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1.
Cardiovasc Ther ; 2021: 8836450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33519970

RESUMO

Background: Thrombocytopenia was intuitively considered to be associated with higher risk of bleeding and multiple comorbidities after percutaneous coronary intervention (PCI). However, controversial results exist, and the real-world clinical impact of thrombocytopenia in patients undergoing PCI is largely unknown. The aim of this study was to evaluate the influence of baseline thrombocytopenia on the prognosis of patients undergoing PCI. Methods: Using the West China Hospital Inpatient Sample database, patients who underwent PCI were identified from August 2012 to January 2019. Baseline thrombocytopenia was defined as a preprocedural platelet count of 100 × 109/L or less obtained from a routine blood sample taken within 48 hours before coronary PCI. The clinical effect of the advanced thrombocytopenia group (≤85 × 109/L), according to the median value of platelet count in the thrombocytopenia cohort, was further assessed. The primary outcome was a composite of in-hospital death, bleeding events, and post-PCI transfusion. Results: Of 9531 patients enrolled in our study, 936 had baseline thrombocytopenia and 8595 patients did not have. There were no significant differences in the primary outcome between the two groups. However, advanced thrombocytopenia was independently associated with higher risk of primary outcome (OR 1.67, 95% CI 1.06 to 2.65, p = 0.029). Acute coronary syndrome (ACS) patients with thrombocytopenia were associated with higher odds of major bleeding (BARC ≥ 2) (OR 2.56, 95% CI 1.24 to 5.44, p = 0.011). Compared with the nonthrombocytopenia group, the thrombocytopenia group with ticagrelor use had higher odds of major bleeding (OR 9.7, 95% CI 1.57 to 60.4 versus OR 0.22, 95% CI 0.03 to 1.69, interaction p = 0.025). Conclusions: It seems feasible for patients with thrombocytopenia to receive PCI, but close attention should be paid to advanced thrombocytopenia, the risk of postprocedure bleeding in ACS patients, and the use of more potent P2Y12 inhibitor.


Assuntos
Síndrome Coronariana Aguda/terapia , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea , Trombocitopenia/complicações , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , China , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Bases de Dados Factuais , Feminino , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombocitopenia/diagnóstico , Trombocitopenia/mortalidade , Fatores de Tempo , Resultado do Tratamento
2.
J Stroke Cerebrovasc Dis ; 30(3): 105547, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33360254

RESUMO

OBJECTIVES: The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants. RESULTS: In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited. CONCLUSIONS: We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.


Assuntos
Plaquetas/efeitos dos fármacos , Clopidogrel/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Oligopeptídeos/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Difosfato de Adenosina/farmacologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/metabolismo , Estudos de Casos e Controles , Clopidogrel/efeitos adversos , Feminino , Humanos , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/diagnóstico , /diagnóstico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Resultado do Tratamento
3.
JAMA ; 324(16): 1640-1650, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107944

RESUMO

Importance: Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention. Objective: To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice. Design, Setting, and Participants: A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019. Exposures: Ticagrelor vs clopidogrel. Main Outcomes and Measures: The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis. Results: After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group. Conclusions and Relevance: Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Clopidogrel/efeitos adversos , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Aspirina/administração & dosagem , Estudos de Casos e Controles , Causas de Morte , Clopidogrel/administração & dosagem , Bases de Dados Factuais/estatística & dados numéricos , Dispneia/induzido quimicamente , Feminino , Hemorragia/induzido quimicamente , Humanos , Isquemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Metanálise em Rede , Pontuação de Propensão , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Recidiva , República da Coreia , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Ticagrelor/administração & dosagem , Estados Unidos
4.
JAMA ; 324(8): 761-771, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32840598

RESUMO

Importance: After percutaneous coronary intervention (PCI), patients with CYP2C19*2 or *3 loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown. Objective: To determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers after PCI. Design, Setting, and Participants: Open-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019. Interventions: Patients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping. CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months. Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients with CYP2C19 LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50. Results: Among 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 with CYP2C19 LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903 CYP2C19 LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02]; P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding in CYP2C19 LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51]; P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07]; P = .16). Conclusions and Relevance: Among CYP2C19 LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT01742117.


Assuntos
Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/genética , Inibidores do Citocromo P-450 CYP2C19/uso terapêutico , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea/efeitos adversos , Medicina de Precisão , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/cirurgia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/terapia , Inibidores do Citocromo P-450 CYP2C19/efeitos adversos , Feminino , Genótipo , Técnicas de Genotipagem , Hemorragia/induzido quimicamente , Heterozigoto , Humanos , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos
5.
Cardiovasc Drugs Ther ; 34(5): 677-684, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32572652

RESUMO

PURPOSE: To compare the effect of ticagrelor with clopidogrel in reducing the risk of ischemic cardiovascular events in patients with late or very late stent thrombosis (LST/VLST) after primary percutaneous coronary intervention (PCI). METHODS: A total of 4538 patients with acute coronary syndrome were screened for angiographically determined LST/VLST. Two hundred and forty-one patients were included in the analysis and grouped according to ticagrelor (n = 81) or clopidogrel (n = 160) at discharge. The clinical outcome was major adverse cardiovascular events (MACE) defined as death, myocardial infarction (MI), ischemic stroke, and revascularization during the 1-yr follow-up period. RESULTS: After propensity score matching, 65 pairs were generated. The incidence of MACE was significantly lower in the ticagrelor group compared with the clopidogrel group (9.3% vs. 21.5%, log-rank p = 0.048). However, no difference was observed in event rates of death, MI, ischemic stroke, and revascularization between the ticagrelor group and the clopidogrel group. CONCLUSION: Following successful primary PCI, patients with LST/VLST who received ticagrelor had fewer ischemic cardiovascular events at 1-yr follow-up, compared with those who received clopidogrel.


Assuntos
Síndrome Coronariana Aguda/terapia , Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Stents , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Clopidogrel/efeitos adversos , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
6.
Circ Cardiovasc Interv ; 13(6): e008649, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32527192

RESUMO

BACKGROUND: Even among biomarker-negative patients undergoing elective percutaneous coronary intervention (PCI), periprocedural thrombotic and bleeding complications can lead to increased morbidity and mortality. Whether stronger platelet inhibition by an intensified oral loading strategy (ILS) before PCI impacts on outcomes among these patients in contemporary practice remains unclear. METHODS: This multicenter, randomized, assessor-blinded trial tested the hypothesis that in elective PCI prasugrel 60 mg (ILS) is superior to standard loading strategy with clopidogrel 600 mg regarding a composite primary end point of all-cause death, any myocardial infarction, definite/probable stent thrombosis, stroke, or urgent vessel revascularization. After PCI, all patients were on clopidogrel 75 mg/day and aspirin. The trial was terminated prematurely because of slower-than-expected recruitment and funding discontinuation. RESULTS: Of 781 patients included in the final analysis, 382 were assigned to ILS and 399 to standard loading strategy. At 30 days, the primary end point occurred in 66 patients (17.3%) assigned to ILS and 74 patients (18.6%) assigned to standard loading strategy (odds ratio, 0.92 [95% CI, 0.63-1.32]; P=0.64). Any myocardial infarction and Bleeding Academic Research Consortium ≥2 bleeding rates were similar among ILS and standard loading strategy groups 16.2% versus 17.5%, odds ratio, 0.91 (95% CI, 0.62-1.32), P=0.62 and 4.2% versus 4.8%, odds ratio 0.87 (95% CI, 0.44-1.73), P=0.70, respectively. CONCLUSIONS: In biomarker-negative stable and unstable angina patients undergoing elective PCI, the trial did not find a conclusive difference in efficacy or safety. This observation should be interpreted in the context of wide CIs and premature termination of the trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02548611.


Assuntos
Clopidogrel/administração & dosagem , Trombose Coronária/prevenção & controle , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Esquema de Medicação , Término Precoce de Ensaios Clínicos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Recidiva , Medição de Risco , Fatores de Risco , Stents , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de Tempo , Resultado do Tratamento
7.
J Cardiovasc Pharmacol Ther ; 25(5): 466-471, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32419491

RESUMO

INTRODUCTION/OBJECTIVES: In patients who have undergone recent percutaneous coronary intervention (PCI), poor adhesion to antiplatelet agents may increase the risk of stent thrombosis and death. We aimed to investigate the adherence to different P2Y12 receptor inhibitors after PCI with drug-eluting stent in stable and unstable patients and to evaluate the factors associated with low adherence. METHOD: In a prospective study conducted between 2014 and 2018, the 8-item Morisky scale was applied at 30 days and 6 months post-PCI to measure P2Y12 receptor inhibitors adherence. Also, we describe the characteristics of patients using different platelet receptor P2Y12 inhibitors. Regression models were used to identify predictors of poor adherence. RESULTS: A total of 214 patients were included (65 ± 12 years, 81% man, 61% acute coronary syndromes). Patients in the clopidogrel group were older than those in the prasugrel (68 ± 12 vs 59 ± 11 years, P < .01, respectively) or ticagrelor group (68 ± 12 vs 62 ± 12 years, P < .01). Patients with low/moderate adherence at 30 days and 6 months represented, respectively, 19.8% and 27.5% of our sample. Current smokers and preexisting cardiovascular disease at presentation were associated with lower adherence at 30 days. CONCLUSIONS: We found substantial rates of moderate and low adherence to P2Y12 receptor inhibitors early after PCI. Current smokers and preexisting cardiovascular disease at presentation were associated with a lower likelihood of adherence. These results highlight the need of monitoring adherence to medical treatment after PCI.


Assuntos
Trombose Coronária/prevenção & controle , Stents Farmacológicos , Adesão à Medicação , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Trombose Coronária/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Fatores de Risco , Fumantes , Fumar/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
9.
Minerva Med ; 111(2): 173-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338843

RESUMO

INTRODUCTION: Clinical data on short mandatory dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy, compared with prolonged DAPT in patients undergoing percutaneous coronary intervention (PCI) are insufficient. We aim to evaluate the effectiveness and safety of P2Y12 inhibitor monotherapy and prolonged DAPT after short mandatory DAPT on cardiovascular events in patients undergoing PCI. EVIDENCE ACQUISITION: A systematic literature search was performed in seven medical databases from building the database until July 2019. Three studies with randomized controlled trial (RCTs), totaling 21,970 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager v. 5.3 software. EVIDENCE SYNTHESIS: Our result of pooled analysis showed that there was noninferior rates of in major adverse cardiac and cerebrovascular events (MACCE), stroke, myocardial infarction and cardiac death between short mandatory DAPT followed by P2Y12 inhibitor monotherapy and prolonged DAPT in patients undergoing PCI. Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5 (OR=0.47, 95% CI: 0.31-0.70, P=0.002), compared with prolonged DAPT in patients undergoing PCI. However, Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy was not associated with BARC type 3-5, compared with prolonged DAPT. CONCLUSIONS: This meta-analysis demonstrated that short mandatory DAPT followed by P2Y12 inhibitor monotherapy compared with prolonged DAPT resulted in noninferior rates of MACCE, all-cause mortality, cardiac death, stroke, myocardial infarction and stent thrombosis. Furthermore, short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5.


Assuntos
Aspirina/efeitos adversos , Cardiopatias/mortalidade , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Aspirina/uso terapêutico , Causas de Morte , Cardiopatias/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Trombose/induzido quimicamente , Trombose/mortalidade
11.
Circ Cardiovasc Qual Outcomes ; 13(3): e006275, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32156164

RESUMO

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.


Assuntos
Cardiologistas/tendências , Serviço Hospitalar de Cardiologia/tendências , Uso de Medicamentos/tendências , Intervenção Coronária Percutânea/tendências , Inibidores da Agregação de Plaquetas/uso terapêutico , Padrões de Prática Médica/tendências , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Clopidogrel/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente/tendências , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Ticagrelor/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
12.
BMC Cardiovasc Disord ; 20(1): 140, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183711

RESUMO

BACKGROUND: Ticagrelor and prasugrel are two third-generation oral P2Y12 inhibitors which are more commonly used in clinical practice. However, dyspnea has been consecutively reported in patients using third-generation oral P2Y12 inhibitors. This study aims to compare the risk of dyspnea in patients treated with third-generation P2Y12 inhibitors compared with clopidogrel. METHODS: We systematically searched the PubMed, Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov and Web of Science for randomized control trials (RCTs) comparing ticagrelor or prasugrel with clopidogrel until July 2019. The primary outcome was the incidence of dyspnea. The risk ratios (RR) and 95% confidence intervals (CI) were estimated using meta-analysis. RESULTS: We included 25 RCTs involving 63,484 patients in this meta-analysis, including 21 studies on ticagrelor and 4 studies on prasugrel. Compared to the clopidogrel group, third-generation oral P2Y12 inhibitors were associated with an increased risk of dyspnea compared with clopidogrel (RR 2.15, 95% CI 1.59-2.92), which was consistent in the analysis of ticagrelor (RR 2.65, 95% CI 1.87-3.76). However, the adverse effect was not found among patients receiving prasugrel therapy (RR 1.03, 95% CI 0.86-1.22). The increased dyspnea risk of ticagrelor was consistent in subgroups with different follow-up durations (≤ 1 month RR 1.87, 95% CI 1.56-2.24; 1-6 months RR 4.19, 95% CI 1.99-8.86; > 6 months 2.45, 95% CI 1.13-5.34). CONCLUSIONS: Ticagrelor has a higher risk of dyspnea than clopidogrel, which was not observed in patients using prasugrel.


Assuntos
Clopidogrel/efeitos adversos , Dispneia/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dispneia/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Adulto Jovem
13.
JACC Cardiovasc Interv ; 13(5): 606-617, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32139218

RESUMO

OBJECTIVES: The aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes. BACKGROUND: Clopidogrel is the most broadly used platelet P2Y12 inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help identify these subjects. Although carriers of loss-of-function alleles of the cytochrome P450 2C19 enzyme have reduced clopidogrel metabolism leading to increased rates of HPR and thrombotic complications, this explains only a fraction of the pharmacodynamic response to clopidogrel, and a number of clinical factors have also been shown to have contributing roles. METHODS: Three prospective and independent studies were used to: 1) develop a risk score integrating genetic and clinical factors to identify patients with HPR while on clopidogrel; 2) investigate the external validity of the risk score; and 3) define clinical outcomes associated with the risk score in a cohort of patients with myocardial infarction treated with clopidogrel. RESULTS: A risk score ABCD-GENE (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) was developed incorporating 5 independent predictors of HPR: 4 clinical (age >75 years, body mass index >30 kg/m2, chronic kidney disease [glomerular filtration rate <60 ml/min], and diabetes mellitus) and 1 genetic (cytochrome P450 2C19 loss-of-function alleles). The C-statistics for the score as an integer variable were 0.71 (95% confidence interval [CI]: 0.68 to 0.75) and 0.64 (95% CI: 0.60 to 0.67) in the pharmacodynamic derivation and validation cohorts, respectively. A cutoff score ≥10 was associated with the best sensitivity and specificity to identify HPR status. The C-statistics for the score were 0.67 (95% CI: 0.64 to 0.71) for all-cause death and 0.66 (95% CI: 0.63 to 0.69) for the composite of all-cause death, stroke, or myocardial infarction at 1 year. Using multiple models for adjustment, the ABCD-GENE score consistently and independently correlated with all-cause death, as well as with the composite of all-cause death, stroke, or myocardial infarction, both as a continuous variable and by using the cutoff of ≥10. The score did not predict bleeding. CONCLUSIONS: The ABCD-GENE score is a simple tool to identify patients with HPR on clopidogrel and who are at increased risk for adverse ischemic events, including mortality, following an acute myocardial infarction. In patients with a high ABCD-GENE score, long-term oral P2Y12 inhibitors other than clopidogrel should be considered.


Assuntos
Regras de Decisão Clínica , Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Resistência a Medicamentos , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Fatores Etários , Idoso , Índice de Massa Corporal , Clopidogrel/efeitos adversos , Clopidogrel/farmacocinética , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Bases de Dados Factuais , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Obesidade/complicações , Obesidade/diagnóstico , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Variantes Farmacogenômicos , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/farmacocinética , Valor Preditivo dos Testes , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Cardiovasc Drugs Ther ; 34(2): 179-188, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32140798

RESUMO

PURPOSE: To compare the risk of cardiovascular events between patients with two CYP2C19 loss-of-function alleles who were prescribed ticagrelor or clopidogrel after percutaneous coronary intervention (PCI). METHODS: Patients with two loss-of-function alleles based on the CYP2C19 genotype were selected from patients enrolled in a retrospective institutional registry. Propensity score matching using logistic regression was performed to adjust for bias between patients prescribed ticagrelor or clopidogrel. Multivariate Cox regression was used to compare the risk of adverse events in the ticagrelor and clopidogrel groups. The primary outcome was the incidence of major adverse cardiac events plus any repeat target vessel revascularization within 12 months after PCI. The safety outcomes were minor and major bleeding events. RESULTS: From 1518 patients carrying two loss-of-function alleles based on the CYP2C19 genotype who underwent PCI, 638 patients treated with ticagrelor or clopidogrel were successfully propensity-score matched. The primary outcome occurred in 25 patients (7.8%) in the ticagrelor group and 47 (14.7%) in the clopidogrel group. The risk of the primary outcome was significantly lower in the ticagrelor group versus the clopidogrel group (HR 0.466, 95% CI 0.286-0.759, p = 0.002). The incidence of major bleeding events did not significantly differ between the ticagrelor and clopidogrel groups (0.3% and 0.9%, respectively), while the ticagrelor group had a higher risk of minor bleeding events (HR 1.959, 95% CI 1.396-2.750, p < 0.001). CONCLUSIONS: In patients with two CYP2C19 loss-of-function alleles, ticagrelor was more effective than clopidogrel in preventing cardiovascular events, while the two antiplatelet agents were associated with similar incidences of major bleeding.


Assuntos
Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/terapia , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea , Variantes Farmacogenômicos , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/mortalidade , Trombose Coronária/prevenção & controle , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
BMC Cardiovasc Disord ; 20(1): 130, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164560

RESUMO

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.


Assuntos
Clopidogrel/uso terapêutico , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Recidiva , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Ticagrelor/efeitos adversos , Resultado do Tratamento
17.
Cardiovasc Drugs Ther ; 34(2): 199-208, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32006144

RESUMO

PURPOSE: Although current guidelines recommend ticagrelor in addition to aspirin as the antiplatelet strategy for medically managed acute coronary syndrome (MMACS) patients, clinical evidence specific to this special population is lacking. Whether potent oral P2Y12 inhibitors should be used in MMACS patients is still under debate. METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, and Cochrane Library to identify studies exploring the efficacy or safety of ticagrelor and prasugrel versus clopidogrel or placebo in MMACS patients. The primary efficacy endpoint was major adverse cardiovascular events (MACE) defined by each study, and the safety endpoint was TIMI non-CABG major bleeding. RESULTS: A total of 6102 records were screened, and 4 studies including 46,346 patients were finally included. The use of potent oral P2Y12 inhibitors significantly lowers the risk of MACE compared with clopidogrel (HR: 0.90; 95% CI: 0.82-0.98; P = .018; I2 = 0%). A significant reduction in risks of all-cause death and myocardial infarction was also observed with the use of potent oral P2Y12 inhibitors compared with clopidogrel. No significant difference in risks of stroke or TIMI non-CABG major bleeding (HR: 1.24; 95% CI: 0.90-1.73; P = .191; I2 = 0%) was observed between potent oral P2Y12 inhibitors and clopidogrel. CONCLUSION: Potent oral P2Y12 inhibitors, especially ticagrelor, decrease the risk of ischemic events in MMACS patients as compared with clopidogrel, without significantly increasing major bleeding.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticagrelor/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Medição de Risco , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
19.
J Cardiovasc Med (Hagerstown) ; 21(4): 281-285, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32108125

RESUMO

: The European Society of Cardiology guidelines for myocardial revascularization state that de-escalation of P2Y12 inhibitor treatment guided by platelet function testing may be considered for acute coronary syndrome (ACS) patients deemed unsuitable for 12-month potent platelet inhibition. De-escalation strategy aim is to harmonize the time-dependency of thrombotic risk, which is high in the first month after ACS, then decreases exponentially, with bleeding risk, which tends to remain more stable after the procedure-related peak. Harmonizing time-dependency of clinical events may be particularly relevant in those at high risk, such as the elderly patients with ACS in whom an individualized antiplatelet therapy may be more appropriate than a 'one-size-fits all' approach. In this review, we outline the current medical evidence on the topic of dual antiplatelet therapy de-escalation. In addition, we include insights from the Elderly ACS 2 study and recently published post-hoc analyses conducted by the authors' consortium, which further expands current knowledge.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Trombose/prevenção & controle , Síndrome Coronariana Aguda/diagnóstico por imagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Terapia Antiplaquetária Dupla/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
J Card Surg ; 35(2): 413-421, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31803992

RESUMO

BACKGROUND: Clopidogrel and other P2Y12 inhibitors have become the standard of care among patients presenting with acute coronary syndromes. A substantial proportion of these patients require surgical revascularization during index hospitalization. HYPOTHESIS: Guidelines recommend a 5-day waiting period off clopidogrel before coronary artery bypass grafting (CABG) to reduce hemorrhagic complications. These recommendations are not routinely followed in clinical practice, while recent studies also propose shorter waiting periods off clopidogrel for patients awaiting in-hospital CABG. METHODS: A preliminary PubMed search was conducted using the following MeSH terms under the publication type "Hemorrhage:" "Clopidogrel," AND "Coronary Artery Bypass." Relevant studies and guidelines were then reviewed and selected based on a predetermined criteria. Studies that formulated the current recommendations for stopping clopidogrel preoperative to CABG are discussed in detail this review. RESULTS: A comprehensive review of recent evidence illustrates mixed bleeding and transfusion outcomes among CABG patients with preoperative exposure to clopidogrel in less than 5 days. CONCLUSIONS: The optimal discontinuation time of clopidogrel before CABG is still poorly defined. The recommendation of a 5-day washout period for clopidogrel should be reconsidered to be on par with current clinical practice.


Assuntos
Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Ponte de Artéria Coronária , Hemorragia Pós-Operatória/prevenção & controle , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Humanos , Hemorragia Pós-Operatória/induzido quimicamente , Fatores de Tempo
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