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1.
Ann Lab Med ; 39(1): 23-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30215226

RESUMO

BACKGROUND: High on-treatment platelet reactivity (HTPR) is the phenomenon wherein patients exhibit normal platelet activity in laboratory testing despite adequate adherence to anti-platelet treatment. We investigated the detection rates of Platelet Function Analyzer (PFA)-100 (Dade Behring AG, Düdingen, Switzerland) for drug-induced platelet dysfunction and analyzed potential contributors to HTPR with practical PFA-100 data over six years. METHODS: We used data from 6,957 patients who underwent PFA-100 testing after receiving aspirin, clopidogrel, or non-steroidal anti-inflammatory drugs (NSAIDs). Of these, 6,163 patients were tested with only the collagen/epinephrine cartridge (Col/EPI) of PFA-100; 794 were tested with both Col/EPI and the collagen/ADP cartridge (Col/ADP). We calculated PFA-100 closure time (CT) for each drug and compared the clinical and laboratory characteristics of the patients with prolonged CTs and normal CTs (i.e., HTPR). RESULTS: In Col/EPI, 73.2% (365/499), 72.6% (390/537), and 55.3% (3,442/6,228) patients showed prolonged CTs for aspirin, clopidogrel, and NSAIDs, respectively. In Col/ADP, prolonged CTs were observed in 37.4% (34/91), 43.2% (35/81), and 29.6% (200/676) of patients receiving aspirin, clopidogrel, and NSAIDs, respectively. Of the patients tested with both cartridges, 88.9% (48/54), 95.3% (41/43), and 89.0% (577/648) of the patients receiving aspirin, clopidogrel, and NSAIDs had prolonged CTs, and 10.0% (79/794) showed normal CTs regardless of drugs. For clopidogrel users (both cartridges), there were more patients with malignancies in the normal CT than prolonged CT group. CONCLUSIONS: PFA-100 is not sufficiently effective for laboratory screening of drug-induced platelet dysfunction. Malignancy may contribute to clopidogrel-related HTPR in PFA-100.


Assuntos
Plaquetas/citologia , Testes de Função Plaquetária/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Criança , Pré-Escolar , Clopidogrel , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/farmacologia , Testes de Função Plaquetária/métodos , Ticlopidina/análogos & derivados , Ticlopidina/farmacologia , Adulto Jovem
2.
Medicine (Baltimore) ; 97(43): e12978, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30412125

RESUMO

BACKGROUND: Limitations have been observed with the use of clopidogrel following percutaneous coronary intervention (PCI) indicating the urgent need of a more potent anti-platelet agent. We aimed to compare the efficacy and safety of ticagrelor versus clopidogrel following PCI. METHODS: Online databases were searched for relevant studies (published between the years 2007 and 2017) comparing ticagrelor versus clopidogrel following coronary stenting. Primary outcomes assessed efficacy whereas secondary outcomes assessed safety. Odds ratios (OR) with 95% confidence intervals (CIs) based on a random effect model were calculated and the analysis was carried out by the RevMan 5.3 software. RESULTS: A total number of 25,632 patients with acute coronary syndrome (ACS) [12,992 patients with ST segment elevation myocardial infarction (STEMI) and 14,215 patients with non-ST segment elevation myocardial infarction (NSTEMI)] were included in this analysis, of whom 23,714 patients were revascularized by PCI. Results of this analysis did not show any significant difference in all-cause mortality, major adverse cardiac events (MACEs), myocardial infarction, stroke and stent thrombosis observed between ticagrelor and clopidogrel with (OR: 0.83, 95% CI: 0.67-1.03; P = .09), (OR: 0.64, 95% CI: 0.41-1.01; P = .06), (OR: 0.77, 95% CI: 0.57-1.03; P = .08), (OR: 0.85, 95% CI: 0.57-1.26; P = .42) and (OR: 0.70, 95% CI: 0.47-1.05; P =.09).However, ticagrelor was associated with a significantly higher minor and major bleeding with (OR: 1.57, 95% CI: 1.30-1.89; P = .00001) and (OR: 1.52, 95% CI: 1.01-2.29; P = 0.04) respectively. Dyspnea was also significantly higher in the ticagrelor group (OR: 2.64, 95% CI: 1.87-3.72; P = .00001). CONCLUSION: Ticagrelor and clopidogrel were comparable in terms of efficacy in these patients with ACS. However, the safety outcomes of ticagrelor should further be investigated.


Assuntos
Adenosina/análogos & derivados , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/análogos & derivados , Adenosina/uso terapêutico , Clopidogrel , Humanos , Período Pós-Operatório , Ticagrelor , Ticlopidina/uso terapêutico
3.
Medicine (Baltimore) ; 97(45): e13010, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30407292

RESUMO

OBJECTIVE: Both Aspirin and Clopidogrel are considered as effective drugs in decreasing ischemic events, which potentially contribute to a promising application regarding the cardiovascular events. In the present study, we evaluated the efficacy of the combination of both Clopidogrel and Aspirin to determine the influence among inflammatory factors, cardiac function, and treatment outcome of patients suffering from ST-segment elevation myocardial infarction (STEMI) in the Hebei province of China. METHODS: To compare the efficacy of this combination therapy with a single Aspirin treatment, we experimented in 68 patients with the administration of both Clopidogrel and Aspirin as well as another 68 patients administered only with Aspirin. An enzyme-linked immunosorbent assay was used to measure the expression of inflammatory factors, thereby evaluating the effect on inflammation. In addition, a series of indexes related to cardiac function and renal function were monitored by use of a color Doppler ultrasound and an automatic biochemical analyzer, respectively. Myocardial injury-related indicators were detected. A multivariate logistic regression analysis was performed so we could identify potential risk factors. In addition, both postoperative hemorrhages and cardiac events were observed to evaluate the treatment outcome of patients with STEMI. RESULTS: Initially, the treatment outcome revealed a better efficacy in patients treated with the combination of both Clopidogrel and Aspirin, with the patients also showing more obviously alleviated myocardial injury, better cardiac and renal functions with lower serum levels of inflammatory factors. The lower incidence of postinfarction angina, recurrent myocardial infarction, stroke, and death also provide evidence that patients showed a better outcome after treatment with both Clopidogrel and Aspirin. CONCLUSION: Taken together, the combination therapy of Clopidogrel and Aspirin provided a better improvement on both the cardiac function and outcome of STEMI patients in the Hebei province of China, with reduced inflammation as well.


Assuntos
Aspirina/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Ticlopidina/análogos & derivados , Idoso , Clopidogrel , Citocinas/sangue , Quimioterapia Combinada , Feminino , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Ticlopidina/administração & dosagem , Resultado do Tratamento
4.
Int J Clin Pharm ; 40(6): 1482-1489, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30367373

RESUMO

Background A significant number of ischemic events occur even when adhering to dual antiplatelet therapy including aspirin and clopidogrel. Objectives The aim of our study was to determine predictors of long-term patient clinical outcome, among variables such as prodrug clopidogrel and intermediary metabolite 2-oxoclopidogrel concentrations, as well as patients' clinical characteristics. Setting Department for the Treatment of Acute Coronary Syndrome in tertiary teaching hospital, Serbia. Methods This study enrolled 88 consecutive patients with first STEMI, treated with primary PCI, within 6 h of the chest pain onset and followed them 40 months. On the third day of hospitalization, blood samples were collected from each patient to measure clopidogrel and its metabolite 2-oxo-clopidogrel concentration by UHPLC-DAD-MS method. Main outcome measure Mortality from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for urgent myocardial revascularization or heart failure. Results The composite clinical outcome of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for urgent myocardial revascularization or heart failure, was registered in 31 patients (35.2%) during the 40-month follow-up. Lower clopidogrel (p < 0.05) and dose-adjusted clopidogrel concentrations (p < 0.05) were associated with the higher incidence of composite outcome events. Their low plasma concentrations may be predicted by fentanyl administration (p < 0.001) and creatinine clearance (p < 0.01). The decrease in dose-adjusted clopidogrel unit for each ng/ml/mg increases the risk 21.7 times (p < 0.05). Conclusion Clopidogrel dose-adjusted plasma concentration in STEMI patients, as well as multivessel coronary artery disease, showed significance in predicting an unfavorable composite clinical outcome after 40-month follow-up.


Assuntos
Clopidogrel/sangue , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/sangue , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dor no Peito/tratamento farmacológico , Dor no Peito/mortalidade , Doença da Artéria Coronariana/mortalidade , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Ticlopidina/sangue , Resultado do Tratamento
6.
Zhonghua Nei Ke Za Zhi ; 57(10): 723-730, 2018 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-30293332

RESUMO

Objective: Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods: Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3 044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results: A total of 59 (1.9%) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95%CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04; 95%CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05; 95%CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions: Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.


Assuntos
Aspirina/efeitos adversos , Hemorragia/induzido quimicamente , Ataque Isquêmico Transitório/complicações , Lipídeos/sangue , Inibidores da Agregação de Plaquetas/efeitos adversos , Acidente Vascular Cerebral/complicações , Ticlopidina/análogos & derivados , Aspirina/administração & dosagem , Clopidogrel , Quimioterapia Combinada , Humanos , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ativador de Plasminogênio Tecidual , Resultado do Tratamento
7.
Lancet ; 392(10151): 940-949, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30166073

RESUMO

BACKGROUND: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. METHODS: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. FINDINGS: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75-1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78-1·20]; p=0·77). INTERPRETATION: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. FUNDING: AstraZeneca, Biosensors, and The Medicines Company.


Assuntos
Adenosina/análogos & derivados , Aspirina/administração & dosagem , Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio/mortalidade , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Adenosina/administração & dosagem , Idoso , Clopidogrel , Angiografia Coronária , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Quimioterapia Combinada , Stents Farmacológicos/efeitos adversos , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados
8.
J Stroke Cerebrovasc Dis ; 27(11): 3373-3379, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30174225

RESUMO

BACKGROUND AND PURPOSE: Adult patients with symptomatically ischemic moyamoya disease (MMD) initially undergo medical treatment alone including antiplatelet drugs when symptomatic cerebral hemispheres do not exhibit hemodynamic compromise. The purpose of the present study subanalyzing the same patient cohort used in a previous study was to determine which antiplatelet drug, clopidogrel or cilostazol, provides better improvement of cerebral perfusion in such patients. METHODS: All patients without cerebral misery perfusion on 15O gas positron emission tomography (PET) did not undergo revascularization surgery and were treated with medication alone, including antiplatelet therapy. Patients ≥50years and <50years initially received clopidogrel and cilostazol, respectively. When a patient suffered side effects of an antiplatelet drug, they were switched to the other antiplatelet drug. Cerebral blood flow (CBF) in the symptomatic hemisphere was measured at inclusion and at 2years after inclusion using 15O gas PET. RESULTS: Of 68 patients, 31 and 38 were treated with clopidogrel and cilostazol, respectively, for 2years after inclusion. For patients treated with clopidogrel, CBF did not differ between first and second PET. For patients treated with cilostazol, CBF was significantly greater in the second PET than in the first PET. On multivariate analysis, cilostazol administration was an independent predictor of CBF improvement in the symptomatic hemisphere (95% confidence interval, 1.34-139.20; P =.0271). CONCLUSIONS: Cilostazol improves cerebral perfusion better than clopidogrel in adult patients with symptomatically ischemic MMD not accompanied by misery perfusion.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular/efeitos dos fármacos , Doença de Moyamoya/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Tetrazóis/uso terapêutico , Ticlopidina/análogos & derivados , Adulto , Velocidade do Fluxo Sanguíneo , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Cilostazol , Clopidogrel , Substituição de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Análise Multivariada , Radioisótopos de Oxigênio/administração & dosagem , Imagem de Perfusão/métodos , Inibidores da Agregação de Plaquetas/efeitos adversos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Tetrazóis/efeitos adversos , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
9.
J Thromb Thrombolysis ; 46(4): 488-495, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30074128

RESUMO

This randomized double-blind crossover study aimed to investigate the influence of cytochrome P450 (CYP) 2C19 polymorphisms on the antiplatelet effects of prasugrel in patients with non-cardioembolic stroke treated with clopidogrel. Patients received clopidogrel 75 mg/day for > 4 weeks. Subsequently, patients received prasugrel 3.75 mg/day (group A; n = 64) or 2.5 mg/day (group B; n = 65) for 4 weeks followed by a 4 week switched-dose regimen. To assess the influence of CYP2C19 polymorphisms, patients were classified as extensive metabolizers (EMs), intermediate metabolizers (IMs), and poor metabolizers (PMs). The primary endpoint was P2Y12 reaction units (PRU) at the end of each 4 week treatment. A significant reduction in PRU was noted after treatment with prasugrel 3.75 mg/day compared with the pre-dose value (after treatment with clopidogrel) (p < 0.0001). By CYP2C19 phenotypes, a significant reduction in PRU was noted in IMs and PMs after treatment with prasugrel 3.75 mg/day and in PMs after treatment with prasugrel 2.5 mg/day, as compared with the pre-dose value (p < 0.0001). The plasma concentration of the active metabolite of clopidogrel was relatively low in PMs compared to EMs and IMs; prasugrel was similar across all CYP2C19 phenotypes. No major or clinically significant hemorrhagic adverse events occurred. By CYP2C19 phenotype, the antiplatelet effects of prasugrel were greater with 3.75 mg/day in IMs and PMs, and with 2.5 mg/day in PMs compared with clopidogrel 75 mg/day, without safety concerns. CYP2C19 polymorphisms did not affect the plasma concentration of the active metabolite of prasugrel or its antiplatelet effects. (JapicCTI-101044).


Assuntos
Citocromo P-450 CYP2C19/genética , Agregação Plaquetária/efeitos dos fármacos , Cloridrato de Prasugrel/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Clopidogrel , Estudos Cross-Over , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Polimorfismo Genético , Guias de Prática Clínica como Assunto , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/metabolismo , Acidente Vascular Cerebral/complicações , Ticlopidina/análogos & derivados , Ticlopidina/metabolismo , Ticlopidina/uso terapêutico
10.
J Neurol ; 265(10): 2396-2403, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30128710

RESUMO

OBJECTIVES: The mechanisms of early neurologic deterioration (END) and prevention strategies for END are not completely understood. The aim of this study was to investigate the association between CYP2C19*2 variants and END, and the effectiveness of antiplatelet therapy for prevention of END according to CYP2C19*2 genotypes in patients with ischemic stroke (IS). MATERIALS AND METHODS: This was a two-center, randomized controlled study. Between August 2009 and December 2011, 570 IS patients were randomly assigned to clopidogrel plus aspirin group (n = 284) or aspirin alone group (n = 286). Platelet aggregation and platelet-leukocyte aggregates were measured before and after 7-10 days of treatment. CYP2C19*2 (rs4244285) genotypes were examined using mass spectrometry. The primary outcome was END during the 10 days of admission. RESULTS: Among the 570 patients, 121 (21.2%) patients suffered from END. Carriers of CYP2C19*2 reduced-function alleles were associated with higher incidence of END (26.8% in carriers vs. 16.6% in noncarriers, P = 0.004). The incidence of END was lower in the clopidogrel plus aspirin group than in the aspirin alone group (17.6 vs. 24.8%, P = 0.032). Stratified analyses revealed that clopidogrel plus aspirin could be more effective in reducing END than aspirin alone for carriers of CYP2C19*2 reduced-function alleles (18.8 vs. 34.9%, P = 0.006). However, there was no significant difference in incidence of END between dual therapy group and monotherapy group for noncarriers (16.7 vs. 16.6%, P = 0.998). CONCLUSIONS: Dual therapy with clopidogrel and aspirin may be adequate for prevention of END in carriers of CYP2C19 reduced-function alleles, but not for noncarriers. Our findings may be useful to guide precise antiplatelet therapy, and decrease the risk of END.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Citocromo P-450 CYP2C19/genética , Doenças Neurodegenerativas/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Aspirina/uso terapêutico , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/genética , Clopidogrel , Quimioterapia Combinada , Feminino , Heterozigoto , Humanos , Incidência , Masculino , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico
11.
Gene ; 678: 226-232, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30096456

RESUMO

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is a recommended treatment for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) to reduce the rate of ischemic events and stent thrombosis. However, high on-treatment platelet reactivity (HTPR) during clopidogrel therapy for some patients may lead to outcome failure and occurrence of cardiovascular events. Amounts of studies have proved that genetic factors may contribute to HTPR. In our study, we explored the predictive value of 10 single nucleotide polymorphisms (SNPs) in 8 genes indicated by exome sequencing with clopidogrel efficacy. METHODS: Two hundred and forty-one Han Chinese CAD patients (mean age: 61 ±â€¯10 years) receiving dual antiplatelet therapy were recruited, among which 118 patients administered with 300 mg loading dose (LD) clopidogrel for 12-24 h and 123 subjects administered with 75 mg/day maintain dose (MD) clopidogrel for at least 5 days before discharge. The platelet reaction index (PRI) was determined to reflect clopidogrel response in the patients. Venous blood samples were drawn from all participants to extract genomic DNA. MassARRAY, Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to determine the genotypes of 10 SNPs. RESULTS: Allelic tests showed significant differences in genotype distribution between HTPR and normal on-treatment platelet reactivity (NTPR) patients for 3 SNPs including CYP2C19 rs4244285 (CYP2C19*2) (co-dominant model: p = 0.003, dominant model: p = 0.004, recessive model: p = 0.012), CRISPLD1 rs12115090 (co-dominant model: p = 0.011, dominant model: p = 0.004), and LTA4H rs11108379 (dominant model: p = 0.041). After adjusting for covariates including clinical characteristics of patients, concomitant medications and complications, we confirmed that carriers of the CYP2C19*2 showed significantly increased risk of HTPR (*2/*2 vs *1/*1: OR = 12.266, 95% CI: 1.336-112.592, p = 0.027; *1/*2 + *2/*2 vs *1/*1: OR = 2.202, 95% CI: 1.083-4.480, p = 0.029). Contrarily, carriers of the CRISPLD1 rs12115090 C allele showed significantly reduced risk of HTPR (CC vs AA: OR = 0.242, 95% CI: 0.078-0.752, p = 0.014; CA + CC vs AA: OR = 0.457, 95% CI: 0.232-0.904, p = 0.024) in Chinese CAD patients. In addition, carriers of the CYP2C19*2 allele showed significantly increased PRI (*1/*2 vs *1/*1: p = 0.008, 2/*2 vs 1/*1: p < 0.001, *2/*2 vs 1/*2: p = 0.011), while patients carrying the rs12115090 C allele showed significantly decreased PRI than the wild-type AA homozygotes (CA vs AA: p = 0.046, CA + CC vs AA: p = 0.023). CONCLUSION: CYP2C19*2 reduced the antiplatelet potency of clopidogrel and increased the risk of HTPR, while CRISPLD1 rs12115090 A>C polymorphism increased the antiplatelet potency of clopidogrel. Genetic tests, especially for CYP2C19*2 are recommended in Han Chinese CAD patients before using of clopidogrel.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Moléculas de Adesão Celular/genética , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Polimorfismo de Nucleotídeo Único , Ticlopidina/análogos & derivados , Idoso , Grupo com Ancestrais do Continente Asiático/etnologia , China/etnologia , Clopidogrel , Doença da Artéria Coronariana/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Ticlopidina/uso terapêutico , Resultado do Tratamento
12.
Turk Kardiyol Dern Ars ; 46(5): 349-357, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30024391

RESUMO

OBJECTIVE: The present study is an investigation of the association between high on-treatment platelet reactivity to clopidogrel (HTPRC) and hepatosteatosis in patients who had elective stent implantation due to coronary artery disease. METHODS: A total of 190 consecutive patients who underwent an elective coronary stent implantation due to coronary artery disease were prospectively enrolled in the study. Eligible patients were given a 300 mg loading dose of clopidogrel before percutaneous coronary intervention. All of the patients underwent an ultrasound assessment for fatty liver. The patients were divided into 2 groups according to the detection of HTPRC: patients with HTPRC and patients without HTPRC. RESULTS: HTPRC was present in 54.2% (103 of 190 patients) of the total study population. The age and body mass index data were similar between the 2 groups. In all, 111 (58.6%) patients had hepatosteatosis. The HTPRC ratio was statistically higher in female patients (p=0.032). Hepatosteatosis was significantly greater in patients with HTPRC (p<0.001); 84 (81.6%) patients with HTPRC had hepatosteatosis (p=0.001). There was also a statistically significant association between the hepatosteatosis grade and HTPRC (p<0.001). The percentage of HTPRC was greater in patients with ≥grade 2 hepatosteatosis than grade 1 (p<0.001). Logistic regression analysis indicated that hepatosteatosis (odds ratio: 9.403, 95% confidence interval: 4.519-19.566; p<0.001), fasting blood glucose, and hypertension were independent predictors of HTPRC. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate a relationship between hepatosteatosis and HTPRC.


Assuntos
Doença da Artéria Coronariana/terapia , Fígado Gorduroso , Inibidores da Agregação de Plaquetas/uso terapêutico , Stents , Ticlopidina/análogos & derivados , Estudos de Casos e Controles , Clopidogrel , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/administração & dosagem , Testes de Função Plaquetária , Complicações Pós-Operatórias , Período Pré-Operatório , Estudos Prospectivos , Ticlopidina/administração & dosagem , Ticlopidina/uso terapêutico , Resultado do Tratamento
13.
Cochrane Database Syst Rev ; 7: CD012584, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30019463

RESUMO

BACKGROUND: Antiplatelet agents are recommended for people with myocardial infarction and acute coronary syndromes, transient ischaemic attack or stroke, and for those in whom coronary stents have been inserted. People who take antiplatelet agents are at increased risk of adverse events when undergoing non-cardiac surgery because of these indications. However, taking antiplatelet therapy also introduces risk to the person undergoing surgery because the likelihood of bleeding is increased. Discontinuing antiplatelet therapy before surgery might reduce this risk but subsequently it might make thrombotic problems, such as myocardial infarction, more likely. OBJECTIVES: To compare the effects of continuation versus discontinuation for at least five days of antiplatelet therapy on the occurrence of bleeding and ischaemic events in adults undergoing non-cardiac surgery under general, spinal or regional anaesthesia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), MEDLINE (1946 to January 2018), and Embase (1974 to January 2018). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included randomized controlled trials of adults who were taking single or dual antiplatelet therapy, for at least two weeks, and were scheduled for elective non-cardiac surgery. Included participants had at least one cardiac risk factor. We planned to include quasi-randomized studies.We excluded people scheduled for minor surgeries under local anaesthetic or sedation in which bleeding that required transfusion or additional surgery was unlikely. We included studies which compared perioperative continuation of antiplatelet therapy versus discontinuation of antiplatelet therapy or versus substitution of antiplatelet therapy with a placebo for at least five days before surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias and synthesized findings. Our primary outcomes were: all-cause mortality at longest follow-up (up to six months); all-cause mortality (up to 30 days). Secondary outcomes included: blood loss requiring transfusion of blood products; blood loss requiring further surgical intervention; risk of ischaemic events. We used GRADE to assess the quality of evidence for each outcome MAIN RESULTS: We included five RCTs with 666 randomized adults. We identified three ongoing studies.All study participants were scheduled for elective general surgery (including abdominal, urological, orthopaedic and gynaecological surgery) under general, spinal or regional anaesthesia. Studies compared continuation of single or dual antiplatelet therapy (aspirin or clopidogrel) with discontinuation of therapy for at least five days before surgery.Three studies reported adequate methods of randomization, and two reported methods to conceal allocation. Three studies were placebo-controlled trials and were at low risk of performance bias, and three studies reported adequate methods to blind outcome assessors to group allocation. Attrition was limited in four studies and two studies had reported prospective registration with clinical trial registers and were at low risk of selective outcome reporting bias.We reported mortality at two time points: the longest follow-up reported by study authors up to six months, and time point reported by study authors up to 30 days. Five studies reported mortality up to six months (of which four studies had a longest follow-up at 30 days, and one study at 90 days) and we found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to mortality up to six months (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.34 to 4.27; 659 participants; low-certainty evidence); the absolute effect is three more deaths per 1000 with continuation of antiplatelets (ranging from eight fewer to 40 more). Combining the four studies with a longest follow-up at 30 days alone showed the same effect estimate, and we found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to mortality at 30 days after surgery (RR 1.21, 95% CI 0.34 to 4.27; 616 participants; low-certainty evidence); the absolute effect is three more deaths per 1000 with continuation of antiplatelets (ranging from nine fewer to 42 more).We found that either continuation or discontinuation of antiplatelet therapy probably makes little or no difference in incidences of blood loss requiring transfusion (RR 1.37, 95% CI 0.83 to 2.26; 368 participants; absolute effect of 42 more participants per 1000 requiring transfusion in the continuation group, ranging from 19 fewer to 119 more; four studies; moderate-certainty evidence); and may make little or no difference in incidences of blood loss requiring additional surgery (RR 1.54, 95% CI 0.31 to 7.58; 368 participants; absolute effect of six more participants per 1000 requiring additional surgery in the continuation group, ranging from seven fewer to 71 more; four studies; low-certainty evidence). We found that either continuation or discontinuation of antiplatelet therapy may make little or no difference to incidences of ischaemic events (to include peripheral ischaemia, cerebral infarction, and myocardial infarction) within 30 days of surgery (RR 0.67, 95% CI 0.25 to 1.77; 616 participants; absolute effect of 17 fewer participants per 1000 with an ischaemic event in the continuation group, ranging from 39 fewer to 40 more; four studies; low-certainty evidence).We used the GRADE approach to downgrade evidence for all outcomes owing to limited evidence from few studies. We noted a wide confidence in effect estimates for mortality at the end of follow-up and at 30 days, and for blood loss requiring transfusion which suggested imprecision. We noted visual differences in study results for ischaemic events which suggested inconsistency. AUTHORS' CONCLUSIONS: We found low-certainty evidence that either continuation or discontinuation of antiplatelet therapy before non-cardiac surgery may make little or no difference to mortality, bleeding requiring surgical intervention, or ischaemic events. We found moderate-certainty evidence that either continuation or discontinuation of antiplatelet therapy before non-cardiac surgery probably makes little or no difference to bleeding requiring transfusion. Evidence was limited to few studies with few participants, and with few events. The three ongoing studies may alter the conclusions of the review once published and assessed.


Assuntos
Procedimentos Cirúrgicos Eletivos , Hemorragia/induzido quimicamente , Isquemia/induzido quimicamente , Inibidores da Agregação de Plaquetas/administração & dosagem , Suspensão de Tratamento , Adulto , Aspirina/administração & dosagem , Causas de Morte , Clopidogrel , Procedimentos Cirúrgicos Eletivos/mortalidade , Hemorragia/terapia , Humanos , Isquemia/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados
14.
J Manag Care Spec Pharm ; 24(8): 800-812, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30058986

RESUMO

BACKGROUND: In patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), newer antiplatelet agents prasugrel and ticagrelor have lower rates of cardiovascular events when compared with clopidogrel. However, it is unclear whether there are differences in economic outcomes when comparing these agents in ACS-PCI patients. OBJECTIVE: To assess aggregated costs and medical resource utilization among ACS-PCI patients prescribed prasugrel, ticagrelor, or generic clopidogrel, using a large commercial insurance claims database. METHODS: Costs attributable to any medical and pharmacy service and resource utilization including number of admissions, length of hospital stay, emergency room visits, and office visits over the 180-day postdischarge period were compared. All-cause and cardiovascular health care costs and resource utilization were separately analyzed for patients enrolled in the data over the continuous follow-up (CFU) period, and for patients continuously taking their initial treatment for 6 months (CTX). Potential confounders collected over a 6-month baseline assessment period were controlled for, using a generalized linear model. RESULTS: Over the 180-day follow-up, prasugrel and ticagrelor patients underwent fewer admissions (rate ratio [RR] = 0.87, 95% CI = 0.80-0.95) from CFU and RR = 0.81, 95% CI = 0.71-0.89 from CTX) compared with clopidogrel patients. The newer agent cohort incurred more overall health care costs than the generic clopidogrel group, with added costs of $957 (95% CI = $236-$1,725) in the CFU group and $1,122 (95% CI = $455-$1,865) in the CTX group, which were smaller than the increase in all-cause outpatient pharmacy costs associated with the newer agents versus clopidogrel (CFU: $1,175, 95% CI = $1,079-$1,278 and CTX: $1,360, 95% CI = $1,256-$1,487). Overall, there was no statistically significant difference in the economic outcomes associated with prasugrel and ticagrelor. There were, however, significant correlations between all-cause and cardiovascular-related outcomes. CONCLUSIONS: The higher price of prasugrel and ticagrelor was partially offset by a decrease in hospital admission compared with generic clopidogrel over a 6-month postdischarge period. Aggregated medical costs and resource utilization were not significantly different between prasugrel and ticagrelor patients. DISCLOSURES: No funding was received for this study. DiDomenico has received an honorarium from Amgen for preparation of a heart failure drug monograph for Pharmacy Practice News and serves as an advisory board member for a heart failure program at Otsuka America Pharmaceuticals and for Novartis Pharmaceuticals. Touchette has received unrestricted grant funding from Cardinal Health, Sunovion Pharmaceuticals, and Takeda and has served as a consultant to and director of the American College of Clinical Pharmacy Practice-Based Research Network on a study funded by Pfizer. Walton has served as a paid consultant for Bristol-Myers Squibb, Baxter, Merck, Genentech, Primus, Takeda, and Abbott. The other authors have nothing to disclose.


Assuntos
Síndrome Coronariana Aguda/terapia , Custos e Análise de Custo , Custos de Cuidados de Saúde/estatística & dados numéricos , Intervenção Coronária Percutânea/economia , Inibidores da Agregação de Plaquetas/economia , Adenosina/análogos & derivados , Adenosina/economia , Adenosina/uso terapêutico , Administração Oral , Idoso , Clopidogrel , Feminino , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Inibidores da Agregação de Plaquetas/uso terapêutico , Período Pós-Operatório , Cloridrato de Prasugrel/economia , Cloridrato de Prasugrel/uso terapêutico , Estudos Retrospectivos , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/economia , Ticlopidina/uso terapêutico
15.
JAMA ; 320(6): 593-594, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30054611

RESUMO

Clinical Question: Among patients at high risk for or with established cardiovascular disease (ie, history of peripheral artery disease, stroke, or coronary artery disease without a coronary stent), is the addition of clopidogrel to aspirin associated with lower risk of mortality and cardiovascular events compared with aspirin alone? Bottom Line: Clopidogrel plus aspirin is associated with a reduced risk for myocardial infarction and ischemic stroke and an increased risk for major bleeding compared with aspirin alone among patients at high risk for or with an established cardiovascular disease but without a coronary stent. However, combined therapy is not associated with lower mortality.


Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/análogos & derivados , Aspirina/efeitos adversos , Doenças Cardiovasculares/mortalidade , Clopidogrel , Quimioterapia Combinada/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Literatura de Revisão como Assunto , Acidente Vascular Cerebral/prevenção & controle , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico
16.
Dtsch Med Wochenschr ; 143(15): 1060-1064, 2018 08.
Artigo em Alemão | MEDLINE | ID: mdl-30060273

RESUMO

Patients with peripheral artery disease are at high-risk for cardiovascular events. Anti-thrombotic treatment is very important for secondary prevention. In symptomatic patients single antiplatelet therapy with clopidogrel or Aspirin is recommended. After peripheral revascularisation transient dual antiplatelet therapy is widely used although there is only little evidence. Following peripheral bypass surgery most patients are treated with single antiplatelet therapy, in some cases (prostetic bypass grafts) dual antiplated therapy can be useful and selected patients with complex venous grafts might profit from anticoagulation with vitamin K antagonists.The recent publication of the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) study showed relevant reduction of MACE (Major Adverse Cariac Events) and MALE (Major Adverse Limb Events) for the combined therapy of rivaroxaban 2 × 2,5 mg compared to Aspirin 100 mg with increased risk for gastrointestinal bleeding. In the current VOYAGER PAD (Vascular Outcomes Study of Aspirin along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) study this concept is tested after peripheral revascularisation.


Assuntos
Fibrinolíticos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Administração Oral , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Implante de Prótese Vascular , Clopidogrel , Quimioterapia Combinada , Alemanha , Fidelidade a Diretrizes , Humanos , Inibidores da Agregação de Plaquetas/uso terapêutico , Cuidados Pós-Operatórios , Rivaroxabana/uso terapêutico , Prevenção Secundária , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Veias/transplante
17.
J Pharm Biomed Anal ; 159: 272-281, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30005242

RESUMO

Cardiovascular disease is a leading cause of morbidity, mortality, and healthcare expenditure worldwide. Importantly, there is interindividual variation in response to cardiovascular medications, leading to variable efficacy and adverse events. Therefore a rapid, selective, sensitive and reproducible multi-analyte HPLC-MS/MS assay for the quantification in human plasma of atorvastatin, its major metabolites 2-hydroxyatorvastatin, atorvastatin lactone and 2-hydroxyatorvastatin lactone, plus bisoprolol and clopidogrel-carboxylic acid has been developed, fully validated, and applied to a large patient study. Fifty microliter plasma samples were extracted with a simple protein precipitation procedure involving acetonitrile with acetic acid (0.1%, v/v). Chromatographic separation was via a 2.7 µm Halo C18 (50 × 2.1 mm ID, 90 Å) column and gradient elution at a flow rate of 500 µL/min consisting of a mobile phase of water (A) and acetonitrile (B), each containing 0.1% formic acid (v/v), over a 6.0 min run time. The six analytes and their corresponding six deuterated internal standards underwent positive ion electrospray ionisation and were detected with multiple reaction monitoring. The developed method was fully validated with acceptable selectivity, carryover, dilution integrity, and within-run and between-run accuracy and precision. Mean extraction recovery for the analytes was 92.7-108.5%, and internal standard-normalised matrix effects had acceptable precision (coefficients of variation 2.2-12.3%). Moreover, all analytes were stable under the tested conditions. Atorvastatin lactone to acid interconversion was assessed and recommendations for its minimisation are made. The validated assay was successfully applied to analyse 1279 samples from 1024 patients recruited to a cardiovascular secondary prevention prospective study.


Assuntos
Atorvastatina/sangue , Bisoprolol/sangue , Doenças Cardiovasculares/sangue , Espectrometria de Massas em Tandem/normas , Ticlopidina/análogos & derivados , Anticolesterolemiantes/sangue , Anticolesterolemiantes/uso terapêutico , Anti-Hipertensivos/sangue , Anti-Hipertensivos/uso terapêutico , Atorvastatina/uso terapêutico , Bisoprolol/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/normas , Cromatografia Líquida de Alta Pressão/tendências , Clopidogrel , Estudos de Coortes , Feminino , Humanos , Masculino , Espectrometria de Massas/normas , Espectrometria de Massas/tendências , Inibidores da Agregação de Plaquetas/sangue , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Prospectivos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/tendências , Ticlopidina/sangue , Ticlopidina/uso terapêutico
18.
Cell Physiol Biochem ; 48(1): 385-396, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016801

RESUMO

BACKGROUND/AIMS: Acute ST-segment elevation of myocardial infarction (STEMI) is the most severe type of acute coronary syndrome (ACS). Particular attention has been focused on studying the pathogenesis of STEMI, and how to prevent thrombosis, reduce inflammatory reaction, stabilize plaques and improve vascular endothelial functions to preserve the survived myocardium. This study aimed to compare the anti-inflammatory endothelium-protective effects, clinical prognosis, and relevant bleeding risks of ticagrelor versus clopidogrel in patients with STEMI who underwent urgent percutaneous coronary intervention (PCI) and provide certain experimental evidence and a theoretical basis for the selection of safe and effective drugs and their proper dosage, thereby further guiding clinical medication. METHODS: We sequentially enrolled 193 patients (104 males and 89 females) admitted to hospital due to acute STEMI. These patients underwent urgent PCI between December 2013 and May 2015 and met the inclusion criteria. They were assigned (1: 1) into two groups according to different treatments, 97 patients in the ticagrelor group (treatment group), and 96 patients in the clopidogrel group (control group). Levels of hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and endothelial cell-specific molecule 1 (ESM-1) taken at admission and 24 h, 4 days, and 7 days after administration, as well as the correlation between the levels of IL-6, hs-CRP, and ESM-1, were determined in the two groups. At the same time, the effects of treatment with ticagrelor and clopidogrel on the efficacy endpoint events (ischemic and safety) were explored. RESULTS: No statistically significant difference was found in the levels of hs-CRP, IL-6, or ESM-1 at admission between the two groups (P> 0.05); Their levels were significantly elevated 24 h after administration, with statistical differences between two groups (P< 0.05). Furthermore, a downward trend with statistically significant differences was found on Day 4 and Day 7 (P< 0.05); ESM-1 levels increased along with increases of hs-CRP and IL-6 levels, indicating ESM-1 was positively correlated with hs-CRP (r=0.523, P< 0.001) and IL-6 (r=0.431, P< 0.001); and the occurrence rates of ischemic endpoint events at 30 days were lower in the treatment group than in the control group. The occurrence of safety endpoint events was higher than in the control group; however, no statistically significant difference was found (P> 0.05). CONCLUSIONS: Compared with clopidogrel, ticagrelor appears to rapidly reduce the prevalence of inflammatory reactions and stabilize the functions of vascular endothelium to improve the stability of atherosclerotic plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome events without any obvious increase in the risk of bleeding in patients with acute STEMI receiving urgent PCI. This renders it a potential drug for clinical practice. At the same time, measurement of ESM-1, a new biological marker for vascular endothelial function disorder, could possibly become a simple, effective, and practical new method for clinical evaluation of risk stratification of patients with acute STEMI at admission.


Assuntos
Adenosina/análogos & derivados , Endotélio Vascular/fisiopatologia , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/análogos & derivados , Adenosina/uso terapêutico , Adulto , Idoso , Biomarcadores/análise , Proteína C-Reativa/análise , Clopidogrel , Feminino , Humanos , Interleucina-6/análise , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Proteínas de Neoplasias/análise , Intervenção Coronária Percutânea , Projetos Piloto , Prognóstico , Proteoglicanas/análise , Ticagrelor , Ticlopidina/uso terapêutico , Resultado do Tratamento
19.
Yonsei Med J ; 59(5): 624-632, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29869460

RESUMO

PURPOSE: This study aimed to compare the effects of ticagrelor and clopidogrel on early neointimal healing assessed with optical coherence tomography (OCT) after drug-eluting stent (DES) implantation in patients with acute myocardial infarction (AMI). MATERIALS AND METHODS: AMI patients were randomly assigned to either the ticagrelor or clopidogrel arm. After DES implantation, OCT was performed to assess the percentages of uncovered struts immediately after procedure and 3 months later. RESULTS: Due to early termination, 83 patients out of 106 initially enrolled patients (24% of planned participants) underwent 3-month OCT. Differences in vascular healing patterns between the two groups, including percentage of uncovered struts on 3-month OCT (9.6% vs. 11.7% in ticagrelor vs. clopidogrel, respectively; p=0.867), neointimal thickness, percentage of malapposed struts, and healing scores did not reach statistical significance. The predictors of uncovered strut on 3-month OCT included greater reference vessel diameter [odds ratio (OR)=1.96, p<0.001] and more malapposed struts (OR=1.12, p=0.003). CONCLUSION: The current study did not explore favorable effect of ticagrelor on 3-month vascular healing after DES implantation. Our findings should only be considered for generating hypothesis, due to insufficient power.


Assuntos
Adenosina/análogos & derivados , Stents Farmacológicos , Neointima/diagnóstico por imagem , Neointima/tratamento farmacológico , Ticlopidina/análogos & derivados , Tomografia de Coerência Óptica/métodos , Adenosina/administração & dosagem , Idoso , Clopidogrel , Angiografia Coronária , Stents Farmacológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio , Estudos Prospectivos , Próteses e Implantes , Ticagrelor , Ticlopidina/administração & dosagem , Resultado do Tratamento
20.
Medicine (Baltimore) ; 97(24): e11060, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29901608

RESUMO

BACKGROUND: The relationship of CYP2C19 genotype and clinical efficacy in stroke or transient ischemic attack (TIA) patients treated with clopidogrel monotherapy or clopidogrel plus aspirin remains unknown. We thus aim to conduct a meta-analysis to appraise evidence on the association of CYP2C19 genotype and clinical efficacy for stroke or TIA. METHODS: An electronic search will be performed for clinical trials that reported the interested efficacy data (stroke, myocardial infarction, or vascular death) and safety data (any bleeding) in clopigogrel-treated patients with stroke or TIA. Odds ratios (ORs) with their confidence intervals (CIs) will be calculated using a meta-analysis. RESULTS: This study will provide the evidence of the relationship between CYP2C19 genotype and clinical efficacy and safety in stroke/TIA patients taking clopidogrel by pooling the results of individual studies. CONCLUSIONS: The results will bring about vigorous evidence in this issue and guide both clinical decision-making and future research.


Assuntos
Aspirina/uso terapêutico , Citocromo P-450 CYP2C19/genética , Ataque Isquêmico Transitório/genética , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/genética , Ticlopidina/análogos & derivados , Aspirina/efeitos adversos , Clopidogrel , Quimioterapia Combinada , Genótipo , Humanos , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação de Plaquetas/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Resultado do Tratamento
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