Fibrinolytics for Myocardial Infarction: Is it worth it?

There are two classes of fibrinolytics; fibrin specific and fibrin non-specific. As a fibrin specific medication, medications like tPA, reteplase, and tenecteplase bind to plasminogen. Plasminogen then gets broken down into plasmin. Plasmin is a proteolytic enzyme that works on breaking down the cross-links between fibrin molecules. Fibrin is a structural component of blood clots.(1)

From CV Physiology (1)

At a non-PCI center, give fibrinolytics if there is a greater than 120-minute delay from first medical contact to PCI. (Class I)

If giving fibrinolytics, administer within the first 30 minutes. (Class I)

Administer fibrinolytics to patients who have had ischemic symptoms for less than 12 hours. (Class I)

Administer fibrinolytics to patients who have evidence of ongoing ischemia 12 to 24 hours after symptom onset or have a large area of the myocardium at risk or hemodynamic instability. (Class II)

Avoid giving fibrinolytics in patients with ST-depression (STD) alone, unless there is a suspected posterior MI or ST-elevation (STE) in aVR. (Class III) (2)

The absolute contraindications of tPA are as follows: 

–Prior intracranial hemorrhage

–Known cerebral vascular lesion

–Known malignant intracranial neoplasm (primary or metastatic)

–Ischemic stroke (within 3 months)

–Suspected aortic dissection 

–Active bleeding or bleeding diathesis

–Significant closed head or facial trauma within 3 months

–Intracranial or intraspinal surgery within 2 months

–Severe uncontrolled hypertension (unresponsive to emergency therapy)

The relative contraindications are as follows: 

–Severe poorly controlled hypertension

–Significant hypertension on presentation >180/>110

–Prior ischemic stroke >3 months

–Dementia

–Known intracranial pathology (not covered in absolute contraindications)

–Traumatic or prolonged (>10 minutes) CPR

–Major surgery (<3 weeks)

–Recent (within 2-4 weeks) internal bleeding 

–Non-compressible vascular punctures

–Pregnancy 

–Active Peptic Ulcer 

–Oral Anticoagulant (2)

In 1994, the Fibrinolytic Therapy Trialist (FTT) Group meta-analyzed nine RCTs (n=58,600) that studied multiple fibrinolytics and found that only 0.7% were harmed by a major bleeding event and 0.4% were harmed by a hemorrhagic stroke.(3) The GUSTO investigators found tenecteplase to be safer than tPA (higher risk of hemorrhagic stroke with tPA than with tenecteplase).(4)

Timing:

The FTT Group Meta-Analysis examined various fibrinolytics and found that there was a significant reduction in 35-day mortality for giving fibrinolytics in ST-elevation/bundle branch block and <12 hours from onset of symptoms (fibrinolytic group: 9.6% vs control group: 11.5%).(5)

Age:

The FTT meta-analysis showed a non-significant difference in mortality (favoring the fibrinolytic group) between patients over the age of 75 receiving fibrinolytics and those who did not get it.(5) 

Success Rate:

One Canadian prospective study by Bainey et al. showed that fibrinolytics within the first hour of symptoms successfully “aborted” MI in approximately 30% of STEMI patients. They reviewed serial ECGs of 2,235 patients with STE and elevated CKs over 5 years and found that for those reperfused within 12 hours:

—16% of patients were considered to have an aborted MI

—Up to 4 hours from symptoms onset, fibrinolytics were superior to PCI. 

An aborted MI was defined as a maximal increase of creatinine kinase <2 times the upper limit of normal with evolutionary ECG changes.(6)

Repercussions of delay:

Fibrinolytics, specifically, tPA, may be less effective the longer its administration is delayed.

1. • ≥ 67 kg: Infuse 15 mg IV over 1-2 min; then 50 mg over 30 min; then 35 mg over next 60 min (i.e. 100mg over 1.5hr)
   • < 67 kg: Infuse 15 mg IV over 1-2 min; then 0.75 mg/kg (max 50 mg) over 30 min; then 0.5 mg/kg over 60 min (max 35 mg)

In addition to fibrinolytics, the American Heart Association STEMI guidelines recommend administering:

—Aspirin 162 mg – 325 mg

—Clopidogrel 300 mg (if over 75 years old: 75 mg)

—Anticoagulation: Heparin gtt administered as 60 U/kg bolus then 12 U/kg gtt. It is possible to also use LMWH administered as 30 mg IV bolus plus 1mg/kg subcutaneous 15 minutes later for patients under 75 years old. If over 75 years old, give 0.75 mg/kg subcutaneous. Another option is fondaparinux administered as 2.5 mg. It is important to consider the creatinine clearance for the latter two options prior to administration.(2)

All patients given fibrinolytics should be transferred for PCI. If there is failed reperfusion, transfer urgently. If the patient has cardiogenic shock or acute severe heart failure, the patient should be transferred immediately for PCI. If there is successful reperfusion and the patient is stable, the patient should be transferred in 3-24 hours.(2)

Upon reassessment at 60 to 90 minutes post-fibrinolytic, expect to see the resolution of STE, presence of a reperfusion arrhythmia, or improvement in chest pain. If there is >70% resolution of STE, successful reperfusion is considered to have occurred, and there is now a patent infarct artery. If there is < 50% STE resolution, assume failed fibrinolysis and urgently transfer for rescue PCI. (2) There is no evidence behind redosing fibrinolytics, and you may increase your patients risk of bleeding by doing so.(7)

Along with the resolution of STE, you may see the development of a reperfusion arrhythmia of which the most common is an accelerated idioventricular rhythm (below).(8) This rhythm is not sensitive or specific for reperfusion and does not require further treatment. You may see a combination of ventricular beats, fusion beats, and capture beats.

from Brown EM Blog (8)