ST elevation myocardial infarction fibrinolytic therapy

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Overview
Since the introduction of pharmacologic reperfusion therapy in the seventies, the main goal of reperfusion treatment has been to restore early, full and sustained patency of the infarct related artery. In the seventies and in the eighties, fibrinolytic therapy was the primary reperfusion strategy that was available for the management of patients with acute ST elevation myocardial infarction (STEMI). An initial analysis consisting of 9 clinical trials by the Fibrinolysis Therapy Trialists (FTT) group demonstrated that there was a significant reduction in the mortality associated with the administration of fibrinolytic therapy compared to control subjects who did not receive fibrinolytic therapy (9.6% vs. 11.5%, p<0.00001).

Mechanism of Benefit
View a clip from the late 70s heralding the advent of fibrinolytic therapy



Fibrinolytic therapy
Thrombolytic therapy is indicated for the treatment of STEMI if the drug can be administered within 12 hours of the onset of symptoms, the patient is eligible based on exclusion criteria, and primary PCI is not immediately available. The effectiveness of thrombolytic therapy is highest in the first 2 hours. After 12 hours, the risk associated with thrombolytic therapy outweighs any benefit. Because irreversible injury occurs within 2–4 hours of the infarction, there is a limited window of time available for reperfusion to work.

Thrombolytic drugs are contraindicated for the treatment of unstable angina and NSTEMI and for the treatment of individuals with evidence of cardiogenic shock.

Although no perfect thrombolytic agent exists, an ideal thrombolytic drug would lead to rapid reperfusion, have a high sustained patency rate, be specific for recent thrombi, be easily and rapidly administered, create a low risk for intra-cerebral and systemic bleeding, have no antigenicity, adverse hemodynamic effects, or clinically significant drug interactions, and be cost effective. Currently available thrombolytic agents include streptokinase, urokinase, and alteplase (recombinant tissue plasminogen activator, rtPA). More recently, thrombolytic agents similar in structure to rtPA such as reteplase and tenecteplase have been used. These newer agents boast efficacy at least as good as rtPA with significantly easier administration. The thrombolytic agent used in a particular individual is based on institution preference and the age of the patient.

Depending on the thrombolytic agent being used, adjuvant anticoagulation with heparin or low molecular weight heparin may be of benefit. With tPA and related agents (reteplase and tenecteplase), heparin is needed to maintain coronary artery patency. Because of the anticoagulant effect of fibrinogen depletion with streptokinase and urokinase  treatment, it is less necessary there.

Side Effects
Intracranial bleeding (ICB) and subsequent cerebrovascular accident (CVA) is a serious side effect of thrombolytic use. The risk of ICB is dependent on a number of factors, including a previous episode of intracranial bleed, age of the individual, and the thrombolytic regimen that is being used. In general, the risk of ICB due to thrombolytic use for the treatment of an acute myocardial infarction is between 0.5 and 1 percent.

Thrombolytic therapy to abort a myocardial infarction is not always effective. The degree of effectiveness of a thrombolytic agent is dependent on the time since the myocardial infarction began, with the best results occurring if the thrombolytic agent is used within two hours of the onset of symptoms. If the individual presents more than 12 hours after symptoms commenced, the risk of intracranial bleed are considered higher than the benefits of the thrombolytic agent. Failure rates of thrombolytics can be as high as 20% or higher.

In cases of failure of the thrombolytic agent to open the infarct-related coronary artery, the patient is then either treated conservatively with anticoagulants and allowed to "complete the infarction" or percutaneous coronary intervention (PCI, see below) is then performed. Percutaneous coronary intervention in this setting is known as "rescue PCI" or "salvage PCI". Complications, particularly bleeding, are significantly higher with rescue PCI than with primary PCI due to the action of the thrombolytic agent.

Class I
1. In the absence of contraindications, fibrinolytic therapy should be administered to STEMI patients with symptom onset within the prior 12 hours and ST elevation greater than 0.1 mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads. (Level of Evidence: A)

2. In the absence of contraindications, fibrinolytic therapy should be administered to STEMI patients with symptom onset within the prior 12 hours and new or presumably new LBBB. (Level of Evidence: A)

Class IIa
1. In the absence of contraindications, it is reasonable to administer fibrinolytic therapy to STEMI patients with symptom onset within the prior 12 hours and 12-lead ECG findings consistent with a true posterior MI. (Level of Evidence: C)

2. In the absence of contraindications, it is reasonable to administer fibrinolytic therapy to patients with symptoms of STEMI beginning within the prior 12 to 24 hours who have continuing ischemic symptoms and ST elevation greater than 0.1 mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads. (Level of Evidence: B)

Class III
1. Fibrinolytic therapy should not be administered to asymptomatic patients whose initial symptoms of STEMI began more than 24 hours earlier. (Level of Evidence: C)

2. Fibrinolytic therapy should not be administered to patients whose 12-lead ECG shows only ST-segment depression except if a true posterior MI is suspected. (Level of Evidence: A)}}

==ACC / AHA Guidelines- Contraindications / Cautions to Fibrinolytic Therapy (DO NOT EDIT) == {{cquote|

Class I
1. Healthcare providers should ascertain whether the patient has neurological contraindications to fibrinolytic therapy, including: any history of intracranial hemorrhage or significant closed head or facial trauma within the past 3 months, uncontrolled hypertension, or ischemic stroke within the past 3 months. (Level of Evidence: A)

2. STEMI patients at substantial (greater than or equal to 4%) risk of ICH should be treated with PCI rather than with fibrinolytic therapy. (Level of Evidence: A)}}

==ACC / AHA Guidelines- Complications of Fibrinolytic Therapy (DO NOT EDIT) ==

{{cquote|

Class I
1. The occurrence of a change in neurological status during or after reperfusion therapy, particularly within the first 24 hours after initiation of treatment, is considered to be due to ICH until proven otherwise. Fibrinolytic, antiplatelet, and anticoagulant therapies should be discontinued until brain imaging scan shows no evidence of ICH. (Level of Evidence: A)

2. Neurology and/or neurosurgery or hematology consultations should be obtained for STEMI patients who have ICH, as dictated by clinical circumstances. (Level of Evidence: C)

3. In patients with ICH, infusions of cryoprecipitate, fresh frozen plasma, protamine, and platelets should be given, as dictated by clinical circumstances. (Level of Evidence: C)

Class IIa
1. In patients with ICH it is reasonable to:

a. Optimize blood pressure and blood glucose levels (Level of Evidence: C)

b. Reduce intracranial pressure with an infusion of mannitol, endotracheal intubation, and hyperventilation (Level of Evidence: C)

c. Consider neurosurgical evacuation of ICH (Level of Evidence: C)}}