What are the risks and benefits of fibrinolytic therapy for an adult patient with a history of cardiovascular disease who is at risk for thrombotic events?

Fibrinolytic Therapy: Risk-Benefit Assessment for Patient Education

For patients with ST-elevation myocardial infarction presenting within 12 hours of symptom onset, fibrinolytic therapy saves approximately 30 lives per 1000 patients treated if given within 6 hours, and 20 lives per 1000 if given between 7-12 hours, but carries a risk of approximately 4 additional strokes per 1000 patients, with half being moderately or severely disabling. 1

Mortality Benefit: The Primary Reason for Treatment

Time is critical—the benefit decreases by approximately 1.6 deaths per hour of delay per 1000 patients treated. 1

• Within 0-6 hours: Prevents approximately 30 deaths per 1000 patients treated 1
• Within 7-12 hours: Prevents approximately 20 deaths per 1000 patients treated 1
• Beyond 12 hours: No convincing evidence of benefit for the group as a whole 1
• After 24 hours: Fibrinolysis should not be administered (Class III contraindication) 1, 2

When combined with aspirin, the mortality reduction increases to approximately 50 lives saved per 1000 patients treated. 1

Stroke Risk: The Primary Hazard

Fibrinolytic therapy causes approximately 3.9 extra strokes per 1000 patients, with all excess hazard appearing on the first day after treatment. 1

Breaking Down the Stroke Risk:

• Total excess strokes: ~4 per 1000 patients 1
• Strokes leading to death: ~2 per 1000 (already counted in mortality benefit) 1
• Non-fatal strokes in survivors: ~2 per 1000 1
• Of non-fatal strokes: Half are moderately or severely disabling 1

Intracranial Hemorrhage Occurs in 0.9-1.0% of Treated Patients 1, 2

Risk factors that increase stroke probability from 0.25% (no risk factors) to 2.5% (three risk factors): 1

• Age ≥65 years 1, 2
• Low body weight ≤70 kg 1, 2
• Hypertension on presentation (≥180/110 mmHg) 1, 2
• Use of tissue plasminogen activator (rtPA/alteplase) 1

Additional predictors of intracranial hemorrhage include female gender, prior cerebrovascular disease, and systolic/diastolic hypertension on admission. 1

Major Non-Cerebral Bleeding

Major bleeding requiring transfusion or life-threatening bleeding occurs in 4-13% of treated patients. 1

Independent predictors of non-cerebral bleeding: 1

• Older age
• Lower body weight
• Female gender

Most bleeding is procedure-related (from catheterization sites, arterial punctures). 1

Absolute Contraindications: When Fibrinolysis Must Not Be Given

Any of these conditions make fibrinolytic therapy absolutely contraindicated: 1, 2, 3, 4

• Previous intracranial hemorrhage at any time 1, 2, 3
• Ischemic stroke within the last 6 months 1, 2, 3
• Known structural cerebral vascular lesions (arteriovenous malformations, aneurysms) 1, 2, 3
• Malignant intracranial neoplasms (primary or metastatic) 1, 2, 3
• Suspected or confirmed aortic dissection 1, 2, 3
• Active bleeding or hemorrhagic diathesis (excluding menstruation) 1, 2, 3
• Significant cranial or facial trauma in the last 3 months 1, 2, 3
• Major trauma or major surgery in the last 3 weeks 2, 3
• Gastrointestinal bleeding in the last month 2, 3
• Non-compressible punctures in the last 24 hours (liver biopsy, lumbar puncture) 2, 3

Relative Contraindications: Careful Risk-Benefit Assessment Required

These conditions require weighing bleeding risk against ischemic benefit: 1, 2, 3

• Transient ischemic attack in the last 6 months 1, 2, 3
• Uncontrolled severe hypertension (SBP ≥180 mmHg or DBP ≥110 mmHg) 1, 2, 3
• History of chronic, severe, uncontrolled hypertension 2, 3
• Traumatic or prolonged cardiopulmonary resuscitation (≥10 minutes) 2, 3
• Recent internal bleeding (2-4 weeks prior) 2, 3
• Pregnancy or within 1 week postpartum 1, 2, 3
• Active peptic ulcer 2, 3
• Current use of anticoagulants (higher INR = higher bleeding risk) 2, 3
• Advanced liver disease 2, 3
• Infective endocarditis 2, 3

Special Populations

Elderly Patients (≥75 Years)

Patients over 75 presenting within 12 hours with ST-elevation or bundle-branch block have mortality significantly reduced from 29.4% to 26% (P=0.03) with fibrinolytic therapy, despite higher stroke risk. 1

The absolute benefit appears similar to younger patients, though stroke incidence increases with advancing age, reducing relative benefit. 1

Cardiogenic Shock

Fibrinolysis lacks efficacy in cardiogenic shock—primary PCI is the optimal strategy in this setting. 1, 2

Clinical Decision Algorithm

Step 1: Check absolute contraindications 2, 3

• If any present → fibrinolysis is contraindicated (Class III)
• Arrange rapid transfer to PCI-capable center

Step 2: Assess time from symptom onset 1

• <6 hours → maximum benefit (~30 deaths prevented per 1000)
• 7-12 hours → substantial benefit (~20 deaths prevented per 1000)
• 12-24 hours → generally not recommended unless persistent ischemic pain with continued ST elevation (Class IIb)

• 24 hours → contraindicated (Class III)

Step 3: Evaluate bleeding risk factors 1, 2, 3

• Count major risk factors: age ≥65, weight ≤70 kg, hypertension ≥180/110, use of rtPA
• 0 risk factors = 0.25% stroke risk
• 3 risk factors = 2.5% stroke risk

Step 4: Consider relative contraindications 2, 3

• If multiple relative contraindications present, weigh against infarct size
• Extensive ECG changes (large MI) favor fibrinolysis despite some bleeding risk

Step 5: Consider PCI availability 1

• If primary PCI available within 120 minutes of first medical contact and high bleeding risk identified → prefer PCI strategy
• If PCI unavailable and no absolute contraindications → proceed with fibrinolysis

Common Pitfalls to Avoid

Do not delay treatment waiting for cardiac biomarker results when clinical suspicion for STEMI is high. 5

Do not use fibrinolysis for patients with ST depression (unless true posterior MI suspected or associated with ST elevation in lead aVR). 1

Do not readminister streptokinase due to antibodies that impair activity and risk of allergic reactions. 1

Brief successful resuscitation does not contraindicate fibrinolysis, but prolonged or traumatic resuscitation increases bleeding risk. 1, 2

Additional Management Considerations

Hypotension with streptokinase administration: Temporarily halt infusion, lay patient flat, elevate feet; occasionally atropine or intravascular volume expansion may be required. 1

Routine hydrocortisone is not indicated for streptokinase administration. 1

Monitor for hypersensitivity reactions (urticaria, anaphylaxis, angioedema) during and for several hours after infusion; discontinue immediately if signs occur. 4