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1.
Einstein (Sao Paulo) ; 20: eAO7001, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674593

RESUMO

OBJECTIVE: Low platelet reactivity levels are associated with higher risk of bleeding in patients receiving dual antiplatelet therapy relative to patients with optimal platelet blockade. This study set out to evaluate the prevalence of low platelet reactivity in patients with acute myocardial infarction treated with ticagrelor and aspirin. METHODS: Patients admitted with acute myocardial infarction who were already undergoing dual antiplatelet therapy with aspirin and ticagrelor were enrolled. Blood samples were collected 1 hour before and 2 hours after the maintenance dose of ticagrelor to investigate trough and the peak effects of the drug respectively. Platelet reactivity was measured by three methods: Multiplate®, PFA-100® with Innovance® PFA-P2Y cartridge and PFA-100® with Collagen/ADP cartridge. Platelet reactivity was assessed in the presence of peak levels of ticagrelor and defined according to previously validated cut-offs for each method (<19 AUC, >299 seconds and >116 seconds respectively). The level of significance was set at p<0.05. RESULTS: Fifty patients were enrolled (44% with ST-elevation). Median duration of DAPT was 3 days (interquartile range, 2-5 days). On average, peak and trough platelet reactivity were markedly low and did not differ between different methods. Low platelet reactivity was common, but varied according to analytic method (PFA-100®/Innovance®PFA-P2Y: 86%; Multiplate®: 74%; PFA-100®/Collagen/ADP: 48%; p<0.001). CONCLUSION: Low platelet reactivity was very common in patients with acute myocardial infarction submitted to dual antiplatelet therapy with ticagrelor and aspirin. Findings of this study justify the investigation of less intensive platelet inhibition strategies aimed at reducing the risk of bleeding in this population, such as lower dose regimens or monotherapy with P2Y12 inhibitors.


Assuntos
Aspirina , Infarto do Miocárdio , Difosfato de Adenosina/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Resultado do Tratamento
2.
J Cardiovasc Pharmacol Ther ; 27: 10742484221096524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35482903

RESUMO

A high platelet-to-lymphocyte ratio (PLR) has recently been associated with ischemic outcomes in cardiovascular disease. Increased platelet reactivity and leukocyte-platelet aggregate formation are directly involved in the progress of atherosclerosis and have been linked to ischemic events following percutaneous coronary intervention (PCI). In order to understand the relation of PLR with platelet reactivity, we assessed PLR as well as agonist-inducible platelet aggregation and neutrophil-platelet aggregate (NPA) formation in 182 acute coronary syndrome (ACS) patients on dual antiplatelet therapy with aspirin and prasugrel (n = 96) or ticagrelor (n = 86) 3 days after PCI. PLR was calculated from the blood count. Platelet aggregation was measured by multiple electrode aggregometry and NPA formation was determined by flow cytometry, both in response to ADP and SFLLRN. A PLR ≥91 was considered as high PLR based on previous data showing an association of this threshold with adverse ischemic outcomes. In the overall cohort and in prasugrel-treated patients, high PLR was associated with higher SFLLRN-inducible platelet aggregation (67 AU [50-85 AU] vs 59.5 AU [44.3-71.3 AU], P = .01, and 73 AU [50-85 AU] vs 61.5 AU [46-69 AU], P = .02, respectively). Further, prasugrel-treated patients with high PLR exhibited higher ADP- (15% [11%-23%] vs 10.9% [7.6%-15.9%], P = .007) and SFLLRN-inducible NPA formation (64.3% [55.4%-73.8%] vs 53.8% [44.1%-70.1%], P = .01) as compared to patients with low PLR. These differences were not seen in ticagrelor-treated patients. In conclusion, high PLR is associated with increased on-treatment platelet reactivity in prasugrel-treated patients, but not in patients on ticagrelor.


Assuntos
Intervenção Coronária Percutânea , Difosfato de Adenosina , Biomarcadores , Humanos , Linfócitos , Intervenção Coronária Percutânea/efeitos adversos , Ativação Plaquetária , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Ticagrelor/efeitos adversos
3.
J Card Surg ; 37(7): 1969-1977, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35397138

RESUMO

BACKGROUND: Compared to conventional aspirin therapy, ticagrelor did not improve vein graft patency 1 year after coronary bypass surgery (CABG) in the ticagrelor antiplatelet therapy to reduce graft events and thrombosis (TARGET) trial. However, it is unknown whether ticagrelor may impact graft patency long-term following surgery. METHODS: In the TARGET multicenter trial, 250 CABG patients were randomized to aspirin 81 mg or ticagrelor 90 mg twice daily. In this observational analysis, 2 years after surgery, vein graft occlusion and clinical events were compared among subjects who agreed to a second year of double-blind study drug administration (N = 156). RESULTS: Two-year graft assessment was performed for 142 patients (80 aspirin patients, 62 ticagrelor patients, 425 total grafts), with an overall 2-year graft occlusion rate of 10.6%. Vein graft occlusion at 2 years, the primary outcome of this study, did not significantly differ between the two groups (15.7% vs. 13.2%, aspirin vs. ticagrelor, p = .71). The incidence of vein grafts with any disease (stenosis or occlusion) did not significantly differ between the groups (19.4% vs. 19.8%, aspirin vs. ticagrelor, p = 1.00), and the number of patients with vein graft disease did not significantly differ between the groups (30.0% vs. 29.0%, aspirin vs. ticagrelor, p = 1.00). Vein grafts developing new disease did not significantly differ between the two groups (1.5% vs. 3.8%, aspirin vs. ticagrelor, p = .41). Freedom from major adverse cardiovascular events at 2 years was similar between the groups (p = .75). CONCLUSION: Compared to conventional aspirin therapy, ticagrelor did not significantly reduce vein graft disease 2 years after CABG.


Assuntos
Aspirina , Inibidores da Agregação Plaquetária , Ponte de Artéria Coronária/efeitos adversos , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/prevenção & controle , Humanos , Ticagrelor/efeitos adversos , Grau de Desobstrução Vascular
4.
Open Heart ; 9(1)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35428703

RESUMO

BACKGROUND: Currently, potent P2Y12 inhibition with the use of prasugrel or ticagrelor is the mainstay of treatment after an acute coronary syndrome (ACS). The 2020 European Society of Cardiology (ESC) Guidelines recommend the use of prasugrel over ticagrelor in patients with non-ST-elevation ACS (NSTE-ACS) intended to receive invasive management (class IIa recommendation), however there are contradictory views regarding this recommendation. AIM: To compare oral P2Y12 inhibitors in NSTE-ACS in terms of efficacy and safety with a focus on patients intended to proceed to invasive management. METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials and Web of Science to identify studies that compared different oral P2Y12 inhibitors (clopidogrel, prasugrel and ticagrelor) in patients with NSTE-ACS. Efficacy outcomes included the major adverse cardiovascular events outcome and safety outcomes included minor and major bleedings. We performed a frequentist network meta-analysis. RESULTS: Nine studies (n=35 441 patients) were included in the systematic review. There was no difference between prasugrel and ticagrelor in the composite cardiovascular end point (prasugrel vs ticagrelor HR=0.80, 95% CI=0.61 to 1.06) in all patients with NSTE-ACS. In patients intended to receive invasive management, prasugrel resulted in a reduction of the composite cardiovascular end point both versus clopidogrel (HR=0.76, 95% CI=0.61 to 0.95) and ticagrelor (HR=0.74, 95% CI=0.56 to 0.98). Inconsistency was moderate and non-significant (I2=27%, total Q p=0.2). Prasugrel ranked as the most efficient treatment in the composite cardiovascular efficacy outcome, all-cause death, myocardial infarction and definite stent thrombosis, while clopidogrel ranked as safest in the bleeding outcomes. CONCLUSION: In patients with NSTE-ACS intended to receive invasive management, an antiplatelet strategy based on prasugrel is more efficient than a similar strategy based on ticagrelor on a moderate level of evidence. This analysis supports the current recommendations by the ESC guidelines.


Assuntos
Síndrome Coronariana Aguda , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Metanálise em Rede , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos
5.
Circ Cardiovasc Interv ; 15(4): e011419, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35369712

RESUMO

BACKGROUND: Coronary microvascular dysfunction after acute coronary syndrome is an important predictor of long-term prognosis. Data is lacking on the effects of oral P2Y12-inhibitors on coronary microvascular function in non-ST-segment-elevation acute coronary syndrome. The aim of this study was to compare the acute effects of ticagrelor versus clopidogrel pretreatment on coronary microvascular function in non-ST-segment-elevation acute coronary syndrome patients. METHODS: Hospitalized non-ST-segment-elevation acute coronary syndrome patients were randomized (1:1) to ticagrelor or clopidogrel. The index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were obtained using an intracoronary pressure-temperature sensor-tipped wire. RESULTS: In total, 128 patients were randomized between March 2018 and July 2020. Mean age 59.2±11.8 years, 84% were male, mean Global Registry of Acute Coronary Events score was 93.7±24.5. Intracoronary physiological measurements were obtained in 118 patients (60 ticagrelor, 58 clopidogrel). In the infarct-related artery, the ticagrelor group had lower baseline index of microcirculatory resistance (22.0 [13.0-34.9] versus 27.7 [19.3-29.8]; P=0.02) and higher baseline resistive reserve ratio (3.0 [2.3-4.4] versus 2.4 [1.7-3.4]; P=0.01) compared with the clopidogrel group. A total of 88 patients underwent percutaneous coronary intervention (PCI; 45 ticagrelor, 43 clopidogrel). The ticagrelor group had lower post-PCI index of microcirculatory resistance (22.0 [15.0-29.0] versus 27.0 [18.5-47.5]; P=0.02) and higher post-PCI resistive reserve ratio (3.0 [1.8-3.8] versus 1.8 [1.5-3.4]; P=0.006) compared with the clopidogrel group. The coronary flow reserve was not significantly different between the 2 groups at baseline or post-PCI. No between-group differences were seen in any of the indices in the non-infarct-related artery. CONCLUSIONS: In non-ST-segment-elevation acute coronary syndrome patients, ticagrelor significantly improved coronary microvascular function before and after PCI compared with clopidogrel. REGISTRATION: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001610224.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Clopidogrel/efeitos adversos , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
6.
Arterioscler Thromb Vasc Biol ; 42(6): 789-798, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35387483

RESUMO

BACKGROUND: Long-term antiplatelet agents including the potent P2Y12 antagonist ticagrelor are indicated in patients with a previous history of acute coronary syndrome. We sought to compare the effect of ticagrelor with that of aspirin monotherapy on vascular endothelial function in patients with prior acute coronary syndrome. METHODS: This was a prospective, single center, parallel group, investigator-blinded randomized controlled trial. We randomized 200 patients on long-term aspirin monotherapy with prior acute coronary syndrome in a 1:1 fashion to receive ticagrelor 60 mg BD (n=100) or aspirin 100 mg OD (n=100). The primary end point was change from baseline in brachial artery flow-mediated dilation at 12 weeks. Secondary end points were changes to platelet activation marker (CD41_62p) and endothelial progenitor cell (CD34/133) count measured by flow cytometry, plasma level of adenosine, IL-6 (interleukin-6) and EGF (epidermal growth factor), and multi-omics profiling at 12 weeks. RESULTS: After 12 weeks, brachial flow-mediated dilation was significantly increased in the ticagrelor group compared with the aspirin group (ticagrelor: 3.48±3.48% versus aspirin: -1.26±2.85%, treatment effect 4.73 [95% CI, 3.85-5.62], P<0.001). Nevertheless ticagrelor treatment for 12 weeks had no significant effect on platelet activation markers, circulating endothelial progenitor cell count or plasma level of adenosine, IL-6, and EGF (all P>0.05). Multi-omics pathway assessment revealed that changes in the metabolism and biosynthesis of amino acids (cysteine and methionine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis) and phospholipids (glycerophosphoethanolamines and glycerophosphoserines) were associated with improved brachial artery flow-mediated dilation in the ticagrelor group. CONCLUSIONS: In patients with prior acute coronary syndrome, ticagrelor 60 mg BD monotherapy significantly improved brachial flow-mediated dilation compared with aspirin monotherapy and was associated with significant changes in metabolomic and lipidomic signatures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03881943.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Adenosina/efeitos adversos , Aspirina/efeitos adversos , Fator de Crescimento Epidérmico , Humanos , Interleucina-6 , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Ticagrelor/efeitos adversos , Resultado do Tratamento
7.
Trials ; 23(1): 203, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248132

RESUMO

BACKGROUND: Current guidelines recommend that patients with acute coronary syndrome (ACS) who have successfully undergone percutaneous coronary intervention (PCI) should continue to use dual antiplatelet therapy (DAPT) for 12 months. The long-term use of standard-dose dual antiplatelet therapy will increase the risk of bleeding. An optimized antiplatelet strategy that can prevent ischemic events and reduce the risk of bleeding remains to be explored. METHODS: The study is a prospective, multicenter, randomized, open-label, controlled study involving 2090 patients from six clinical centers in China. Through the interactive web response system (IWRS), ACS patients undergoing successful PCI will be randomly divided into the low-dose ticagrelor group or the normal-dose ticagrelor group, after taking 100 mg aspirin and 90 mg ticagrelor bid for 1 week. The primary endpoint is a composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, repeat revascularization, and stroke. The secondary endpoints are bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria, cardiovascular death, acute myocardium infarction, and coronary revascularization at 1 year. DISCUSSION: Recent studies have confirmed that 90 mg ticagrelor alone can safely and effectively reduce bleeding without increasing ischemic events of patients with ACS after PCI. Compared with standard-dose DAPT, whether low-dose ticagrelor combined with aspirin can ensure the anti-ischemic effect while reducing the bleeding risk remains unclear in Chinese patients. The TIGER study will be the first large-scale, multicenter study to compare the efficacy and safety of low-dose and standard-dose ticagrelor combined with aspirin in ACS patients 1 week after successful PCI. TRIAL REGISTRATION: Clinicaltrials.gov NCT04255602. Registered on 5 February 2020.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Quimioterapia Combinada , Humanos , Estudos Multicêntricos como Assunto , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticagrelor/efeitos adversos , Resultado do Tratamento
8.
Eur Heart J ; 43(24): 2303-2313, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35296876

RESUMO

AIMS: Post-acute coronary syndrome (ACS) P2Y12 inhibitor non-adherence is common and associated with greater risk of major adverse cardiovascular events (MACEs). Non-adherence can follow different trajectories from an inability to initiate, implement, or continue therapy for the intended duration. We aimed to evaluate P2Y12 inhibitor adherence trajectories among ACS patients treated with percutaneous coronary intervention (PCI), their frequency, and association with MACE. METHODS AND RESULTS: We conducted a cohort study of adults discharged alive after PCI for ACS (2012-16) using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry linked with administrative data. The primary outcome was P2Y12 inhibitor adherence trajectory in the year after PCI assessed using group-based trajectory modelling. We used logistic regression and Cox proportional-hazards regression to assess associations of trajectories with risk factors and MACE, respectively. We included 12 844 patients (mean age 62.4 years, 23.6% female). Five trajectories were identified: early consistent non-adherence (11.0%), rapid decline (7.7%), delayed initiation (6.0%), gradual decline (20.5%), and persistent adherence (54.8%). Compared with persistent adherence, rapid decline [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01-1.49] and delayed initiation (HR 1.41, 95% CI 1.12-1.78) were associated with higher MACE in the overall cohort, whereas early consistent non-adherence was associated with higher MACE only in the subgroup receiving a drug-eluting stent (HR 2.44, 95% CI 1.60-3.71). CONCLUSION: After PCI for ACS, patients followed one of five distinct P2Y12 inhibitor adherence trajectories. Rapid decline and delayed initiation were associated with a higher risk of MACE, whereas early consistent non-adherence was only associated with higher MACE risk in patients with a drug-eluting stent.


Assuntos
Síndrome Coronariana Aguda , Stents Farmacológicos , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/etiologia , Clopidogrel/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Prognóstico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/efeitos adversos , Resultado do Tratamento
9.
BMJ Open ; 12(3): e060404, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35351733

RESUMO

INTRODUCTION: In order to reduce the risk of bleeding in patients on P2Y12 receptor inhibitors presenting for non-emergent coronary artery bypass grafting (CABG), current guidelines recommend a preoperative discontinuation period of at least three, five and seven days for ticagrelor, clopidogrel and prasugrel, respectively, to allow for recovery of platelet function. However, there is still substantial interinstitutional variation in preoperative management and relevant covariates of CABG-related bleeding are largely elusive so far. METHODS AND ANALYSIS: We will search PubMed (July 2013 to November 2021) and EMBASE (January 2014 to November 2021) using the following terms, MeSH terms and their synonyms: clopidogrel, prasugrel, ticagrelor, dual antiplatelet, P2Y12 receptor inhibitor, CABG, bleeding, haemorrhage. Two independent reviewers will screen all abstracts and full papers for eligibility. Disagreements will be solved by consulting with a third reviewer.The primary outcome is the incidence of Bleeding Academic Research Consortium type-4 bleeding depending on type of P2Y12 receptor inhibitor and preoperative withdrawal period. The secondary outcomes are mortality and ischaemic events according to the Academic Research Consortium 2 Consensus Document. We will perform an individual patient data meta-analysis (IPD-MA) with drug-specific preoperative withdrawal time and adjust for demographic and procedural variables. Subgroup analyses will be performed for anaemic patients and patients undergoing non-emergent versus urgent/emergent surgery. ETHICS AND DISSEMINATION: This IPD-MA consists of secondary analyses of existing non-identifiable data and meets the criteria for waiver of ethics review by the local Research Ethics Committee. Data sharing and transfer will be subject to a confidentiality agreement and a data use agreement. Findings will be disseminated through peer-reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42022291946.


Assuntos
Síndrome Coronariana Aguda , Antagonistas do Receptor Purinérgico P2Y , Clopidogrel/efeitos adversos , Humanos , Metanálise como Assunto , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Revisões Sistemáticas como Assunto , Ticagrelor/efeitos adversos
10.
BMC Cardiovasc Disord ; 22(1): 111, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35300607

RESUMO

BACKGROUND: Studies show inconsistent results regarding the impact of CYP2C19 genotype on the pharmacodynamics (PD) and clinical outcomes of ticagrelor. With the implementation of genotype-guided individualized antiplatelet therapy, the association between CYP2C19 polymorphism and the efficacy and safety of ticagrelor for patients is still worthy of exploring and studying. METHODS: This systematic review protocol has been registered in the PROSPERO network (No. CRD 42020158920). Electronic databases of PubMed, EmBase, and the Cochrane Library were systematically searched from inception to January 6th, 2022 to select studies investigating the impact of CYP2C19 genotype on PD and clinical outcomes of ticagrelor. The results were presented as odds ratio (OR) or weight mean difference with its 95% confidence interval (CI) by using the random-effects model. Trial sequential analysis (TSA) was used to control risk of random errors and detect the robustness of outcomes. RESULTS: Eight studies recruited a total of 6405 patients treated with ticagrelor. Mostly trials reported no significant effect of any or no CYP2C19 loss-of-function (LOF) allele (*2 or *3) on all the endpoints. Compared with no LOF allele carriers, subgroup analysis suggested any LOF allele in Asian patients was associated with a significant decreased risk of bleeding events (OR: 0.41; 95% CI: 0.22-0.75; P = 0.004). Furthermore, any LOF allele carriers didn't yield any impact on the risk of MACEs (OR: 1.11; 95% CI: 0.76-1.64; P = 0.586), stroke (OR: 1.71; 95% CI: 0.99-2.96; P = 0.054), definite stent thrombosis (OR: 0.88; 95% CI: 0.17-4.60; P = 0.882), bleeding (OR: 0.63; 95% CI: 0.27-1.46; P = 0.281), myocardial infarction (OR: 0.81; 95% CI: 0.30-2.20; P = 0.682), and revascularization (OR: 0.81; 95% CI: 0.33-2.00; P = 0.649) in all patients. The results of TSA were indicated that more further trials would be required. CONCLUSIONS: This qualitative and quantitative study suggested Asian patients carrying any CYP2C19 LOF allele might have a lower risk of bleeding events comparing with no LOF allele carriers when treated with ticagrelor. However, we did not prove an important role of CYP2C19 genotype on the risk of PD and clinical endpoints in the whole cohort. In future, more large-scale prospective studies and more different ethnic populations should be included.


Assuntos
Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Clopidogrel/efeitos adversos , Citocromo P-450 CYP2C19/genética , Genótipo , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Polimorfismo Genético , Estudos Prospectivos , Ticagrelor/efeitos adversos , Resultado do Tratamento
11.
Ned Tijdschr Geneeskd ; 1662022 01 24.
Artigo em Holandês | MEDLINE | ID: mdl-35138719

RESUMO

Although current literature indicates both a clinical and a cost-effective benefit of routine genotype-guided treatment of patients treated with clopidogrel, this strategy is not recommended in guidelines. In cardiology, but also in neurology and vascular surgery, the current scientific evidence for this is still insufficient. Nevertheless, the role of pharmacogenetics will gain importance in today's medical world, where the demand for personalised medicine is on the rise. The implementation of genotyping in the clinic will nonetheless be a practical challenge due to a lack of clarity about who will bear the associated costs. In patients with coronary artery disease and a higher bleeding risk, it is valuable to determine the CYP2C19 genotype prior to treatment with clopidogrel. Pending further studies, we recommend that specialists prescribing clopidogrel should determine the CYP2C19 genotype in patients at high risk of recurrent ischemic events.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/terapia , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/uso terapêutico , Fibrinolíticos/uso terapêutico , Genótipo , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/efeitos adversos , Resultado do Tratamento
12.
J Cardiovasc Pharmacol ; 79(5): 620-631, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35170490

RESUMO

ABSTRACT: The efficacy and safety of clopidogrel compared with ticagrelor as part of dual antiplatelet therapy in patients, and in older patients, with acute coronary syndrome is reviewed. PubMed, Embase, the Cochrane Library, MEDLINE, and HTA databases were searched (September 2, 2020) for randomized controlled trials (RCTs). Pooled risk differences (clopidogrel minus ticagrelor) were estimated using random-effects meta-analyses, and certainty of evidence was assessed according to Grading of Recommendations Assessment, Development, and Evaluation. In all, 29 RCTs were identified. The risk difference for all-cause mortality was 0.6% (-0.03% to 1.3%), cardiovascular (CV) mortality: 0.6% (95% confidence interval: 0.01% to 1.1%), myocardial infarction (MI): 0.9% (0.4% to 1.3%), stent thrombosis: 0.7% (0.4 to 1.1%), clinically significant bleeding: -1.9% (-3.7% to -0.2%), major bleeding: -0.9% (-1.6% to -0.1%), and dyspnea: -5.8% (-7.7% to -3.8%). In older patients, there were no differences between the comparison groups regarding all-cause mortality, CV mortality, and MI, whereas the risk of clinically significant bleeding and major bleeding was lower in the clopidogrel group, -5.9% (-11 to -0.9%, 1 RCT) and -2.4% (-4.4% to -0.3%), respectively. Compared with ticagrelor, clopidogrel may result in little or no difference regarding all-cause mortality. Although not evident in older patients, it cannot be excluded that clopidogrel may be slightly less efficient in reducing the risk of CV mortality and MI, whereas ticagrelor is probably more efficacious in reducing the risk of stent thrombosis. Clopidogrel results in a reduced risk of dyspnea and clinically significant bleeding and in older people probably in a reduced risk of major bleeding.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Trombose , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Clopidogrel/efeitos adversos , Dispneia/induzido quimicamente , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Trombose/induzido quimicamente , Trombose/prevenção & controle , Ticagrelor/efeitos adversos , Resultado do Tratamento
13.
JAMA ; 327(3): 227-236, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040887

RESUMO

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Heparina/administração & dosagem , Pacientes Internados , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , COVID-19/sangue , COVID-19/mortalidade , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Comorbidade , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Mortalidade Hospitalar , Humanos , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Oxigenoterapia/estatística & dados numéricos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Receptores Purinérgicos P2Y12 , Respiração Artificial/estatística & dados numéricos , Trombose/epidemiologia , Ticagrelor/administração & dosagem , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Ann Thorac Cardiovasc Surg ; 28(3): 186-192, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35046210

RESUMO

OBJECTIVE: To analyze the results of hemoadsorption in patients with cardiac surgery to thoracic aortic surgery, who had been loaded beforehand with either Factor Xa inhibitor rivaroxaban or P2Y12 receptor antagonist ticagrelor. METHODS: We investigated 21 of 171 consecutive patients (median age 71 [interquartile range 62, 76] years) who underwent emergency cardiac operations for acute type A aortic dissection between 2014 and 2020. These patients were pretreated with rivaroxaban (n = 9) or ticagrelor (n = 12). In ten of 21 cases (since 2017), we installed a hemoadsorber into the heart-lung machine and compared the results to eleven patients done without hemoadsorber before that time. RESULTS: The operation time was significantly shorter in the adsorber group (286 ± 40 min vs. 348 ± 79 min; p = 0.045). The postoperative 24-hour drainage volume was significantly lower after adsorption (p <0.001; 482 ± 122 ml vs. 907 ± 427 ml) and no rethoracotomy had to be performed (compared to two rethoracotomies [18.9%] among patients without adsorber use). Also, patients without hemoadsorption required significantly more platelet transfusions (p = 0.049). CONCLUSIONS: In patients with acute type A aortic dissection who were pretreated with rivaroxaban and ticagrelor, the intraoperative use of CytoSorb hemoadsorption during cardiopulmonary bypass is reported for the first time. The method was found to be effective to prevent from bleeding and to improve the outcome in aortic dissection.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Procedimentos Cirúrgicos Cardíacos , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Rivaroxabana/efeitos adversos , Ticagrelor/efeitos adversos , Resultado do Tratamento
15.
Catheter Cardiovasc Interv ; 99 Suppl 1: 1395-1402, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35032148

RESUMO

OBJECTIVES: To evaluate the effectiveness and safety of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) undergoing complex percutaneous coronary intervention (PCI). BACKGROUND: It remains inconclusive whether ticagrelor is superior to clopidogrel in ACS patients undergoing complex PCI in real-world practice. METHODS: Based on an all-comers PCI registry, we compared the long-term effectiveness and safety between ticagrelor and clopidogrel in ACS patients undergoing complex PCI, defined as PCI procedures for complex lesions including bifurcation, chronic total occlusion, ostial, tortuous, calcific, diffused, thrombus-containing, and restenotic lesions. The primary ischemic outcome was a composite of cardiac death, myocardial infarction, or stroke. The safety outcome comprised Bleeding Academic Research Consortium (BARC) types 2, 3, and 5 bleeding. Propensity score matching (PSM) was performed to reduce bias. RESULTS: Among ACS patients who underwent complex PCI, 4373 (35.2%) and 8065 (64.8%) received dual antiplatelet therapy based on ticagrelor and clopidogrel, respectively. The incidences of composite ischemic events (before PSM: 1.74% vs. 2.84%; after PSM: 1.50% vs. 2.65%; p < 0.01 for both) and all-cause death (before PSM: 1.23% vs. 2.12%, p < 0.01; after PSM: 1.09% vs. 1.81%, p = 0.02) were significantly lower in the ticagrelor-treated than in the clopidogrel-treated group. There was no significant difference in BARC types 2, 3, and 5 bleeding between groups. CONCLUSIONS: Whilst the risk of major bleeding was comparable between the two drugs, ticagrelor was associated with a significantly lower risk of ischemic events than clopidogrel in ACS patients undergoing complex PCI.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/terapia , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Ticagrelor/efeitos adversos , Resultado do Tratamento
16.
Catheter Cardiovasc Interv ; 99 Suppl 1: 1424-1431, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35077608

RESUMO

This study evaluated clinical outcomes of switching from clopidogrel to ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). The clinical benefit of in-hospital switching from clopidogrel to ticagrelor in these patients remains unclear. Among patients with ACS initially receiving clopidogrel, logistic regression was used to identify independent predictors of switching to ticagrelor. Multivariable Cox regression was used to compare efficacy and safety between switching to ticagrelor and continuing clopidogrel. The primary endpoint was net adverse clinical events (NACEs) at 12 months, a composite of major adverse cardiovascular events (MACE) and Bleeding Academic Research Consortium (BARC) type 2/3/5 bleeding. Among 10,519 patients initially receiving clopidogrel, 1405 (13.4%) were switched to ticagrelor at discharge. Stent number, left main artery lesions, diabetes, male sex, age, estimated glomerular filtration rate of <45 ml/min/1.73 m2 , and history of PCI or stroke were identified as independent predictors of switching to ticagrelor. The rate of NACE (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.18-1.91) or BARC type 2/3/5 bleeding (HR: 2.01; 95% CI: 1.52-2.66) was significantly higher in patients switching to ticagrelor than in those continuing clopidogrel. The risk of MACE was comparable between both the groups (HR: 0.71; 95% CI: 0.41-1.22). In real-world practice, in-hospital switching from clopidogrel to ticagrelor was independently associated with several clinical factors. Patients switching to ticagrelor had a higher rate of NACE or BARC type 2/3/5 bleeding than those continuing clopidogrel, without any reduction in the MACE rate.


Assuntos
Síndrome Coronariana Aguda , Diabetes Mellitus Tipo 2 , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/terapia , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Hospitais , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Ticagrelor/efeitos adversos , Resultado do Tratamento
17.
J Cardiovasc Pharmacol ; 79(5): 632-640, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35091511

RESUMO

ABSTRACT: The risk of bleeding is high in East Asians, whether East Asian patients with acute coronary syndrome choose ticagrelor or clopidogrel is still controversial. In this study, PubMed, EMBASE, Cochrane Library database, and other sources were systematically searched. The primary efficacy outcome was all-cause death, the primary safety outcomes were any bleeding, PLATO major bleeding, and fatal bleeding. The secondary outcomes included vascular-cause death, myocardial infarction, stent thrombosis, stroke, and dyspnea. A total of 8 randomized controlled trials with 3597 patients met inclusion criteria. Compared with clopidogrel, ticagrelor had significantly higher incidence of any bleeding [risk ratio (RR), 1.63; 1.33-1.99; P < 0.00001], PLATO major bleeding (RR 1.56; 1.15-2.12; P = 0.004), and dyspnea (RR 2.60; 1.68-4.00; P < 0.00001). However, ticagrelor was associated with a significantly reduced risk of stent thrombosis (RR 0.42; 0.19-0.92; P = 0.03). There was no significant difference in the risk of all-cause death (RR 0.87; 0.64-1.24; P = 0.44), fatal bleeding (RR 2.49; 0.79-7.86; P = 0.12), vascular-cause death (RR 0.88; 1.60-0.30; P = 0.52), myocardial infarction (RR 0.89; 0.65-1.23; P = 0.49), and stroke (RR 0.84; 0.47-1.50; P = 0.56) between the 2 groups. The present findings demonstrated that ticagrelor was associated with a higher risk of any bleeding, PLATO major bleeding, and dyspnea compared with clopidogrel in East Asian patients with acute coronary syndrome. However, it significantly reduced the risk of stent thrombosis. (Registered by PROSPERO, CRD42021255215).


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Trombose , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Dispneia/diagnóstico , Dispneia/tratamento farmacológico , Dispneia/epidemiologia , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Trombose/tratamento farmacológico , Ticagrelor/efeitos adversos , Resultado do Tratamento
18.
Pharmacoepidemiol Drug Saf ; 31(2): 235-246, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34802175

RESUMO

PURPOSE: We aimed to describe characteristics of new users of ticagrelor or clopidogrel following a recent coronary event, and to compare incidences of selected safety outcomes. METHODS: This observational cohort study used data from national Swedish registers. Patients first dispensed ticagrelor or clopidogrel (June 2011-December 2013) were identified from the Prescribed Drug Register and followed until censoring or 31 December 2014. Cohorts were restricted to patients with a recent coronary event-related hospital contact identified in the Patient Register. RESULTS: The study included 45 987 unique, naïve users of ticagrelor (73% men; mean age 66 years) or clopidogrel (69% men; mean age 69 years). Corresponding to indication, diagnoses before initiation were acute coronary syndrome (93%), myocardial infarction (76%), and percutaneous coronary intervention (69%). The most common medications used in the year before initiation of study therapy were antithrombotic agents (clopidogrel 62%, ticagrelor 43%), mainly low-dose acetylsalicylic acid. Ticagrelor users had a higher incidence (per 1000 person-years) of respiratory bleeding (24.6 [95% confidence interval (CI): 22.1-27.3]; vs clopidogrel users: 14.4 [13.1-15.8]) and dyspnea (25.9 [23.3-28.7]; vs clopidogrel users: 16.8 [15.4-18.4]). Epistaxis accounted for 83-93% of respiratory bleeds. Adjusted analyses found increased risks of gout and acute renal failure with ticagrelor. CONCLUSIONS: Clopidogrel users were older with a higher prevalence of concomitant medications than ticagrelor users. Our study showed increased incidences of dyspnea and respiratory bleeding (mainly epistaxis) among current ticagrelor users compared with clopidogrel users, and increased risks of gout and acute renal failure after adjustment.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/epidemiologia , Idoso , Clopidogrel/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos , Suécia/epidemiologia , Ticagrelor/efeitos adversos , Resultado do Tratamento
19.
Br J Clin Pharmacol ; 88(1): 145-154, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34080719

RESUMO

AIMS: This study aimed to evaluate and compare the effectiveness and safety between clopidogrel and ticagrelor in acute coronary syndrome (ACS) with renal dysfunction. METHODS: We conducted a retrospective cohort study on patients on chronic dialysis and whose admission diagnosis between 1 July 2013 and 31 December 2016 included ACS. The primary effectiveness endpoint was a major adverse cardiovascular event (MACE), and the primary safety endpoint was a major bleeding event. The application of propensity scores through the inverse probability of treatment weighting (IPTW) was applied to the study groups. Cox regression was used to estimate hazard ratios (aHRs) of study endpoints. In addition, the competing risk was adjusted using the Fine and Gray competing risk model. RESULTS: There were 1915 patients in the clopidogrel group and 270 patients in the ticagrelor group. At 12 months, the ticagrelor group had higher risks for MACE (aHR with IPTW: 1.29; 95% CI 1.16-1.44); death (aHR with IPTW: 1.65; 95% CI 1.47-1.86) and cardiac death (subdistribution HR [SHR] with IPTW: 1.64; 95% CI 1.41-1.91), compared with those in the clopidogrel group. For major bleeding event, the risk was significantly higher with ticagrelor than with clopidogrel (SHR with IPTW: 1.49; 95% CI 1.34-1.65). In terms of the risk for any bleeding event, there was no significant difference between the two groups (SHR with IPTW: 1.05; 95% CI 0.95-1.17). CONCLUSIONS: Compared with clopidogrel, ticagrelor was associated with higher MACE, death, cardiac death and major bleeding risk within 12 months in patients with ACS and on dialysis.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Diálise Renal , Estudos Retrospectivos , Taiwan/epidemiologia , Ticagrelor/efeitos adversos , Resultado do Tratamento
20.
J Pharm Pract ; 35(2): 235-243, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33107382

RESUMO

BACKGROUND: Clopidogrel is the most commonly prescribed P2Y12 inhibitor for acute coronary syndrome (ACS) or stent placement, though ticagrelor or prasugrel may be preferred. Medication-related factors may influence selection of therapy. OBJECTIVES: To determine which factors most greatly influence cardiology-provider and patient selection of P2Y12 inhibitor to guide shared-decision making (SDM). METHODS: Single-center study assessed survey responses from 32 cardiology-providers who prescribed and 105 patients who received clopidogrel, prasugrel, or ticagrelor for ACS or stent placement. Respondents ranked factors influencing P2Y12 inhibitor selection and reported preference of therapy. Patients reported experience with shared decision-making process. RESULTS: Cardiology-providers ranked risk of bleeding, comfort/experience, and cost as most influential. Patients ranked risk of drug interaction, adverse effects, and reduction in myocardial infarction as most influential. Significant differences between cardiology-providers and patients were found for 5 of 8 factors. Cardiology-providers ranked once daily administration (p = 0.01), risk of bleeding (p = 0.002), and cost (p < 0.001) as more important than patients. Patients ranked risk of adverse effects (p = 0.007) and drug interactions (p = 0.005) as more important than cardiology-providers. Cardiology-providers prescribed ticagrelor 42.3% of the time following ACS, though 78.1% ranked it as their preferred agent. Patients were prescribed ticagrelor 9.3% of the time, though 55.7% ranked it as their preferred agent. Use of SDM was reported by 21.6% of patients and 88.5% were unaware that multiple P2Y12 inhibitors existed. CONCLUSION: Significant differences exist between cardiology-providers and patients regarding factors influencing P2Y12 inhibitor selection, specifically safety-related factors, once daily administration, and cost. Most patients were not involved in SDM.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel , Hemorragia/induzido quimicamente , Humanos , Preferência do Paciente , Seleção de Pacientes , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Resultado do Tratamento
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