What is the recommended hub-and-spoke pharmacoinvasive protocol for a patient with ST-segment-elevation myocardial infarction presenting to a peripheral facility unable to perform primary percutaneous coronary intervention within 90 minutes, including fibrinolytic therapy, antiplatelet and anticoagulant regimen, timing of transfer, and criteria for rescue PCI?

Hub-and-Spoke Pharmacoinvasive Strategy for STEMI

Initial Management at the Spoke (Non-PCI-Capable) Facility

For STEMI patients presenting to a peripheral facility unable to perform primary PCI within 90 minutes, administer fibrinolytic therapy immediately if the anticipated first-medical-contact-to-device time exceeds 120 minutes, followed by urgent transfer to a PCI-capable hub for routine angiography within 3-24 hours. 1

Time-Critical Decision Algorithm (First 10 Minutes)

• Obtain and interpret a 12-lead ECG within 10 minutes of first medical contact to confirm STEMI diagnosis 1, 2
• Calculate the anticipated first-medical-contact-to-device time by adding current time + door-in-door-out time (target ≤30 minutes) + transport time + door-to-balloon time at receiving facility 1
• If total anticipated time ≤120 minutes: Transfer immediately for primary PCI without fibrinolysis 1
• If total anticipated time >120 minutes: Administer fibrinolytic therapy within 10-30 minutes of diagnosis, then transfer 1, 2

Immediate Pharmacologic Therapy at Spoke Facility

Antiplatelet Regimen:

• Aspirin 150-325 mg orally (or 250-500 mg IV if unable to swallow) immediately 2, 3
• Clopidogrel 300 mg loading dose (for patients ≤75 years) or 75 mg (for patients >75 years) 1, 2, 4
• Do NOT use prasugrel or ticagrelor with fibrinolysis—these are reserved for the PCI phase 2, 3

Fibrinolytic Agent (Choose One):

• Tenecteplase (preferred): Single weight-adjusted IV bolus 30-50 mg (0.53 mg/kg); reduce dose by 50% if age ≥75 years 2, 4
• Alteplase or reteplase are acceptable alternatives 2, 3

Anticoagulation:

• Enoxaparin (preferred): 30 mg IV bolus, followed 15 minutes later by 1 mg/kg subcutaneous every 12 hours (reduce to 0.75 mg/kg if age ≥75 years; avoid if creatinine clearance <30 mL/min) 2, 3
• Unfractionated heparin (alternative): 60 U/kg IV bolus (maximum 4000 units), then 12 U/kg/hour infusion (maximum 1000 U/hour) adjusted to aPTT 50-75 seconds 1, 4
• Continue anticoagulation until revascularization or for duration of hospital stay (up to 8 days) 2, 3

Transfer Protocol

Timing and Logistics:

• Achieve door-in-door-out time ≤30 minutes at the spoke facility 1
• Initiate transfer immediately after fibrinolytic administration—do not wait to assess reperfusion success 1
• Alert the receiving PCI center immediately to prepare the catheterization laboratory 2, 3
• Continue anticoagulation and antiplatelet therapy during transport 1

Management at the Hub (PCI-Capable) Facility

Routine Early Angiography Strategy (Preferred Approach)

For high-risk patients, immediate transfer for PCI within 3-6 hours after fibrinolysis is reasonable, even without evidence of failed reperfusion. 1

High-risk criteria include:

• Extensive ST-segment elevation (≥2 mm in ≥2 anterior leads or ≥1 mm in inferior leads with additional features) 1
• New left bundle branch block 1
• Previous myocardial infarction 1
• Killip class II-III heart failure 1
• Left ventricular ejection fraction ≤35% 1
• Systolic blood pressure <100 mmHg or heart rate >100 bpm 1
• ST-segment depression ≥2 mm in anterior leads (for inferior MI) 1
• ST-segment elevation ≥1 mm in right-sided lead V4R (indicating RV involvement) 1

Timing of Routine Angiography:

• Perform coronary angiography 3-24 hours after fibrinolysis in stable patients 1, 2, 3
• Median time from fibrinolysis to catheterization should be 2-3 hours for high-risk patients 1
• PCI should be performed during the same procedure if anatomy is suitable 1, 5

Rescue PCI Criteria (Immediate Catheterization Required)

Perform immediate rescue PCI if any of the following occur:

• <50% ST-segment resolution at 60-90 minutes after fibrinolytic administration 1, 2, 5
• Hemodynamic instability or cardiogenic shock 1, 2
• Electrical instability (sustained ventricular arrhythmias) 1
• Recurrent or persistent chest pain despite fibrinolysis 1, 5

Antithrombotic Regimen at Hub Facility

Before/During PCI:

• Switch to potent P2Y12 inhibitor: Prasugrel 60 mg or ticagrelor 180 mg loading dose (clopidogrel only if these unavailable) 2, 3
• Unfractionated heparin 50-70 U/kg IV bolus (lower dose because patient already anticoagulated) 1, 2
• Bivalirudin is acceptable but requires prior UFH administration to reduce acute stent thrombosis risk 1
• GP IIb/IIIa inhibitors may be considered for bailout situations but are not routine 1, 2

Post-PCI:

• Dual antiplatelet therapy (aspirin 75-100 mg + prasugrel 10 mg or ticagrelor 90 mg twice daily) for 12 months 2, 3
• Proton pump inhibitor for patients at high GI bleeding risk 2, 3

Critical Pitfalls to Avoid

• Do NOT use "facilitated PCI" (full-dose fibrinolysis immediately before planned PCI)—this increases mortality and is contraindicated 1
• Do NOT delay transfer to observe for reperfusion success—immediate transfer improves outcomes even in standard-risk patients 1, 5
• Do NOT use prasugrel or ticagrelor with fibrinolysis—only clopidogrel is appropriate in this phase 2, 3
• Do NOT give GP IIb/IIIa inhibitors routinely with fibrinolysis—this increases bleeding without benefit 1
• Do NOT perform routine thrombus aspiration at the hub facility—this is contraindicated 2, 3
• Do NOT defer stenting at the hub facility—immediate stenting is standard of care 2, 3

Evidence Strength and Nuances

The pharmacoinvasive strategy is supported by two landmark trials: TRANSFER-AMI (1059 patients) and CARESS-in-AMI (600 patients), both demonstrating that immediate transfer for routine early PCI (within 6 hours) after fibrinolysis reduces the composite endpoint of death, reinfarction, and recurrent ischemia by approximately 40% compared to a conservative "rescue-only" approach. 1 The ASSENT-4 PCI trial, which tested facilitated PCI (fibrinolysis immediately before planned PCI), was terminated early due to increased mortality, definitively establishing that fibrinolysis must be followed by a delay before PCI. 1, 4

Real-world registry data from the Mayo Clinic STEMI network (1,701 patients) and University of Ottawa system (1,216 patients) confirm that pharmacoinvasive strategies achieve similar mortality to primary PCI when transfer times exceed 120 minutes, though with a trend toward increased bleeding. 6, 7 The key distinction is that pharmacoinvasive therapy requires planned routine early angiography, not just rescue PCI for failed reperfusion. 8, 5, 9