What is the role of thrombolysis in ocular myocardial infarction (OMI)?

Role of Thrombolysis in Acute Myocardial Infarction

Thrombolytic therapy is a life-saving intervention for ST-elevation myocardial infarction (STEMI) when administered within 12 hours of symptom onset, particularly when primary PCI cannot be performed within 120 minutes of first medical contact. 1

Primary Indication and Timing

Fibrinolytic therapy should be initiated within 10 minutes of STEMI diagnosis when primary PCI is not available within the recommended time window. 1 The benefit is greatest when treatment begins within the first 2-4 hours of symptom onset, with mortality reduction of up to 53% when combined with aspirin. 1

• Patients presenting within 12 hours of symptom onset with ST-segment elevation or new left bundle branch block qualify for thrombolysis if PCI is not immediately accessible 1, 2
• Pre-hospital administration is strongly recommended to minimize time delays, with studies showing feasibility and safety when initiated at a mean of 1.2 hours versus 2.0 hours in-hospital 3
• The "time is muscle" principle applies: every 30-minute delay reduces the mortality benefit, as myocardial necrosis progresses from subendocardium to subepicardium within 15-30 minutes of complete occlusion 1

Preferred Agents and Dosing

Fibrin-specific agents should be preferred over non-specific agents. 1

• Tenecteplase (TNK-tPA) is the optimal choice: single-bolus weight-adjusted administration is equivalent to accelerated alteplase for 30-day mortality but safer regarding non-cerebral bleeding and easier for pre-hospital use 1
• Alteplase (tPA) administered as accelerated 90-minute infusion (100 mg total) achieves approximately 50% epicardial patency within 90 minutes 1, 2
• Streptokinase may cause hypotension and should never be re-administered due to antibody formation and allergic reaction risk 1

Mandatory Adjunctive Therapy

All patients receiving fibrinolysis must receive dual antiplatelet therapy and anticoagulation. 1

Antiplatelet Regimen:

• Aspirin 75-100 mg: first dose chewed or given IV, then daily oral administration 1
• Clopidogrel: added to aspirin, reduces cardiovascular events and overall mortality in fibrinolysis patients 1
• Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and should not be used 1
• GP IIb/IIIa inhibitors provide no benefit and increase bleeding risk 1

Anticoagulation:

• Enoxaparin is superior to unfractionated heparin: reduces death and reinfarction at 30 days despite increased non-cerebral bleeding, with net clinical benefit favoring enoxaparin 1
• Dose adjustment required: reduced dose for patients ≥75 years or creatinine clearance <30 mL/min 1
• Continue until revascularization or minimum 48 hours, maximum 8 days 1
• Fondaparinux shown superior to placebo or UFH when combined with streptokinase 1

Pharmacoinvasive Strategy (Post-Fibrinolysis Management)

All patients receiving fibrinolysis must be transferred to a PCI-capable center for routine early angiography within 2-24 hours after successful lysis. 1

Immediate Rescue PCI Indications:

• Failed fibrinolysis (ST-segment resolution <50% at 60-90 minutes) 1
• Evidence of reocclusion or reinfarction with recurrent ST-elevation 1
• Re-administration of fibrinolysis is not beneficial and should be discouraged 1

Routine Early Angiography:

• Even with successful fibrinolysis (>50% ST-resolution, reperfusion arrhythmia, chest pain resolution), perform angiography within 2-24 hours 1
• Shorter time from symptom onset to angiography (<4 hours) associated with reduced death/reinfarction at 30 days and 1 year 1
• This strategy reduces reinfarction and recurrent ischemia compared to "watchful waiting" without increasing stroke or major bleeding 1

Absolute Contraindications

Do not administer thrombolysis if any of the following are present: 1, 4

• Active internal bleeding 1, 4
• History of hemorrhagic stroke or stroke of unknown origin at any time 1, 4
• Ischemic stroke within preceding 6 months 1, 4
• Central nervous system damage or neoplasms 1, 4
• Recent major trauma, surgery, or head injury within preceding 3 weeks 1, 4
• Gastrointestinal bleeding within last month 1, 4
• Known active bleeding disorder 1, 4
• Blood pressure >200/120 mmHg 4
• Diabetic hemorrhagic retinopathy 4

Relative Contraindications

Exercise caution and perform individualized risk-benefit assessment for: 1, 4

• Transient ischemic attack in preceding 6 months 4
• Current oral anticoagulant therapy 4
• Pregnancy or within 1 week postpartum 4
• Non-compressible vascular punctures 4
• Traumatic but successful cardiopulmonary resuscitation (prolonged CPR increases bleeding risk) 1, 4
• Refractory hypertension (systolic BP >180 mmHg) 4
• Advanced liver disease 4
• Infective endocarditis 4
• Active peptic ulcer 4

Note: Short successful resuscitation does not contraindicate fibrinolysis, but refractory cardiac arrest makes lytic therapy ineffective and increases bleeding risk. 1

Bleeding Risk and Management

Intracranial hemorrhage occurs in 0.9-1.0% of patients, with major non-cerebral bleeding in 4-13%. 1

High-Risk Features for ICH:

• Advanced age 1
• Female sex 1
• Low body weight (<70 kg female, <80 kg male) 1
• Previous cerebrovascular disease 1
• Systolic and diastolic hypertension on admission (graded increase beginning at >160-170 mmHg systolic) 1

If ICH Occurs:

• Stop all antiplatelet and anticoagulant therapy immediately 5
• Emergency brain imaging with neurological and neurosurgical consultation 1
• Consider protamine, fresh frozen plasma, prothrombin complex concentrates, activated factor VII, and platelets 1

Critical Pitfalls to Avoid

• Never delay fibrinolysis for angiographic confirmation: this increases bleeding complications without benefit 4
• Never use GP IIb/IIIa inhibitors with fibrinolysis: no perfusion benefit and increased bleeding 1
• Never re-administer streptokinase: antibodies impair activity and increase allergic reactions 1
• Never give prasugrel or ticagrelor with fibrinolysis: unstudied and potentially harmful 1
• Never pursue "watchful waiting" after successful fibrinolysis: routine early angiography (2-24 hours) is mandatory 1

Mortality Benefit

Thrombolytic therapy reduces 30-day mortality by 18% overall (18 deaths avoided per 1000 patients treated), with greater benefit when combined with aspirin and administered early. 1, 2 The GISSI trial established this as standard care, demonstrating significant improvement in survival and ventricular function when administered within 12 hours of symptom onset. 1