Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 459
Filtrar
1.
PLoS One ; 15(12): e0236260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370281

RESUMO

BACKGROUND: Antiplatelet therapy is a cornerstone of secondary stroke prevention, but the responsiveness to antiplatelet medication varies among patients. Clopidogrel is a pro-drug that requires hepatic transformation to reach its active metabolite. Single nucleotide polymorphisms (SNPs) in key enzymes or the target adenosine diphosphate (ADP) receptor on the platelet surface are believed to be involved in clopidogrel-mediated platelet inhibition and decreased antiplatelet effect with high-on-treatment platelet reactivity (HTPR). OBJECTIVE: This study investigated whether specific SNPs in key hepatic enzymes (CYP2C19*2, *3, *17, CYP3A4*1G, and NR1I2) or the ADP receptor (PR2Y12) are associated with HTPR to clopidogrel. PATIENTS & METHODS: This observational study included patients with ischemic stroke (IS) and transient ischemic attacks (TIAs) receiving clopidogrel at a dose of 75 mg/day. Patients were genotyped for eight different SNPs in the genes encoding CYP2C19, CYP3A4, NR1I2, and the P2Y12 receptor. RESULTS: Of the 103 patients that were included, 30.7% carried the CYP2C19*2 allele and had higher platelet reaction unit (PRU) values than non-carriers, but no patients showed HTPR. Carriers of the *17 allele had higher platelet inhibition but showed no difference in PRU values compared with non-carriers. The remaining SNPs were neither associated with PRU nor with platelet inhibition. CONCLUSIONS: Patients with IS and TIAs treated with 75 mg clopidogrel/day do not have HTPR. A genetic analysis of CYP2C19*2, *3, *17, CYP3A4*1G, and NR1I2 revealed no associations with clopidogrel HTPR. CYP2C19*2 carriers and patients with HTPR in the acute phase after ischemic stroke or transient ischemic attacks exhibit higher PRU values, but not long-term treatment HTPR.


Assuntos
Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , Inibidores da Agregação de Plaquetas/uso terapêutico , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Dinamarca , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária
2.
J Int Med Res ; 48(10): 300060520966151, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33108941

RESUMO

OBJECTIVE: No data are available to develop uniform recommendations for reperfusion therapies in ST-segment elevation myocardial infarction (STEMI) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to fill the evidence gap regarding STEMI reperfusion strategy during the COVID-19 era. METHODS: Clinical characteristics and outcomes for 17 patients with STEMI who received fibrinolysis during the COVID-19 pandemic were compared with 20 patients who received primary percutaneous coronary intervention (PPCI), and were further compared with another 41 patients who received PPCI in the pre-COVID-19 period. RESULTS: In patients with STEMI, fibrinolysis achieved a comparable in-hospital and 30-day primary composite end point, as compared with those who received PPCI during the COVID-19 pandemic. No major bleeding was detected in either group. Compared patients with STEMI who received PPCI in the pre-COVID-19 period, we found a remarkable extension of chest pain onset-to-first medical contact (FMC) and FMC-to-wire crossing times, significantly increased number and length of stents, and much worse thrombolysis in myocardial infarction flow in patients with STEMI who received PPCI during the COVID-19 pandemic. CONCLUSION: Owing to its considerable efficacy and safety and advantages in conserving medical resources, we recommend fibrinolysis as a reasonable alternative for STEMI care during the COVID-19 pandemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Fibrinolíticos/uso terapêutico , Pandemias , Pneumonia Viral/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Idoso , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Feminino , Fibrinólise , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Reperfusão Miocárdica/métodos , Intervenção Coronária Percutânea/métodos , Proteínas Recombinantes/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Stents , Análise de Sobrevida , Resultado do Tratamento
3.
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
4.
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
5.
Am J Cardiol ; 134: 83-90, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32892987

RESUMO

The optimal antiplatelet strategy after left atrial appendage (LAA) occlusion able to protect from device-related thrombosis, paying the lowest price in terms of bleeding increase, is unclear. In a real-world, observational study we performed a head-to-head comparison of single versus dual antiplatelet therapy (SAPT vs DAPT) in patients who underwent LAA occlusion. We included 610 consecutive patients, stratified according to the type of post-procedural antiplatelet therapy (280 on SAPT and 330 on DAPT). Primary outcome measure was the incidence of the net composite end point including Bleeding Academic Research Consortium classification 3-5 bleeding, major adverse cardiovascular events or device-related thrombosis at 1-year follow-up. The use of SAPT compared with DAPT was associated with similar incidence of the primary net composite end point (9.3% vs 12.7% p = 0.22), with an adjusted hazard ratio (HR) of 0.69, 95% confidence interval 0.41 to 1.15; p = 0.15) at multivariate analysis. However, SAPT significantly reduced Bleeding Academic Research Consortium classification 3-5 bleeding (2.9% vs 6.7%, p = 0.038; adjusted HR 0.37, 0.16 to 0.88; p = 0.024). The occurrence of ischemic events (major adverse cardiovascular events or device-related thrombosis) was not significantly different between the 2treatment strategies (7.8% vs 7.4%; adjusted HR 1.34, 0.70 to 2.55; p = 0.38). In patients who underwent LAA occlusion, post-procedural use of SAPT instead of DAPT was associated with reduction of bleeding complications, with no significant increase in the risk of thrombotic events. These hypothesis-generating findings should be confirmed in a specific, randomized study.


Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Terapia Antiplaquetária Dupla/estatística & dados numéricos , Hemorragia/epidemiologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Implantação de Prótese , Acidente Vascular Cerebral/prevenção & controle , Trombose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Fibrilação Atrial/complicações , Doenças Cardiovasculares/mortalidade , Clopidogrel/uso terapêutico , Embolia/etiologia , Embolia/prevenção & controle , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Dispositivo para Oclusão Septal , Acidente Vascular Cerebral/etiologia
6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 48(9): 765-771, 2020 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-32957760

RESUMO

Objective: To investigate the effects of clopidogrel resistence and CYP2C19 genotype on the clinical prognosis of acute coronary syndrome(ACS) patients undergoing percutaneous coronary intervention(PCI). Methods: This study was a retrospective cohort study. ACS patients who underwent PCI in Beijing Anzhen Hospital from October 2015 to January 2017 were recruited. The inhibition rate of adenosine diphosphate(ADP) was monitored by thromboelastography. All of these patients were divided into clopidogrel resistance and non-resistance group according to the monitoring results. CYP2C19 genotype was detected by TaqMan probe-based real-time quantitative PCR. Patients were divided into slow, medium and fast metabolic group, according to the CYP2C19 genotype. After 12 months of follow-up, the end points included all-cause death, cardiac death, angina, myocardial infarction, stent thrombosis, ischemic stroke and hemorrhage were collected. Combined thrombotic events were defined as a composite of angina, myocardial infarction, stent thrombosis and ischemic stroke. The differences of the incidence of clinical events between groups were compared. Cox regression was used to analyze the effects of clopidogrel resistance and CYP2C19 genotype on the combined thrombotic events, cardiac death and hemorrhage. Results: A total of 1 696 patients were included, and the age was (59.4±9.6) years, with 1 280(75.5%) males. There were 471 cases(27.8%) in clopidogrel resistance group, and 1 225 cases(72.2%) in clopidogrel non-resistance group. There were 218 patients(12.9%) were in slow metabolic group, 668(39.4%) in medium metabolic group, and 810 (47.8%) in fast metabolic group. The median follow-up time was 13.3 months, and 131 cases were lost to follow-up, with a loss follow-up rate of 7.7%. Compared with the clopidogrel non-resistance group, the clopidogrel resistance group had a higher incidence of myocardial infarction(7.6%(36/471) vs. 5.1%(62/1 225), P=0.041), a lower incidence of hemorrhage (13.2%(62/471) vs. 17.9%(219/1 225), P=0.020) and minor hemorrhage(11.5%(54/471) vs. 15.8% (194/1 225), P=0.022). There were no statistically significant difference in all-cause death, cardiac death, angina, stent thrombosis, ischemic stroke and severe bleeding between clopidogrel resistance and non-resistance group(all P>0.05). There was no statistically significant difference in the incidence of endpoint events among different CYP2C19 genotypes (all P>0.05). Cox regression analysis showed that clopidogrel resistance was an independent factor of combined thrombotic events (OR=2.334, 95%CI 1.215-4.443, P=0.016) and bleeding events (OR=0.481, 95%CI 0.174-0.901, P=0.023). While CYP2C19 genotype was not independent factor for combined thrombotic events, cardiac death and hemorrhage (all P>0.05). Conclusion: For ACS patients after PCI, clopidogrel resistance can increase the risk of combined thrombotic events, but also reduce the risk of bleeding; while CYP2C19 genotype is not an independent factor for clinical prognosis.


Assuntos
Síndrome Coronariana Aguda , Clopidogrel , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/genética , Clopidogrel/farmacologia , Clopidogrel/uso terapêutico , Citocromo P-450 CYP2C19/genética , Genótipo , Humanos , Masculino , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
7.
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
8.
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
9.
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
12.
Am Heart J ; 227: 100-106, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32730905

RESUMO

BACKGROUND: New antithrombotic strategies that reduce primary thrombosis and restenosis might improve vascular outcomes in patients with peripheral artery disease (PAD) undergoing arterial angioplasty. The study objective is to evaluate the potential benefit of apixaban plus aspirin compared with standard of care dual antiplatelet therapy (DAPT) in reducing thrombotic restenosis and artery re-occlusion in patients undergoing endovascular infrapopliteal revascularization. STUDY DESIGN: This multicenter, parallel-group, prospective, randomized, open-label, blinded-endpoint adjudication, proof-of-concept, exploratory trial aims to randomize 200 patients 72 hours after successful infrapopliteal angioplasty for critical limb ischemia (CLI). Patients will be randomly assigned in a 1:1 ratio to receive oral apixaban (2.5 mg twice daily) plus aspirin (100 mg once daily) for 12 months or clopidogrel (75 mg daily) for at least 3 months on a background of aspirin (100 mg once daily) for 12 months. The primary endpoint is the composite of target lesion revascularization (TLR), major amputation, or restenosis/occlusion (RAS) in addition to major adverse cardiovascular events - MACE (myocardial infarction, stroke or cardiovascular death) at 12 months. The primary safety endpoint is the composite of major bleeding or clinically relevant non-major bleeding at 12 months. SUMMARY: This study will evaluate the efficacy and safety of apixaban 2.5 mg twice daily plus aspirin compared with DAPT (clopidogrel plus aspirin) in patients with CLI undergoing endovascular infrapopliteal revascularization and might prove the concept of an alternative antithrombotic regimen for these patients to be tested in a future large randomized clinical trial.


Assuntos
Angioplastia , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Isquemia/cirurgia , Perna (Membro)/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Inibidores da Agregação de Plaquetas/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Trombose/prevenção & controle , Angioplastia/métodos , Estado Terminal , Inibidores do Fator Xa , Humanos , Estudos Multicêntricos como Assunto , Artéria Poplítea , Estudo de Prova de Conceito , Estudos Prospectivos
13.
Aliment Pharmacol Ther ; 52(4): 646-654, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32657466

RESUMO

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


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Clopidogrel/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/efeitos adversos , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/epidemiologia , Idoso , Clopidogrel/uso terapêutico , Estudos de Coortes , Feminino , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Cloridrato de Prasugrel/uso terapêutico , Estudos Retrospectivos , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle , Ticagrelor/uso terapêutico , Resultado do Tratamento , Estados Unidos/epidemiologia
14.
Stroke Vasc Neurol ; 5(2): 128-137, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32606085

RESUMO

BACKGROUND: The effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear. METHODS: Data of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models. RESULTS: Among the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p<0.001) and >1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, p<0.001) was associated with higher mRS scores. Severe CSVD (HR 10.70, 95% CI 1.16 to 99.04, p=0.04), but not ICAS, was associated with a higher risk of bleeding events. Six-point modified CSVD score improved the predictive power for bleeding events and disability. INTERPRETATION: CSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes. TRIAL REGISTRATION NUMBER: NCT00979589.


Assuntos
Doenças de Pequenos Vasos Cerebrais/complicações , Arteriosclerose Intracraniana/complicações , Ataque Isquêmico Transitório/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Angiografia Cerebral , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , China , Clopidogrel/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/tratamento farmacológico , Ataque Isquêmico Transitório/diagnóstico , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Prognóstico , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico
15.
J Cardiothorac Surg ; 15(1): 155, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600365

RESUMO

BACKGROUND: Coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) can be the only option for complete revascularization in some patients with diffuse coronary artery disease. Unfortunately, CE can cause the lack of endothelium, resulting in increased risk of thrombotic events. Therefore, antithrombotic therapy is very important after surgery. However, there's no consistent protocol exists till now. The aim of this study was to compare the effectiveness and safety of dual antiplatelet therapies (DAPT) including aspirin plus clopidogrel (AC) or ticagrelor (AT) after CE + CABG. METHOD: A total of 137 continuous patients (mean age 60.0 ± 9.0 years) underwent CE + CABG from January 2016 to July 2018 in our center, and patients who received dual antiplatelet therapy (DAPT) after surgery (n = 121) were included in this study. All of the patients received aspirin 100 mg daily therapy after surgery, and 67 of the patients received extra clopidogrel 75 mg (AC) daily therapy, whereas 54 received extra ticagrelor 90 mg (AT) twice daily. All patients continued aspirin monotherapy after 1 year. Occurrence of ischemic events and bleeding events between two groups were compared. Kaplan-Meier survival was used to compare freedom from major adverse cardiovascular and cerebrovascular events (MACCE) between two groups, and log-rank test was used to confirm statistical difference. RESULTS: Follow-up was completed by 99.2%, and median follow-up time was 30.0(22.5, 35.2) months. No operative death was observed, while perioperative myocardial infarction was observed in 2(1.7%) patients (AC 1.5% vs. AT 1.9%, p = ns). One patient in AC group suffered from cardiac tamponade. During the follow-up period, no death was observed. Ischemic events including nonfatal myocardial infarction, repeat revascularization and ischemic stroke were observed in 6(5.0%) patients (AC 4.5% vs. AT 5.6%, p = ns). Overt bleeding had occurred in 3(2.5%) patients (AC 3.0% vs. AT 1.9%, p = ns). Kaplan-Meier analysis indicated that MACCE-free survival of the two groups at 3 years was 97.0% in the AC group versus 94.1% in the AT group (p = ns). CONCLUSION: In patients undergoing CE + CABG, DAPT therapy can be effective and safe with comparable results between AC and AT therapy in terms of ischemic and bleeding events. Further studies are needed.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Terapia Antiplaquetária Dupla , Endarterectomia , Idoso , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Estudos de Coortes , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Terapia Antiplaquetária Dupla/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/induzido quimicamente , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Resultado do Tratamento
16.
Medicine (Baltimore) ; 99(29): e20582, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702814

RESUMO

The morbidity of coronary artery disease (CAD) in the Uygur population of Xinjiang was much higher than the national average. Clopidogrel is the most commonly used medication worldwide in dual antiplatelet therapy for CAD, and the response of clopidogrel is affected by CYP2C19, PON1, and ABCB1 genetic polymorphisms. The distribution of CYP2C19*17, ABCB1, and PON1 genetic polymorphisms in Han and Uygur populations with CAD of Xinjiang has not been investigated.This study aimed to investigate the frequencies of CYP2C19, PON1, and ABCB1 genetic polymorphisms, and to identify the metabolizer phenotype of CYP2C19 in Han and Uygur populations with CAD in Northwestern Xinjiang, China. We identified 602 Han and 527 Uygur patients from 2014 through 2019 and studied genotypes for selected allele polymorphisms using sequencing by hybridization.There were significantly different allele frequencies and genotype frequencies between the 2 ethnic groups in terms of CYP2C19*2, *3, *17, ABCB1 and PON1, (P < .05). For CYP2C19*17, the frequency of TT genotype was 2.5% in Uygur patients, but it was undetectable in Han patients. In both the intermediate and poor metabolizer groups, the genotypes polymorphisms CYP2C19*2, *3, *17 were significantly less common in Uygur patients than in Han patients (P < .001). By contrast, the proportion of ultra-metabolizers as defined by CYP2C19*2, *3, *17 polymorphisms significantly higher in Uygur patients (18.6%) than in Han patients (1.7%, P < .001). The CYP2C19*2 frequency was significantly different between Han patients and Han healthy groups (P < .001), while the CYP2C19*3 frequency was significantly different between Uygur patients and Uygur healthy groups (P < .001).Our study supports the notion of interethnic differences in terms of CYP2C19, PON1, and ABCB1 polymorphisms and CYP2C19 genotype-defined clopidogrel metabolic groups. These finding could provide valuable data and insights into personalized CAD treatment for the Uygur and Han populations in Xinjiang.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/genética , Polimorfismo de Nucleotídeo Único/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Idoso , Arildialquilfosfatase/genética , China/etnologia , Clopidogrel/uso terapêutico , Comorbidade , Doença da Artéria Coronariana/mortalidade , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Grupos Étnicos/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico
17.
Am J Cardiol ; 130: 56-63, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32680674

RESUMO

In light of recent studies describing the antibacterial properties of ticagrelor, the association between treatment with ticagrelor and subsequent risk for infection following acute coronary syndrome (ACS) is taking on increased importance. A single center, retrospective, matched cohort analysis was performed. All patients older than 30 years of age admitted between January 1, 2013 and November 1, 2019 for an ACS and discharged with dual antiplatelet therapy (DAPT) were included. The primary outcome was defined as hospital admissions due to infections likely caused by gram-positive bacteria up to 1 year following the ACS hospitalization. The base cohort included 3,909 patients. About 2,035 (52.1%) were treated with ticagrelor and 1,874 (47.9%) with clopidogrel. Patients treated with ticagrelor had a 64% lower risk of gram-positive infection during the first year following hospitalization after adjusting for demographic and co-morbidity factors compared with those treated with clopidogrel (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21 to 0.61; p <0.001). In a cohort starting from 1 year (conclusion of DAPT period) and up to 3 years following ACS hospitalization, the risk of gram-positive infection was comparable in both groups (HR, 0.70; 95% CI, 0.41 to 1.19; p = 0.182). Treatment with ticagrelor was not associated with a reduced risk of gram-negative infections (HR, 0.48; 95% CI, 0.21 to 1.06; p = 0.07). In conclusion, DAPT regimen that includes aspirin and ticagrelor is associated with reduced risk of gram-positive infection compared with the combination of aspirin and clopidogrel.


Assuntos
Síndrome Coronariana Aguda/complicações , Infecções por Bactérias Gram-Positivas/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/uso terapêutico , Estudos de Coortes , Feminino , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco
18.
J Stroke Cerebrovasc Dis ; 29(8): 104983, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689651
19.
Brasília; s.n; 24 jul. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117704

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 21 artigos e 15 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Metilprednisolona/uso terapêutico , Vacinas/uso terapêutico , Heparina/uso terapêutico , Estudos de Coortes , Azitromicina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Células-Tronco Mesenquimais , Darunavir/uso terapêutico , Adalimumab/uso terapêutico , Rituximab/uso terapêutico , Infliximab/uso terapêutico , Clopidogrel/uso terapêutico , Ticagrelor/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticoagulantes/uso terapêutico
20.
Arch Med Res ; 51(6): 515-523, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32487324

RESUMO

BACKGROUND: Platelet hyper adhesiveness orchestrates with inflammation and vascular muscle proliferation leading to atheroma formation and endothelial dysfunction. OBJECTIVES: The current study aims to compare the prophylactic role of Aspirin and Clopidogrel therapy against isoproterenol-induced acute myocardial infarction (AMI), in mice on high-fat, cholesterol-rich diet (HFD-C). METHODS: The animals received HFD-C with Aspirin or Clopidogrel for 8 weeks and were subjected to AMI by isoproterenol. The blood lipids, inflammatory cytokines, myocardial enzymes, redox state, long pentraxin (PTX3), and matrix metalloproteinases (MMP-2 and MMP-9) activities were investigated. RESULTS: Antiplatelet therapy moderated the hyperlipidemia induced by HFD-C in the current study. Essentially, the total cholesterol and LDL-C levels were lower with Aspirin than with Clopidogrel therapy. Yet Aspirin and Clopidogrel each comparably lowered CK-MB, AST, MMP-2, MMP-9, and the lipid peroxidation product malondialdehyde (MDA) in the hyperlipidemic animals exposed to AMI. However, the decline in cTn-T, LDH and PTX3 levels was greater after Clopidogrel than Aspirin administration. Therefore, Clopidogrel provides greater protection against AMI than Aspirin in the hyperlipidemic mice. This could be explained by the suppression of the proinflammatory cytokines IL-6, TNF-α, TGF-1ß and stabilization of the extracellular matrix through the inhibition of MMP-2 and MMP-9 activities. Furthermore, Clopidogrel demonstrated significant antioxidative action in the AMI animals, resulting in diminished MDA production and preserved CAT activity. CONCLUSION: Beside its therapeutic role in the thrombotic vascular events, Clopidogrel confers significant protection against ischemic myocardial injury by counteracting the platelet-mediated inflammation and oxidative stress associated with HFD-C consumption in animals.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Inflamação/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA