Chapter 39  ·  Module 5

Antiplatelet Therapy

Targets, drug classes, clinical evidence, and DAPT strategy at a glance

Abbreviations: TXA2 = thromboxane A2  ·  COX-1 = cyclooxygenase-1  ·  ADP = adenosine diphosphate  ·  GP IIb/IIIa = glycoprotein IIb/IIIa  ·  PAR-1 = protease-activated receptor 1  ·  ACS = acute coronary syndrome  ·  PCI = percutaneous coronary intervention  ·  DAPT = dual antiplatelet therapy  ·  TIA = transient ischemic attack  ·  CrCl = creatinine clearance

Antiplatelet Drug Targets in the Activation Cascade

Target Drug Class Agents Key Feature
COX-1 / TXA2 Cyclooxygenase inhibitor Aspirin Irreversible; permanent for platelet lifetime (7–10 days); 75–100 mg maintenance
P2Y12 (ADP receptor) P2Y12 inhibitors Clopidogrel (irreversible, CYP2C19-dependent); Prasugrel (irreversible, less CYP); Ticagrelor (reversible, direct); Cangrelor (IV, reversible) Sustained ADP blockade required for stable aggregation; combined with aspirin in DAPT
GP IIb/IIIa (fibrinogen receptor) GP IIb/IIIa inhibitors Abciximab (antibody fragment); Eptifibatide (peptide); Tirofiban (non-peptide) Final common pathway; most potent inhibition; highest bleeding risk; IV only
PAR-1 (thrombin receptor) PAR-1 antagonist Vorapaxar Secondary prevention post-MI or PAD; contraindicated in prior stroke or TIA

P2Y12 Inhibitor Comparison

Prodrug / Irreversible

Clopidogrel

  • CYP2C19-dependent; variable response
  • Load 300–600 mg; maintain 75 mg daily
  • Use when bleeding risk high or genotype normal

Prodrug / Irreversible

Prasugrel

  • Faster, more potent, less CYP2C19 variability
  • Load 60 mg; maintain 10 mg daily
  • Avoid: prior stroke/TIA; age ≥75; weight <60 kg

Direct / Reversible

Ticagrelor

  • No prodrug activation; faster onset/offset
  • Load 180 mg; 90 mg twice daily (ACS)
  • Dyspnea ~13%; preferred in most ACS

IV / Reversible

Cangrelor

  • Immediate onset; offset 60–90 min
  • Niche: PCI without oral pre-loading
  • Give clopidogrel/prasugrel AFTER infusion ends

DAPT Duration Rules — Core Framework

ACS + drug-eluting stent: 12 months minimum; extend if high ischemic risk and tolerated. Elective PCI + drug-eluting stent: 6 months standard; 1 to 3 months if high bleeding risk with new-generation stent. De-escalation after 3 months: consider P2Y12 monotherapy (ticagrelor preferred from TWILIGHT trial) — discontinue aspirin first. AF + recent PCI: transition to direct oral anticoagulant plus clopidogrel (drop aspirin) after 1 to 4 weeks of triple therapy. Perioperative hold times: aspirin 7 to 10 days; clopidogrel 5 days; prasugrel 7 days; ticagrelor 5 days; cangrelor 1 hour.