Fibrinolysis for Acute Myocardial Infarction

Armstrong, Paul W.; Collen, D.

doi:10.1161/01.cir.103.23.2862

Cited by 63 publications

(34 citation statements)

References 59 publications

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“…They not only reduce the potential for medication errors but also greatly simplify the prospects of prehospital fibrinolysis. [2][3][4] Although these newer agents do not confer additional mortality reduction over that achieved by the 90-minute weightadjusted accelerated t-PA regimen, the enhanced fibrin specificity of TNK-tPA results in a significant reduction in systemic bleeding. 4 Whereas conjunctive therapy with intravenous glycoprotein IIb/IIIa (IV GP IIb/IIIa) inhibitors enhances epicardial flow and myocardial perfusion and reduces reinfarction, these advantages have not resulted in the expected improvement in survival.…”

Section: Evolution Of Pharmacological Reperfusion Regimensmentioning

confidence: 99%

“…Simultaneously, 4 key questions need to be addressed: (1) What is the time from symptom onset to medical contact? (2) What is the risk of the myocardial infarction based on initial clinical and electrocardiographic assessment? (3) What are the risks of fibrinolytic therapy particularly as it relates to systemic and intracranial bleeding?…”

Section: Choice Of Reperfusion Strategymentioning

confidence: 99%

“…These have comprehensively examined the efficacy, safety, and impact of novel therapeutic third-generation fibrinolytics and advances in conjunctive therapies aimed at enhancing restoration of myocardial flow in the epicardial infarct-related coronary artery. [1][2][3] …”

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confidence: 99%

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Fibrinolysis for Acute Myocardial Infarction

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Section: Evolution Of Pharmacological Reperfusion Regimensmentioning

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Section: Choice Of Reperfusion Strategymentioning

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Fibrinolysis for Acute Myocardial Infarction

2003

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“…Restoration of epicardial coronary flow post-acute MI improves clinical outcome [15]. Recanalization can be achieved by means of thrombolysis or primary angioplasty.…”

Section: Discussionmentioning

confidence: 99%

Low dose tenecteplase restores vessel patency in a clinically relevant porcine animal model

Tseliou¹,

Ntalianis²,

Diakos³

et al. 2016

J Transl Sci

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Thrombolysis remains the treatment of choice in patients who are far from the catheterization laboratories. Although full dose is advisable low dose has not been preclinically tested. Here we tested the hypothesis that low dose tenecteplase, a recombinant fibrin-specific plasminogen activator can induce efficient thrombolysis even in lower doses than the hitherto indicated, compared to full-dose thrombolytic therapy for ST-segment myocardial infarction. Farm pigs (30-35 kg, n=23) were imposed in a clinically relevant model of thrombosis. We used both the common carotid arteries (CA) and the left anterior descending artery (LAD) below the first diagonal. The vessels were initially externally injured (application of pressure by forceps) followed by an appropriate for the vessel dose of thrombin (100 IU for the LAD and 190 IU for CA). Occluding thrombi was achieved in 80% for the LAD and 57% for the CA. Ten minutes post occlusion the animals were allocated under continuous electrocardiogram and ultrasonic flow meter monitoring to one of the following groups: Group A) half-dose tenecteplase (2000 IU); Group B) Full dose tenecteplase (5000 IU); Group C) saline only. All animals received 60IU heparin and antiplatelet agents. The follow-up was 120 minutes post therapy administration. Sixty minutes after lytic drug administration recanalization occurred in 58% of the occluded arteries in Group A, in 85% in Group B and in 20% in Group C (P=0.028). Both tenecteplase regimens were effective for treating carotid artery thrombosis (71% Group A vs. 75% in Group B vs. 33% in Group C, P=0.286), but low dose was significantly less effective in reestablishing flow in proximally occluded LADs (25 % in Group A vs. 100% in Group B vs. 0% in Group C, P=0.015). All vessels with restored flow at 60 minutes remained patent at least for 1 hr. In Group A, at 60 minutes after tenecteplase administration, flow velocity in LAD reached 30% of the baseline value and 45% in carotids, while in Group B flow was 160% and 55% respectively, suggesting restoration of larger lumen diameter in the treated vessels. Post reperfusion ventricular arrhythmias that required treatment occurred equally in all groups. No differences in hemodynamic tested parameters were observed between the groups. In conclusion, we developed a clinically relevant model useful for testing the efficacy of different thrombolytic regimens. Our data demonstrate that low dose tenecteplase can be successfully used for treating thrombosis of larger diameter vessels, such as the carotids, but appears inadequate for treating LAD thrombotic occlusions.

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“…37 In other series, CNS bleeding rates are over 2% and mortality is 55%. 38 These illustrate the extreme importance of identifying patients at increased risk of bleeding. 39 In 2016, the ACCP proposed the following criteria: 40 Absolute contraindications for thrombolytics: history of CNS bleeding, ischemic stroke (< 3 months), CNS surgery or major trauma (< 1 month), active bleeding, CNS tumor or structural cerebral anomaly, aortic dissection, prolonged cardiopulmonary resuscitation (> 10 minutes), blood disorder, INR > 1.7, or thrombocytopenia (< 100,000/mm 3 ).…”

Section: Risk Of Bleeding With Systemic Fibrinolytic Agentsmentioning

confidence: 99%

Terapia fibrinolítica sistêmica no tromboembolismo pulmonar

Ceresetto

Marques

2017

J. vasc. bras.

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Pulmonary thromboembolism remains a major therapeutic challenge for specialists and, despite investment and the consequent developments in diagnosis, prophylaxis, and treatment, the condition is still the leading cause of avoidable deaths in hospital settings. There is still great uncertainty with relation to the profile of patients who will actually benefit from systemic fibrinolytic treatment, without being exposed to serious risk of bleeding. There are tools that can help to identify patients who will benefit, including risk stratification and estimation of the prognosis of the event, with clinical scores for right ventricular failure, markers of right ventricular dysfunction and dilatation, and thrombotic mass assessment, whether alone or in combination. The only points of consensus with relation to fibrinolytic therapy for treatment of pulmonary thromboembolism are as follows: it should not be routinely indicated, none of the scores or markers alone should be used to justify its use, and patients with hemodynamic instability are the most likely to benefit. Furthermore, each case should be evaluated for risk of bleeding, especially central nervous system bleeding.Keywords: fibrinolytics; pulmonary embolism; hemorrhage. ResumoO tromboembolismo pulmonar permanece como um grande desafio terapêutico para os médicos especialistas, pois, apesar de todo investimento e desenvolvimento em seu diagnóstico, profilaxia e tratamento, essa condição continua sendo a principal causa de morte evitável em ambiente hospitalar. Ainda restam muitas dúvidas em relação a qual perfil de paciente vai se beneficiar de fato da terapia fibrinolítica sistêmica, sem ficar exposto a um grande risco de sangramento. A estratificação de risco e a avaliação do prognóstico do evento, através de escores clínicos de insuficiência ventricular direita, marcadores de dilatação e disfunção do ventrículo direito e avaliação da massa trombótica, associados ou de forma isolada, são ferramentas que podem auxiliar na identificação do paciente que irá se beneficiar dessa terapia. Os únicos consensos em relação à terapia fibrinolítica no tratamento do tromboembolismo pulmonar são: não deve ser indicada de forma rotineira; nenhum dos escores ou marcadores, isoladamente, devem justificar seu uso; e os pacientes com instabilidade hemodinâmica são os mais beneficiados. Além disto, deve-se avaliar cada caso em relação ao risco de sangramento, especialmente no sistema nervoso central.Palavras-chave: fibrinolíticos; embolia pulmonar; hemorragia.

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Fibrinolysis for Acute Myocardial Infarction

Cited by 63 publications

References 59 publications

Fibrinolysis for Acute Myocardial Infarction

Fibrinolysis for Acute Myocardial Infarction

Low dose tenecteplase restores vessel patency in a clinically relevant porcine animal model

Terapia fibrinolítica sistêmica no tromboembolismo pulmonar

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