Basic Neuroscience · Neuropharmacology
Antiplatelet Therapy
Antiplatelet agents used in neurology — mechanism, onset and reversibility, typical dosing, and precautions. A one-page printable version is available via the Download PDF button above. Verify all doses and indications before prescribing.
| Agent | Mechanism | Onset · Reversibility | Typical dosing | Precautions |
|---|---|---|---|---|
| Aspirin (COX-1 inhibitor) | Irreversibly acetylates COX-1 → ↓ thromboxane A2. | Onset <1 h (chewed). Irreversible (~7–10 d). | Acute stroke 81–300 mg; then 81 mg daily. | GI bleeding (dose-related); NSAIDs blunt its effect — take ASA first. |
| Clopidogrel (Plavix; P2Y12 prodrug) | Irreversible P2Y12 blocker; prodrug — needs CYP2C19 activation. | Onset 2–6 h. Irreversible (~5–7 d). | Load 300–600 mg; then 75 mg daily. | Avoid if CYP2C19 slow metabolizer or P2Y12 test >180 PRU (test 8 h after loading, or day 7 if no load). Avoid CYP inhibitors1. |
| Ticagrelor (Brilinta; P2Y12 direct) | Reversible, direct-acting P2Y12 (not a prodrug). | Onset 0.5–2 h. Reversible (~3–5 d, BID). | Load 180 mg; then 90 mg BID. | Avoid CYP3A drugs2. Caution: digoxin, opioids, simvastatin / lovastatin. Dyspnea common. |
| Prasugrel (Effient; P2Y12 prodrug) | Irreversible P2Y12; faster / more reliable than clopidogrel. | Onset ~0.5 h. Irreversible (~7–10 d). | Load 60 mg; then 10 mg daily (cardiology). | CONTRAINDICATED with prior stroke / TIA — excess intracranial hemorrhage. |
| Dipyridamole + ASA (Aggrenox) | Dipyridamole inhibits PDE & adenosine reuptake → ↑ cAMP; paired with aspirin. | Onset hours. Aspirin component irreversible. | ASA 25 mg / ER-dipyridamole 200 mg BID. | Headache (common, limits tolerability); caution in CAD. |
| Cilostazol (PDE3 inhibitor) | Inhibits PDE3 → ↑ cAMP; antiplatelet + vasodilator. | Onset hours. Reversible. | 100 mg BID. | Contraindicated in heart failure. Avoid in acute coronary syndromes. Caution with CYP3A4 & CYP2C19 inhibitors. |
| IV agents (cangrelor; GP IIb/IIIa) | Cangrelor = IV reversible P2Y12. Abciximab / eptifibatide / tirofiban = GP IIb/IIIa blockers. | Onset minutes. Rapid on/off. | Weight-based IV infusion. | Peri-procedural in neuro-intervention (stenting, thrombectomy rescue). Bridging when oral route unavailable. |
| Vorapaxar (Zontivity; PAR-1 antagonist) | Blocks thrombin receptor PAR-1 on platelets. | Very long-acting. Effectively irreversible. | 2.08 mg daily (add-on). | CONTRAINDICATED with prior stroke / TIA / ICH — intracranial bleeding. |
1 CYP inhibitors (avoid with clopidogrel): omeprazole, esomeprazole, fluconazole, voriconazole, fluoxetine, fluvoxamine.
2 CYP3A drugs (avoid with ticagrelor): ketoconazole, clarithromycin, rifampin, phenytoin, phenobarbital.
Key Interactions — Medications to Avoid
| Combination | Why it matters | What to do |
|---|---|---|
| Aspirin + ibuprofen / NSAIDs | Blunts aspirin’s antiplatelet effect & ↑ GI bleeding. | Take aspirin first; prefer acetaminophen. |
| Clopidogrel + omeprazole (or esomeprazole) | ↓ clopidogrel efficacy (CYP2C19 inhibition). | Use pantoprazole. |
| Clopidogrel + CYP2C19 loss-of-function | Poor activation → ↓ efficacy. | Prefer ticagrelor. |
| Ticagrelor + CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital) | ↓ ticagrelor efficacy. | Use a non-enzyme-inducing AED. |
| Ticagrelor + strong CYP3A4 inhibitors (clarithromycin, ketoconazole) | ↑ ticagrelor levels → ↑ bleeding. | Avoid; switch antibiotic / antifungal. |
| Prasugrel or Vorapaxar + prior stroke / TIA | Markedly ↑ intracranial hemorrhage. | Contraindicated — use clopidogrel, ticagrelor, or ASA. |
| Any antiplatelet + SSRIs / SNRIs | Additive bleeding risk (esp. GI). | Weigh need; consider GI protection; counsel on bleeding. |
| Dual therapy (antiplatelet + anticoagulant) | Markedly ↑ risk of bleeding. | Minimize duration; avoid long-term use. |