Why is Brilinta (ticagrelor) given with heparin in a patient presenting with ST-Elevation Myocardial Infarction (STEMI)?

Why Brilinta (Ticagrelor) is Given with Heparin for STEMI

In STEMI patients undergoing primary PCI, ticagrelor and heparin address two distinct but complementary thrombotic mechanisms: ticagrelor blocks platelet aggregation via P2Y12 receptor inhibition, while heparin prevents thrombin-mediated coagulation, and both are mandatory components of guideline-directed therapy to reduce mortality and prevent stent thrombosis. 1

The Dual Antithrombotic Strategy

The combination targets the two fundamental pathways of arterial thrombosis in STEMI:

• Anticoagulation (heparin) prevents thrombin generation and fibrin formation in the culprit coronary artery, which is essential during the acute phase and throughout the PCI procedure 1
• Antiplatelet therapy (ticagrelor) blocks ADP-mediated platelet activation and aggregation, preventing both acute thrombotic complications and long-term ischemic events 1

Guideline-Mandated Approach for Primary PCI

The 2017 ESC Guidelines explicitly state that anticoagulants and dual antiplatelet therapy (DAPT) are the cornerstone of pharmacological management in acute STEMI 1:

• Unfractionated heparin is the recommended anticoagulant for primary PCI (enoxaparin or bivalirudin are alternatives) 1
• Loading dose of ticagrelor (or prasugrel) plus aspirin should be administered as soon as possible 1
• This combination is a Class I recommendation, meaning it is indicated for all patients without contraindications 1

Why Both Are Required Simultaneously

Neither agent alone adequately prevents the thrombotic complications of STEMI:

• Heparin without antiplatelet therapy fails to prevent platelet-mediated thrombosis, which is the dominant mechanism in arterial occlusion 1
• Ticagrelor without anticoagulation leaves the coagulation cascade unopposed, risking thrombus propagation during and after PCI 1
• Stent thrombosis risk is dramatically reduced when both pathways are blocked—studies show ticagrelor reduces definite stent thrombosis rates (0.2% vs 1.2% at 30 days compared to delayed administration) 2

Ticagrelor-Specific Advantages in STEMI

Ticagrelor offers superior outcomes compared to clopidogrel in the primary PCI setting:

• Faster and more potent platelet inhibition than clopidogrel, which is critical in the hyperacute phase of STEMI 3, 4
• Reduced microvascular injury as measured by index of microcirculatory resistance (22.2 vs 34.4 U, p=0.005) 3
• Improved left ventricular remodeling with reduced LV end-systolic volume index and lower rates of positive remodeling (OR 0.56, p=0.030) 5
• Lower stent thrombosis rates when administered early 2

Heparin Administration During Primary PCI

Unfractionated heparin dosing during PCI requires weight-based adjustment 1:

• Weight-adjusted IV bolus followed by additional boluses to maintain therapeutic activated clotting time (ACT) 1
• Target ACT: 250-300 seconds (HemoTec) or 300-350 seconds (Hemochron) when no GP IIb/IIIa inhibitor is planned 1
• Continue through PCI and for the duration of hospitalization as clinically indicated 1

Critical Timing Considerations

The synergy between these agents is time-dependent:

• Administer ticagrelor loading dose (180 mg) as early as possible, ideally in the ambulance or emergency department before catheterization 1, 2
• Initiate heparin immediately upon STEMI diagnosis and continue throughout the PCI procedure 1
• Crushed ticagrelor tablets in semi-upright position achieve faster absorption (median Tmax 2 vs 4 hours) and stronger early antiplatelet effect, which may be beneficial in the acute setting 4

Maintenance Therapy After PCI

Following successful primary PCI, the antithrombotic regimen transitions:

• Continue ticagrelor 90 mg twice daily for 12 months (Class I recommendation) 1
• Discontinue heparin after PCI completion once hemostasis is achieved 1
• Maintain aspirin 75-100 mg daily indefinitely 1

Common Pitfalls to Avoid

• Do not delay ticagrelor waiting for catheterization—early administration (prehospital) is safe and reduces stent thrombosis 2
• Do not use fondaparinux alone during PCI as it increases catheter thrombosis risk and requires additional UFH 1, 6
• Do not switch between enoxaparin and UFH during the acute phase, as this increases bleeding risk 1
• Do not use clopidogrel instead of ticagrelor for primary PCI—clopidogrel is reserved for fibrinolysis patients, while ticagrelor/prasugrel are preferred for primary PCI 1, 7