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1.
Brasília; CONITEC; nov. 2020.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1145484

RESUMEN

INTRODUÇÃO: A síndrome coronariana aguda (SCA) é um termo abrangente para: infarto agudo do miocárdio (IAM) com supradesnivelamento do segmento ST, IAM sem supradesnivelamento do segmento ST e angina instável (1,2). A incidência é muito variável entre diferentes países e regiões do mundo (3­8). De acordo com a Organização Mundial da Saúde, doenças isquêmicas do coração foram responsáveis por 12% das mortes observadas em países de média e baixa renda, e aproximadamente 16% das mortes em países da alta renda em 2008 (9). Em particular, pacientes com diabetes mellitus (DM) possuem maior potencial pró-trombótico (3,4) e consequente maior potencial de beneficiarem-se de antiagregantes plaquetários (aspirina, clopidogrel) após uma angioplastia. O prasugrel é um anti-agregante plaquetário da mesma classe do clopidogrel, hoje incorporado ao SUS, e do ticagrelor, cuja incorporação foi rejeitada pela CONITEC. PERGUNTA: O prasugrel é eficaz, seguro e custo-efetivo em relação ao clopidogrel para a redução de eventos cardiovasculares em pacientes com síndrome coronariana aguda (SCA) e diabetes mellitus (DM) que realizaram angioplastia? EVIDÊNCIAS CIENTÍFICAS: Um único ensaio clínico randomizado (TRITON TIMI 38) avaliou prasugrel versus clopidogrel, 23% dos participantes eram diabéticos. Estudo patrocinado pelo demandante. Baixo risco de viés. A análise em pacientes diabéticos é baseada em uma análise de subgrupo. A qualidade da evidência é limitada pois não houve randomização para diabéticos e o estudo não foi controlado para o tipo e gravidade da doença. Ainda, a interação para diabetes não foi significativa (P = 0,09), ou seja, a análise deste subgrupo como um grupo independente não é adequada. A razão de chances, que no estudo pivotal era de 0,76 para redução de infarto foi recalculada para 0,60 no subgrupo de diabéticos. Analisando os resultados do subgrupo de pacientes diabéticos para o desfecho primário composto de morte cardiovascular, infarto e AVC, foram observados eventos em 17,0% no grupo clopidogrel e 12,2% no grupo prasugrel (HR=0,70; IC 0,58 - 0,85). Para morte cardiovascular, 4,2% no grupo clopidogrel e 3,4% no grupo prasugrel (HR=0,85; IC 0,58 - 1,24); IAM não fatal: 13,2% no grupo clopidogrel e 8,2% no grupo prasugrel (HR=0,60; IC 0,48 - 0,76); Trombose de stent: 3,6% no grupo clopidogrel e 2,0% no grupo prasugrel (HR=0,52; IC 0,33 - 0,84). O prasugrel apresentou maior risco de sangramentos não relacionada à cirurgia de revascularização miocárdica: 4,3% no grupo clopidogrel e 5,3% no grupo prasugrel (HR=1,30; IC 0,92 - 1,82). AVALIAÇÃO ECONÔMICA: A avaliação econômica do prasugrel apresentada pelo demandante baseou-se nos resultados do estudo pivotal e em um modelo de custo-efetividade e custo-utilidade utilizado previamente no NICE. Como resultados, prasugrel demonstrou-se ser mais efetivo e com maior custo em relação ao clopidogrel, apresentando uma razão de custo-utilidade incremental (RCEI) de R$ 9.325,00 mil/QALY. O modelo foi refeito pelo parecerista externo, obtendo um novo valor de RCEI de R$ 12.324,53/QALY e com 100% das simulações com valor igual ou inferior a R$ 15.591,13/QALY. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 89ª reunião ordinária, no dia 06 de agosto de 2020, recomendou a não incorporação no SUS de prasugrel para tratamento de pacientes diabéticos com síndrome coronariana aguda pós angioplastia. A recomendação levou em consideração que a população alvo foi mal definida, gerando incertezas no impacto orçamentário e na proposta de redução de preços. A operacionalização da proposta de redução de preços necessita de esclarecimentos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 89ª reunião ordinária, no dia 06 de agosto de 2020, recomendou a não incorporação no SUS de prasugrel para tratamento de pacientes diabéticos com síndrome coronariana aguda pós angioplastia. A recomendação levou em consideração que a população alvo foi mal definida, gerando incertezas no impacto orçamentário e na proposta de redução de preços. A operacionalização da proposta de redução de preços necessita de esclarecimentos. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 92ª reunião ordinária, no dia 05 de novembro de 2020, deliberaram por recomendar a não incorporação no SUS do cloridrato de prasugrel para pacientes diabéticos com síndrome coronariana aguda submetidos à angioplastia primária. Os membros presentes entenderam que o medicamento atenderia um subgrupo de pacientes específico e que ainda há incertezas quanto ao seu benefício e segurança. Foi assinado o Registro de Deliberação nº 573.


Asunto(s)
Humanos , Angioplastia/instrumentación , Diabetes Mellitus/fisiopatología , Síndrome Coronario Agudo/fisiopatología , Clorhidrato de Prasugrel/uso terapéutico , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía
2.
Am J Cardiol ; 132: 22-28, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32771221

RESUMEN

Prasugrel and ticagrelor are preferred over clopidogrel for patients with acute coronary syndrome who underwent percutaneous coronary intervention. We sought to determine the relative merits of 1 agent over the other. Multiple databases were queried to identify relevant randomized control trials (RCTs) and observational cohort studies. Random-effects model was used to calculate an unadjusted odds ratio (OR) for major adverse cardiovascular and cerbrovascular events (MACCE) and its components. A total of 27 (7 RCTs, 20 observational cohort studies) studies comprising 118,266 (prasugrel 62,716, ticagrelor 51,196) patients were included. At 30 days, prasugrel was associated with a significantly lower odds of MACCE (OR 0.75, 95% confidence interval [CI] 0.67 to 0.85, p ≤0.0001) and mortality (OR 0.65, 95% CI 0.59 to 0.71, p ≤0.0001). At 1 year, the overall odds of mortality favored prasugrel (OR 0.79, 95% CI 0.68 to 0.92, p = 0.002), but no significant interdrug difference was seen in terms of MACCE (OR 0.89, 95% CI 0.76 to 1.05, p = 0.16). There was no significant difference in the odds of overall myocardial infarction, revascularization, stent thrombosis, stroke, and major bleeding events between the 2 groups on both 30-day and 1-year follow-up. A subgroup analysis of RCTs data showed no significant difference between prasugrel and ticagrelor in terms of any end point at all time points. In conclusion, prasugrel might have lower odds of MACCE and mortality at 30 days. However, there was no difference in the safety and efficacy end points of 2 drugs at 1 year. The observed transient prasugrel-related mortality benefits were subject to the bias of nonrandomized assignment.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Clorhidrato de Prasugrel/uso terapéutico , Ticagrelor/uso terapéutico , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/cirugía , Quimioterapia Combinada , Salud Global , Humanos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tasa de Supervivencia/tendencias
3.
Aliment Pharmacol Ther ; 52(4): 646-654, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32657466

RESUMEN

BACKGROUND: Gastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y12 inhibiting antiplatelet agents. Compared with clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events with similar or possibly higher major bleeding events. The comparative GIB rates of these medications remain poorly understood. AIM: To compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees . METHODS: Propensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1-year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH). RESULTS: We identified 37 019 patients with ACS (non-ST elevation ACS [NSTE-ACS] and ST-elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54-0.81) in GIB overall and with NSTE-ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42-0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64-0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49-0.85) in STEMI patients but no reduction of GIB risk in NSTE-ACS patients. CONCLUSIONS: In the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Clopidogrel/efectos adversos , Hemorragia Gastrointestinal/inducido químicamente , Intervención Coronaria Percutánea , Clorhidrato de Prasugrel/efectos adversos , Ticagrelor/efectos adversos , Síndrome Coronario Agudo/epidemiología , Anciano , Clopidogrel/uso terapéutico , Estudios de Cohortes , Femenino , Hemorragia Gastrointestinal/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/efectos adversos , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Clorhidrato de Prasugrel/uso terapéutico , Estudios Retrospectivos , Tromboembolia/epidemiología , Tromboembolia/prevención & control , Ticagrelor/uso terapéutico , Resultado del Tratamiento , Estados Unidos/epidemiología
5.
Lancet ; 395(10233): 1374-1381, 2020 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-32334703

RESUMEN

BACKGROUND: Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding [superiority hypothesis]). Co-primary net clinical benefit outcome consisted of all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013-001403-37). FINDINGS: Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 [18%] of 500 patients) than in the ticagrelor group (118 [24%] of 502; hazard ratio 0·71, 95% CI 0·54 to 0·94; p=0·02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 [28%]) versus ticagrelor (161 [32%]; absolute risk difference -4%, 95% CI -10·0 to 1·4; p=0·03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35). INTERPRETATION: In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk. FUNDING: ZonMw.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Ticagrelor/uso terapéutico , Síndrome Coronario Agudo/mortalidad , Anciano , Anciano de 80 o más Años , Clopidogrel/efectos adversos , Femenino , Humanos , Masculino , Infarto del Miocardio/prevención & control , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Accidente Cerebrovascular/prevención & control , Ticagrelor/efectos adversos
6.
JAMA Netw Open ; 3(4): e202004, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32239221

RESUMEN

Importance: Prasugrel was approved at a lower dose in 2014 in Japan than in the West because East Asian patients are considered more susceptible to bleeding than Western patients. However, real-world outcomes with low-dose prasugrel treatment remain unclear. Objective: To investigate the association of low-dose prasugrel vs standard-dose clopidogrel administration with short-term outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Design, Setting, and Participants: This study used data from the Japan Cardiovascular Database-Keio Interhospital Cardiovascular Studies registry, a large, ongoing, multicenter, retrospective cohort of consecutive patients who underwent PCI. The present cohort study evaluated 2770 patients with acute coronary syndrome who underwent PCI and received either low-dose prasugrel (loading dose, 20 mg; maintenance dose, 3.75 mg) or clopidogrel (loading dose, 300 mg; maintenance dose, 75 mg) in combination with aspirin between 2014 and 2018. Propensity score-matching analysis was conducted to balance the baseline characteristics of patients receiving low-dose prasugrel and those receiving clopidogrel. Data analysis was conducted in June 2019. Exposures: Prescription of either low-dose prasugrel or standard-dose clopidogrel prior to PCI. Main Outcomes and Measures: Primary ischemic events (in-hospital death, recurrent myocardial infarction, and ischemic stroke) and primary bleeding events, defined as bleeding complications within 72 hours after PCI consistent with the National Cardiovascular Data Registry CathPCI Registry definition. Results: Of 2559 patients included in the study, the mean (SD) age was 67.8 (12.7) years, and 78.2% were male. In total, 1297 patients (50.7%) received low-dose prasugrel, and 1262 patients (49.3%) received clopidogrel. After propensity score matching, primary ischemic events among patients receiving low-dose prasugrel and those receiving clopidogrel were comparable (odds ratio [OR], 1.42; 95% CI, 0.90-2.23), but primary bleeding events were significantly higher among patients receiving prasugrel (OR, 2.91; 95% CI, 1.63-5.18). This increase in bleeding events was associated with the presence of a profile of high-bleeding risk (≥75 years of age, body weight <60 kg, or history of stroke or transient ischemic attack) (OR, 4.08; 95% CI, 1.86-8.97), being female (OR, 3.84; 95% CI, 1.05-14.0), or the presence of ST-segment elevation myocardial infarction (OR, 2.07; 95% CI, 1.05-4.09) or chronic kidney disease (OR, 4.78; 95% CI, 1.95-11.7). Conclusions and Relevance: Since its approval, low-dose prasugrel has been used by nearly 80% of patients who undergo PCI. Despite the modified dose, bleeding events were higher among patients receiving low-dose prasugrel than among patients receiving clopidogrel, with no difference in ischemic events between the 2 groups. These results suggest the importance of a risk assessment of bleeding prior to selecting a P2Y12 inhibitor, even for the use of a lower approved dose, when treating patients of East Asian descent.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/efectos adversos , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Síndrome Coronario Agudo/cirugía , Anciano , Anciano de 80 o más Años , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Isquemia Encefálica/inducido químicamente , Isquemia Encefálica/patología , Estudios de Casos y Controles , Clopidogrel/administración & dosificación , Clopidogrel/uso terapéutico , Muerte , Quimioterapia Combinada , Femenino , Hemorragia/epidemiología , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/epidemiología , Infarto del Miocardio/fisiopatología , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/uso terapéutico , Sistema de Registros , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Accidente Cerebrovascular/epidemiología
7.
Am J Cardiol ; 125(12): 1815-1822, 2020 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-32305225

RESUMEN

Dual antiplatelet therapy combining aspirin with a P2Y12-receptor inhibitor reduces atherothrombotic events following an acute coronary syndromes (ACS), but the relative merits of different P2Y12 inhibitors remain unclear, despite several recent large-scale trials. We performed a network meta-analysis, representing the largest evidence to date to inform P2Y12 inhibitor choice in patients with ACS. Fourteen studies were included, for a total population of 145,019 patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review. A network meta-analysis using a frequentist approach with surface under the cumulative ranking probability calculation was performed. Major adverse cardiovascular events (MACE), all-cause death, myocardial infarction (MI), definite stent thrombosis (ST) and major bleeding at 30-day and 1-year all-cause death and MI were the study endpoints. At 30-day, prasugrel was superior to both clopidogrel and ticagrelor in MACE, all-cause death and definite ST endpoints. Both prasugrel and ticagrelor were superior to clopidogrel in MI endpoint. Ticagrelor also reduced all-cause death compared with clopidogrel. Ticagrelor, prasugrel, and clopidogrel resulted equivalent in terms of the safety outcome of 30-day major bleeding. No significant difference was found among clopidogrel, prasugrel, and ticagrelor with respect to 1-year MACE outcome. Both prasugrel and ticagrelor reduced the occurrence of 1-year all-cause death compared with clopidogrel. Prasugrel reduced 1-year MI rate as compared with clopidogrel, while ticagrelor did not. At probability analyses, prasugrel ranked best in all 30-day and 1-year efficacy and safety endpoints. In conclusion, in this network meta-analysis, prasugrel showed the highest efficacy in reducing adverse outcomes in ACS patients and had the highest probability of being the best P2Y12 inhibitor to reduce hard adverse events both at 30-day and 1-year follow-up.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Síndrome Coronario Agudo/mortalidad , Aspirina/uso terapéutico , Causas de Muerte , Clopidogrel/uso terapéutico , Oclusión de Injerto Vascular/epidemiología , Hemorragia/epidemiología , Humanos , Infarto del Miocardio/epidemiología , Clorhidrato de Prasugrel/uso terapéutico , Stents , Ticagrelor/uso terapéutico
8.
Circ Cardiovasc Qual Outcomes ; 13(3): e006275, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32156164

RESUMEN

Background Ticagrelor and prasugrel are potent P2Y12 inhibitors with superior efficacy compared with clopidogrel among patients with ST-segment-elevation myocardial infarction (STEMI), though use in recent practice is not well described. In this retrospective study, we assessed trends, predictors, and variation in use of P2Y12 inhibitors in patients with STEMI in the United States. Methods and Results We identified 169 505 STEMI patients in the Chest Pain-Myocardial Infarction Registry from October 2013 through March 2017. We determined national utilization rates of P2Y12 inhibitors at discharge, patient predictors for each medication, and variation in use between hospitals. In a subset of 9655 Medicare patients ≥65 years old, we compared 1-year adjusted risks of death, myocardial infarction, stroke, and bleeding based on hospital quartile of potent P2Y12 inhibitor use. Rates of ticagrelor use increased from 18.0% to 44.0%, while rates of prasugrel and clopidogrel use decreased from 24.6% to 13.5% and 57.4% to 42.6%, respectively. Prior percutaneous coronary intervention was the strongest clinical predictor for use of ticagrelor (adjusted odds ratio, 1.13 [95% CI, 1.09-1.18]) and prasugrel (adjusted odds ratio, 1.27 [95% CI, 1.21-1.34]) compared with clopidogrel. Predictors of clopidogrel use included no insurance, insurance with Medicare or Medicaid, and features associated with higher bleeding risk. The median hospital usage rate for newer P2Y12 inhibitors was 51.3% (interquartile range, 35.0%-65.9%), with substantial variation between hospitals (adjusted median odds ratio, 2.92 [95% CI, 2.77-3.10]). Among patients ≥65 years old, there were no differences in adjusted 1-year risks of adverse outcomes across hospital quartiles of potent P2Y12 inhibitor use. Conclusions Almost one-half of STEMI patients by 2017 were discharged on ticagrelor while far fewer received prasugrel. Patient characteristics are associated with P2Y12 inhibitor selection, though substantial hospital variation exists. Identifying barriers to use of more potent P2Y12 inhibitors may improve patient-centered decision-making for STEMI patients.


Asunto(s)
Cardiólogos/tendencias , Servicio de Cardiología en Hospital/tendencias , Utilización de Medicamentos/tendencias , Intervención Coronaria Percutánea/tendencias , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pautas de la Práctica en Medicina/tendencias , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Receptores Purinérgicos P2Y12/efectos de los fármacos , Infarto del Miocardio con Elevación del ST/terapia , Anciano , Clopidogrel/uso terapéutico , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente/tendencias , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/mortalidad , Ticagrelor/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología
9.
Cerebrovasc Dis ; 49(2): 152-159, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32208397

RESUMEN

INTRODUCTION: The safety of prasugrel in elderly and/or low body weight Japanese patients with ischemic stroke who have a relatively high bleeding risk with antiplatelet therapy remains unknown. OBJECTIVE: We aimed to investigate the safety and efficacy of long-term prasugrel monotherapy for stroke prevention compared with clopidogrel in elderly and/or low body weight Japanese patients with non-cardioembolic ischemic stroke. METHODS: In this randomized, double-blind, comparative, phase III study, elderly (age ≥75 years) and/or low body weight (≤50 kg) Japanese patients with a previous history of non-cardioembolic ischemic stroke were assigned to a prasugrel 3.75 mg (PRA3.75) group, a prasugrel 2.5 mg (PRA2.5) group, or a clopidogrel 50 mg (CLO50) group and followed up for 48 weeks. The primary safety endpoint was the combined incidence of primary safety events, defined as life-threatening, major, and other clinically relevant bleeding. The efficacy endpoint was a composite of ischemic stroke, myocardial infarction, and death from other vascular causes. RESULTS: A total of 654 patients (age 76.4 ± 7.3 years, body weight 55.6 ± 9.3 kg, women 43.9%) from 74 medical institutions within Japan were enrolled. The combined incidence (95% CI) of primary safety events was 4.2% (1.9-7.8%), 1.9% (0.5-4.7%), and 3.6% (1.6-6.9%) in the PRA3.75 group (n = 216), PRA2.5 group (n = 215), and CLO50 group (n = 223), respectively (hazard ratios [HR] PRA3.75/CLO50, 1.13 [0.44-2.93]; PRA2.5/CLO50, 0.51 [0.15-1.69]). The incidences of bleeding leading to treatment discontinuation (95% CI) were 2.3% (0.8-5.3%), 0.9% (0.1-3.3%), and 2.2% (0.7-5.2%) in the PRA3.75, PRA2.5, and CLO50 groups, respectively (HRs PRA3.75/CLO50, 1.01 [0.29-3.48]; PRA2.5/CLO50, 0.41 [0.08-2.12]). There was no significant difference in all bleeding events between groups. The incidence of ischemic stroke, myocardial infarction, and death from other vascular causes was lower, but not significantly so, in patients treated with prasugrel than in patients treated with clopidogrel: PRA3.75, 0.0% (0/216); PRA2.5, 3.3% (7/215); and CLO50, 3.6% (8/223; HRs PRA3.75/CLO50, 0.00 [0.00-0.00]; PRA2.5/CLO50, 0.90 [0.32-2.47]). CONCLUSIONS: Elderly and/or low body weight -Japanese patients with previous non-cardioembolic ischemic stroke who received PRA3.75 showed similar results in terms of primary safety endpoint, and a numerically lower incidence of ischemic stroke, myocardial infarction, and death from other vascular causes, compared with those who received CLO50.


Asunto(s)
Peso Corporal , Isquemia Encefálica/tratamiento farmacológico , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Grupo de Ascendencia Continental Asiática , Peso Corporal/etnología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etnología , Isquemia Encefálica/mortalidad , Clopidogrel/efectos adversos , Método Doble Ciego , Femenino , Estado de Salud , Hemorragia/inducido químicamente , Humanos , Incidencia , Japón , Masculino , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etnología , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Resultado del Tratamiento
10.
BMJ Case Rep ; 13(3)2020 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-32169992

RESUMEN

A patient undergoes intracranial stent insertion for stent-assisted coiling of a basilar tip aneurysm and left middle cerebral artery aneurysm. A flow diverting stent is also placed across an anterior communicating artery aneurysm. Prior to the procedure, the patient takes dual antiplatelet medications, being aspirin and clopidogrel. Because of the concern regarding in-stent thrombus and thromboembolic complications related to intracranial stenting and the high rate of clopidogrel resistance, preoperative platelet function testing (PFT) was undertaken to ensure platelet inhibition. In this case, PFT was performed on a platelet function analyser which demonstrated platelet inhibition. Ten days following the procedure, the patient represented with thromboembolic stroke. Repeat PFT performed with whole blood impedance aggregometry and despite full medication compliance demonstrated clopidogrel resistance. Clopidogrel was then ceased and prasugrel commenced. This case demonstrates the importance of appropriate platelet inhibition in patients with intracranial stents and the controversy surrounding PFT.


Asunto(s)
Aneurisma Intracraneal/tratamiento farmacológico , Stents/efectos adversos , Accidente Cerebrovascular/etiología , Tromboembolia/complicaciones , Anciano , Aspirina/uso terapéutico , Clopidogrel/uso terapéutico , Diagnóstico Diferencial , Resistencia a Medicamentos , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Ataque Isquémico Transitorio/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria/métodos , Clorhidrato de Prasugrel/uso terapéutico , Cuidados Preoperatorios/normas , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento , Privación de Tratamiento
11.
BMC Cardiovasc Disord ; 20(1): 130, 2020 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-32164560

RESUMEN

BACKGROUND: For patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the efficacy and safety of novel P2Y12 antagonists, including prasugrel or ticagrelor, has not been established relative to that of the clopidogrel-based triple-antiplatelet treatments (TAPTs; in combination with glycoprotein IIb/IIIa inhibitor). The present meta-analysis evaluated the efficacy and safety of prasugrel- or ticagrelor-based TAPTs relative to that of clopidogrel TAPTs in patients with STEMI undergoing PCI. METHODS: The databases PubMed, Embase, and Cochrane's Library were systematically searched for relevant randomized controlled trials concerning prasugrel or ticagrelor (test) relative to clopidogrel (control). Depending on heterogeneity, studies were pooled with a random effects or a fixed effects model. Outcomes of blood flow after PCI were evaluated, including TIMI (thrombolysis in myocardial infarction), bleeding events, and major adverse cardiovascular events (MACEs). RESULTS: Seven studies comprising 11,874 patients conformed to the inclusion criteria. The pooled results with the fixed effects model indicated that after PCI patients in the prasugrel or ticagrelor groups were as likely as those treated with clopidogrel to achieve TIMI grade 3 flow or experience bleeding events. However, compared with the control, the test groups had significantly less risk of MACE (OR: 0.81, 95% CI: 0.70-0.94, P = 0.004), especially at the 1-year follow-up (OR: 0.79, 95% CI: 0.66-0.95, P = 0.01). CONCLUSIONS: A prasugrel- or ticagrelor-based TAPT may reduce the rate of MACEs, without increasing bleeding in STEMI patients undergoing PCI. However, due to the limited RCT studies and variations in study weight, results of this meta-analysis should be confirmed in a large RCT with adequate sample size and follow-up duration.


Asunto(s)
Clopidogrel/uso terapéutico , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Infarto del Miocardio con Elevación del ST/terapia , Ticagrelor/uso terapéutico , Anciano , Anciano de 80 o más Años , Clopidogrel/efectos adversos , Quimioterapia Combinada , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Recurrencia , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/mortalidad , Ticagrelor/efectos adversos , Resultado del Tratamiento
12.
J Cardiovasc Pharmacol Ther ; 25(3): 201-211, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32027168

RESUMEN

BACKGROUND AND OBJECTIVES: Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450 (CYP), primarily CYP2C19. Patients with CYP2C19 loss-of-function alleles are at increased risk of major adverse cardiovascular events, while more expensive novel antiplatelet agents (ticagrelor and prasugrel) are unaffected by the CYP2C19 mutations. This systematic review aims to answer the question about whether overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost-effective strategy in post-PCI ACS. METHODS: A systematic literature search of PubMed, EMBASE, EconLit, and PharmGKB was done to identify all the economic evaluations related to genotype-guided therapy compared to the universal use of antiplatelets in ACS patients. Quality of Health Economic Studies tool was used for quality assessment. RESULTS: The search identified 13 articles, where genotype-guided treatment was compared to universal clopidogrel, ticagrelor, and/or prasugrel. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while 5 studies showed that it was dominant. One study specified that genotype-guided with ticagrelor is cost-effective only in both CYP2C19 intermediate and poor metabolizers. Genotype-guided therapy was dominant when compared to universal prasugrel, ticagrelor, or both in 5, 1, and 3 studies, respectively. Only 2 studies reported that universal ticagrelor was cost-effective compared to genotype-guided treatment. All the included articles had good quality. CONCLUSION: Based on current economic evaluations in the literature, implementing CYP2C19 genotype-guided therapy is a cost-effective approach in guiding the selection of medication in patients with ACS undergoing PCI.


Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/economía , Citocromo P-450 CYP2C19/genética , Costos de los Medicamentos , Pruebas de Farmacogenómica/economía , Variantes Farmacogenómicas , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Medicina de Precisión/economía , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Toma de Decisiones Clínicas , Clopidogrel/economía , Clopidogrel/uso terapéutico , Citocromo P-450 CYP2C19/metabolismo , Humanos , Selección de Paciente , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/farmacocinética , Clorhidrato de Prasugrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Valor Predictivo de las Pruebas , Ticagrelor/economía , Ticagrelor/uso terapéutico , Resultado del Tratamiento
13.
Am J Cardiol ; 125(8): 1280-1283, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-32081368

RESUMEN

Intraocular bleeding is a devastating clinical event due to its potentially blinding nature. It is not known if determine if dual antiplatelet therapy using aspirin and potent P2Y12 inhibitors increases this risk. We searched MEDLINE and ClinicalTrials.gov for randomized controlled trials that were phase III, randomly assigned patients to dual antiplatelet therapy with either aspirin and a potent P2Y12 inhibitor or aspirin and clopidogrel, had follow-up of 6 months, and at least 200 patients. Corresponding authors were contacted for intraocular bleeding data. Inverse-variance, weighted, fixed-effects meta-analysis was undertaken, with random-effects meta-analysis performed as a sensitivity analysis. Four trials enrolling 42,850 patients were included. The median follow-up ranged from 12 to 14 months. There was overall low risk of bias. Pooled analysis demonstrated no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (risk ratio 0.89, 95% confidence interval 0.58 to 1.36). There was no significant heterogeneity observed across trials (I2 statistic 0%, p = 0.98). The use of random-effects meta-analysis did not change the effect estimate or confidence intervals, and the results appeared similar when stratified by potent P2Y12 inhibitor (p = 0.97). In conclusion, this collaborative meta-analysis of dual antiplatelet trials does not suggest that the risk of intraocular bleeding is increased with the use of potent P2Y12 inhibitors compared with clopidogrel. Our results suggest that these potent P2Y12 inhibitors may continue to be used cautiously where indicated as part of dual antiplatelet therapy, even in those at high risk of spontaneous intraocular bleeding.


Asunto(s)
Aspirina/uso terapéutico , Hemorragia del Ojo/epidemiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ticagrelor/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Clopidogrel/uso terapéutico , Terapia Antiplaquetaria Doble/métodos , Hemorragia del Ojo/inducido químicamente , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Am J Cardiol ; 125(8): 1142-1147, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-32087994

RESUMEN

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.


Asunto(s)
Síndrome Coronario Agudo/cirugía , Anemia/epidemiología , Enfermedad de la Arteria Coronaria/cirugía , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Hemorragia Posoperatoria/epidemiología , Síndrome Coronario Agudo/epidemiología , Anciano , Anciano de 80 o más Años , Angina Inestable/epidemiología , Angina Inestable/cirugía , Anticoagulantes/uso terapéutico , Antitrombinas/uso terapéutico , Aspirina/uso terapéutico , Causas de Muerte , Clopidogrel/uso terapéutico , Comorbilidad , Enfermedad de la Arteria Coronaria/epidemiología , Stents Liberadores de Fármacos , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/mortalidad , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/mortalidad , Heparina/uso terapéutico , Hirudinas , Humanos , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/mortalidad , Estimación de Kaplan-Meier , Masculino , Infarto del Miocardio/epidemiología , Infarto del Miocardio/cirugía , Fragmentos de Péptidos/uso terapéutico , Cuidados Posoperatorios , Hemorragia Posoperatoria/inducido químicamente , Hemorragia Posoperatoria/mortalidad , Clorhidrato de Prasugrel/uso terapéutico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Medición de Riesgo , Stents , Ticagrelor/uso terapéutico , Enfermedades Urológicas/inducido químicamente , Enfermedades Urológicas/epidemiología , Enfermedades Urológicas/mortalidad
16.
Cardiovasc Drugs Ther ; 34(1): 53-63, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32062795

RESUMEN

PURPOSE: Since ticagrelor inhibits the cellular uptake of adenosine, thereby increasing extracellular adenosine concentration and biological activity, we hypothesized that ticagrelor has adenosine-dependent antiplatelet properties. In the current study, we compared the effects of ticagrelor and prasugrel on platelet activation in acute coronary syndrome (ACS). METHODS: Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to adenosine diphosphate (ADP), the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, the TLR-4 agonist lipopolysaccharide (LPS), the protease-activated receptor (PAR)-1 agonist SFLLRN, and the PAR-4 agonist AYPGKF were measured by flow cytometry in blood from 80 ticagrelor- and 80 prasugrel-treated ACS patients on day 3 after percutaneous coronary intervention. Residual platelet aggregation to arachidonic acid (AA) and ADP were assessed by multiple electrode aggregometry and light transmission aggregometry. RESULTS: ADP-induced platelet activation and aggregation, and AA-induced platelet aggregation were similar in patients on ticagrelor and prasugrel, respectively (all p ≥ 0.3). Further, LPS-induced platelet surface expression of P-selectin and activated GPIIb/IIIa did not differ significantly between ticagrelor- and prasugrel-treated patients (both p > 0.4). In contrast, Pam3CSK4-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly lower in ticagrelor-treated patients (both p ≤ 0.005). Moreover, SFLLRN-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly less pronounced in patients on ticagrelor therapy compared to prasugrel-treated patients (both p < 0.03). Finally, PAR-4 mediated platelet activation as assessed by platelet surface expression of activated GPIIb/IIIa following stimulation with AYPGKF was significantly lower in patients receiving ticagrelor (p = 0.02). CONCLUSION: Ticagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACS patients more strongly than prasugrel.


Asunto(s)
Síndrome Coronario Agudo/terapia , Plaquetas/efectos de los fármacos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Receptores Proteinasa-Activados/metabolismo , Ticagrelor/uso terapéutico , Receptores Toll-Like/metabolismo , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Anciano , Plaquetas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selectina-P/metabolismo , Intervención Coronaria Percutánea/efectos adversos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Transducción de Señal , Resultado del Tratamiento
17.
Xenobiotica ; 50(8): 929-938, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32065000

RESUMEN

We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after a loading dose of 60 mg prasugrel or 180 mg ticagrelor in patients with ST-elevation myocardial infarction (STEMI). Further, we assessed the contribution of CYP2C19 polymorphisms and medication to the CYP enzymatic activity.Patients with STEMI were randomly assigned to the treatment with prasugrel (n = 51) or ticagrelor (n = 46). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotyped for CYP2C19 *2 and *17 alleles.In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose positively correlated with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002), a marker of CYP2C19 metabolic activity, and negatively with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = -0.35, p = 0.018).CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio, but without any effect on the ADP-induced platelet reactivity. The treatment with amiodarone, a CYP3A4 inhibitor, influenced neither the metabolic ratios nor the ADP-induced platelet reactivity.The CYP3A4 and CYP2C19 metabolic activity is associated with ADP-induced platelet reactivity in prasugrel-treated, but not ticagrelor-treated patients with STEMI.


Asunto(s)
Citocromo P-450 CYP2C19/metabolismo , Citocromo P-450 CYP3A/metabolismo , Clorhidrato de Prasugrel/farmacología , Ticagrelor/farmacología , Adenosina Difosfato/metabolismo , Femenino , Humanos , Masculino , Clorhidrato de Prasugrel/uso terapéutico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Ticagrelor/uso terapéutico
18.
Life Sci ; 247: 117429, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32061670

RESUMEN

AIMS: Hypercholesterolemia is a hazard for increasing susceptibility of the heart to myocardial infarction (MI) by inducing platelet hyperaggregability. Clopidogrel and prasugrel have documented cardioprotective effects in clinical studies. Herein, we investigated whether clopidogrel and prasugrel could protect against isoproterenol-induced acute MI (A-MI) under hypercholesterolemic conditions in rats. MAIN METHODS: Dietary hypercholesterolemic rats were subjected to acute doses of isoproterenol. Serum lipids, inflammatory markers, aortic endothelin1 and endothelial nitric oxide synthase (eNOS) mRNAs expression and immunexpression of BCL2 were determined. KEY FINDINGS: Hypercholesterolemic rats showed infiltration of inflammatory cells and reduction in aortic wall thickness, deposition of fibrous tissue between cardiac muscle fibers. Protective doses of prasugrel or clopidogrel for 28 days before A-MI increased survival, amended the ECG parameters -including ST segment elevation- and improved the histopathological picture in hypercholesterolemic rats. This was coupled with reductions in platelet aggregation, creatine kinase-MB activity, endothelin 1, systemic inflammation and cardiac lipid peroxidation and increment in aortic eNOS expression. Clopidogrel and prasugrel groups showed enhanced BCL2 expression in cardiac fibers and aortic wall. SIGNIFICANCE: Prasugrel and clopidogrel protected against A-MI via anti-aggregatory and anti-inflammatory effects. These results add to the value of these drugs in correcting cardiovascular dysfunction in patients vulnerable to A-MI after confirmation by appropriate human studies.


Asunto(s)
Clopidogrel/uso terapéutico , Hipercolesterolemia/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Animales , Sistema Cardiovascular/efectos de los fármacos , Forma MB de la Creatina-Quinasa/metabolismo , Endotelina-1/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Modelos Animales , Mortalidad , Óxido Nítrico Sintasa de Tipo III/metabolismo , Agregación Plaquetaria/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Resultado del Tratamiento
19.
Cardiovasc Interv Ther ; 35(2): 117-129, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31970683

RESUMEN

Antiplatelet therapy, the cornerstone of post coronary stenting antithrombotic therapy, reduces the rate of hard clinical endpoints in patients treated both conservatively and invasively following an acute coronary syndrome, as well as in those patients with chronic stable coronary disease who receive a coronary stent. The development of newer antiplatelet and direct anticoagulant agents provides new options in the antithrombotic management of patients with coronary artery disease, enabling different therapeutic combinations to be tailored to an individual patient's bleeding and ischemic risk profile. In this review, we will summarize the history of dual antiplatelet therapy, discuss the latest evidence and future perspectives in treating patients with coronary artery disease.


Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Terapia Antiplaquetaria Doble , Síndrome Coronario Agudo/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Clopidogrel/uso terapéutico , Stents Liberadores de Fármacos , Cardiopatías/tratamiento farmacológico , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y , Medición de Riesgo , Ticagrelor/uso terapéutico
20.
Cardiovasc Diabetol ; 19(1): 3, 2020 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-31910903

RESUMEN

BACKGROUND: Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM. MATERIALS AND METHODS: 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions. RESULTS: Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20µmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 µmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 µg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083). CONCLUSIONS: Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.


Asunto(s)
Aspirina/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Clopidogrel/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Clorhidrato de Prasugrel/uso terapéutico , Trombosis/prevención & control , Anciano , Aspirina/efectos adversos , Biomarcadores/sangre , Clopidogrel/efectos adversos , Estudios Cruzados , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Método Doble Ciego , Femenino , Fibrina/metabolismo , Humanos , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Selectina-P/sangre , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Prevención Primaria , Prevención Secundaria , Trombosis/sangre , Trombosis/diagnóstico , Factores de Tiempo , Resultado del Tratamiento
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