What is the recommended pharmacoinvasive management for an acute ST‑segment elevation myocardial infarction (STEMI) patient in Asia when primary percutaneous coronary intervention (PCI) cannot be performed within 120 minutes?

Pharmacoinvasive Strategy for STEMI in Asia

Immediate Reperfusion Decision

When primary PCI cannot be performed within 120 minutes of first medical contact in Asia, administer fibrinolytic therapy immediately (within 10-30 minutes of diagnosis) followed by routine early angiography and PCI within 3-24 hours. 1

This pharmaco-invasive approach is the most feasible and desirable pathway for STEMI networks in low- and middle-income countries, including much of Asia, where geographic constraints and limited PCI infrastructure make timely primary PCI impossible for many patients. 1

Time-Based Algorithm for Reperfusion Selection

The decision hinges on three critical variables: symptom onset time, anticipated PCI delay, and patient risk profile. 1

Patients Presenting <2 Hours After Symptom Onset

• If PCI delay >60 minutes: Administer fibrinolysis immediately 1
• If PCI delay 60-120 minutes: Either fibrinolysis or PCI is reasonable 1
• If PCI delay <60 minutes: Proceed with primary PCI 1

The mortality benefit of fibrinolysis is greatest within the first 2 hours ("golden hour"), achieving up to 50% mortality reduction when given within 60-90 minutes of symptom onset. 1

Patients Presenting 2-3 Hours After Symptom Onset

• If PCI delay 60-120 minutes: Either fibrinolysis or PCI is acceptable 1
• If PCI delay >120 minutes: Administer fibrinolysis 1

Patients Presenting 3-12 Hours After Symptom Onset

• If PCI delay ≤120 minutes: Primary PCI is preferred 1
• If PCI delay >120 minutes: Administer fibrinolysis followed by routine early PCI 1

Patients Presenting >12 Hours After Symptom Onset

• Primary PCI is the only option regardless of delay, because fibrinolysis becomes significantly less effective beyond 6 hours 1
• Exception: If ongoing ischemia with large myocardium at risk or hemodynamic instability exists, fibrinolysis may be considered if PCI is unavailable 1

Mandatory Primary PCI (Regardless of Time Delay)

These clinical scenarios require immediate PCI even if transfer exceeds 120 minutes: 1

• Cardiogenic shock or acute severe heart failure (Killip class >1)
• Contraindications to fibrinolytic therapy (active bleeding, recent stroke, terminal illness)
• Failed fibrinolysis (persistent symptoms or <50% ST-segment resolution at 60-90 minutes)

High-risk patients with Killip class >1 may benefit from primary PCI even with treatment delays up to 120 minutes. 1

Fibrinolytic Protocol

Agent Selection and Dosing

Use fibrin-specific agents: 1

• Tenecteplase: Single weight-adjusted IV bolus (30-50 mg based on weight)
• Alteplase: 90-minute weight-based infusion (15 mg bolus, then 0.75 mg/kg over 30 min, then 0.5 mg/kg over 60 min)
• Reteplase: 10 U + 10 U IV boluses 30 minutes apart

For Asian populations, half-dose alteplase has been studied and appears feasible, though full-dose fibrin-specific agents remain the guideline standard. 2

Adjunctive Antithrombotic Therapy

Immediately with fibrinolysis: 1

• Aspirin: 150-325 mg orally or 250-500 mg IV
• Clopidogrel: 300 mg loading dose (prasugrel and ticagrelor are NOT recommended with fibrinolysis)
• Anticoagulation: Enoxaparin preferred (30 mg IV bolus, then 1 mg/kg SC every 12 hours) or unfractionated heparin (60 U/kg IV bolus, then 12 U/kg/hr infusion)

Continue anticoagulation for at least 48 hours and up to 8 days or until revascularization. 1

Post-Fibrinolysis Transfer and PCI Timing

Initiate immediate transfer to a PCI-capable center after fibrinolysis without waiting to assess reperfusion success. 3, 4

Routine Early PCI (Pharmaco-Invasive Strategy)

• Perform angiography 3-24 hours after fibrinolysis in hemodynamically stable patients 1
• Optimal timing appears to be 3-12 hours after lysis for best myocardial perfusion 2
• Earlier PCI (3-6 hours) may be preferable to later timing (>24 hours) 1

The TRANSFER-AMI trial demonstrated that routine early PCI (within 6 hours) after tenecteplase reduced the composite endpoint of death, reinfarction, recurrent ischemia, heart failure, and shock compared to standard treatment (11.0% vs 17.2%, P=0.004). 3

Rescue PCI

Perform immediate rescue PCI if: 1

• <50% ST-segment resolution at 60-90 minutes after fibrinolysis
• Hemodynamic instability develops
• Refractory ischemia persists

Hub-and-Spoke Network Implementation

For resource-limited Asian settings, establish a structured treatment format: 1

• Primary health centers without ECG: Administer aspirin 300-350 mg and transfer immediately
• Facilities with ECG capability: Confirm STEMI, administer fibrinolysis if PCI delay >120 minutes, then transfer
• PCI-capable hubs: Provide 24/7 service with direct catheterization laboratory access

Alternative Strategy for Resource-Constrained Settings

When routine early PCI after fibrinolysis is not feasible, a reasonable approach is: 1

• Triage only high-risk patients (cardiogenic shock, failed fibrinolysis, electrical instability) to angiography/PCI
• Use noninvasive risk stratification (predischarge exercise treadmill test or stress imaging) for stable low-risk patients
• Perform PCI only for ischemia-driven indications in this low-risk group

Critical Pitfalls to Avoid

Do NOT combine immediate fibrinolysis with immediate PCI (facilitated PCI)—this increases intracranial hemorrhage without mortality benefit and is Class III: Harm. 1

Do NOT delay transfer after fibrinolysis to "see if it works"—immediate transfer with planned early PCI improves outcomes regardless of initial reperfusion success. 3, 4

Do NOT use fondaparinux as the sole anticoagulant for PCI after fibrinolysis—it increases catheter thrombosis risk. 1

Do NOT switch between enoxaparin and unfractionated heparin during the acute phase—this increases bleeding risk. 5

Do NOT use prasugrel or ticagrelor with fibrinolysis—reserve these potent P2Y12 inhibitors for primary PCI; use clopidogrel with fibrinolysis. 1, 5

Evidence Quality and Regional Considerations

The pharmaco-invasive strategy is supported by moderate-quality evidence from multiple randomized trials and is specifically endorsed for low- and middle-income countries where primary PCI infrastructure is limited. 1 The STREAM and STEPP-AMI trials from India demonstrated that pharmaco-invasive outcomes may be similar to primary PCI at 1 year when primary PCI cannot be delivered within guideline timelines. 1

The 120-minute threshold represents the point at which the mortality benefit of primary PCI over fibrinolysis disappears due to time-dependent myocardial salvage loss. 1, 6 Every 30-minute delay in reperfusion increases mortality, making the choice of fastest reperfusion strategy paramount. 7, 6