In the PLATO trial, ticagrelor versus clopidogrel in ACS patients showed a mortality benefit. Which specific mechanism accounts for ticagrelor's mortality benefit beyond platelet inhibition?
- A Inhibition of adenosine reuptake via equilibrative nucleoside transporter 1 (ENT-1) ✓
- B Reversible P2Y12 receptor blockade reducing bleeding duration
- C Direct thrombin inhibition at low doses
- D Upregulation of prostacyclin synthesis
Correct answer: A. Inhibition of adenosine reuptake via equilibrative nucleoside transporter 1 (ENT-1)
Explanation
Ticagrelor inhibits the equilibrative nucleoside transporter 1 (ENT-1), preventing adenosine reuptake and raising local adenosine levels. Adenosine has cardioprotective, vasodilatory, and anti-inflammatory effects, and contributes to ischemic preconditioning. This mechanism is thought to contribute to ticagrelor's mortality benefit observed in PLATO (9% relative risk reduction in cardiovascular death vs. clopidogrel) beyond platelet P2Y12 inhibition alone. Ticagrelor-related dyspnea is also mediated through this adenosine pathway.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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