Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 318
Filtrar
1.
Medicine (Baltimore) ; 100(12): e25185, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761699

RESUMO

BACKGROUND: Dual anti-platelet therapy (DAPT) with aspirin and clopidogrel has been the mainstay of treatment for patients with acute coronary syndrome (ACS). However, the recurrence of thrombotic events, potential aspirin and clopidogrel hypo-responsiveness, and other limitations of DAPT have led to the development of newer oral anti-thrombotic drugs. Apixaban, a new non-vitamin K antagonist, has been approved for use. In this meta-analysis, we aimed to compare the bleeding outcomes observed with the addition of apixaban to DAPT for the treatment of patients with ACS. METHODS: Online databases including EMBASE, Cochrane Central, http://www.ClinicalTrials.gov, MEDLINE and Web of Science were searched for English based publications comparing the use of apixaban added to DAPT for the treatment of patients with ACS. Different categories of bleeding events and cardiovascular outcomes were assessed. The analysis was carried out by the RevMan software version 5.4. Odds ratios (OR) with 95% confidence intervals (CI) were used to represent the data following analysis. RESULTS: This research analysis consisted of 4 trials with a total number of 9010 participants. Thrombolysis in myocardial infarction (TIMI) defined major bleeding (OR: 2.45, 95% CI: 1.45-4.12; P = .0008), TIMI defined minor bleeding (OR: 3.12, 95% CI: 1.71-5.70; P = .0002), International society of thrombosis and hemostasis (ISTH) major bleeding (OR: 2.49, 95% CI: 1.80-3.45; P = .00001) and Global Use of Strategies to Open Occluded Arteries (GUSTO) defined severe bleeding (OR: 3.00, 95% CI: 1.56-5.78; P = .01) were significantly increased with the addition of apixaban to DAPT versus DAPT alone in these patients with ACS. However fatal bleeding (OR: 10.96, 95% CI: 0.61-198.3; P = .11) was not significantly different. CONCLUSIONS: Addition of the novel oral anticoagulant apixaban to the DAPT regimen significantly increased bleeding and therefore did not show any beneficial effect in these patients with ACS. However, due to the extremely limited data, we apparently have to rely on future larger studies to confirm this hypothesis.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Quimioterapia Combinada , Humanos , Fatores de Risco
2.
Ann Intern Med ; 174(2): JC21, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33524286

RESUMO

SOURCE CITATION: Brouwer J, Nijenhuis VJ, Delewi R, et al. Aspirin with or without clopidogrel after transcatheter aortic-valve implantation. N Engl J Med. 2020;383:1447-57. 32865376.


Assuntos
Aspirina , Substituição da Valva Aórtica Transcateter , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Substituição da Valva Aórtica Transcateter/efeitos adversos
4.
Int Heart J ; 62(1): 171-174, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33455983

RESUMO

A 41-year-old woman with chest pain for 6 hours was admitted to our chest pain center, presenting with acute myocardial infarction. Coronary angiography showed acute total occlusion in the proximal left anterior descending artery due to late stent thrombosis. After thrombus aspiration and intracoronary administration of 0.5 mg tirofiban, repeated angiography showed that no obvious residual stenosis remained. The patient underwent drug-coated balloon angioplasty 69 days ago and was then administered dual antiplatelet treatment (aspirin and clopidogrel) uninterruptedly. Genetic testing found that both cytochrome P450 2C19 (CYP2C19) (G681A) and glycoprotein Ia (GPIa) (C807T, G873A) were hybrid mutant types, demonstrating that the patient was possibly resistant to clopidogrel and aspirin simultaneously. Thus, clopidogrel was replaced by ticagrelor and no more cardiovascular adverse events occurred during the 2-year follow-up.


Assuntos
Oclusão Coronária/etiologia , Reestenose Coronária/etiologia , Infarto do Miocárdio/diagnóstico , Doença Aguda , Adulto , Assistência ao Convalescente , Angioplastia Coronária com Balão/métodos , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico por imagem , Reestenose Coronária/terapia , Citocromo P-450 CYP2C19/genética , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/métodos , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/uso terapêutico , Humanos , Integrina alfa2/genética , Mutação/genética , Infarto do Miocárdio/etiologia , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Stents/efeitos adversos , Trombectomia/métodos , Trombose/terapia , Ticagrelor/administração & dosagem , Ticagrelor/uso terapêutico , Tirofibana/administração & dosagem , Tirofibana/uso terapêutico , Resultado do Tratamento
5.
Clin Appl Thromb Hemost ; 27: 1076029620980067, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33443453

RESUMO

This study aimed to investigate the long-term safety and benefits of antiplatelet therapy in patients with cerebral infarction with thrombocytopenia, as evidence regarding this was limited. This cohort trial assessed patients with acute cerebral infarction with thrombocytopenia treated in the Neurology Department of Shanghai Tenth People's Hospital from January 2016 to December 2018, and enrolled patients were followed up for 9 months. The patients were divided into non-antiplatelet and antiplatelet groups based on the actual intake of antiplatelet drugs. Primary endpoints included hemorrhagic events, recurrence of cerebral infarction, and activity of daily living (ADL) score changes. To balance baseline clinical data, propensity score matching was applied, and there were finally 65 matched patients, including 30 and 35 in the antiplatelet and non-antiplatelet groups, respectively. There were no differences in hemorrhagic and cerebral infarction recurrence rates between the 2 groups. ADL score change was higher in the antiplatelet group than in the non-antiplatelet group (10 vs 5, p = 0.039). In multivariate regression analysis, antiplatelet therapy significantly predicted a positive change in ADL scores [B = 8.381, 95% confidence interval (0.56-16.19)]. In patients with acute cerebral infarction with thrombocytopenia, antiplatelet therapy could the improve the quality of life in the chronic stage.


Assuntos
Infarto Cerebral/complicações , Infarto Cerebral/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Aspirina/uso terapêutico , China , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação de Plaquetas/efeitos adversos , Pontuação de Propensão , Qualidade de Vida , Segurança , Resultado do Tratamento
6.
Yonsei Med J ; 62(1): 75-85, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33381937

RESUMO

PURPOSE: Antiplatelet drugs are essential in patients with cardiovascular disease who undergo stent placement. We hypothesized that risks of mortality would differ according to adherence to antiplatelet agents, number of antiplatelet agents, and antiplatelet regimens in patients undergoing stent placement or angioplasty. MATERIALS AND METHODS: Between 2002 and 2013, we initially enrolled 8671 subjects who underwent stent placement or angioplasty in the National Health Insurance Service-National Sample Cohort in Korea. Using the International Classification of Diseases, 10th revision, the incidence of all-cause death, including cardiovascular disease, cerebrovascular disease, and cancer, was defined. Using a nested case-control study design, controls were matched to cases at a ratio of 4:1, and a total of 5415 subjects were eligible for this study. RESULTS: During a median follow-up period of 3.51 years, the incidence rate of all-cause death was 40 per 1000 person-years. We found that adherence to antiplatelet monotherapy significantly decreased risk of death by cerebro-cardiovascular disease, compared with discontinuation of antiplatelets [adjusted odds ratio (OR) 0.62, 95% confidence interval (CI) (0.41-0.96)]. Compared with dual antiplatelet therapy (DAPT), aspirin and clopidogrel monotherapy significantly reduced death by cerebro-cardiovascular disease [adjusted OR 0.65, 95% CI (0.44-0.95) and adjusted OR 0.58, 95% CI (0.35-0.96), respectively]. There was no significant difference of mortality between aspirin monotherapy and clopidogrel monotherapy. CONCLUSION: Our study demonstrated that adherence to antiplatelet therapy and antiplatelet monotherapy, compared with DAPT, in patients with stent placement or angioplasty may have a beneficial effect on mortality in cerebro-cardiovascular disease.


Assuntos
Angioplastia/efeitos adversos , Stents Farmacológicos/efeitos adversos , Inibidores da Agregação de Plaquetas/farmacologia , Idoso , Angioplastia/mortalidade , Aspirina/uso terapêutico , Estudos de Casos e Controles , Clopidogrel/efeitos adversos , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Resultado do Tratamento
7.
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
9.
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
10.
J Stroke Cerebrovasc Dis ; 29(11): 105115, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066893

RESUMO

BACKGROUND AND AIM: Ipsilateral nonstenotic carotid disease is increasingly recognized as an etiology of ischemic stroke, however tailored treatment strategies are lacking. We aimed to examine clinical characteristics and treatment effects in patients with minor ischemic stroke associated with ipsilateral nonstenotic carotid disease in the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. METHODS: We performed an exploratory analysis of the interaction of the treatment effects of aspirin plus clopidogrel versus aspirin monotherapy, stratified by presence of ipsilateral nonstenotic carotid disease in patients with minor ischemic stroke in the POINT trial. RESULTS: For this exploratory analysis, 167 patients presenting with ischemic stroke and ipsilateral nonstenotic carotid disease, defined as 1%-49% carotid stenosis ipsilateral to the corresponding territory of ischemic stroke, and 833 patients no carotid disease were included. Compared to patients with no carotid disease, patients with ipsilateral nonstenotic carotid disease were older (68.5 ± 11.3 years versus 61.3 ± 12.8 years; P < 0.001), and had a higher prevalence of hypertension (76.6% versus 59.2%, P < 0.001), ischemic heart disease (13.8% versus 5.4%, P < 0.001), and tobacco use (past: 34.1% versus 25.2%, P = 0.005; present: 27.5% versus 22.8%, P = 0.005). 5.4% of patients with ipsilateral nonstenotic carotid disease had recurrent ischemic stroke within 14 days. Patients receiving dual antiplatelet therapy had a numerical reduction in recurrent ischemic stroke compared to patients receiving aspirin monotherapy, however the exploratory analysis was underpowered to detect a statistically significant difference in treatment effect (HR 0.50, 95% CI 0.18-1.40, P = 0.19). CONCLUSION: Patients with minor ischemic stroke and ipsilateral nonstenotic carotid disease had a high risk of early stroke recurrence in the POINT trial. Dual antiplatelet therapy provided a non-statistically significant reduction in recurrent ischemic stroke with no difference in safety outcomes compared to aspirin monotherapy. Further study is needed to determine if early and short duration dual antiplatelet therapy is beneficial for all patients with ipsilateral nonstenotic carotid disease.


Assuntos
Aspirina/uso terapêutico , Doenças das Artérias Carótidas/tratamento farmacológico , Clopidogrel/uso terapêutico , Ataque Isquêmico Transitório/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Prevenção Secundária , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Aspirina/efeitos adversos , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/mortalidade , Clopidogrel/efeitos adversos , Comorbidade , Método Duplo-Cego , Terapia Antiplaquetária Dupla , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/mortalidade , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
11.
N Engl J Med ; 383(15): 1447-1457, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-32865376

RESUMO

BACKGROUND: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Hemorragia/induzido quimicamente , Inibidores da Agregação de Plaquetas/uso terapêutico , Trombose/prevenção & controle , Substituição da Valva Aórtica Transcateter , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Feminino , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Período Pós-Operatório , Trombose/epidemiologia
12.
Vasc Endovascular Surg ; 54(8): 712-717, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32856558

RESUMO

BACKGROUND: Platelet inhibitory therapy is prescribed to prevent arterial thromboembolism in patients with atherosclerotic disease. Although taken by millions of people, around 30% are resistant to the treatment they are being prescribed. AIMS: To determine whether symptoms of cerebral ischemia, or pre-operative cerebral emboli, in patients admitted for a carotid endarterectomy were associated with resistance to aspirin or clopidogrel. METHODS: Venous blood from 133 patients immediately before carotid endarterectomy (CEA) was analyzed for resistance to aspirin and clopidogrel by multiplate impedance aggregometry. The number of emboli/hour entering the ipsilateral middle cerebral artery was counted by transcranial Doppler (TCD) on the day before surgery in 33 of these patients. RESULTS: Resistance was found in 21 (26.3%) of 100 patients taking aspirin and 14 (42%) of 33 taking clopidogrel. Mean (sd) residual platelet aggregation was significantly higher at 41.9(32) Au in patients who had suffered recent symptoms of cerebral ischemia compared with 30.8(16) Au in asymptomatic patients (p = 0.012). Residual platelet aggregation also correlated significantly with the number of emboli/hour counted by TCD in the ipsilateral middle cerebral artery (r = 0.45, p = 0.009). CONCLUSION: Antiplatelet resistance was associated with the frequency of cerebral emboli and recent symptoms of cerebral ischemia in patients with carotid disease. Definitive clinical studies are needed to explore whether testing for antiplatelet resistance should be undertaken routinely in patients starting platelet inhibitory therapy for cardiovascular disease.


Assuntos
Aspirina/uso terapêutico , Doenças das Artérias Carótidas/tratamento farmacológico , Clopidogrel/uso terapêutico , Resistência a Medicamentos , Infarto da Artéria Cerebral Média/prevenção & controle , Embolia Intracraniana/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Aspirina/efeitos adversos , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Clopidogrel/efeitos adversos , Feminino , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/etiologia , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana
13.
Am Heart J ; 228: 8-16, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745734

RESUMO

BACKGROUND: Gastrointestinal injury is a common complication in patients treated with antiplatelet agents after percutaneous coronary intervention (PCI). However, the effects of different antiplatelet regimens on the incidence and severity of gastrointestinal injury have not been well studied, principally due to the lack of a low-risk sensitive and accurate detection system. TRIAL DESIGN: OPT-PEACE is a multicenter, randomized, double-blind, placebo-controlled trial. Gastrointestinal injury will be evaluated with the ANKON magnetically controlled capsule endoscopy system (AMCE), a minimally invasive approach for detecting mucosal lesions in the stomach, duodenum and small intestine. Patients without AMCE-detected gastrointestinal erosions, ulceration or bleeding after drug-eluting stent implantation are enrolled and treated with open-label aspirin (100 mg/d) plus clopidogrel (75 mg/d) for 6 months. Thereafter, 480 event-free patients will undergo repeat AMCE and are randomly assigned in a 1:1:1 ratio to receive aspirin plus clopidogrel, aspirin plus placebo or clopidogrel plus placebo for an additional 6 months. A final AMCE is performed at 12 months. The primary endpoint is the incidence of gastric or intestinal mucosal lesions (erosions, ulceration, or bleeding) within 12 months after enrollment. CONCLUSIONS: OPT-PEACE is the first study to investigate the incidence and severity of gastrointestinal injury in patients receiving different antiplatelet therapy regimens after stent implantation. This trial will inform clinical decision-making for personalized antiplatelet therapy post-PCI.


Assuntos
Aspirina , Endoscopia por Cápsula/métodos , Clopidogrel , Doença da Artéria Coronariana , Hemorragia Gastrointestinal , Intervenção Coronária Percutânea , Adulto , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/cirurgia , Método Duplo-Cego , Stents Farmacológicos , Terapia Antiplaquetária Dupla/métodos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco Ajustado/métodos
14.
Am Heart J ; 228: 1-7, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32739652

RESUMO

BACKGROUND: Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is the cornerstone for prevention ischemic events in patients with acute coronary syndromes (ACS) and undergoing percutaneous coronary intervention. However, the optimal antiplatelet strategy for ACS patients with both high bleeding and high ischemic risks is unclear. STUDY DESIGN: The OPT-BIRISK trial is a multicenter, double-blinded, placebo-controlled randomized study designed to test the superiority of extended antiplatelet therapy with clopidogrel monotherapy compared with aspirin and clopidogrel for reduction of bleeding events in ACS patients with both high bleeding and high ischemic risks ("bi-risk"). A total of 7,700 patients who completed 9- to 12-month dual antiplatelet therapy after new-generation drug-eluting stent implantation for the treatment of ACS will be randomized to receive clopidogrel monotherapy or aspirin plus clopidogrel for 9 months followed by aspirin monotherapy for 3 months. The primary end point is Bleeding Academic Research Consortium type 2, 3, or 5 bleedings at 9 months after randomization. The key secondary end point is major adverse cardiac and cerebral events at 9 months after randomization, defined as a composite of all-cause death, myocardial infarction, stroke, or coronary artery revascularization. CONCLUSIONS: OPT-BIRISK is the first large-scale randomized trial aimed to explore the optimal antiplatelet strategy for bi-risk ACS patients after percutaneous coronary intervention in current clinical practice. The results will add evidence regarding de-escalation antiplatelet therapy for patients at special risk.


Assuntos
Síndrome Coronariana Aguda , Aspirina , Clopidogrel , Hemorragia , Risco Ajustado/métodos , Acidente Vascular Cerebral , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Adulto , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Método Duplo-Cego , Stents Farmacológicos/efeitos adversos , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/métodos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
15.
Am J Cardiol ; 133: 61-70, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32811654

RESUMO

Patients who underwent complex percutaneous coronary intervention (PCI) are known to be at high risk for both ischemic and bleeding complications. The risk/benefit tradeoff of extending dual antiplatelet therapy (DAPT) >12 months with clopidogrel and aspirin for TWILIGHT-like patients who are at high risk of bleeding or ischemic events and undergo complex PCI is unclear. Eight thousand three hundred and fifty-eight consecutive patients fulfilling the "TWILIGHT-like" criteria who underwent PCI from January 2013 to December 2013 were prospectively enrolled in Fuwai PCI Registry. We identified 2,677 of "TWILIGHT-like" complex PCI patients who were events free at 1 year after the index procedure. "TWILIGHT-like" patients were identified based on at least 1 clinical and 1 angiographic feature. Median follow-up was 29 months. Risk of primary efficacy outcome, major adverse cardiac and cerebrovascular events (composite of all-cause death, myocardial infarction, or stroke), was reduced with DAPT >12 months versus DAPT≤ 12 months (hazard ratio [HR]adj 0.374, 95% confidence interval [CI] 0.235 to 0.595; HRmatched 0.292 [0.151 to 0.561]; HRIPTW 0.356 [0.225 to 0.562]), with directional consistency for cardiovascular death and definite/probable stent thrombosis. In contrast, >12-month DAPT was comparable to ≤12-month DAPT for the risk of clinically relevant bleeding ([HR]adj 1.189, 95% CI 0.474 to 2.984; HRmatched 1.577 [0.577 to 4.312]; HRIPTW 1.239 [0.502 to 3.059]). Importantly, there was also a significant net benefit in favor of prolonged DAPT treatment. In conclusion, among "TWILIGHT-like" patients after complex PCI, continuing duration of DAPT> 12 months was associated with a net clinical benefit and lower rates of ischemic events without increasing the risk of clinically relevant bleeding than DAPT≤ 12 months, suggesting that long-term DAPT may have a favorable risk-benefit ratio in this high-risk population.


Assuntos
Doença da Artéria Coronariana/terapia , Terapia Antiplaquetária Dupla/efeitos adversos , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , China , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Estudos de Coortes , Esquema de Medicação , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Resultado do Tratamento
16.
Medicine (Baltimore) ; 99(30): e21312, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791719

RESUMO

Bleeding complications of acute coronary syndromes (ACS) after percutaneous coronary intervention (PCI) are strongly associated with adverse patient outcomes, and gastrointestinal bleeding (GIB) is the most common major bleeding event, especially in the early post-PCI period. Current guidelines recommend routinely conducting bleeding risk assessments. The existing tools are mainly used to evaluate the overall bleeding risk and guide the adjustment of antithrombotic strategies after 1 year. However, there are no specific tools for GIB risk assessment.Between January 2015 and June 2015, 4943 ACS patients underwent PCI were consecutively enrolled in the derivation cohort. GIB, cardiovascular, and cerebrovascular events were recorded within 1 year of follow-up. A validation cohort including 1000 patients who met the same inclusion and exclusion criteria was also established by propensity-score matching baseline characteristics. Multivariable cox proportional-hazards regression model was used to derive a risk-scoring system, and predictive variables were selected. A risk score nomogram based on the risk prediction model was created to estimate the 1-year risk of GIB.In this study, we found that the usage of clopidogrel (hazard ratio, HR: 2.52, 95% confidence intervals, CI: 1.573-4.021) and glycoprotein IIb/IIIa receptor inhibitors (HR: 1.863, 95% CI: 1.226-2.829), history of peptic ulcers (HR: 3.601, 95% CI: 1.226-2.829) or tumor (HR: 4.884, 95% CI: 1.226-2.829), and cardiac insufficiency (HR: 11.513, 95% CI: 7.282-18.202), renal insufficiency (HR: 2.010, 95% CI: 1.350-2.993), and prolonged activated partial thromboplastin time (HR: 4.639, 95% CI: 2.146-10.032) were independent risk factors for GIB 1 year after PCI. Based on these 7 factors, a nomogram and scoring system was established. The area under curve of risk score was 0.824 in the deviation cohort and 0.810 in the verification cohort. In both cohorts, the GIB score was significantly better than that of 3 classical bleeding scores (all P < .05).This score could well predict the risk of GIB within 1 year after PCI and could be used to guide antithrombotic strategies.


Assuntos
Síndrome Coronariana Aguda/complicações , Hemorragia Gastrointestinal/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Síndrome Coronariana Aguda/terapia , Idoso , Regras de Decisão Clínica , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Estudos de Coortes , Feminino , Hemorragia Gastrointestinal/diagnóstico , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Úlcera Péptica/complicações , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Insuficiência Renal/complicações , Projetos de Pesquisa/normas , Medição de Risco
17.
PLoS One ; 15(8): e0237022, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764775

RESUMO

BACKGROUND: Major bleedings other than gastrointestinal (GI) and intracranial (ICH) and mortality rates associated with antiplatelet drugs in real-world clinical practice are unknown. The objective was to estimate major bleeding risk and mortality among new users of antiplatelet drugs in real-world clinical practice. METHODS AND FINDINGS: A population-based prospective cohort using the French national health data system (SNIIRAM), identified 69,911 adults living within five well-defined geographical areas, who were new users of antiplatelet drugs in 2013-2015 and who had not received any antithrombotics in 2012. Among them, 63,600 started a monotherapy and 6,311 a dual regimen. Clinical data for all adults referred for bleeding was collected from all emergency departments within these areas, and medically validated. Databases were linked using common key variables. The main outcome measure was time to major bleeding (GI, ICH and other bleedings). Secondary outcomes were death, and event-free survival (EFS). Hazard ratios (HR) were derived from adjusted Cox proportional hazard models. We used Inverse Propensity of Treatment Weighting as a stratified sensitivity analysis according to the antiplatelet monotherapy indication: primary prevention without cardiovascular (CV) risk factors, with CV risk factors, and secondary prevention. We observed 250 (0.36%) major haemorrhages, 81 ICH, 106 GI and 63 other types of bleeding. Incidences were twice as high in dual therapy as in monotherapy. Compared to low-dose aspirin (≤ 100 mg daily), high-dose (> 100 up to 325 mg daily) was associated with an increased risk of ICH (HR = 1.80, 95%CI 1.10 to 2.95). EFS was improved by high-dose compared to low-dose aspirin (1.41, 1.04 to 1.90 and 1.32, 1.03 to 1.68) and clopidogrel (1.30, 0.73 to 2.3 and 1.7, 1.24 to 2.34) respectively in primary prevention with and without CV risk factors. CONCLUSION: The incidence of major bleeding and mortality was low. In monotherapy, low-dose aspirin was the safest therapeutic option whatever the indication. TRIAL REGISTRATION: NCT02886533.


Assuntos
Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Estudos de Coortes , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , França/epidemiologia , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/mortalidade , Hemorragia/epidemiologia , Humanos , Incidência , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/mortalidade , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação de Plaquetas/administração & dosagem , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
18.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...