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Antithrombotic therapies

Antithrombotic therapies

Antithrombotic therapies

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Antiplatelet Agents - The First Responders

  • Aspirin (ASA): Irreversibly inhibits COX-1, leading to ↓ Thromboxane A₂ (TXA₂) and reduced platelet aggregation. Load with 325mg in ACS.
  • P2Y12 Inhibitors: Block ADP-mediated platelet activation. A loading dose (e.g., Clopidogrel 600mg) is crucial for rapid effect.
AgentOnsetPotencyReversibilityUnique CIs/SEs
ClopidogrelSlowModerateIrreversibleProdrug; variable response
PrasugrelFastHighIrreversibleCI: Prior stroke/TIA
TicagrelorFastestHighReversibleSE: Dyspnea, bradycardia

Antiplatelet drug mechanisms on platelet activation

Parenteral Anticoagulants - The Clot Inhibitors

These agents are co-administered with antiplatelets in acute MI to prevent clot propagation.

AgentTargetMonitoringReversalHIT Risk
Unfractionated Heparin (UFH)Xa & IIaaPTTProtamine Sulfate↑↑↑
LMWH (Enoxaparin)Xa > IIaAnti-Xa (renal)Protamine (partial)↑↑
BivalirudinDirect IIaaPTTNone
FondaparinuxSelective XaNoneNone↓↓↓

⭐ Fondaparinux, a selective Factor Xa inhibitor, has the lowest risk of Heparin-Induced Thrombocytopenia (HIT).

Fibrinolytic Therapy - The Clot Dissolvers

Used for STEMI when primary PCI is unavailable within 120 mins of first medical contact and symptom onset is <12 hours. These agents create plasmin to break down fibrin clots.

  • Agents (Thrombolytics):
    • Alteplase (tPA)
    • Tenecteplase (TNK-tPA)
    • Reteplase (rPA)

⭐ The most feared complication of fibrinolytic therapy is intracranial hemorrhage.

⚠️ Key Absolute Contraindications: Prior intracranial hemorrhage, known cerebral AVM or malignant neoplasm, ischemic stroke within 3 months, active bleeding.

Secondary Prevention - The DAPT Duration Dilemma

  • Standard post-MI care involves Dual Antiplatelet Therapy (DAPT): Aspirin + a P2Y12 inhibitor (e.g., Clopidogrel, Ticagrelor) for a duration of 12 months.
  • The primary clinical decision is balancing the prevention of future ischemic events (stent thrombosis, MI) against the increased risk of bleeding.
  • The DAPT score is a validated tool to guide this decision:
    • A high score (≥2) suggests ischemic risk outweighs bleeding risk, favoring longer therapy (e.g., up to 30 months).
    • A low score (<2) suggests bleeding risk is higher, favoring a shorter course (e.g., 6 months).

⭐ For patients with a high bleeding risk (e.g., history of major bleed, on oral anticoagulants), a shorter DAPT duration of 3-6 months is often considered, irrespective of the DAPT score.

High‑Yield Points - ⚡ Biggest Takeaways

  • Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (e.g., clopidogrel, ticagrelor) is the cornerstone of MI treatment.
  • Aspirin provides rapid, irreversible COX-1 inhibition; administer immediately.
  • P2Y12 inhibitors prevent ADP-mediated platelet aggregation; ticagrelor and prasugrel are more potent than clopidogrel.
  • Prasugrel is contraindicated in patients with a history of stroke or TIA due to ↑ bleeding risk.
  • GP IIb/IIIa inhibitors (e.g., abciximab) are used for high-risk patients undergoing PCI.
  • Parenteral anticoagulation (e.g., heparin, bivalirudin) is essential during the acute phase and PCI.

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