For an adult presenting with typical chest pain ≤12 hours and ECG criteria for STEMI in an Asian region where primary PCI cannot be performed within 120 minutes, what pharmacoinvasive reperfusion protocol—including choice and dosing of fibrinolytic (tenecteplase or alteplase), antiplatelet and anticoagulant therapy, timing of transfer for coronary angiography/PCI, and key system implementation steps—should be applied?

Pharmacoinvasive Strategy Implementation in Asia

Immediate Actions at First Medical Contact (0–10 Minutes)

When primary PCI cannot be performed within 120 minutes of STEMI diagnosis in Asian regions, initiate fibrinolytic therapy immediately and arrange urgent transfer to a PCI-capable center—this pharmacoinvasive approach reduces death, reinfarction, and heart failure compared to fibrinolysis alone. 1, 2

• Obtain and interpret a 12-lead ECG within 10 minutes of first medical contact to confirm STEMI diagnosis (ST-elevation ≥1 mm in two contiguous leads or new/presumed new LBBB). 1, 2
• Administer aspirin 150–325 mg orally (or 250–500 mg IV if unable to swallow) immediately—do not delay for any reason. 1, 2
• Activate the regional STEMI network and arrange immediate transfer to the nearest PCI-capable center while preparing fibrinolytic therapy. 1, 2
• Avoid routine supplemental oxygen unless oxygen saturation is <90%. 1, 2

Fibrinolytic Agent Selection and Dosing

Tenecteplase is the preferred fibrinolytic agent due to its single-bolus administration, fibrin-specificity, and superior outcomes compared to streptokinase. 2, 3, 4, 5

Tenecteplase Dosing (Preferred)

• Administer as a single IV bolus over 5 seconds based on weight: 5, 2
  • <60 kg: 30 mg
  • 60–69 kg: 35 mg
  • 70–79 kg: 40 mg
  • 80–89 kg: 45 mg
  • ≥90 kg: 50 mg
• For patients ≥75 years old, reduce the dose by 50% to minimize stroke risk (e.g., 25 mg for a 70 kg patient). 2, 3
• Target door-to-needle time ≤30 minutes (ideally ≤10 minutes). 1, 2

Alternative: Alteplase or Streptokinase

• Alteplase: 15 mg IV bolus, then 0.75 mg/kg over 30 minutes (max 50 mg), then 0.5 mg/kg over 60 minutes (max 35 mg). 1, 2, 3
• Streptokinase (if cost-limited): 1.5 million units IV over 30–60 minutes; never re-administer (antibodies persist ≥10 years). 3

Adjunctive Antiplatelet Therapy

• Clopidogrel loading dose: 300 mg orally for patients ≤75 years; 75 mg for patients >75 years (prasugrel and ticagrelor are contraindicated with fibrinolysis). 1, 2, 3
• Continue clopidogrel 75 mg daily plus aspirin 75–100 mg daily until PCI. 2, 3, 4

Anticoagulation Strategy

Enoxaparin is the preferred anticoagulant with fibrinolysis; unfractionated heparin is an acceptable alternative. 2, 3

Enoxaparin (Preferred)

• Age <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours. 2, 3
• Age ≥75 years: No IV bolus; 0.75 mg/kg subcutaneous every 12 hours. 2, 3
• Creatinine clearance <30 mL/min: 1 mg/kg subcutaneous every 24 hours. 3
• Continue until revascularization or up to 8 days. 2, 3

Unfractionated Heparin (Alternative)

• 60 U/kg IV bolus (maximum 4000 units), then 12 U/kg/hour infusion (maximum 1000 units/hour). 3, 6
• Target aPTT 50–70 seconds; aPTT >70 seconds increases mortality and bleeding. 3
• Continue for 24–48 hours or until revascularization. 3, 6

Assessment of Reperfusion Success (60–90 Minutes Post-Fibrinolysis)

At 60–90 minutes after fibrinolytic administration, assess ST-segment resolution in the lead with the greatest initial ST-elevation. 2, 3, 4, 7

Successful Reperfusion (≥50% ST-Resolution)

• Transfer immediately to PCI-capable center for routine angiography within 3–24 hours (ideally 2–12 hours). 1, 2, 8, 9, 10
• Maintain door-in-door-out time ≤30 minutes at the referring hospital. 1, 2
• Continue dual antiplatelet therapy and anticoagulation during transfer. 2, 3

Failed Reperfusion (<50% ST-Resolution)

• Arrange immediate rescue PCI without delay—this is a medical emergency. 1, 2, 3, 4, 7
• Failed reperfusion carries a 2.92-fold higher risk of death, shock, and heart failure compared to successful fibrinolysis. 7

Additional Indications for Immediate Rescue PCI

Perform emergency rescue PCI regardless of ST-segment resolution if any of the following occur: 2, 3, 4

• Hemodynamic instability or cardiogenic shock
• Sustained ventricular arrhythmias (VT/VF)
• Worsening chest pain or recurrent ischemia
• New or worsening heart failure

PCI Strategy After Successful Fibrinolysis

• Perform coronary angiography 2–24 hours after fibrinolytic administration in stable patients. 1, 2, 8, 9, 10
• Do not perform angiography <2 hours after fibrinolysis unless rescue PCI is required (increased bleeding without benefit). 1, 8, 9
• Administer prasugrel 60 mg or ticagrelor 180 mg loading dose at the time of PCI (switch from clopidogrel). 2, 11
• Use unfractionated heparin 70–100 U/kg IV bolus during PCI (reduce to 60 U/kg if GPIIb/IIIa inhibitor is used). 2, 6
• Prefer radial access and drug-eluting stents. 2

Key System Implementation Steps for Asian Regions

Pre-Hospital Phase

• Establish regional STEMI networks linking non-PCI hospitals, PCI centers, and emergency medical services with standardized written protocols. 1, 2, 10
• Train EMS personnel to perform 12-lead ECGs at the scene and transmit to receiving hospitals. 1, 2
• Enable pre-hospital fibrinolysis when trained personnel are available and transfer time exceeds 120 minutes. 1, 2, 3

Hospital Phase

• Non-PCI hospitals must achieve door-to-needle time ≤30 minutes and door-in-door-out time ≤30 minutes. 1, 2
• PCI-capable centers must provide 24/7 catheterization laboratory availability with direct transfer bypassing the emergency department. 1, 2
• Implement continuous quality improvement programs tracking time metrics and clinical outcomes. 1, 2

Transfer Protocols

• Arrange immediate transfer after fibrinolysis—do not wait to assess reperfusion success before initiating transfer. 1, 2, 8, 10
• Maintain continuous cardiac monitoring and IV access during transfer. 2, 4
• Alert the receiving PCI center of estimated arrival time and reperfusion status. 2, 10

Critical Pitfalls to Avoid

• Do not delay fibrinolysis to "wait and see" if primary PCI becomes available—every 30-minute delay increases mortality. 1, 2
• Do not use prasugrel or ticagrelor with fibrinolysis (only clopidogrel is safe). 1, 2, 3, 11
• Do not perform routine angiography <2 hours after fibrinolysis in stable patients (facilitated PCI increases bleeding and mortality). 1, 8, 9
• Do not re-administer streptokinase if used initially—switch to tenecteplase or alteplase for re-occlusion. 3
• Do not use fondaparinux as anticoagulation for PCI (it is contraindicated). 2
• Do not keep patients at non-PCI hospitals >24 hours after successful fibrinolysis—transfer immediately for routine angiography. 1, 2, 8, 10

Special Considerations for Asian Populations

• Lower body weight (<60 kg) is more common in Asian populations; use weight-adjusted tenecteplase dosing and consider prasugrel 5 mg maintenance dose (instead of 10 mg) after PCI. 2, 5, 11
• Elderly patients (≥75 years) require 50% dose reduction of tenecteplase and modified enoxaparin dosing (no IV bolus, 0.75 mg/kg subcutaneous). 2, 3
• Cost constraints may necessitate streptokinase use; if so, ensure immediate transfer for rescue PCI capability. 3