Anti-Platelet Therapy in ACS — Clinical Reasoning (25 High-Yield Questions)

PLT-001 • Question 1

A 58-year-old with chest pain and ECG consistent with STEMI is awaiting emergent PCI. Which immediate therapy has the clearest mortality benefit and should be given ASAP (if no true allergy)?

Clopidogrel loading dose only Chewed aspirin loading dose Warfarin Dipyridamole Vorapaxar

PLT-002 • Question 2

A 67-year-old undergoes drug-eluting stent placement for NSTEMI. Standard antiplatelet plan is:

Aspirin + P2Y12 inhibitor (DAPT), then usually aspirin long-term P2Y12 inhibitor alone for 12 months Warfarin alone for 12 months GP IIb/IIIa inhibitor indefinitely Aspirin + heparin indefinitely

PLT-003 • Question 3

A patient on clopidogrel after stent has recurrent stent thrombosis. Genetic testing shows CYP2C19 loss-of-function. Best explanation and next step:

Clopidogrel is active drug; switch to dipyridamole Clopidogrel is a prodrug; switch to ticagrelor or prasugrel if appropriate Aspirin blocks CYP2C19; stop aspirin Use warfarin instead of antiplatelets Add ibuprofen to enhance effect

PLT-004 • Question 4

A 72-year-old with prior ischemic stroke needs antiplatelet therapy after ACS/PCI. Which P2Y12 agent is generally avoided due to excess bleeding risk in prior stroke/TIA?

Clopidogrel Prasugrel Ticagrelor Cangrelor Aspirin

PLT-005 • Question 5

A 61-year-old develops dyspnea shortly after starting a new P2Y12 inhibitor post-ACS. Which agent is most associated with this effect?

Clopidogrel Prasugrel Ticagrelor Cangrelor Abciximab

PLT-006 • Question 6

A patient with active GI bleeding presents with NSTEMI. What is the most accurate statement about antiplatelets in this situation?

Aspirin is always given regardless of bleeding Antiplatelets increase bleeding risk; decisions balance ischemic vs bleeding risk and often require GI stabilization/consultation P2Y12 inhibitors stop bleeding by vasoconstriction GP IIb/IIIa inhibitors are preferred because they are reversible Warfarin is first-line

PLT-007 • Question 7

Which drug irreversibly inhibits platelet COX-1, decreasing thromboxane A2 for the life of the platelet?

Ibuprofen Aspirin Ticagrelor Eptifibatide Dipyridamole

PLT-008 • Question 8

A patient takes ibuprofen regularly for back pain and also takes low-dose aspirin for secondary prevention. Why is the timing important?

Ibuprofen increases aspirin absorption Ibuprofen can competitively block aspirin access to COX-1 if taken first, reducing aspirin’s antiplatelet effect Aspirin blocks ibuprofen metabolism No interaction exists It increases risk of torsades

PLT-009 • Question 9

Which antiplatelet blocks the final common pathway of platelet aggregation by inhibiting GP IIb/IIIa?

Clopidogrel Aspirin Abciximab Vorapaxar Cilostazol

PLT-010 • Question 10

A patient receives eptifibatide during high-risk PCI. The key adverse effect to monitor is:

Severe hypertension Thrombocytopenia and bleeding Hyperkalemia Cough Pulmonary fibrosis

PLT-011 • Question 11

Which P2Y12 inhibitor is IV, reversible, and useful when rapid on/off platelet inhibition is needed around PCI?

Clopidogrel Prasugrel Ticagrelor Cangrelor Dipyridamole

PLT-012 • Question 12

A 59-year-old on ticagrelor after ACS asks why he’s also on aspirin. Best explanation:

Ticagrelor only works in presence of aspirin They inhibit different platelet activation pathways (TXA2 vs ADP), providing additive protection (DAPT) Aspirin prevents dyspnea Aspirin reduces LDL Aspirin prevents clopidogrel activation

PLT-013 • Question 13

A 63-year-old with ACS is also on chronic anticoagulation for atrial fibrillation. What is the big-picture issue when combining anticoagulation with DAPT?

It lowers bleeding risk Markedly increases bleeding risk; regimen/duration must be minimized and individualized It prevents stent thrombosis completely with no downside It causes hyperkalemia It treats hypertension

PLT-014 • Question 14

Which agent is a PAR-1 (thrombin receptor) antagonist used as an adjunct in selected high-risk patients but limited by bleeding risk?

Vorapaxar Prasugrel Eptifibatide Aspirin Cangrelor

PLT-015 • Question 15

A patient asks why aspirin 'works' at 81 mg. The correct explanation is:

Low doses selectively inhibit platelet COX-1 in the portal circulation; platelets cannot resynthesize COX Aspirin has a placebo effect at 81 mg Low doses activate platelets Only high-dose aspirin inhibits COX-1 Aspirin works by blocking P2Y12

PLT-016 • Question 16

A 70-year-old with ACS receives a P2Y12 inhibitor. Which mechanism best matches this class?

Blocks thromboxane A2 receptor Blocks ADP-mediated activation of GP IIb/IIIa expression Directly chelates fibrinogen Inhibits vitamin K epoxide reductase Activates plasminogen

PLT-017 • Question 17

A patient on clopidogrel is started on omeprazole and later has recurrent ischemic symptoms. Mechanistic concern is:

Omeprazole induces CYP2C19 increasing clopidogrel effect Omeprazole inhibits CYP2C19 potentially reducing clopidogrel activation Clopidogrel inhibits proton pumps No interaction exists Omeprazole causes thrombocytopenia

PLT-018 • Question 18

A 65-year-old has minor elective surgery coming up. Which statement is most accurate about aspirin’s platelet effect duration?

Wears off in 6 hours Wears off in 24 hours Lasts for platelet lifespan (~7–10 days) because inhibition is irreversible Lasts 1 month Reversible in 48 hours

PLT-019 • Question 19

A patient with ACS is allergic to aspirin (true anaphylaxis). Most reasonable antiplatelet alternative strategy (simplified exam answer):

No antiplatelet therapy P2Y12 inhibitor-based regimen (e.g., clopidogrel/ticagrelor) with cardiology guidance Warfarin monotherapy Heparin indefinitely Vorapaxar monotherapy

PLT-020 • Question 20

Which combination is most likely to increase bleeding risk without improving antiplatelet benefit in ACS and is generally discouraged?

Aspirin + P2Y12 inhibitor Aspirin + GP IIb/IIIa during PCI Aspirin + NSAID chronic use P2Y12 inhibitor + aspirin post stent Cangrelor + PCI

PLT-021 • Question 21

A patient with NSTEMI is being loaded with a P2Y12 inhibitor. Which factor most increases concern for prasugrel use?

Age 30 Prior TIA History of seasonal allergies LDL 120 Mild asthma

PLT-022 • Question 22

Which statement best distinguishes ticagrelor from clopidogrel?

Ticagrelor is a prodrug requiring CYP2C19 activation Ticagrelor binds P2Y12 reversibly and does not require metabolic activation Ticagrelor blocks COX-1 Ticagrelor is a GP IIb/IIIa inhibitor Ticagrelor is a vitamin K antagonist

PLT-023 • Question 23

A patient after PCI asks why platelets are targeted at all in ACS. Best explanation:

ACS is primarily due to slow venous clotting ACS is driven by platelet-rich thrombus forming on ruptured plaque in coronary arteries ACS is caused by low vitamin K ACS is mainly due to infection Platelets are unrelated to coronary thrombosis

PLT-024 • Question 24

A patient has a stent and now needs long-term NSAIDs. Which approach best reduces GI bleeding risk while preserving antiplatelet therapy (general best practice)?

Stop aspirin and continue NSAIDs Use gastroprotection (e.g., PPI) and minimize NSAIDs; avoid ibuprofen timing conflict Replace aspirin with acetaminophen Add another NSAID Switch to warfarin

PLT-025 • Question 25

Which antiplatelet targets the 'final common pathway' of aggregation by preventing fibrinogen cross-linking of platelets?

Aspirin Clopidogrel Eptifibatide Vorapaxar Dipyridamole