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1.
Clin Res Cardiol ; 108(7): 772-778, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30564950

RESUMO

INTRODUCTION: Symptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined. METHODS: In a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3 years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) 'post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV. RESULTS: Confirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up. CONCLUSIONS: CTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae.


Assuntos
Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Embolia Pulmonar/diagnóstico , Recuperação de Função Fisiológica , Tenecteplase/uso terapêutico , Terapia Trombolítica/métodos , Função Ventricular Direita/fisiologia , Doença Aguda , Progressão da Doença , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
2.
Eur Heart J Acute Cardiovasc Care ; 7(6): 504-513, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28627230

RESUMO

AIMS: The STREAM study randomly assigned ST-elevation myocardial infarction (STEMI) patients to receive a pharmacoinvasive versus primary percutaneous coronary intervention reperfusion strategy. We assessed whether there was an association between outcomes based on randomisation at a community hospital versus a prehospital location. METHODS/RESULTS: Community hospital patients (358/1866 (19.2%)) were compared to prehospital patients and their outcomes categorised into pharmacoinvasive according to their treatment assignment. Compared to prehospital patients, community hospital patients had more diabetes (17.8% vs. 11.5%, P=0.001), higher Killip Class >1 (9.4% vs. 5.0%, P=0.002) and thrombolysis in myocardial infarction risk scores ⩾5 (18.2% vs. 12.4%, P=0.005). The 30-day primary endpoint (death, shock, congestive heart failure and re-infarction) for community hospital patients was 14.9% versus 13.2% for prehospital patients ( P=0.403). Community hospital pharmacoinvasive patients tended to receive less rescue (35.1% vs. 42.8%, P=0.062); when deployed their rescue was delayed 43 minutes. Community hospital patients undergoing primary percutaneous coronary intervention experienced a delay of 31 minutes versus prehospital patients. Pharmacoinvasive patients receiving scheduled angiography from a community hospital and prehospital patients had comparable times to angiography (17.7 vs. 18.7 hours) and low event rates (6.2% vs. 8.0%). Although the interaction between randomisation location and treatment received on the primary endpoint was not significant ( Pinteraction=0.065) those pharmacoinvasive patients requiring rescue from community hospitals had worse outcomes than prehospital rescue patients (odds ratio 2.28, 95% confidence interval 1.16-4.49). CONCLUSION: Within STREAM, STEMI patients randomly assigned at community hospitals had a higher baseline risk but similar outcomes compared to those studied prehospital patients irrespective of successful pharmacoinvasive therapy or primary percutaneous coronary intervention. However, worse outcomes in the pharmacoinvasive patients requiring rescue in community hospitals emphasises their need for immediate transfer to a percutaneous coronary intervention-capable hospital.


Assuntos
Serviços Médicos de Emergência , Fibrinolíticos/uso terapêutico , Hospitais Comunitários , Intervenção Coronária Percutânea/métodos , Medição de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Terapia Trombolítica/métodos , Alberta/epidemiologia , Angiografia Coronária , Eletrocardiografia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento
3.
J Am Coll Cardiol ; 69(12): 1536-1544, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28335835

RESUMO

BACKGROUND: The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown. OBJECTIVES: This study investigated the long-term prognosis of patients with intermediate-risk PE and the effect of thrombolytic treatment on the persistence of symptoms or the development of late complications. METHODS: The PEITHO (Pulmonary Embolism Thrombolysis) trial was a randomized (1:1) comparison of thrombolysis with tenecteplase versus placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction on imaging, and a positive cardiac troponin test result. Both treatment arms received standard anticoagulation. Long-term follow-up was included in the third protocol amendment; 28 sites randomizing 709 of the 1,006 patients participated. RESULTS: Long-term (median 37.8 months) survival was assessed in 353 of 359 (98.3%) patients in the thrombolysis arm and in 343 of 350 (98.0%) in the placebo arm. Overall mortality rates were 20.3% and 18.0%, respectively (p = 0.43). Between day 30 and long-term follow-up, 65 deaths occurred in the thrombolysis arm and 53 occurred in the placebo arm. At follow-up examination of survivors, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% versus 30.1% of the patients (p = 0.23). Echocardiography (performed in 144 and 146 patients randomized to thrombolysis and placebo, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 4 (2.1%) versus 6 (3.2%) cases (p = 0.79). CONCLUSIONS: Approximately 33% of patients report some degree of persistent functional limitation after intermediate-risk PE, but CTEPH is infrequent. Thrombolytic treatment did not affect long-term mortality rates, and it did not appear to reduce residual dyspnea or RV dysfunction in these patients. (Pulmonary Embolism Thrombolysis study [PEITHO]; NCT00639743).


Assuntos
Fibrinolíticos/uso terapêutico , Embolia Pulmonar/prevenção & controle , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/mortalidade , Tenecteplase , Resultado do Tratamento
5.
Drugs Aging ; 33(2): 109-18, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26849132

RESUMO

Elderly patients constitute a large and growing proportion of ST-elevation myocardial infarction (STEMI) patients, yet they have been under-represented or even excluded from reperfusion trials. Despite evidence that fibrinolysis improves outcomes irrespective of age, many elderly STEMI patients still remain undertreated or subject to major delays to primary percutaneous coronary intervention (PCI). The fear of an excessive risk of intracranial hemorrhage (ICH) in these patients can lead to avoidance of potentially life-saving reperfusion treatment, despite the fact that current STEMI guidelines do not exclude the elderly from a pharmaco-invasive strategy. Age-specific dose reductions have been succesfully made to antithrombotic drugs such as clopidogrel and enoxaparin as an adjunct to fibrinolysis, but until recently no dose adjustments for elderly patients have been applied to the fibrinolytic agents. In the pharmaco-invasive STREAM trial, halving the bolus of tenecteplase for patients aged >75 years because of an unacceptably high ICH rate in the elderly was associated with a more favorable safety/efficacy profile. Whether a pharmaco-invasive strategy including half-dose tenecteplase, age- and weight-adjusted enoxaparin, and a tailored P2Y12 inhibitor followed by routine angiography represents a safe and efficacious alternative reperfusion therapy for elderly patients remains to be prospectively assessed in a clinical trial in this age group.


Assuntos
Angioplastia Coronária com Balão/métodos , Fibrinolíticos/farmacologia , Infarto do Miocárdio , Terapia Trombolítica/métodos , Idoso , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco Ajustado
6.
Eur Stroke J ; 1(3): 213-221, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31008282

RESUMO

Introduction: The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3-4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. Patients and methods: Inclusion of at least 1000 patients treated within 3-4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3-4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0-2, favourable outcome (mRS 0-1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. Results: 4157 patients from 81 centres in 12 EU countries were entered prospectively (N = 1118 in the 3-4.5 h, N = 3039 in the 0-3 h time window) and 3454 retrospective patients in the 0-3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3-4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3-4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). Discussion: Main weakness is the observational design of the study. Conclusion: This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke.

7.
Am Heart J ; 169(6): 890-898.e1, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26027628

RESUMO

BACKGROUND: Elderly patients with ST-segment elevation myocardial infarction (STEMI) have worse outcomes and a greater risk of intracranial bleeding than nonelderly patients. Baseline characteristics, clinical outcomes, and the relationship of the tenecteplase (TNK) dose reduction to the efficacy, safety, and electrocardiographic indicators of reperfusion efficacy were evaluated in STEMI patients ≥75 years. METHODS: The STREAM trial evaluated early presenting STEMI patients who could not undergo primary percutaneous coronary intervention within 1 hour of first medical contact. Because of excess intracranial hemorrhage (ICH) in patients ≥75 years, the dose of TNK was reduced by 50%. RESULTS: Before dose amendment, there were 3 (7.1%) of 42 elderly patients with ICH; 2 of these were fatal, whereas no ICH occurred in the 93 elderly patients who received half-dose TNK postamendment. The median extent of ST-segment elevation resolution (≥50%) and proportion of patients with ≥2 mm in the electrocardiogram lead with greatest ST-segment elevation was comparable in elderly patients preamendment and postamendment (63.2% vs 56.0% and 43.6% vs 40.0%, respectively). Patients requiring rescue coronary intervention after TNK was also similar (42.9% vs 44.1%). The primary composite end point (30-day all-cause death, cardiogenic shock, congestive heart failure, and reinfarction) was 31.0% before versus 24.7% postamendment. CONCLUSIONS: Our data, from a modest-sized population of elderly STEMI patients, indicate that half-dose TNK reduces the likelihood of ICH without compromising reperfusion efficacy. These observations are hypothesis generating and warrant further confirmation in randomized clinical trials in the elderly.


Assuntos
Fibrinolíticos/administração & dosagem , Hemorragias Intracranianas/prevenção & controle , Infarto do Miocárdio/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Fibrinolíticos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Radiografia , Tenecteplase , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
8.
Am J Cardiol ; 114(6): 811-9, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25108302

RESUMO

Although a fibrinolytic pharmacoinvasive strategy is recommended for patients with ST elevation myocardial infarction (STEMI) unable to undergo timely primary percutaneous coronary intervention (PCI), there are limited data addressing outcomes specific to those with successful or unsuccessful pharmacologic reperfusions. Accordingly, we evaluated a contemporary pharmacoinvasive strategy for failed and successful reperfusions within the STrategic Reperfusion Early After Myocardial infarction study. Of 1,823 per-protocol-treated patients with STEMI, we examined clinical outcomes and angiographic and electrocardiographic metrics in 3 groups as follows: fibrinolysis requiring rescue (rescue, n = 348), fibrinolysis with scheduled angiography (scheduled, n = 516), and primary PCI (n = 927). Compared with pharmacoinvasive patients undergoing scheduled angiography, rescue patients were more likely to have anterior wall myocardial infarction, more baseline ST-segment elevation and deviation, as well as Q waves in the distribution of their ST elevation. Residual ST elevation ≥ 2 mm 30 minutes after angiography occurred in 27.9%, 7.9%, and 24.8% of patients who underwent rescue, scheduled, and primary PCI, respectively. Thirty-day composite event rates (all-cause death, cardiogenic shock, heart failure, and reinfarction) were 18.7%, 5.5%, and 13.9%; all-cause death: 6.1%, 2.1%, and 3.9%; cardiogenic shock: 7.5%, 2.0%, and 5.4%; heart failure: 11.8%, 2.3%, and 7.6%; and reinfarction: 1.5%, 1.4%, and 2.2%, for rescue, scheduled, and primary PCI, respectively. Compared with successfully reperfused patients undergoing scheduled angiography, the adjusted relative risk of the primary outcome was 2.92 (95% confidence interval 1.92 to 4.45) in rescue patients. In conclusion, pharmacoinvasive-treated patients requiring rescue angiography had greater baseline risk with more co-morbidities and worse 30-day outcomes compared with successful fibrinolytic-treated patients. Residual ST elevation after reperfusion assists in defining prognosis.


Assuntos
Eletrocardiografia , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Terapia Trombolítica/métodos , Idoso , Angiografia Coronária , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento
9.
Circulation ; 130(14): 1139-45, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25161043

RESUMO

BACKGROUND: In the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial, a pharmaco-invasive (PI) strategy was compared with primary percutaneous coronary intervention (pPCI) in ST-segment-elevation myocardial infarction patients presenting within 3 hours after symptom onset but unable to undergo pPCI within 1 hour. At 30 days, the PI approach was associated with a nominally but nonstatistically significant lower incidence of the composite primary end point of death, shock, congestive heart failure, and reinfarction when compared with pPCI. The aim of the present study was to determine the effect of these strategies on 1-year mortality. METHODS AND RESULTS: Vital status at 1 year was available in 936 of 944 (99.2%) and 941 of 948 (99.3%) patients in the PI and pPCI arm, respectively. At 1 year, all-cause mortality rates (6.7% versus 5.9%) were similar for PI and pPCI-treated patients (P=0.49; risk ratio, 1.13; 95% confidence interval, 0.79-1.62). Cardiac mortality rates were similar as well (4.0% versus 4.1%, P=0.93; risk ratio, 0.98; 95% confidence interval, 0.62-1.54). Overall, only 34 patients died between day 30 and 1 year, 20 in the PI arm and 14 in the pPCI arm, of whom 20 died of noncardiac reasons (13 in the PI and 7 in the pPCI arm). There was no significant difference in 1-year all-cause mortality between the 2 groups among the prespecified key subgroups. CONCLUSIONS: At 1 year, mortality rates in the PI and pPCI arms were similar in ST-segment-elevation myocardial infarction patients presenting within 3 hours after symptom onset and unable to undergo pPCI within 1 hour. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00623623.


Assuntos
Anticoagulantes/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/mortalidade , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Cateterismo Cardíaco , Eletrocardiografia , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Infarto do Miocárdio/diagnóstico , Choque Cardiogênico/mortalidade , Tenecteplase , Tempo para o Tratamento , Resultado do Tratamento
10.
N Engl J Med ; 370(15): 1402-11, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24716681

RESUMO

BACKGROUND: The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial. METHODS: In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization. RESULTS: Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42). CONCLUSIONS: In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).


Assuntos
Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Embolia Pulmonar/mortalidade , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Tenecteplase , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento , Troponina/sangue , Disfunção Ventricular Direita/etiologia
11.
N Engl J Med ; 368(15): 1379-87, 2013 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-23473396

RESUMO

BACKGROUND: It is not known whether prehospital fibrinolysis, coupled with timely coronary angiography, provides a clinical outcome similar to that with primary percutaneous coronary intervention (PCI) early after acute ST-segment elevation myocardial infarction (STEMI). METHODS: Among 1892 patients with STEMI who presented within 3 hours after symptom onset and who were unable to undergo primary PCI within 1 hour, patients were randomly assigned to undergo either primary PCI or fibrinolytic therapy with bolus tenecteplase (amended to half dose in patients ≥75 years of age), clopidogrel, and enoxaparin before transport to a PCI-capable hospital. Emergency coronary angiography was performed if fibrinolysis failed; otherwise, angiography was performed 6 to 24 hours after randomization. The primary end point was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days. RESULTS: The primary end point occurred in 116 of 939 patients (12.4%) in the fibrinolysis group and in 135 of 943 patients (14.3%) in the primary PCI group (relative risk in the fibrinolysis group, 0.86; 95% confidence interval, 0.68 to 1.09; P=0.21). Emergency angiography was required in 36.3% of patients in the fibrinolysis group, whereas the remainder of patients underwent angiography at a median of 17 hours after randomization. More intracranial hemorrhages occurred in the fibrinolysis group than in the primary PCI group (1.0% vs. 0.2%, P=0.04; after protocol amendment, 0.5% vs. 0.3%, P=0.45). The rates of nonintracranial bleeding were similar in the two groups. CONCLUSIONS: Prehospital fibrinolysis with timely coronary angiography resulted in effective reperfusion in patients with early STEMI who could not undergo primary PCI within 1 hour after the first medical contact. However, fibrinolysis was associated with a slightly increased risk of intracranial bleeding. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00623623.).


Assuntos
Angioplastia Coronária com Balão , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Terapia Trombolítica/métodos , Idoso , Clopidogrel , Angiografia Coronária , Quimioterapia Combinada , Eletrocardiografia , Enoxaparina/efeitos adversos , Enoxaparina/uso terapêutico , Feminino , Fibrinolíticos/efeitos adversos , Insuficiência Cardíaca/prevenção & controle , Humanos , Hemorragias Intracranianas/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Tenecteplase , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico
12.
J Am Coll Cardiol ; 57(19): 1867-73, 2011 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-21545942

RESUMO

OBJECTIVES: This study investigated the occurrence of intraluminal thrombus and its potential implications with facilitated percutaneous coronary interventions (fPCIs). BACKGROUND: The effect of fPCI on the presence and consequences of intraluminal thrombus is unknown. METHODS: Thrombolysis In Myocardial Infarction (TIMI) flow grade, frame count, and thrombus grade; distal embolization; and slow flow in the infarct-related artery were assessed in a blinded fashion on coronary angiograms in 1,342 patients from the ASSENT-4 PCI (Assessment of the Safety and Efficacy of a New Treatment Strategy With Percutaneous Coronary Intervention) trial. Residual TIMI thrombus grade ≥2 and/or distal embolization and/or slow flow, reflecting thrombus burden (TB), following PCI were correlated with ST-segment resolution, epicardial blood flow, and clinical outcome. The clinical composite endpoint was death, congestive heart failure, or shock. RESULTS: In the fPCI group, more TIMI flow grade 2/3 in the infarct-related artery at the first angiogram (73.7% vs. 33.4%, p < 0.001) and a higher TB following PCI (19.7% vs. 13.4%, p = 0.002) were found in comparison with the primary PCI group. Post-PCI TIMI thrombus grade was significantly associated with ST-segment resolution (p < 0.001) and TIMI frame count (p < 0.0001) in both groups. In the fPCI group, the presence of post-PCI thrombus was associated with a significantly worse outcome at 90 days (clinical composite endpoint: 32.1% vs. 18.6%, p = 0.023). Multivariable logistic regression showed that facilitation with tenecteplase (p = 0.005) and TB (odds ratio: 2.43, 95% confidence interval: 1.30 to 4.51, p = 0.0052) were independent predictors of 90-day mortality. CONCLUSIONS: In ASSENT-4 PCI, despite more patency, residual TB was significantly higher in fPCI patients and was associated with less efficient tissue reperfusion and worse clinical outcomes. (A Trial Evaluating the Efficacy and Safety of Tenecteplase Together With Unfractionated Heparin Prior to Early Percutaneous Coronary Intervention [PCI] as Compared to Standard Primary PCI in Patients With Acute Myocardial Infarction [ASSENT-4 PCI]; NCT00168792).


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Cardiopatias/diagnóstico por imagem , Heparina/efeitos adversos , Trombose/diagnóstico por imagem , Ativador de Plasminogênio Tecidual/efeitos adversos , Idoso , Angioplastia Coronária com Balão/métodos , Angiografia Coronária/métodos , Feminino , Cardiopatias/etiologia , Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tenecteplase , Trombose/etiologia , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento
13.
Am Heart J ; 160(1): 30-35.e1, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20598969

RESUMO

BACKGROUND: Primary percutaneous coronary intervention (PCI) has emerged as the preferred therapy for acute ST-elevation myocardial infarction (STEMI) provided it is performed in a timely fashion at an expert 24/7 facility. Fibrinolysis is a well-accepted alternative, especially in patients presenting early after symptom onset. The STREAM study will provide novel information on whether prompt fibrinolysis at first medical contact, followed by timely catheterization or rescue coronary intervention in STEMI patients presenting within 3 hours of symptom onset, represents an appropriate alternative strategy to primary PCI. METHODS: Acute STEMI patients presenting early after symptom onset are eligible if PCI is not feasible within 60 minutes of first medical contact. This is an open-label, prospective, randomized, parallel, comparative, international multicenter trial. Patients are randomized to fibrinolysis combined with enoxaparin, clopidogrel, and aspirin, and cardiac catheterization within 6 to 24 hours or rescue coronary intervention if reperfusion fails within 90 minutes of fibrinolysis versus PCI performed according to local guidelines. Composite efficacy end points at 30 days include death, shock, heart failure, and reinfarction. Safety end points include ischemic stroke, intracranial hemorrhage, and major nonintracranial bleeding. Follow-up is extended to 1 year and includes all-cause mortality. DISCUSSION: Continuing delays in achieving timely PCI remain a difficult issue. Many patients fail to achieve the desired reperfusion times of 90 to 120 minutes after first medical contact. The STREAM results will provide useful additional data on which to base informed therapeutic decisions.


Assuntos
Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Terapia Trombolítica/métodos , Idoso , Aspirina/uso terapêutico , Cateterismo Cardíaco , Causas de Morte , Clopidogrel , Quimioterapia Combinada , Eletrocardiografia , Enoxaparina/uso terapêutico , Seguimentos , Humanos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Estudos Prospectivos , Taxa de Sobrevida/tendências , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
14.
N Engl J Med ; 359(25): 2651-62, 2008 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-19092151

RESUMO

BACKGROUND: Approximately 70% of persons who have an out-of-hospital cardiac arrest have underlying acute myocardial infarction or pulmonary embolism. Therefore, thrombolysis during cardiopulmonary resuscitation may improve survival. METHODS: In a double-blind, multicenter trial, we randomly assigned adult patients with witnessed out-of-hospital cardiac arrest to receive tenecteplase or placebo during cardiopulmonary resuscitation. Adjunctive heparin or aspirin was not used. The primary end point was 30-day survival; the secondary end points were hospital admission, return of spontaneous circulation, 24-hour survival, survival to hospital discharge, and neurologic outcome. RESULTS: After blinded review of data from the first 443 patients, the data and safety monitoring board recommended discontinuation of enrollment of asystolic patients because of low survival, and the protocol was amended. Subsequently, the trial was terminated prematurely for futility after enrolling a total of 1050 patients. Tenecteplase was administered to 525 patients and placebo to 525 patients; the two treatment groups had similar clinical profiles. We did not detect any significant differences between tenecteplase and placebo in the primary end point of 30-day survival (14.7% vs. 17.0%; P=0.36; relative risk, 0.87; 95% confidence interval, 0.65 to 1.15) or in the secondary end points of hospital admission (53.5% vs. 55.0%, P=0.67), return of spontaneous circulation (55.0% vs. 54.6%, P=0.96), 24-hour survival (30.6% vs. 33.3%, P=0.39), survival to hospital discharge (15.1% vs. 17.5%, P=0.33), or neurologic outcome (P=0.69). There were more intracranial hemorrhages in the tenecteplase group. CONCLUSIONS: When tenecteplase was used without adjunctive antithrombotic therapy during advanced life support for out-of-hospital cardiac arrest, we did not detect an improvement in outcome, in comparison with placebo. (ClinicalTrials.gov number, NCT00157261.)


Assuntos
Reanimação Cardiopulmonar/métodos , Fibrinolíticos/uso terapêutico , Parada Cardíaca/terapia , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Distribuição de Qui-Quadrado , Método Duplo-Cego , Feminino , Fibrinolíticos/efeitos adversos , Seguimentos , Parada Cardíaca/tratamento farmacológico , Parada Cardíaca/mortalidade , Humanos , Hemorragias Intracranianas/induzido quimicamente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Tenecteplase , Ativador de Plasminogênio Tecidual/efeitos adversos , Falha de Tratamento
15.
CMAJ ; 174(10): 1421-6, 2006 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-16682709

RESUMO

BACKGROUND: The optimal antithrombotic therapy to accompany tenecteplase in cases of acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We undertook a prespecified pooled analysis of data from the ASSENT-3 and ASSENT-3 PLUS trials. METHODS: We created a combined database of the 2040 and 818 patients who received enoxaparin in ASSENT-3 and ASSENT-3 PLUS, respectively, and compared them with the 2038 and 821 patients who received unfractionated heparin. RESULTS: The efficacy end point (a composite of 30-day mortality, reinfarction or refractory ischemia) was 12.2% with enoxaparin versus 16.0% with unfractionated heparin (p < 0.001); the combined end point of efficacy plus safety (a composite of 30-day mortality, reinfarction, refractory ischemia, intracranial hemorrhage [ICH] or major systemic bleeding) was 15.0% versus 18.0%, respectively (p = 0.003) [corrected] The 1049 patients urgently revascularized had greater benefit from enoxaparin (15.4% v. 10.1%, p = 0.013), yet the excess in major systemic bleeding evident with enoxaparin (3.3% v. 2.4%, p = 0.01) was largely confined to the 3492 patients without or before revascularization. Although ICH rates in the groups were similar (1.3% v. 0.9%, p = 0.26), an excess of ICH occurred among those administered enoxaparin during the ASSENT-3 PLUS trial (6.7% v. 0.8%, p = 0.013), especially among women over 75 years of age. INTERPRETATION: These data demonstrated the benefit of enoxaparin used in conjunction with tenecteplase, but raised caution about its prehospital use to treat STEMI in elderly women.


Assuntos
Enoxaparina/uso terapêutico , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Área Sob a Curva , Quimioterapia Combinada , Tratamento de Emergência , Humanos , Hemorragias Intracranianas/epidemiologia , Modelos Logísticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Tenecteplase , Ativador de Plasminogênio Tecidual/uso terapêutico
16.
Am J Cardiol ; 94(3): 279-83, 2004 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-15276088

RESUMO

We investigated the effect of smaller dose, weight-adjusted heparin with earlier monitoring of activated partial thromboplastin time on the incidence of ischemic and hemorrhagic complications in patients with ST-elevation myocardial infarction treated with full-dose tenecteplase. We compared the outcomes of patients enrolled in the Second Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT-2; n = 8,461) who received heparin stratified by weight (patients weighing >67 kg received a 5,000-U bolus plus infusion at 1,000 U/hour; those weighing < or =67 kg received a 4,000-U bolus plus infusion at 800 U/hour) with patients in ASSENT-3 who received weight-adjusted heparin (60-U/kg bolus, maximum 4,000 U/hour, followed by a 12-U/kg/hour infusion, maximum 1,000 U/hour). Compared with patients in ASSENT-2, those in ASSENT-3 had similar rates of 30-day mortality, recurrent infarction, and intracranial hemorrhage, less major bleeding (2.2% vs 4.7%, p <0.001), and less refractory ischemia (6.5% vs 8.6%, p <0.001). After adjustment for baseline characteristics, patients in ASSENT-3 had similar rates of 30-day mortality (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.77 to 1.19) and intracranial hemorrhage (OR 1.02, 95% CI 0.61 to 1.69) but less major bleeding (OR 0.49, 95% CI 0.35 to 0.67) than did patients in ASSENT-2. These findings support the use of smaller dose, weight-adjusted heparin in patients with ST-elevation myocardial infarction treated with tenecteplase.


Assuntos
Heparina de Baixo Peso Molecular/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Intervalos de Confiança , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Eletrocardiografia , Feminino , Seguimentos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Incidência , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/epidemiologia , Tempo de Tromboplastina Parcial , Probabilidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Tenecteplase , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
17.
Clin Pharmacokinet ; 41(15): 1229-45, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12452736

RESUMO

Tenecteplase is a novel fibrinolytic protein bioengineered from human tissue plasminogen activator (alteplase) for the therapy of acute ST-segment elevation myocardial infarction. Specific mutations at three sites in the alteplase molecule result in 15-fold higher fibrin specificity, 80-fold reduced binding affinity to the physiological plasminogen activator inhibitor PAI-1 and 6-fold prolonged plasma half-life (22 vs 3.5 minutes). Consequently, tenecteplase can be administered as a single intravenous bolus of 30-50mg (0.53 mg/kg bodyweight) over 5-10 seconds, in contrast to the 90-minute accelerated infusion regimen of alteplase. Tenecteplase plasma concentration-time profiles have been obtained from a total of 179 patients with acute myocardial infarction. Tenecteplase exhibited biphasic disposition; the initial disposition phase was predominant with a mean half-life of 17-24 minutes, and the mean terminal half-life was 65-132 min. Over the clinically relevant dose range of 30-50mg, mean clearance (CL) was 105 ml/min. The mean initial volume of distribution V(1) was 4.2-6.3L, approximating plasma volume, and volume of distribution at steady state was 6.1-9.9L, suggesting limited extravascular distribution or binding. Bodyweight and age were found to influence significantly both CL and V(1). Total bodyweight explained 19% of the variability in CL and 11% of the variability in V(1), and a 10kg increase in total bodyweight resulted in a 9.6 ml/min increase in CL. This relationship aided the development of a rationale for the weight-adjusted dose regimen for tenecteplase. Age explained only a further 11% of the variability in CL. The percentage of patients who achieved normal coronary blood flow was clearly related to AUC. More than 75% of patients achieved normal flow at 90 minutes after administration when their partial AUC(2-90) exceeded 320 microg.min/ml, corresponding to an average plasma concentration of 3.6 microg/ml. Systemic exposure to tenecteplase at all times after bolus administration of 30-50mg was higher than for alteplase 100mg. Tenecteplase has demonstrated equivalent efficacy and improved safety compared with the current gold standard alteplase in a large mortality trial (ASSENT-2). This suggests that the reduced clearance, greater fibrin specificity and higher PAI-1 resistance of tenecteplase allow higher plasma concentrations and thus a more rapid restoration of coronary patency to be attained, while providing a reduction in major non-cerebral bleeding events.


Assuntos
Fibrinolíticos/farmacocinética , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/farmacocinética , Ativador de Plasminogênio Tecidual/uso terapêutico , Doença Aguda , Animais , Biotransformação , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Humanos , Infarto do Miocárdio/metabolismo , Tenecteplase , Distribuição Tecidual , Ativador de Plasminogênio Tecidual/biossíntese
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