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1.
Lancet ; 395(10235): 1487-1495, 2020 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386592

RESUMO

BACKGROUND: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. METHODS: In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). FINDINGS: A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. INTERPRETATION: Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. FUNDING: Italian Ministry of Education.


Assuntos
Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Clopidogrel/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Ticlopidina/uso terapêutico , Idoso , Aterosclerose/complicações , Transtornos Cerebrovasculares/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle
2.
Minerva Med ; 111(2): 173-180, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32338843

RESUMO

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


Assuntos
Aspirina/efeitos adversos , Cardiopatias/mortalidade , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Aspirina/uso terapêutico , Causas de Morte , Cardiopatias/induzido quimicamente , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Trombose/induzido quimicamente , Trombose/mortalidade
3.
EuroIntervention ; 15(18): e1605-e1614, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-31845894

RESUMO

AIMS: Antiplatelet treatment in the elderly post percutaneous coronary interventions (PCI) remains a complex issue. Here we report the results of the pre-specified subgroup analysis of the GLOBAL LEADERS trial evaluating the long-term safety and cardiovascular efficacy of ticagrelor monotherapy among patients categorised according to the pre-specified cut-off value of 75 years of age. METHODS AND RESULTS: This was a pre-specified analysis of the randomised GLOBAL LEADERS trial (n=15,991), comparing 23-month ticagrelor monotherapy (after one month of DAPT) with the reference treatment (12-month DAPT followed by 12 months of aspirin). Among elderly patients (>75 years; n=2,565), the primary endpoint (two-year all-cause mortality or new Q-wave core lab-adjudicated myocardial infarction [MI]) occurred in 7.2% and 9.4% of patients in the ticagrelor monotherapy and the reference group, respectively (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.58-0.99, p=0.041; pint=0.23); BARC-defined bleeding type 3/5 occurred in 5.2% and 4.1%, respectively (HR 1.29, 95% CI: 0.89-1.86; p=0.180; pint=0.06). The elderly with stable CAD had a higher rate of BARC 3/5 type bleeding (HR 2.05, 95% CI: 1.18-3.55) with ticagrelor monotherapy versus the reference treatment (pint=0.02). Elderly patients had a lower rate of definite or probable stent thrombosis (ST) with ticagrelor monotherapy (0.4% vs 1.4%, p=0.015, pint=0.01), compared with the reference group. CONCLUSIONS: In this pre-specified, exploratory analysis of the overall neutral trial, there was no differential treatment effect of ticagrelor monotherapy (after one-month dual therapy with aspirin) found in elderly patients undergoing PCI with respect to the rate of the primary endpoint of all-cause death or new Q-wave MI. The lower rate of ST in the elderly with ticagrelor monotherapy is hypothesis-generating. ClinicalTrials.gov identifier: NCT01813435.


Assuntos
Aspirina/uso terapêutico , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Humanos , Intervenção Coronária Percutânea/métodos , Tempo , Resultado do Tratamento
4.
Platelets ; 31(1): 15-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30759033

RESUMO

Switching from a potent P2Y12 blocker to clopidogrel is not uncommon for antiplatelet therapy in patients undergoing percutaneous coronary intervention. This meta-analysis aimed to investigate the efficacy and safety of this de-escalation strategy. Medical literature databases were searched for analysis comparing continued potent antiplatelet therapy and switching to clopidogrel with no language restrictions from inception to 07/May/2018. The primary endpoints of major adverse cardiovascular events (MACE) and major bleeding together with additional efficacy outcomes were assessed by random-effects and fixed-effects meta-analysis. A total of 17 896 patients in 13 studies were eligible for analysis, while 17 579 (98.2%) patients presented as acute coronary syndrome and 4105 (23%) patients received the de-escalation therapy. Incidence of MACE was virtually identical in both de-escalation and standard potent antiplatelet therapy groups (odds ratio 0.91, 95% CI 0.73-1.14; P = 0.43). Insignificant difference was also observed in major bleeding (0.99, 0.62-1.60; P = 0.97), all-cause death (0.95, 0.61-1.46; P = 0.81), cardiovascular death (0.66, 0.31-1.42; P = 0.29), myocardial infarction (1.12, 0.80-1.58; P = 0.51), stent thrombosis (1.09, 0.50-2.36; P = 0.83), unplanned revascularization (1.09, 0.83-1.41; P = 0.54), and stroke (1.16, 0.62-2.19; P = 0.64). In conclusion, de-escalation of antiplatelet therapy is associated with nonsignificant differences in both ischemic events and major bleeding compared with standard potent antiplatelet therapy in patients undergoing percutaneous coronary intervention. The feasibility and even superiority of this strategy need to be elucidated by further randomized trials.


Assuntos
Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Trombose/prevenção & controle , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/terapia , Quimioterapia Combinada , Humanos , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Trombose/etiologia , Trombose/mortalidade
5.
Platelets ; 31(1): 120-123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31066332

RESUMO

Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Infarto do Miocárdio/complicações , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Gerenciamento Clínico , Feminino , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/prevenção & controle , Tempo para o Tratamento , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
Am J Cardiol ; 125(5): 670-672, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883679

RESUMO

Platelet expression of FcγRIIa was quantified after myocardial infarction (MI) and we found that patients with high platelet FcγRIIa expression (>11,000/platelet) had a fourfold greater risk of subsequent MI, stroke, and death. This analysis of the original cohort of 197 patients was designed to determine whether platelet expression of FcγRIIa could be used in combination with clinical risk scores (GRACE [Global Registry of Acute Coronary Events] and DAPT [Dual Antiplatelet Therapy]) to refine cardiovascular risk assessment. Platelet expression of FcγRIIa quantified with the use of flow cytometry was broadly distributed in patients stratified into high and low risk groups based on clinical risk scores. In patients identified as high risk by the GRACE score, 62% had high platelet FcγRIIa expression. Similarly, in patients identified as high risk by DAPT, 55% had high platelet FcγRIIa expression. High platelet FcγRIIa expression discriminated high and low risk cohorts in patients with high cardiovascular risk defined by either the GRACE score (high platelet FcγRIIa 18.9% vs low platelet FcγRIIa 0%; odds ratio = 15.7, p = 0.06) or the DAPT score (high platelet FcγRIIa 15.4% vs low platelet FcγRIIa 3.7%; odds ratio = 5.6, p = 0.03) assessment. Platelet expression of FcγRIIa merits additional study to determine whether low platelet FcγRIIa expression can be used to guide early transition to aspirin monotherapy and high platelet FcγRIIa expression can be used to guide continuation of DAPT.


Assuntos
Plaquetas/metabolismo , Infarto do Miocárdio/epidemiologia , Receptores de IgG/metabolismo , Acidente Vascular Cerebral/epidemiologia , Aspirina/uso terapêutico , Doenças Cardiovasculares , Estudos de Coortes , Quimioterapia Combinada , Citometria de Fluxo , Seguimentos , Humanos , Incidência , Mortalidade , Infarto do Miocárdio/metabolismo , Inibidores da Agregação de Plaquetas/uso terapêutico , Modelos de Riscos Proporcionais , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Recidiva , Medição de Risco
7.
Am Heart J ; 218: 100-109, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31715433

RESUMO

For 4 decades, antithrombotic therapy with aspirin has been a cornerstone of secondary prevention for patients with chronic atherosclerotic cardiovascular disease (ASCVD). Unfortunately, despite the use of evidence-based therapies, patients with ASCVD continue to have recurrent major adverse cardiovascular events including death, myocardial infarction, and stroke-at a rate of approximately 2%-4% per year. To combat this continuing risk, several recent trials have evaluated the efficacy and safety of more intensive antithrombotic strategies through prolonged dual antiplatelet therapy (DAPT), combining a P2Y12 receptor antagonists and low-dose aspirin, or alternatively applying a dual pathway inhibition approach, combining low-dose non-vitamin K antagonist anticoagulant and low-dose aspirin. Both combination strategies have been shown to reduce recurrent ischemic events but at the cost of increased bleeding events. The clinical application of these antithrombotic strategies requires clinicians to assess and balance the risk of recurrent ischemic and bleeding events in an individual patient. Furthermore, clinicians may also need to adapt their antithrombotic strategies to achieve best patient outcomes, as ASCVD is a progressive disease and the risks of cardiovascular ischemic and bleeding events may shift over time. This state-of-the-art article reviews evidence from the trials and provides a practical approach to the application of DAPT and dual pathway antithrombotic therapy in the long-term management of patients with chronic ASCVD.


Assuntos
Aterosclerose/complicações , Doença da Artéria Coronariana/complicações , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Doença Crônica , Progressão da Doença , Quimioterapia Combinada/métodos , Fibrinolíticos/efeitos adversos , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico
8.
Acta Med Indones ; 51(3): 282-286, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31699954

RESUMO

Dual antiplatelet therapy (DAPT) is the mainstay of secondary prevention treatment for acute coronary syndrome (ACS) and ischemic stroke, especially after coronary intervention. DAPT consists of aspirin and P2Y12 receptor inhibitor (e.g. clopidogrel), and the use of DAPT has been increased over time. The most serious and common adverse effect is gastrointestinal bleeding. Guidelines in managing such condition are available among Gastroenterologist Societies and Cardiologist Societies. Most guidelines are consistent with each other to continue the use of aspirin while withholding P2Y12. However, European Society of Cardiologist (ESC) guideline in 2017 recommends P2Y12 receptor inhibitor as the preferred antiplatelet for patient with upper gastrointestinal bleeding. This review will look on the guidelines and other supporting evidence for the justification on the antiplatelet of choice.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/prevenção & controle , Aspirina/efeitos adversos , Clopidogrel/uso terapêutico , Quimioterapia Combinada , Humanos , Guias de Prática Clínica como Assunto , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Prevenção Secundária , Sociedades Médicas , Acidente Vascular Cerebral/prevenção & controle
9.
Expert Rev Cardiovasc Ther ; 17(10): 717-727, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31583920

RESUMO

Introduction: Inhibition of P2Y12 platelet receptors consists a crucial target of pharmacologic treatment in acute coronary syndrome patients. Several controversial issues however still remain and these are analyzed.Areas covered: The significance of early and strong platelet inhibition in the early phase of STEMI and the role of pretreatment are discussed. Concerns regarding morphine administration are raised. The role of crushing integral tablets to expedite the onset of action of oral P2Y12 inhibitors is emphasized. New data on the intravenous cangrelor are reported. Antiplatelet therapies as adjunct to thrombolysis, as well as the role of de-escalation antiplatelet therapy are analyzed.Expert opinion: Pharmacodynamic studies convincingly demonstrate a gap in the onset of antiplatelet action in STEMI cases, even when prasugrel or ticagrelor loading dose is used. The clinical benefit, however, of the early platelet inhibition and pretreatment is not entirely clear. Morphine delays the onset of action of oral agents, while this is expedited by crushing the integral tablets. Cangrelor devoids of these deficiencies by achieving fast and strong platelet inhibition in all clinical scenarios. Concomitant administration of novel antiplatelet agents with thrombolysis and de-escalation of antiplatelet treatment necessitate further study to reach definite conclusion.


Assuntos
Síndrome Coronariana Aguda/terapia , Intervenção Coronária Percutânea/métodos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Administração Intravenosa , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/administração & dosagem
10.
Cardiovasc Hematol Agents Med Chem ; 17(2): 144-151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31629400

RESUMO

INTRODUCTION: Recent findings have shown that in Acute Ischemic Stroke (AIS) patients, elevated troponin is associated with increased mortality. However, due to concerns of cerebral hypoperfusion and hemorrhagic transformation, current practice has been slow to apply proven cardiac therapies to these patients. This study aims to determine this rate of utilization. MATERIALS AND METHODS: A single-center review of 83 patients with AIS and measured troponin was conducted. Patients were stratified based on elevated and non-elevated troponin. Between groups, we measured the utilization of evidence-based cardiac therapies and used a univariate logistic regression to compare outcomes of mortality, re-hospitalization, recurrent acute ischemic stroke, recurrent acute myocardial infarction, and a composite of these outcomes. RESULTS: Of 83 patients, 25 had elevated troponin and 58 had non-elevated troponin. There was no statistical difference in the use of cardiac therapies between the two groups. Adenosine diphosphate P2Y12 antagonists were infrequently used in both elevated and non-elevated troponin groups at 32% vs. 24% (p = 0.64), as were Angiotensin-Converting Enzyme Inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) at 56% vs. 69% (p = 0.38). Those in the elevated troponin group encountered a statistically significant increase in composite endpoint 64% vs. 33% (Odds Ratio [OR] 7.28, 95% Confidence interval [CI] 2.19-28.88, p<0.01). CONCLUSION: Cardiac therapies are underutilized in patients with acute ischemic stroke and elevated troponin levels. In turn, this low usage may explain the increase in morbidity and mortality seen in these patients and the use of such therapies should be considered when treating this subset of patients as the cardio protective nature of these therapies may outweigh the risks associated with them in AIS patients.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Acidente Vascular Cerebral/sangue , Troponina/sangue , Idoso , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações
11.
J Thromb Thrombolysis ; 48(4): 661-667, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31506887

RESUMO

Few randomized controlled trials (RCTs) have compared ticagrelor to clopidogrel after thrombolytic therapy in patients with ST-segment elevation myocardial infarction (STEMI). To assess the quality of the current evidence, a trial sequential analysis (TSA) of all the available RCTs was performed. A literature search through electronic databases for relevant RCTs was completed. Trial sequential boundaries were applied to the meta-analysis to guard against statistical error, calculate the information size (IS), and assess the quality of the currently available evidence. The safety outcome was bleeding at 30-days and the efficacy outcome was major adverse cardiovascular events at 30-days. There were 3 RCTs with a total of 3999 patients were included. For the safety and efficacy outcomes, there was no difference between the ticagrelor and clopidogrel groups (RR 0.94; 95% CI 0.56-1.60, p = 0.83) and (RR 0.87; 95% CI 0.49-1.52, p = 0.62), respectively. The corresponding TSA revealed an IS of 20,928 and 37,266 for safety and efficacy outcomes, respectively. The Z-curves for both outcomes failed to cross the conventional boundary of significance and TSA boundary, indicating no statistical difference between the ticagrelor and clopidogrel group and lack of firm evidence from the currently available RCTs to draw conclusion. Based on the current available RCTs, there is not enough evidence to support or refute better outcomes with ticagrelor in patients with STEMI treated with thrombolytics. Larger RCTs with enough power are needed before firm recommendations can be applied.


Assuntos
Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Ticagrelor/uso terapêutico , Clopidogrel/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Terapia Trombolítica
12.
Can J Cardiol ; 35(10): 1377-1385, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31492492

RESUMO

BACKGROUND: Robust comparisons between oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) in ST-elevation myocardial infarction (STEMI) patients who undergo primary percutaneous coronary intervention are lacking. We sought to evaluate outcomes on the basis of P2Y12 inhibitor therapy in patients from the Thrombectomy With PCI Versus PCI Alone in Patients With STEMI Undergoing Primary PCI (TOTAL) trial. METHODS: We grouped 9932 patients according to P2Y12 inhibitor at hospital discharge: clopidogrel (n = 6500; 65.5%), prasugrel (n = 1244; 12.5%), or ticagrelor (n = 2188; 22.0%). The primary composite end point of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association class IV heart failure was examined at 1 year. Secondary efficacy and safety end points were also assessed. Cox proportional hazard ratios were determined and adjusted for confounders via propensity scoring. RESULTS: Baseline characteristics differing between the 3 groups were mainly age 75 years or older, diabetes, and previous stroke. After adjustment, ticagrelor use was associated with a lower rate of the primary composite outcome compared with clopidogrel (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.57-0.91; P < 0.02) and prasugrel (aHR, 0.65; 95% CI, 0.48-0.89; P = 0.02). Prasugrel use was not associated with a lower rate of the primary outcome compared with clopidogrel (aHR, 1.09; 95% CI, 0.86-1.39; P > 0.99). Neither prasugrel nor ticagrelor were associated with increased risk of stroke compared with clopidogrel. Compared with clopidogrel, ticagrelor was associated with significantly lower rates of major bleeding. CONCLUSIONS: In this observational analysis of STEMI patients who underwent primary percutaneous coronary intervention, ticagrelor was associated with improved outcomes compared with clopidogrel and prasugrel. An appropriately powered randomized trial is needed to confirm these findings.


Assuntos
Clopidogrel/uso terapêutico , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Ticagrelor/uso terapêutico , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
13.
Lancet ; 394(10206): 1335-1343, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31492505

RESUMO

BACKGROUND: We aimed to assess the safety of edoxaban in combination with P2Y12 inhibition in patients with atrial fibrillation who had percutaneous coronary intervention (PCI). METHODS: ENTRUST-AF PCI was a randomised, multicentre, open-label, non-inferiority phase 3b trial with masked outcome evaluation, done at 186 sites in 18 countries. Patients had atrial fibrillation requiring oral anticoagulation, were aged at least 18 years, and had a successful PCI for stable coronary artery disease or acute coronary syndrome. Participants were randomly assigned (1:1) from 4 h to 5 days after PCI using concealed, stratified, and blocked web-based central randomisation to either edoxaban (60 mg once daily) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist (VKA) in combination with a P2Y12 inhibitor and aspirin (100 mg once daily, for 1-12 months). The edoxaban dose was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, bodyweight ≤60 kg, or concomitant use of specified potent P-glycoprotein inhibitors) were present. The primary endpoint was a composite of major or clinically relevant non-major (CRNM) bleeding within 12 months. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of their assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02866175, is closed to new participants, and follow-up is completed. FINDINGS: From Feb 24, 2017, through May 7, 2018, 1506 patients were enrolled and randomly assigned to the edoxaban regimen (n=751) or VKA regimen (n=755). Median time from PCI to randomisation was 45·1 h (IQR 22·2-76·2). Major or CRNM bleeding events occurred in 128 (17%) of 751 patients (annualised event rate 20·7%) with the edoxaban regimen and 152 (20%) of 755 patients (annualised event rate 25·6%) patients with the VKA regimen; hazard ratio 0·83 (95% CI 0·65-1·05; p=0·0010 for non-inferiority, margin hazard ratio 1·20; p=0·1154 for superiority). INTERPRETATION: In patients with atrial fibrillation who had PCI, the edoxaban-based regimen was non-inferior for bleeding compared with the VKA-based regimen, without significant differences in ischaemic events. FUNDING: Daiichi Sankyo.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/uso terapêutico , Intervenção Coronária Percutânea , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/cirurgia , Idoso , Fibrilação Atrial/complicações , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Stents , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
14.
N Engl J Med ; 381(17): 1621-1631, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31479209

RESUMO

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).


Assuntos
Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Citocromo P-450 CYP2C19/genética , Genótipo , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Medicina de Precisão , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Método Simples-Cego , Stents , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico
15.
N Engl J Med ; 381(12): 1103-1113, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31475793

RESUMO

BACKGROUND: There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. METHODS: In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. RESULTS: The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority). CONCLUSIONS: As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).


Assuntos
Fibrilação Atrial/tratamento farmacológico , Doença das Coronárias/terapia , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Ponte de Artéria Coronária , Doença das Coronárias/complicações , Quimioterapia Combinada/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Modelos de Riscos Proporcionais , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Rivaroxabana/efeitos adversos
16.
N Engl J Med ; 381(15): 1411-1421, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31475795

RESUMO

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear. METHODS: We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. RESULTS: At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P = 0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P<0.001). For both coprimary outcomes, the benefit of complete revascularization was consistently observed regardless of the intended timing of nonculprit-lesion PCI (P = 0.62 and P = 0.27 for interaction for the first and second coprimary outcomes, respectively). CONCLUSIONS: Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479.).


Assuntos
Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Doenças Cardiovasculares/mortalidade , Terapia Combinada , Doença da Artéria Coronariana/complicações , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/métodos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Recidiva , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Prevenção Secundária , Stents
17.
N Engl J Med ; 381(16): 1524-1534, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31475799

RESUMO

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Trombose Coronária/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Stents , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos
18.
Cardiovasc Drugs Ther ; 33(5): 533-546, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31367811

RESUMO

PURPOSE: Perform a cost-effectiveness analysis comparing strategies for selecting P2Y12 inhibitors in acute coronary syndrome (ACS). METHODS: Six strategies for selection of P2Y12 inhibitors in ACS were compared from the US healthcare system perspective: (1) clopidogrel for all (universal clopidogrel); (2) ticagrelor guided by platelet reactivity assay (PRA; clopidogrel + phenotype); (3) ticagrelor use only in CYP2C19 poor metabolizers (genotype + conservative ticagrelor); (4) ticagrelor use in both CYP2C19 intermediate and poor metabolizers (genotype + liberal ticagrelor); (5) ticagrelor use only in patients with CYP2C19 polymorphisms and clopidogrel nonresponse by PRA (genotype + phenotype); and (6) ticagrelor for all (universal ticagrelor). A decision model was developed to model major adverse cardiovascular events and bleeding during 1 year of treatment with a P2Y12 inhibitor. Model inputs were identified from the literature. Lifetime costs were adjusted to 2017 US dollars; quality-adjusted life-years (QALYs) were projected using a Markov model. The primary endpoint was the incremental cost-effectiveness compared to the next best option along the cost-effectiveness continuum. Sensitivity analyses were performed on all model inputs to assess their influence on the incremental cost-effectiveness. RESULTS: In the base case analysis, incremental cost-effectiveness ratios (ICER) for the clopidogrel + phenotype, genotype + liberal ticagrelor, and universal ticagrelor strategies were $12,119/QALY, $29,412/QALY, and $142,456/QALY, respectively. Genotype + conservative ticagrelor and genotype + phenotype were not cost-effective due to second-order dominance. Genotype + liberal ticagrelor compared to clopidogrel + phenotype demonstrated the highest acceptance (97%) at a willingness to pay (WTP) threshold of $100,000/QALY. CONCLUSION: Cost-effective strategies to personalize P2Y12 inhibition in ACS include clopidogrel +phenotype and genotype + liberal ticagrelor. Universal ticagrelor may be considered cost-effective at a higher WTP threshold ($150,000/QALY). Genotype + liberal ticagrelor exhibited the highest acceptability compared to clopidogrel + phenotype over the widest range of WTP thresholds and may be preferred.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/economia , Custos de Medicamentos , Testes Farmacogenômicos/economia , Inibidores da Agregação de Plaquetas/economia , Inibidores da Agregação de Plaquetas/uso terapêutico , Medicina de Precisão/economia , Antagonistas do Receptor Purinérgico P2Y/economia , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/diagnóstico , Tomada de Decisão Clínica , Análise Custo-Benefício , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Técnicas de Apoio para a Decisão , Árvores de Decisões , Genótipo , Humanos , Cadeias de Markov , Modelos Econômicos , Seleção de Pacientes , Variantes Farmacogenômicos , Fenótipo , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento
20.
Thromb Res ; 181: 92-98, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376607

RESUMO

INTRODUCTION: P2Y12 receptor antagonists reduce risk of thrombotic complications after stent implantation but increase bleeding risk. Activation of P2Y12 receptors by ADP causes Gi-protein-mediated inhibition of adenylate cyclase (AC), thus limiting platelet response to anti-aggregatory effect of prostacyclin (PGI2). However, P2Y12 blockade reverses this ADP-induced suppression of the platelet PGI2/AC signaling pathway. We previously demonstrated that impairment of this pathway predicts poor response to clopidogrel. OBJECTIVES: To identify clinical correlates of variability in PGI2/AC signaling, and to assess the impact of such variability on individual responses to the direct P2Y12 receptor antagonists ticagrelor (in vivo) and 2-methyl-thioadenosine-monophosphate (2MeSAMP) (in vitro). PATIENTS/METHODS: We compared the inhibitory effects of prostaglandin E1 (PGE1) and the PGI2 analog Iloprost (Ilt) on platelet aggregation in whole blood samples from healthy control subjects (n = 17), and patients with stable angina pectoris (SAP; n = 35) or acute coronary syndromes (ACS; n = 23), with or without associated diabetes/hyperglycemia. RESULTS: Compared to control subjects, patients with ACS and - to a lesser extent - those with SAP, exhibited impaired responses to PGE1, accentuated in the presence of hyperglycemia. Efficacy of ticagrelor treatment, measured as change in platelet reactivity index, was directly related to pre-treatment PGE1 response, both at univariate and multivariate analysis. There was a strong correlation between extent of inhibition of platelet aggregation, whether by PGE1 or Ilt, and the anti-aggregatory effect of 2MeSAMP in vitro. CONCLUSIONS: The integrity of PGI2/AC signaling, which is impaired in the presence of ACS and hyperglycemia, predetermines the anti-aggregatory efficiency of P2Y12 receptor antagonists.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/tratamento farmacológico , Adenilil Ciclases/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Transdução de Sinais
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