Antiplatelet therapy

Antiplatelet MOA - Plugging the Problem

• Aspirin (ASA): Irreversibly inhibits COX-1, blocking Thromboxane A₂ ($TXA_2$) synthesis → ↓ platelet aggregation.
• $P2Y_{12}$ Receptor Blockers: Inhibit ADP-mediated platelet activation & aggregation.
  • Clopidogrel/Prasugrel: Irreversible binding.
  • Ticagrelor: Reversible binding.
• GPIIb/IIIa Inhibitors: (e.g., Abciximab) Directly block the final common pathway, preventing fibrinogen cross-linking.

⭐ Ticagrelor is a reversible allosteric inhibitor of $P2Y_{12}$, unlike the irreversible thienopyridines (Clopidogrel, Prasugrel). Its faster offset is crucial for patients needing urgent surgery.

Drug Classes - The Antiplatelet Arsenal

• Aspirin (ASA): Irreversibly inhibits COX-1, blocking thromboxane A₂ (TXA₂) synthesis. Crucial first-line agent.

  • Loading dose: 162-325 mg (chewable).

• P2Y₁₂ Receptor Blockers: Inhibit ADP-mediated platelet aggregation. 📌 Mnemonic: "TCP" for Ticagrelor, Clopidogrel, Prasugrel.

-   Agents: Abciximab, Eptifibatide, Tirofiban.
-   Use: Typically reserved for high-risk patients undergoing PCI.

⭐ Prasugrel is contraindicated in patients with a history of stroke or TIA due to an increased risk of significant bleeding.

DAPT Strategy - The ACS Battle Plan

• Core Principle: Combine Aspirin + a P2Y12 inhibitor to prevent stent thrombosis and recurrent ischemic events.
• Aspirin:
  • Loading Dose: 162-325 mg (non-enteric coated, chewable) STAT.
  • Maintenance Dose: 81 mg daily, lifelong.
• P2Y12 Inhibitors ("The Grels"):
  • Ticagrelor (Brilinta): Preferred for most ACS (STEMI/NSTEMI). Reversible, faster onset.
  • Prasugrel (Effient): Most potent. Use only in patients undergoing PCI. ⚠️ Contraindicated in prior TIA/stroke.
  • Clopidogrel (Plavix): Used when others are contraindicated, in fibrinolysis, or high bleeding risk.
• Standard Duration: 12 months for most ACS patients. Duration may be tailored using the DAPT score (ischemic vs. bleeding risk).

⭐ In patients managed with fibrinolysis for STEMI, clopidogrel is the only P2Y12 inhibitor with proven safety and efficacy in that specific setting.

Side Effects - The Bleeding Edge

• Primary Risk: Bleeding
  • Major: Intracranial Hemorrhage (ICH), GI Bleed.
  • Minor: Epistaxis, ecchymosis, hematuria.
  • ⚠️ Assess bleed risk (e.g., prior history, age >75).
• Drug-Specific Effects:
  • Aspirin: GI upset, peptic ulcers.
  • Clopidogrel/Prasugrel: ⚠️ Thrombotic Thrombocytopenic Purpura (TTP).
  • Ticagrelor: Dyspnea (common, often transient), ↑uric acid, bradyarrhythmias.

⭐ Prasugrel is contraindicated in patients with a history of stroke or TIA due to an increased risk of intracranial bleeding.

• Dual antiplatelet therapy (DAPT) with Aspirin and a P2Y12 inhibitor is the cornerstone of ACS management.
• Continue Aspirin indefinitely and a P2Y12 inhibitor for at least 12 months after the event.
• Prasugrel is contraindicated in patients with a history of stroke or TIA due to ↑ bleeding risk.
• A common side effect of Ticagrelor is dyspnea.
• GP IIb/IIIa inhibitors (e.g., Abciximab) are potent agents for high-risk PCI cases.