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1.
Ther Adv Cardiovasc Dis ; 13: 1753944719893274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31823688

RESUMO

Oral antiplatelet drugs are crucially important for patients with acute coronary syndrome or stable coronary artery disease undergoing percutaneous coronary intervention (PCI). In recent decades, several clinical trials have focused on reducing periprocedural ischemic events in patients undergoing PCI by means of more rapid platelet inhibition with the use of intravenous antiplatelet drugs. Glycoprotein IIb/IIIa receptor inhibitors (GPIs) block the final common pathway of platelet aggregation and enable potent inhibition in the peri-PCI period. In recent years, however, the use of GPIs has decreased due to bleeding concerns and the availability of more potent oral P2Y12 inhibitors. Cangrelor is an intravenous P2Y12 receptor antagonist. In a large-scale regulatory trial, cangrelor administration during PCI allowed for rapid, potent and rapidly reversible inhibition of platelet aggregation, with an anti-ischemic benefit and no increase in major bleeding. This article aims to provide an overview of general pharmacology, supporting evidence and current status of intravenous antiplatelet therapies (GPIs and cangrelor), with a focus on contemporary indications for their clinical use.


Assuntos
Síndrome Coronariana Aguda/terapia , Monofosfato de Adenosina/análogos & derivados , Plaquetas/efeitos dos fármacos , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Administração Intravenosa , Animais , Plaquetas/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
2.
Tex Heart Inst J ; 46(3): 203-206, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31708704

RESUMO

The platelet aggregation inhibitor ticagrelor, a P2Y12 receptor antagonist, is widely used after angioplasty in patients with acute coronary syndrome. Clinical trial data have shown that it is well tolerated by most patients. We present the case of a 62-year-old woman whose ticagrelor-related asymptomatic and persistent sinus pauses after angioplasty resolved when ticagrelor was replaced with prasugrel.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Angioplastia Coronária com Balão/métodos , Parada Cardíaca/induzido quimicamente , Complicações Pós-Operatórias , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/tratamento farmacológico , Eletrocardiografia , Feminino , Parada Cardíaca/diagnóstico , Humanos , Pessoa de Meia-Idade , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos
3.
Expert Opin Drug Saf ; 18(12): 1119-1125, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31580164

RESUMO

Introduction: The non-vitamin K antagonist oral anticoagulants (NOACs) are changing the landscape for stroke prevention in atrial fibrillation (AF) and prevention or treatment of venous thromboembolism (VTE). In patients with AF and concomitant acute coronary syndrome (ACS), the treatment regimen of combined NOACs and P2Y12 inhibitors is gaining popularity.Areas covered: We conducted a review of safety evaluation and effectiveness of apixaban for AF and ACS treatment, both alone and in combination with different antiplatelet treatment regimens. The aim was to provide an overview of apixaban including mechanism of action, indications, adverse events and tolerability.Expert opinion: Apixaban is recommended as a safe, well tolerated and effective oral anticoagulant for reducing the risk of ischemic events among AF patients. It is of value in prevention and treatment of VTE and pulmonary embolism. Comparing to VKA, apixaban was superior in preventing stroke or systemic embolism with lower major bleeding events among AF patients. When combined with dual antiplatelet therapy apixaban may cause dose-related increase in bleeding which reduces the benefit of this treatment regimen among ACS patients but without AF. In those with ACS and concomitant AF, the combination of apixaban with P2Y12 inhibitor appears to be safe and effective.


Assuntos
Inibidores do Fator Xa/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Síndrome Coronariana Aguda/tratamento farmacológico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Humanos , Intervenção Coronária Percutânea/métodos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
4.
N Engl J Med ; 381(17): 1621-1631, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31479209

RESUMO

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).


Assuntos
Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Citocromo P-450 CYP2C19/genética , Genótipo , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Medicina de Precisão , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Método Simples-Cego , Stents , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico
5.
N Engl J Med ; 381(16): 1524-1534, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31475799

RESUMO

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Trombose Coronária/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Stents , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos
6.
Blood Coagul Fibrinolysis ; 30(6): 263-269, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31259779

RESUMO

: High on-treatment platelet reactivity (HPR) on P2Y12-inhibitors in patients treated with dual antiplatelet therapy is strongly associated with adverse ischaemic events. Studies have shown conflicting results with regard to the correlation and agreement between the different tests. Several assays are available to establish HPR. A composite advice based on more than one test might be a better way to identify HPR patients. To compare HPR rates and agreement between individual platelet function tests and a panel of three tests In our large percutaneous coronary intervention centre, all patients who suffered a stent thrombosis were invited back to a dedicated clinic. Platelet function testing was performed in all patients and matched control patients. HPR rates were compared between individual tests and with a composite comprised of three tests. A total of 242 patients were included, of whom in 193 patients all tests were available. HPR rates ranged from 14.6% [VerifyNow cut-off >235 platelet reactivity units (PRU)] to 49.7% (Vasodilator-Stimulated Phosphoprotein Assay). HPR according to the composite advice (≥2 out of 3 tests indicating HPR) was present in 29.8% of patients. The best correlation with the composite advice was observed with light transmittance aggregometry (kappa = 0.78) and VerifyNow (lower cut-off >208 PRU; kappa = 0.68). VerifyNow with cut-off more than 235 PRU identified the smallest proportion of patients with HPR, whereas Vasodilator-Stimulated Phosphoprotein Assay seemed to 'over-identify' HPR. In this real life patient cohort, a large variability was observed between four different platelet function tests. The use of a composite advice based on three tests is a promising alternative.


Assuntos
Testes de Função Plaquetária/normas , Padrões de Prática Médica , Humanos , Isquemia/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Testes de Função Plaquetária/métodos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Reprodutibilidade dos Testes , Stents/efeitos adversos , Trombose/etiologia
7.
JAMA ; 321(24): 2428-2437, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237645

RESUMO

Importance: Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited. Objective: To determine whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI. Design, Setting, and Participants: The SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018. Interventions: Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498). Main Outcomes and Measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%. Results: Among 2993 patients who were randomized (mean age, 64 years; 795 women [26.6%]), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% [1-sided 95% CI, -∞% to 1.3%]; P = .007 for noninferiority). There were no significant differences in all-cause death (21 [1.4%] vs 18 [1.2%]; hazard ratio [HR], 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 [0.8%] vs 17 [1.2%]; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 [0.8%] vs 5 [0.3%]; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02). Conclusions and Relevance: Among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02079194.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Stents Farmacológicos , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos
8.
Eur J Clin Pharmacol ; 75(9): 1201-1210, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31197411

RESUMO

PURPOSE: The POPular Risk Score was developed for the selective intensification of P2Y12 inhibitor treatment with prasugrel instead of clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI) with stent implantation. This score is based on platelet reactivity (VerifyNow P2Y12 assay), CYP2C19 genotyping, and clinical risk factors. Our aim was to determine if the use of this score in clinical practice is associated with a reduction in thrombotic events without increasing bleeding events. METHODS: In a single-center prospective cohort study, patients with a high risk score were treated with prasugrel and patients with a low risk score with clopidogrel. The risk score-guided cohort was compared with a historic cohort of clopidogrel-treated patients. The endpoint consisted of all-cause death, myocardial infarction, stroke, or stent thrombosis during 1 year of follow-up. TIMI major and minor bleeding events were also analyzed. RESULTS: The guided cohort contained 1127 patients, 26.9% of whom were switched to prasugrel according to the POPular Risk Score. The historic cohort contained 893 patients. The incidence of the combined thrombotic endpoint was significantly lower in the guided cohort as compared with the historic cohort (8.4% versus 3.7%, p < 0.001). This strategy was safe with respect to bleeding (4.0% versus 1.3%, p < 0.001, for TIMI major or minor bleeding). Results were comparable after multivariate and propensity score matched and weighted analysis. CONCLUSION: Selective intensification of P2Y12 inhibitor treatment after non-urgent PCI based on the POPular Risk Score is associated with a reduction in thrombotic events without an increase in bleeding events.


Assuntos
Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Clopidogrel/efeitos adversos , Citocromo P-450 CYP2C19/metabolismo , Feminino , Genótipo , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Testes de Função Plaquetária , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Risco , Acidente Vascular Cerebral/prevenção & controle , Trombose/prevenção & controle
9.
Vascul Pharmacol ; 116: 4-7, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30876967

RESUMO

The pharmacological and clinical differences of the three recommended oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) enable physicians to switch from one agent to another that it is considered more appropriate in the specific clinical setting. Moreover, the recent availability of cangrelor, the only intravenous P2Y12 inhibitor with a rapid onset and offset of its antiplatelet action, makes it necessary to switch from this agent to an oral P2Y12 inhibitor for a continued platelet inhibition after percutaneous coronary intervention. Several pharmacodynamic studies have provided information on how to change drug, in terms of timing and dosage, without running the risk of a temporary impairment of platelet inhibition. In addition, several studies have assessed the impact of the switching between P2Y12 inhibitors on clinical outcomes. Overall, these evidences have prompted the development of an extensive expert consensus document, have set the basis for recent practice guidelines recommendations, and have stimulated several systematic overviews. The present article provides a brief and schematic summary on the topic of switching between P2Y12 inhibitors, focusing on three main practical issues: why and how to switch therapies and what are the clinical consequences of such strategy.


Assuntos
Plaquetas/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Substituição de Medicamentos , Inibidores da Agregação de Plaquetas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Administração Intravenosa , Administração Oral , Plaquetas/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Tomada de Decisão Clínica , Clopidogrel/administração & dosagem , Substituição de Medicamentos/efeitos adversos , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Receptores Purinérgicos P2Y12/sangue , Ticagrelor/administração & dosagem , Resultado do Tratamento
10.
Intern Med J ; 49 Suppl 1: 5-8, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30815979

RESUMO

BACKGROUND: Recently, new evidence from large scale trials and updated guidelines have emerged on the risks and benefits of extended dual antiplatelet therapy (DAPT) for patients with acute coronary syndrome (ACS). AIMS: To discuss, clarify and advise on the application of the evidences and guidelines on individual patient selection for extended DAPT, with regard to balancing risk factors, particularly in Asian populations. METHODS: A total of 14 local cardiologists from Hong Kong with extensive experience in cardiology and cardiac interventions convened in a series of 3 advisory board meetings from October 2016 to September 2017, which included reviews of new evidence in the literature and discussions of the latest clinical trends, using an anonymous, electronic voting system for arriving at consensuses. RESULTS: Recommendations were produced for the following nine risk factors: old age (>65), chronic kidney disease (CKD), diabetes mellitus (DM), recurrent myocardial infarction (MI), multi-vessel disease (MVD), multiple stents, bioresorbable vascular scaffold (BVS) stent, left main stenting and peripheral artery disease (PAD). Strong ischaemic risk factors include DM, recurrent MI, MVD and/or >3 stents; less-strong ischaemic factors include CKD, left main stenting, BVS stent and PAD. Old age can be an unclear risk factor due to variations in physical fitness even among patients of identical age. DISCUSSION: The strengths and limitations of the results were acknowledged. CONCLUSION: ACS patients with ischaemic risk factors could be considered for extended DAPT beyond 12 months, while balancing the risk of bleeding.


Assuntos
Síndrome Coronariana Aguda/terapia , Stents Farmacológicos/efeitos adversos , Inibidores da Agregação de Plaquetas/administração & dosagem , Guias de Prática Clínica como Assunto , Síndrome Coronariana Aguda/diagnóstico , Comitês Consultivos , Esquema de Medicação , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Hong Kong , Humanos , Infarto do Miocárdio/etiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Fatores de Risco , Trombose/etiologia , Trombose/prevenção & controle
11.
Ann Thorac Surg ; 107(6): 1690-1698, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30898561

RESUMO

BACKGROUND: We evaluated perioperative bleeding after coronary artery bypass grafting (CABG) in patients preoperatively treated with ticagrelor or clopidogrel, stratified by discontinuation of these P2Y12 inhibitors. METHODS: All patients from the prospective, European Multicenter Registry on Coronary Artery Bypass Grafting (E-CABG) treated with ticagrelor or clopidogrel undergoing isolated primary CABG were eligible. The primary outcome measure was severe or massive bleeding defined according to the Universal Definition of Perioperative Bleeding, stratified by P2Y12 inhibitor discontinuation. Secondary outcome measures included four additional definitions of major bleeding. Propensity score matching was performed to adjust for differences in preoperative and perioperative covariates. RESULTS: Of 2,311 patients who were included, 1,293 (55.9%) received clopidogrel and 1,018 (44.1%) ticagrelor preoperatively. Mean time between discontinuation and the operation was 4.5 ± 3.2 days for clopidogrel and 4.9 ± 3.0 days for ticagrelor. In the propensity score-matched cohort, ticagrelor-treated patients had a higher incidence of major bleeding according to Universal Definition of Perioperative Bleeding when ticagrelor was discontinued 0 to 2 days compared with 3 days before the operation (16.0% vs 2.7%, p = 0.003). Clopidogrel-treated patients had a higher incidence of major bleeding according to the Universal Definition of Perioperative Bleeding when clopidogrel was discontinued 0 to 3 days compared with 4 to 5 days before the operation (15.6% vs 8.3%, p = 0.031). CONCLUSIONS: In patients receiving ticagrelor 2 days before CABG and in those receiving clopidogrel 3 days before CABG, there was an increased rate of severe bleeding. Postponing nonemergent CABG for at least 3 days after discontinuation of ticagrelor and 4 days after clopidogrel should be considered.


Assuntos
Clopidogrel/efeitos adversos , Ponte de Artéria Coronária , Inibidores da Agregação de Plaquetas/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Idoso , Clopidogrel/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Hemorragia Pós-Operatória/epidemiologia , Período Pré-Operatório , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticagrelor/administração & dosagem
12.
Minerva Cardioangiol ; 67(2): 94-101, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30895761

RESUMO

BACKGROUND: The optimal management of patients with aspirin intolerance undergoing stent implantation represents a challenge for physicians. The aim of this study was to assess the overall number of patients discharged with mono antiplatelet therapy after percutaneous coronary intervention (PCI). The most frequent aspirin intolerance symptoms in this population and the overall incidence of patient-oriented composite endpoints (POCE). METHODS: From January 2006 to June 2016 all patients discharged with mono-antiplatelet therapy because of aspirin intolerance/hypersensitivity/allergy and treated by means of PCI were included. Data about percutaneous treatments and aspirin intolerance were collected. POCE were evaluated at a twelve-month clinical follow-up comparing safety and efficacy of clopidogrel monotherapy versus new P2Y12 inhibitors. RESULTS: We collected 70 patients, that is 0.3% of the total amount of PCI in the considered period, 25 (35%) of them were women and the remaining 45 (65%) were men. An acute coronary syndrome (ACS) was the clinical presentation in 47 (67.1%) patients, with NSTEMI in 19 (27.1%) of them. Forty-six patients (65.7%) were treated with clopidogrel and 24 (34.3%) with new P2Y12 inhibitors. At one-year follow-up, 18 (25.7%) patients suffered a new clinically relevant adverse event, 5 (7.1%) died, 3 (4.3%) required a target vessel revascularization and 10 (14.3%) patients a target lesion revascularization. CONCLUSIONS: Our study evaluated patients with ACS or stable coronary artery disease undergoing PCI and treated with mono-antiplatelet therapy with P2Y12 inhibitors due to aspirin intolerance shows a 25% incidence of POCE at one year. Further studies with adequate sample size are required to evaluate the efficacy and safety of mono antiplatelet therapy in this clinical scenario.


Assuntos
Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Stents , Resultado do Tratamento
13.
Scand Cardiovasc J ; 53(2): 55-61, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30909763

RESUMO

BACKGROUND: The efficacy of clopidogrel is often attenuated in the setting of renal impairment. High on-treatment platelet reactivity (HPR) is an independent correlate of adverse event. Here we performed a quantitative evaluation of the prevalence and impact of HPR in patients with chronic kidney disease (CKD). METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 March 2018 for cohort studies assessing the risk ratio (RR) of prevalence of HPR in CKD versus non-CKD patients and association of cardiovascular outcome with HPR in CKD patients treated with clopidogrel. Outcome measures included major adverse cardiac event, myocardial infarction and stent thrombosis. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. RESULTS: Ten studies comprising a total of 3028 CKD patients and 11138 non-CKD patients were included in the evaluation. Compared to patients with normal renal function, patients with CKD had a significantly higher risk of HPR (OR: 1.34, 95% CI: 1.23-1.46). In CKD patients, HPR was associated with increased risk of MACE (RR 2.99, 95% CI 1.19 to 7.53; p < 0.00001), myocardial infarction (RR1.74, 95% CI 1.29 to 2.33; p = 0.0002), and stent thrombosis (RR 2.98, 95% CI 1.42 to 6.26; p = 0.004). CONCLUSIONS: Based on pooled analysis, CKD appeared correlated with HPR and this association had prognostic significance. Further studies with standardised laboratory methods and specifically defined protocols are required to validate the clinical relevance of such response variability to clopidogrel in CKD patients.


Assuntos
Plaquetas/efeitos dos fármacos , Clopidogrel/uso terapêutico , Doença das Coronárias/terapia , Rim/fisiopatologia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Insuficiência Renal Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Plaquetas/metabolismo , Clopidogrel/efeitos adversos , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Stents , Resultado do Tratamento
14.
Cardiovasc Drugs Ther ; 33(2): 129-137, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30783954

RESUMO

PURPOSE: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. METHODS: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. RESULTS: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. CONCLUSIONS: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. CLINICAL TRIAL REGISTRATION: NCT02101437.


Assuntos
Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Doença da Artéria Coronariana/terapia , Resistência a Medicamentos , MicroRNAs/sangue , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Aspirina/efeitos adversos , Plaquetas/metabolismo , Cilostazol/uso terapêutico , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/genética , Resistência a Medicamentos/genética , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Método Simples-Cego , Stents , Taiwan , Ticagrelor/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
15.
Int J Clin Pharmacol Ther ; 57(4): 175-181, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30738497

RESUMO

INTRODUCTION: P2Y12 inhibitors show different bleeding-related safety profiles in premarketing trials. However, little is known about their potential safety from spontaneous reporting systems and postmarketing data. OBJECTIVE: To describe and evaluate the bleeding-related adverse events associated with use of P2Y12 inhibitors utilizing data from the FDA Adverse Event Reporting System (FAERS) database. MATERIALS AND METHODS: We identified adverse events reports listing clopidogrel, prasugrel, or ticagrelor as the primary suspected agent in the FAERS database from the 1st quarter of 2014 to the 4th quarter of 2016. Using MedDRA version 20.0, we identified search terms for bleeding-related adverse events, within which we filtered for gastrointestinal bleeding and intracranial bleeding. RESULTS: We identified 2,252, 2,450, and 549 adverse event reports attributed to clopidogrel, ticagrelor, and prasugrel use, respectively. Prasugrel had the highest proportional reporting ratio (PRR) (4.63; 95% confidence intervals (CI): 4.21 - 5.10) and reporting odds ratio (ROR) (7.46, 95% CI: 6.30 - 8.83) for bleeding followed by clopidogrel (PRR: 4.56; 95% CI: 4.34 - 4.78; ROR: 7.21; 95% CI: 6.63 - 7.84) and ticagrelor (PRR: 2.79; 95%CI: 2.61 - 2.98; ROR: 3.42; 95% CI: 3.12 - 3.74). Within intracranial bleeding events, both ticagrelor and prasugrel had a similarly higher incidence of fatal events than clopidogrel. Meanwhile, the incidence of gastrointestinal bleeding events leading to hospitalization was highest with clopidogrel. CONCLUSION: Reports on bleeding differed among P2Y12 inhibitors with respect to type and outcome. Although FAERS is subject to significant limitations, our results show that the safety profiles of P2Y12 inhibitors in the spontaneous reporting system did not differ from the results of premarketing studies.
.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticlopidina/efeitos adversos , Humanos , Estados Unidos , United States Food and Drug Administration
16.
J Am Heart Assoc ; 8(2): e010956, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30636561

RESUMO

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3 days), subacute (4-30 days), and late (31-365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( Padj<0.001) without a difference in ADBRs ( Padj=0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( Padj<0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( Padj<0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Infarto do Miocárdio/etiologia , Cloridrato de Prasugrel/efeitos adversos , Síndrome Coronariana Aguda/cirurgia , Idoso , Clopidogrel/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Hemorragia/epidemiologia , Humanos , Incidência , Itália/epidemiologia , Masculino , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/administração & dosagem , Prognóstico , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Método Simples-Cego , Taxa de Sobrevida/tendências , Fatores de Tempo
17.
Eur Heart J Cardiovasc Pharmacother ; 5(2): 100-104, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30657876

RESUMO

Antiplatelet therapy is a mainstay of cardiovascular therapy and is well established in clinical routine. Recently, the potential risk of solid cancers with P2Y12 inhibitor therapy has been an issue of growing interest. The alleged association primarily originated from the findings of an US Food and Drug Administration (FDA) review of the randomized controlled TRITON-TIMI 38 trial and the following results of the DAPT trial. The higher risk of cancer was predominately observed with the newer, more potent P2Y12 inhibitors and in the setting of prolonged dual antiplatelet therapy (DAPT). Current European Society of Cardiology (ESC) Guidelines suggest consideration of prolonged DAPT beyond the recommended duration of 6 months in stable coronary artery disease and 12 months in acute coronary syndrome if ischaemic risk prevails over the risk of bleeding. Several trials, studies and meta-analyses have addressed the potential interplay of cancer and P2Y12 inhibition since then. The effect of P2Y12 inhibition on cancer has been investigated extensively in basic research as well. In this review, we summarize current available evidence of cancer risk with P2Y12 inhibitor therapy and discuss the resulting clinical implications.


Assuntos
Neoplasias/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Animais , Esquema de Medicação , Quimioterapia Combinada , Humanos , Incidência , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo
18.
J Surg Res ; 236: 224-229, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30694760

RESUMO

BACKGROUND: A significant portion of patients sustaining traumatic brain injury (TBI) are on antiplatelet medications. The reversal of P2Y12 agents after intracranial hemorrhage (ICH) remains unclear. The aim of our study is to evaluate outcomes after TBI in patients who are on preinjury P2Y12 inhibitors and received a platelet transfusion. METHODS: We analyzed our prospectively maintained TBI database from 2013 to 2016 and included all patients with isolated ICH who were on P2Y12 inhibitors (Clopidogrel, Prasugrel, Ticagrelor). Regression analysis was performed adjusting for demographics and injury parameters. Outcome measures included progression of ICH, adverse discharge disposition (skilled nursing facility), and mortality. RESULTS: A total 243 patients with ICH on preinjury P2Y12 inhibitor met our inclusion criteria and were analyzed. Mean age was 55 ± 18 y, 58% were males and 60% were white and median injury severity score was 13 [9-18]. 73.6% received platelet transfusion after admission. The median packs of platelet transfusion were 1 [1-2] units. After controlling for confounders, patients who received platelet transfusion had a lower rate of progression (OR: 0.68, P = 0.01) and decreased rate of neurosurgical intervention (OR: 0.80, P = 0.03). Overall mortality was 12.3%. Patients on P2Y12 inhibitors who received platelet transfusion had lower odds of discharge to a skilled nursing facility (OR: 0.75, P = 0.02) and mortality (OR: 0.85, P = 0.04). CONCLUSIONS: Platelet transfusion after isolated traumatic ICH in patients on P2Y12 inhibitors is associated with improved outcomes. Platelet transfusion was associated with decreased risk of progression of ICH, neurosurgical intervention, and mortality. Further randomized studies to validate the use of platelet transfusion and define the optimal dose in patients on P2Y12 inhibitors are warranted.


Assuntos
Lesões Encefálicas Traumáticas/terapia , Hemorragia Intracraniana Traumática/terapia , Inibidores da Agregação de Plaquetas/efeitos adversos , Transfusão de Plaquetas , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Idoso , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Progressão da Doença , Feminino , Humanos , Escala de Gravidade do Ferimento , Hemorragia Intracraniana Traumática/etiologia , Hemorragia Intracraniana Traumática/mortalidade , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Estudos Prospectivos , Estudos Retrospectivos , Instituições de Cuidados Especializados de Enfermagem/estatística & dados numéricos , Análise de Sobrevida , Resultado do Tratamento
19.
Vascul Pharmacol ; 115: 1-12, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30685502

RESUMO

Platelet P2Y12 receptors play a key role in platelet activation and thrombus formation. Accordingly, P2Y12 receptor antagonists are the cornerstone of secondary prevention of atherothrombotic events in patients undergoing percutaneous coronary intervention (PCI). The availability of different oral P2Y12 antagonists (clopidogrel, prasugrel, ticagrelor) along with the introduction of the first intravenous P2Y12 antagonist cangrelor offer an opportunity to individualize antiplatelet therapy according to the changing clinical setting. The recent International Expert Consensus provided the first recommendations on switching between the P2Y12 antagonists. While the consensus greatly helps to guide switching between P2Y12 antagonists, a number of controversial clinical scenarios remain where the evidence regarding the optimal switch strategy is scarce. In such clinical scenarios, understanding of the (i) pharmacological properties of P2Y12 antagonists, (ii) recent evidence from pharmacodynamics studies, clinical trials and registries, and (iii) factors affecting the efficacy and safety of the P2Y12 antagonists, all summarized below, are crucial to choose the optimal switch strategy.


Assuntos
Doença das Coronárias/terapia , Substituição de Medicamentos , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Animais , Tomada de Decisão Clínica , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Técnicas de Apoio para a Decisão , Árvores de Decisões , Esquema de Medicação , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/farmacocinética , Guias de Prática Clínica como Assunto , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Fatores de Risco , Resultado do Tratamento
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