y 2) evaluar la respuesta a una carga de prasugrel en pacientes con HPR bajo tratamiento con clopidogrel. Material y métodos Se incluyeron en forma prospectiva y consecutiva 83 pacientes sin riesgo hemorrágico alto sometidos a ATC exitosa bajo tratamiento antiagregante dual: aspirina más clopidogrel (600 mg de carga o mantenimiento de 75 mg/día por más de 7 días; n = 42) o prasugrel (60 mg de carga o mantenimiento de 10 mg/día por más de 7 días, n = 41). La selección de la tienopiridina quedó a cargo del médico tratante. La función plaquetaria se evaluó a las 12-24 horas pos-ATC con el método VerifyNow®. Se definió HPR a la presencia de ≥ 230 unidades de reactividad plaquetaria (URP). Los pacientes con HPR recibieron una dosis de carga de prasugrel de 60 mg y se repitió la evaluación de la función plaquetaria a las 2 horas. Resultados No hubo diferencias significativas en las características basales de ambos grupos. A las 12-24 horas pos-ATC, los pacientes tratados con prasugrel presentaron menos URP en comparación con el grupo clopidogrel [mediana 49 (9-78) vs. 160 (82-224); p < 0,001]. Se observó HPR en el 24% de los pacientes del grupo clopidogrel y cero en el grupo prasugrel (p < 0,001). Todos los pacientes con HPR bajo tratamiento con clopidogrel lograron corregirla luego de la carga de prasugrel. Conclusiones En pacientes sometidos a ATC exitosa, el tratamiento con prasugrel logró una mayor inhibición de la agregación plaquetaria (IAP) en comparación con la administración de clopidogrel. Por su parte, los pacientes con HPR bajo tratamiento con clopidogrel lograron alcanzar una IAP óptima con la administración adicional de prasugrel.

Dual antiplatelet therapy with aspirin and clopidogrel is an essential treatment to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). However, a significant interindividual variability exists in response to clopidogrel treatment, which is responsible for failure in the therapeutic effect and in the development of high residual platelet reactivity (HRPR). Prasugrel could reduce this prothrombotic state. Objectives To evaluate: 1) the antiaggregant response in clopidogrel or prasugrel pretreated patients undergoing successful PCI, and 2) the response to prasugrel loading in patients with low residual platelet reactivity on clopidogrel therapy. Material and Methods Eighty three patients were prospectively included in the study. They underwent successful PCI under dual antiplatelet therapy: aspirin plus clopidogrel (600 mg loading dose or a maintenance dose of 75 mg for more than 7 days; n=42) or prasugrel (60 mg loading dose or a maintenance dose of 10 mg for more than 7 days; n=41). The selection of thienopyridine was left at the discretion of the treating physician. Patients with high hemorrhagic risk were excluded. Platelet function was tested 12-24 hours after PCI with the VerifyNowTM P2Y12 Assay. High residual platelet reactivity (HRPR) was defined as P2Y12-reaction units (PRU) ≥ 230. In case of HRPR, patients received a loading dose of prasugrel 60 mg and platelet function was reassessed 2 hours later. Results Baseline characteristics did not differ in patients who initially received clopidogrel or prasugrel. At 12-24 hours post PCI, patients treated with prasugrel presented significantly less PRU compared with the clopidogrel cohort (median 49 (9-78) vs. 160 (82-224); p < 0.001). HRPR was observed in 24% of patients in the clopidogrel group and in no patients in the prasugrel cohort (p < 0.001). All patients with HRPR on clopidogrel treatment corrected this value after the loading dose of prasugrel. Conclusions After successful PCI, prasugrel administration achieved greater platelet inhibition compared to clopidogrel. Moreover, in patients with high-on treatment platelet reactivity with clopidogrel, optimal platelet inhibition was accomplished by additional prasugrel administration.

Hemoptise relacionada ao uso de clopidogrel em regime ambulatorial / Hemoptysis associated with clopidogrel in an ambulatory regimen

O clopidogrel é um agente antiagregante plaquetário indicado no tratamento das síndromes coronarianas agudas e na prevenção de recorrência de eventos isquêmicos cerebro vasculares ou após implantes de próteses nas artérias coronárias.Seu principal efeito colateral são hemorragias, raramente graves, com poucos casos relatados de sangramento pulmonar em geral associado ao uso de doses elevadas concomitantes a outros agentes antiplaquetários em procedimentos invasivos intracoronarianos. Relata-se o caso de um homem de 65 anos com hemoptise 37 dias após o início de clopidogrel que foi internado por agravamento do sintoma, teve o medicamento suspenso, vários exames realizados e alta concedida no oitavo dia de hospitalização, assintomático. Como nenhum outro fator causal foi identificado, atribuiu-se o sangramento à droga em questão. Ressalta-se ainda a possibilidade de ocorrência dessa complicação pulmonar, potencialmente fatal, mesmo quando o clopidogrel é usado isoladamente, em regime ambulatorial e nas doses de manutenção recomendadas.

Clopidogrel is a platelet aggregation inhibitor recommended in the treatment of acute coronary syndromes and in the prevention of recurrent ischaemia after cerebrovascular events or coronary stenting. Bleeding, rarely severe, is the major complication of its use. Alveolar hemorrhage is a much rarer occurrence, with only a few cases related in the literature, usually when the drug is associated with another platelet aggregation inhibitor during percutaneous coronary interventions or after massive ingestion. The authors report a case of 65-years-old male patient with hemoptysis after 37 days of clopidogrel use for prophylaxis of a cerebrovascular event, in an ambulatory regimen, in habitual dose and not associated with another platelet aggregation inhibitor. Based on the clinical history, the exclusion of other etiologies and the reversion of the condition after interrupting the drug the diagnosis of pulmonary hemorrhage associated with clopidogrel was made.They also emphasize the importance of thinking in this life-threatening possibility in a patient with hemoptysis during clopidogrel use, even in an ambulatory regimen and usual doses.