Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
JAMA Cardiol ; 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31215979

RESUMO

Importance: The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice. Objective: To study the safety and efficacy of different antithrombotic regimens using a network meta-analysis of randomized controlled trials in this population. Data Sources: PubMed, EMBASE, EBSCO, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens. Study Selection: Four randomized studies were included (n = 10 026; WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS). Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis between 4 regimens using a Bayesian random-effects model. A pre hoc statistical analysis plan was written, and the review protocol was registered at PROSPERO. Data were analyzed between November 2018 and February 2019. Main Outcomes and Measures: The primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding; secondary safety outcomes were combined TIMI major and minor bleeding, trial-defined primary bleeding events, intracranial hemorrhage, and hospitalization. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE); secondary efficacy outcomes were individual components of MACE. Results: The overall prevalence of ACS varied from 28% to 61%. The mean age ranged from 70 to 72 years; 20% to 29% of the trial population were women; and most patients were at high risk for thromboembolic and bleeding events. Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT. Conclusions and Relevance: A regimen of NOACs plus P2Y12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y12 inhibitor as the preferred regimen post-percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.

2.
EuroIntervention ; 15(8): 700-706, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30834895

RESUMO

AIMS: Clopidogrel is the P2Y12 inhibitor of choice in patients who undergo PCI and have an indication for oral anticoagulation (OAC). Prediction of the bleeding risk is of major interest in this population. The aim of this analysis was to investigate whether an enhanced platelet inhibition by clopidogrel measured by platelet function testing (PFT) with the Multiplate Analyzer is associated with an increased bleeding risk in patients on triple antithrombotic therapy. METHODS AND RESULTS: This investigation was performed in a cohort of 524 patients from the randomised ISAR-TRIPLE trial; 458 (87.4%) had PFT results available in the first 24 hours after PCI. Patients belonging to the lowest quintile according to PFT were considered as enhanced responders to clopidogrel. The primary endpoint was major bleeding according to TIMI criteria at nine months. The median of ADP-induced platelet aggregation in the whole population was 163 AU*min (107-241). Patients in the lowest quintile had values below 93 AU*min. These enhanced responders (92 patients) had a significantly higher risk of TIMI major bleeding (hazard ratio [HR] 3.13, 95% confidence interval [CI]: 1.38-7.09, p=0.01) and overall mortality (HR 3.42, 95% CI: 1.55-7.52, p=0.004) compared with the remaining patients (366 patients). No significant difference was observed for the secondary combined ischaemic endpoint (HR 1.27, 95% CI: 0.47-3.47, p=0.64). CONCLUSIONS: Enhanced platelet inhibition delivered by clopidogrel is associated with an increased risk for major bleeding and death in patients on OAC who undergo PCI. These results support the use of PFT to identify patients with an increased risk for bleeding.


Assuntos
Anticoagulantes/efeitos adversos , Clopidogrel/farmacologia , Stents Farmacológicos , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Agregação Plaquetária/efeitos dos fármacos , Anticoagulantes/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticlopidina/efeitos adversos , Resultado do Tratamento
3.
Int J Cardiol ; 273: 90-91, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30274748
4.
Catheter Cardiovasc Interv ; 92(7): 1239-1246, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30019824

RESUMO

OBJECTIVES: We aimed to assess the impact of omitting aspirin on clinical outcomes in a real-world collective of patients receiving oral anticoagulation (OAC) therapy who were treated with a current-generation drug-eluting stent (DES) or an everolimus-eluting bioresorbable vascular scaffold (BVS). BACKGROUND: Limited data are available regarding the clinical benefit of triple antithrombotic therapy (TAT) with aspirin compared with dual antithrombotic therapy (DAT) without aspirin in patients undergoing percutaneous coronary intervention (PCI) and requiring OAC. METHODS: In total, 237 patients were analyzed. The primary outcome was a composite of major adverse cardiac and cerebrovascular events (MACCE) within 1 year after PCI. Secondary outcomes were the individual components of the primary endpoint, cardiovascular death, and any bleeding according to Bleeding Academic Research Consortium (BARC) or Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTS: Eighty-nine patients (37.6%) received DAT, and 148 (62.4%) received TAT. The rate of MACCE was significantly higher in DAT patients than in TAT patients (16 (18%) vs. 11 (7.4%); hazard ratio [HR] 2.73, 95% confidence interval [CI] 1.24-6.03; P = 0.01). The results of the multivariable Cox proportional hazards model including corrections for imbalances in baseline characteristics confirmed a significant independent association between DAT and MACCE (HRadj 3.14, 95% CI 1.31-7.54; P = 0.01). Major bleeding did not differ significantly between treatment groups. CONCLUSION: DAT was associated with a significantly higher rate of MACCE than TAT after DES or BVS implantation. Further studies are required to evaluate the safety and efficacy of dual versus TAT after PCI in clinical practice.


Assuntos
Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Doença da Artéria Coronariana/terapia , Fibrinolíticos/administração & dosagem , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Implantes Absorvíveis , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Doença da Artéria Coronariana/mortalidade , Quimioterapia Combinada , Stents Farmacológicos , Feminino , Fibrinolíticos/efeitos adversos , Alemanha , Hemorragia/induzido quimicamente , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
5.
Catheter Cardiovasc Interv ; 88(1): E12-22, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26354765

RESUMO

OBJECTIVE: To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI-S) who also require chronic oral anticoagulation. BACKGROUND: Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI-S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. METHODS: A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI-S or MI and requiring chronic anticoagulation. Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. RESULTS: A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow-up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all-cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61-1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51-1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35-1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03-1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38-0.92, P = 0.02]. CONCLUSIONS: All-cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. © 2015 Wiley Periodicals, Inc.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Varfarina/administração & dosagem , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Distribuição de Qui-Quadrado , Comorbidade , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Estudos Observacionais como Assunto , Razão de Chances , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/efeitos adversos , Fatores de Risco , Stents , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Varfarina/efeitos adversos
8.
Biomed Res Int ; 2015: 798486, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26229963

RESUMO

BACKGROUND: A relevant number of patients receive triple therapy with clopidogrel, aspirin, and oral anticoagulation. Clopidogrel's efficacy on ADP induced platelet function may be influenced by concomitant antithrombotic therapies. Data regarding the effect of dabigatran on platelet function is limited to in vitro studies and healthy individuals. METHODS: The "Dabi-ADP-1" and "Dabi-ADP-2" trials randomized patients with atrial fibrillation to either dabigatran or phenprocoumon for a 2-week period. In Dabi-ADP-1 (n = 70) patients with clopidogrel therapy were excluded and in Dabi-ADP-2 (n = 46) patients had to be treated concomitantly with clopidogrel. The primary endpoint was ADP-induced platelet aggregation between dabigatran and phenprocoumon at 14 days. Secondary endpoints were ADPtest HS-, TRAP-, and COL-induced platelet aggregation. RESULTS: There was no significant difference regarding the primary endpoint between both groups in either trial (Dabi-ADP-1: Dabigatran: 846 [650-983] AU × min versus phenprocoumon: 839 [666-1039] AU × min, P = 0.90 and Dabi-ADP-2: 326 [268-462] versus 350 [214-535], P = 0.70) or regarding the secondary endpoints, ADPtest HS-, TRAP-, and COL-induced platelet aggregation. CONCLUSION: Dabigatran as compared to phenprocoumon has no impact on ADP-induced platelet aggregation in atrial fibrillation patients neither with nor without concomitant clopidogrel therapy.


Assuntos
Difosfato de Adenosina/farmacologia , Fibrilação Atrial , Dabigatrana/administração & dosagem , Femprocumona/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/sangue , Fibrilação Atrial/tratamento farmacológico , Clopidogrel , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ticlopidina/administração & dosagem
9.
PLoS One ; 10(7): e0131570, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26208329

RESUMO

BACKGROUND: The placement of an implantable cardioverter defibrillator (ICD) has become routine practice to protect high risk patients from sudden cardiac death. However, implantation-related myocardial micro-damage and its relation to different implantation strategies are poorly characterized. METHODS: A total of 194 ICD recipients (64±12 years, 83% male, 95% primary prevention of sudden cardiac death, 35% cardiac resynchronization therapy) were randomly assigned to one of three implantation strategies: (1) ICD implantation without any defibrillation threshold (DFT) testing, (2) estimation of the DFT without arrhythmia induction (modified "upper limit of vulnerability (ULV) testing") or (3) traditional safety margin testing including ventricular arrhythmia induction. High-sensitive Troponin T (hsTnT) levels were determined prior to the implantation and 6 hours after. RESULTS: All three groups showed a postoperative increase of hsTnT. The mean delta was 0.031±0.032 ng/ml for patients without DFT testing, 0.080±0.067 ng/ml for the modified ULV-testing and 0.064±0.056 ng/ml for patients with traditional safety margin testing. Delta hsTnT was significantly larger in both of the groups with intraoperative ICD testing compared to the non-testing strategy (p≤0.001 each). There was no statistical difference in delta hsTnT between the two groups with intraoperative ICD testing (p = 0.179). CONCLUSION: High-sensitive Troponin T release during ICD implantation is significantly higher in patients with intraoperative ICD testing using shock applications compared to those without testing. Shock applications, with or without arrhythmia induction, did not result in a significantly different delta hsTnT. Hence, the ICD shock itself and not ventricular fibrillation seems to cause myocardial micro-damage. TRIAL REGISTRATION: ClinicalTrials.gov NCT01230086.


Assuntos
Desfibriladores Implantáveis , Cardioversão Elétrica/métodos , Troponina T/sangue , Fibrilação Ventricular/sangue , Idoso , Análise de Variância , Arritmias Cardíacas/sangue , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/prevenção & controle , Biomarcadores/sangue , Terapia de Ressincronização Cardíaca/métodos , Creatina Quinase Forma MB/sangue , Morte Súbita Cardíaca/prevenção & controle , Determinação de Ponto Final/métodos , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/prevenção & controle
10.
J Am Coll Cardiol ; 65(16): 1619-1629, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25908066

RESUMO

BACKGROUND: Patients receiving oral anticoagulation (OAC) who undergo drug-eluting stent (DES) implantation require additional dual antiplatelet therapy with aspirin and clopidogrel. Such triple therapy confers an elevated bleeding risk, and its optimal duration is not known. OBJECTIVES: The goal of this study was to evaluate whether shortening the duration of clopidogrel therapy from 6 months to 6 weeks after DES implantation was associated with a superior net clinical outcome in patients receiving concomitant aspirin and OAC. METHODS: In this randomized, open-label trial, we enrolled patients receiving OAC who underwent DES implantation at 3 European centers between September 2008 and December 2013. A total of 614 patients receiving concomitant aspirin and OAC were randomized to either 6-week clopidogrel therapy (n=307) or 6-month clopidogrel therapy (n=307). The primary endpoint was a composite of death, myocardial infarction (MI), definite stent thrombosis, stroke, or Thrombolysis In Myocardial Infarction (TIMI) major bleeding at 9 months. RESULTS: The primary endpoint occurred in 30 patients (9.8%) in the 6-week group compared with 27 patients (8.8%) in the 6-month group (hazard ratio [HR]: 1.14; 95% CI: 0.68 to 1.91; p=0.63). There were no significant differences for the secondary combined ischemic endpoint of cardiac death, MI, definite stent thrombosis, and ischemic stroke (12 [4.0%] vs. 13 [4.3%]; HR: 0.93; 95% CI: 0.43 to 2.05; p=0.87) or the secondary bleeding endpoint of TIMI major bleeding (16 [5.3%] vs. 12 [4.0%]; HR: 1.35; 95% CI: 0.64 to 2.84; p=0.44). CONCLUSIONS: Six weeks of triple therapy was not superior to 6 months with respect to net clinical outcomes. These results suggest that physicians should weigh the trade-off between ischemic and bleeding risk when choosing the shorter or longer duration of triple therapy. (Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation [ISAR-TRIPLE]; NCT00776633).


Assuntos
Aspirina/administração & dosagem , Stents Farmacológicos , Inibidores da Agregação de Plaquetas/administração & dosagem , Ticlopidina/análogos & derivados , Idoso , Aspirina/efeitos adversos , Clopidogrel , Feminino , Humanos , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
11.
Am Heart J ; 167(4): 459-465.e1, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24655693

RESUMO

BACKGROUND: An increasing number of patients undergoing coronary stenting need lifelong anticoagulation and therefore require a triple therapy typically consisting of aspirin, clopidogrel, and a vitamin K antagonist. Triple therapy confers an elevated bleeding risk as compared with dual therapy; however, omission of either antiplatelet or anticoagulation therapy might increase the risk of stent thrombosis or thrombembolic events. Although guidelines recommend a duration of dual antiplatelet therapy of 6 to 12months after drug-eluting stent (DES) implantation, the optimal duration of dual antiplatelet therapy in patients receiving oral anticoagulation is not known. HYPOTHESIS: We postulate that 6-week clopidogrel therapy after DES implantation as compared with 6-month therapy is associated with improved clinical outcomes in patients undergoing DES implantation receiving concomitant aspirin and vitamin K antagonists. STUDY DESIGN: The ISAR-TRIPLE is a randomized, open-label trial that examines the restriction of clopidogrel therapy from 6 months to 6 weeks after DES implantation in the setting of concomitant aspirin and oral anticoagulant. Patients are randomized in a 1:1 fashion to either 6-week or 6-month clopidogrel therapy. The primary end point is a composite of death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding. The secondary end point comprises ischemic and bleeding complications. According to sample size calculations, a total of 600 patients are required to be enrolled. Clinical follow-up is scheduled at 6 weeks and at 6 and 9 months after randomization. SUMMARY: There is clinical equipoise regarding the optimal duration of triple therapy after DES implantation in patients who need vitamin K antagonist therapy. The ISAR-TRIPLE trial aims to test the hypothesis that a 6-week triple therapy compared with a 6-month triple therapy improves net clinical outcomes.


Assuntos
Aspirina/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Terapia Trombolítica/métodos , Ticlopidina/análogos & derivados , Administração Oral , Clopidogrel , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Seguimentos , Humanos , Inibidores da Agregação de Plaquetas/administração & dosagem , Ticlopidina/administração & dosagem
13.
J Am Coll Cardiol ; 61(20): 2060-6, 2013 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-23524219

RESUMO

OBJECTIVES: This study sought to evaluate whether prasugrel may serve as an alternative to clopidogrel in patients with triple therapy. BACKGROUND: Approximately 10% of patients who receive dual antiplatelet therapy after percutaneous coronary intervention have an indication for oral anticoagulation and are thus treated with triple therapy. The standard adenosine diphosphate receptor blocker in this setting is clopidogrel. Data regarding prasugrel as part of triple therapy are not available. METHODS: We analyzed a consecutive series of 377 patients who underwent drug-eluting stent implantation and had an indication for oral anticoagulation between February 2009 and December 2011 and were treated with a 6-month regimen of aspirin and oral anticoagulation with either prasugrel or clopidogrel. The primary endpoint was a composite of Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding at 6 months. The secondary endpoint was a composite of death, myocardial infarction, ischemic stroke, or definite stent thrombosis. RESULTS: Twenty-one patients (5.6%) received prasugrel instead of clopidogrel. These patients had a higher-risk profile at baseline, and the majority had high platelet reactivity to clopidogrel. TIMI major and minor bleeding occurred significantly more often in the prasugrel compared with the clopidogrel group (6 [28.6%) vs. 24 [6.7%]; unadjusted hazard ratio (HR): 4.6, 95% confidence interval [CI]: 1.9 to 11.4], p < 0.001; adjusted HR: 3.2, 95% CI: 1.1 to 9.1], p = 0.03). There was no significant difference regarding the combined ischemic secondary endpoint (2 [9.5%] vs. 25 [7.0%]; unadjusted HR: 1.4, 95% CI: 0.3 to 6.1], p = 0.61). CONCLUSIONS: These findings suggest that substitution of prasugrel for clopidogrel in patients needing triple therapy increases the risk of bleeding. However, specific randomized trials are needed to define the role of newer adenosine diphosphate receptor antagonists in this setting.


Assuntos
Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Stents Farmacológicos , Isquemia Miocárdica/terapia , Piperazinas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Tiofenos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/mortalidade , Seleção de Pacientes , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Cloridrato de Prasugrel , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados , Vitamina K/antagonistas & inibidores
14.
J Electrocardiol ; 46(2): 100-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23336998

RESUMO

BACKGROUND: It is the general perception, that ST-elevation myocardial infarction is associated with transmural ischemia while Non-ST elevation myocardial infarction is found in non-transmural subendocardial ischemia. This association, however, derives primarily from post mortem studies. METHODS: A total of 220 patients with acute myocardial infarction (MI) who had PCI on admission and contrast-enhanced cardiac magnetic resonance imaging (CMR) within one week were included into the study. Size and transmural extent of MI was quantified by CMR and correlated with the ECG on admission. RESULTS: Based on the ECG findings, 57% were classified as STEMI and 43% as NSTEMI. CMR infarct size was significantly larger in STEMI than NSTEMI (23.2 vs. 14.2 LV%, p<0.001). As assessed by CMR, STEMI patients were transmural in 63% as compared to 27% of patients with NSTEMI (p<0.001). In a multivariable logistic regression model, total infarct size was significantly associated with presence of STEMI (OR: 1.045, 95% CI [1.014-1.077], p=0.004) whereas the number of transmural segments did not significantly add further information for a STEMI/NSTEMI classification (p=0.054, change of c-index from 0.69 to 0.70). CONCLUSIONS: The electrocardiographic STEMI/NSTEMI classification does rather characterize the total size of MI than the transmural extent as assessed by CMR.


Assuntos
Eletrocardiografia/estatística & dados numéricos , Gadolínio DTPA , Imagem Cinética por Ressonância Magnética/estatística & dados numéricos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Miocárdio Atordoado/diagnóstico , Miocárdio Atordoado/epidemiologia , Comorbidade , Meios de Contraste , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
15.
Curr Pharm Des ; 18(33): 5224-39, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22724411

RESUMO

In patients with stable and unstable coronary disease and those undergoing coronary stenting, the activation of platelets plays a central role in the occurrence of major thrombotic events such as death, myocardial infarction and stent thrombosis. Antiplatelet therapy for primary and secondary prevention of thromboembolic events is a cornerstone for the management of these patients and for many years the cyclooxygenase-1 (COX-1) inhibitor aspirin and the second generation thienopyridine clopidogrel which targets the ADP P2Y12 receptor on platelets served as the main antiplatelet agents for these indications. Clopidogrel in particular is very efficient in reducing ischemic cardiovascular events but exposes patients to an increased risk of bleeding. Therefore the optimal dosage and duration of clopidogrel therapy is of utmost importance. Furthermore, platelet function studies have revealed that responsiveness to clopidogrel is not uniform and that a low response is linked to a higher incidence of thrombotic events. Causes are multifactorial and several genetic and non-genetic factors including patients' co-morbidities and co-medications have been identified. As a result clopidogrel's long lasting monopole as the only antiplatelet agent in patients undergoing coronary stenting is currently challenged by the newer P2Y12 blockers such as prasugrel and ticagrelor, which provide a stronger and more consistent inhibition of platelets. In the setting of acute coronary syndromes, this more potent platelet inhibition led to less thrombotic events with these newer agents, but at the cost of a higher bleeding risk. This review provides an overview of the indication, dosage and duration of clopidogrel therapy and discusses its role in light of the recent introduction of newer P2Y12 receptor antagonists, the combination with newer oral anticoagulants such as dabigatran, apixaban and rivaroxaban as well as the emerging use of platelet function testing in clinical practice.


Assuntos
Plaquetas/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticlopidina/análogos & derivados , Plaquetas/metabolismo , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Clopidogrel , Desenho de Drogas , Interações de Medicamentos , Resistência a Medicamentos , Quimioterapia Combinada , Fibrinolíticos/efeitos adversos , Fibrinolíticos/química , Hemorragia/induzido quimicamente , Humanos , Seleção de Pacientes , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/química , Testes de Função Plaquetária , Guias de Prática Clínica como Assunto , Inibidores da Bomba de Prótons/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/química , Receptores Purinérgicos P2Y12/sangue , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Fatores de Risco , Ticlopidina/efeitos adversos , Ticlopidina/química , Ticlopidina/uso terapêutico , Resultado do Tratamento
17.
Am Heart J ; 161(3): 605-10, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21392618

RESUMO

BACKGROUND: Clopidogrel is a prodrug that is metabolized to its active metabolite by the hepatic cytochrome P450 system. Calcium-channel blockers (CCBs) are metabolized by the same pathway and may therefore attenuate the antiplatelet effect of clopidogrel. The aim of this study was to assess the impact of CCB therapy on the pharmacodynamic effect and the clinical efficacy of clopidogrel after drug-eluting stent placement. METHODS: A total of 1,608 consecutive patients were previously enrolled in a study that aimed to assess the relation between platelet reactivity and outcomes after coronary stenting. Here, this cohort was analyzed according to concomitant CCB therapy at admission. The primary pharmacodynamic end point was adenosine diphosphate-induced platelet aggregation (in AU · min) with multiple electrode platelet aggregometry after loading with 600 mg clopidogrel. The primary clinical end point was combination of death or definite stent thrombosis (ST) at 30 days. Secondary end points included definite ST alone, myocardial infarction, stroke, and death. RESULTS: Two hundred thirty-two patients (14.4%) were on CCBs on admission. Compared with patients with CCB medication, patients without CCB medication showed no significant difference in median [interquartile range] platelet aggregation values (232 [142-365] vs 223 [141-368] AU · min, P = .53). There was also no significant difference regarding the clinical end point of death or ST (2 [0.9%] vs 16 [1.2%], odds ratio 0.74, 95% CI 0.17-3.2, P = .69) between both groups. CONCLUSION: In our population, concomitant CCB therapy did not alter clopidogrel-mediated platelet aggregation and did not have a measurable impact on ST and mortality after coronary stenting.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação de Plaquetas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Idoso , Clopidogrel , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Trombose Coronária/epidemiologia , Sinergismo Farmacológico , Stents Farmacológicos , Determinação de Ponto Final , Feminino , Humanos , Masculino , Testes de Função Plaquetária , Ticlopidina/farmacologia
18.
Thromb Haemost ; 104(3): 626-32, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20664905

RESUMO

Clopidogrel is a prodrug that is converted via the hepatic cytochrome P450 system into its active thiol metabolite. Evidence is accumulating that proton pump inhibitors (PPIs) inhibit this enzymatic pathway and may therefore attenuate the antiplatelet effect of clopidogrel. The objective of this study was to investigate whether patients on clopidogrel therapy after drug-eluting stent (DES) placement who also receive a PPI are at higher risk of stent thrombosis (ST). This is a retrospective analysis of patients who received dual antiplatelet treatment including clopidogrel after DES placement. Outcomes were compared according to PPI therapy. The primary endpoint was the incidence of definite ST at 30 days. Secondary endpoints were death, combined death or ST and myocardial infarction (MI). The study population included 3,338 patients and 698 patients (20.9%) received PPIs. Patients receiving a PPI had a higher risk profile at baseline. Multivariate analysis showed that PPI treatment was not independently associated with the occurrence of ST [adjusted HR 1.8 (95% CI: 0.7-4.7), p=0.23] or MI [adjusted HR 1.3 (0.8-2.3), p=0.11]. PPI treatment was significantly associated with death [adjusted HR 2.2 (1.1-4.3), p=0.02] and death or ST [adjusted HR 3.3(1.7-6.7), p=0.02]. Concomitant treatment with a PPI in patients receiving dual antiplatelet treatment after coronary stenting is not an independent predictor of ST. The higher mortality is probably due to confounding as patients on PPIs had a higher risk profile at baseline.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Aspirina/uso terapêutico , Stents Farmacológicos , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Distribuição de Qui-Quadrado , Clopidogrel , Comorbidade , Interações de Medicamentos , Quimioterapia Combinada , Feminino , Alemanha , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Modelos de Riscos Proporcionais , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose/etiologia , Trombose/mortalidade , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
19.
Eur Heart J ; 31(10): 1205-11, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20159881

RESUMO

AIMS: A relevant proportion of patients receiving aspirin and clopidogrel after percutaneous coronary intervention (PCI) also require oral anticoagulation with a coumarin derivative such as phenprocoumon. Both clopidogrel and phenprocoumon are metabolized by the hepatic cytochrome P450 system and a drug-drug interaction may exist at this level. The aim of this study was to investigate the impact of phenprocoumon on the antiplatelet effects of clopidogrel in patients with coronary artery disease. METHODS AND RESULTS: Patients (n = 1223) eligible for this study were under dual maintenance antiplatelet treatment with aspirin and clopidogrel. Adenosine diphosphate-induced platelet aggregation (in AU*min) was measured with multiple electrode platelet aggregometry on a Multiplate analyzer (Dynabyte, Munich, Germany). From the entire study population, 124 (10.1%) patients were under concomitant phenprocoumon treatment at the time point of platelet function testing. Platelet aggregation (median [interquartile range]) was significantly higher in patients with (n = 124) concomitant phenprocoumon treatment compared with patients without (n = 1099) phenprocoumon treatment (308 [190-493] AU*min vs. 224 [145-390] AU*min; P = 0.0001, adjusted P = 0.002). CONCLUSION: Phenprocoumon significantly attenuates the antiplatelet effects of clopidogrel. The impact of this interaction on the risk of thrombotic and bleeding events after PCI requires further investigations.


Assuntos
Anticoagulantes/farmacologia , Doença da Artéria Coronariana/tratamento farmacológico , Femprocumona/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Difosfato de Adenosina/farmacologia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão , Anticoagulantes/administração & dosagem , Aspirina/uso terapêutico , Clopidogrel , Estudos Transversais , Interações de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Femprocumona/administração & dosagem , Ticlopidina/antagonistas & inibidores , Ticlopidina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA