Advanced Pharmacology · Topic 9 of 13

Antiplatelet Agents & DAPT

Pharmacology · antiplatelet therapy

Antiplatelet Agents & DAPT

Aspirin plus a P2Y12 inhibitor protects a new stent; stopping either too early causes stent thrombosis, so time surgery and holds deliberately.

Key numbers

Aspirin 162–325 mg chewed, then 81 mg162–325 mg chewed

Load a P2Y12 inhibitor for ACS-PCITicagrelor 180 mg load

DAPT for 12 months after ACS12 months after ACS

Stopping DAPT early causes stent thrombosis≥ 12 mo after ACS-PCI

Hold clopidogrel 5, ticagrelor 3–5, prasugrel 7 days5 · 3–5 · 7 days

01 · GiveAspirin 162–325 mg chewed, then 81 mg

Aspirin irreversibly blocks platelet cyclooxygenase and thromboxane A2: give 162–325 mg non-enteric-coated, chewed, as soon as ACS is suspected, then 81 mg daily long term.

02 · GiveLoad a P2Y12 inhibitor for ACS-PCI

For ACS with PCI, load ticagrelor 180 mg (then 90 mg twice daily) or prasugrel 60 mg (then 10 mg daily), preferred over clopidogrel 300–600 mg (then 75 mg daily).

03 · The ruleDAPT for 12 months after ACS

Continue aspirin plus a P2Y12 inhibitor for 12 months after ACS by default; after elective PCI, 6–12 months, or a shorter 1–3 months when bleeding risk is high, then single antiplatelet therapy.

Management

Orders

Hold clopidogrel 5, ticagrelor 3–5, prasugrel 7 days must knowBefore surgery with major bleeding risk, stop clopidogrel 5 days, ticagrelor 3–5 days and prasugrel 7 days ahead; continue aspirin after stenting when bleeding risk allows, and restart the P2Y12 inhibitor once hemostasis allows.

Ticagrelor: aspirin ≤ 100 mg, expect dyspneaTicagrelor is a reversible, directly acting P2Y12 inhibitor: pair it with aspirin 75–100 mg daily only; it causes dyspnea in 14–21% and bradyarrhythmias, and is contraindicated after intracranial hemorrhage.

Add a PPI for GI bleeding riskGive a proton pump inhibitor with dual antiplatelet therapy to patients at risk of gastrointestinal bleeding.

GP IIb/IIIa inhibitors only for high-risk PCIGlycoprotein IIb/IIIa inhibitors (eptifibatide, tirofiban) block fibrinogen and von Willebrand factor binding to platelets; reserve them for PCI with large thrombus burden or no-reflow, and never give them with fibrinolytics.

Eptifibatide: halve the infusion if CrCl < 50Eptifibatide is 180 mcg/kg IV bolus (repeated at 10 minutes for PCI) then 2 mcg/kg/min, reduced to 1 mcg/kg/min when CrCl is under 50 mL/min; it is contraindicated in patients on dialysis.

Cangrelor: IV P2Y12 inhibitor for PCICangrelor, an IV P2Y12 inhibitor for P2Y12-naive patients at PCI, is 30 mcg/kg bolus then 4 mcg/kg/min for at least 2 hours; give prasugrel or clopidogrel only after the infusion stops (ticagrelor any time).

With fibrinolysis, use clopidogrelWith STEMI fibrinolysis, use clopidogrel: 300 mg load then 75 mg daily under age 75, or 75 mg without a load at 75 or older; ticagrelor and prasugrel are not given with the lytic.

Red flags & don'ts

Avoid harm

Stopping DAPT early causes stent thrombosis complicationPremature DAPT interruption causes stent thrombosis (presenting as acute MI): delay elective surgery 12 months after a DES for ACS (6 months for stable disease); interrupting DAPT within 30 days of a stent is harmful.

No prasugrel after stroke or TIA avoidPrasugrel is contraindicated after any stroke or TIA, generally avoided at 75 or older, reduced to 5 mg daily under 60 kg, and given only to patients going to PCI — never with a fibrinolytic.

Clopidogrel needs CYP2C19; avoid omeprazole interactionClopidogrel is a prodrug activated mainly by CYP2C19: poor metabolizers get less platelet inhibition (consider another P2Y12 inhibitor), and omeprazole or esomeprazole blunt its effect and should be avoided.

The rules

Know these

Ticagrelor monotherapy after 1 month of DAPTTo reduce bleeding after ACS-PCI, patients tolerating ticagrelor-based DAPT can stop aspirin at 1 month or later and continue ticagrelor alone (Class 1 in the 2025 ACS guideline).

On an anticoagulant: drop aspirin at 1–4 weeksPatients needing long-term oral anticoagulation (e.g., AF) stop aspirin 1–4 weeks after PCI and continue the anticoagulant — a DOAC preferred — plus a P2Y12 inhibitor, preferably clopidogrel.

Ticagrelor or clopidogrel?

Commonly confused

Binding	Reversible, active drug
Load, then maintenance	180 mg, then 90 mg twice daily
Hold before surgery	3–5 days
Watch for	Dyspnea, bradyarrhythmias; aspirin ≤ 100 mg
With fibrinolysis	Not given with the lytic

More detail

Reference

Show 7 reference facts

Clopidogrel has rarely caused thrombotic thrombocytopenic purpura, sometimes within 2 weeks of starting; it needs urgent plasma exchange.

Aspirin, clopidogrel and prasugrel inhibit platelets irreversibly, so their effect lasts until new platelets form (aspirin about 5–7 days); ticagrelor is reversible, and platelet function recovers 3–5 days after stopping it.

There is no true antiplatelet reversal agent: platelet transfusion has uncertain benefit and, in intracerebral hemorrhage without planned surgery, worsens outcomes.

After minor stroke or high-risk TIA, short-course DAPT is used: aspirin plus clopidogrel for 21 days, or ticagrelor 180 mg then 90 mg twice daily plus aspirin for up to 30 days.

If thrombocytopenia develops on eptifibatide, stop both eptifibatide and heparin; bleeding and hypotension are its most common adverse effects.

Patients with ACS who are not revascularized still receive aspirin plus a P2Y12 inhibitor (ticagrelor or clopidogrel) for at least 12 months, with a proton pump inhibitor.

Aspirin taken only for primary prevention is stopped before noncardiac surgery (except carotid surgery); aspirin for secondary prevention may be continued when cardiac risk outweighs bleeding risk.

Pearl

Hold times run 3–5–7: ticagrelor 3–5 days, clopidogrel 5, prasugrel 7.

Sources · Merck Manual Professional — Medications for Acute Coronary Syndromes · Merck Manual Professional — Acquired Platelet Dysfunction (Jun 2026) · Plavix (clopidogrel) prescribing information — DailyMed · Brilinta (ticagrelor) prescribing information — DailyMed · Effient (prasugrel) prescribing information — DailyMed · Kengreal (cangrelor) prescribing information — DailyMed · Eptifibatide injection prescribing information (Baxter) — DailyMed · Rao SV et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes (summary of key recommendations, Medical Dialogues, March 2025) · ACC — 2021 ACC/AHA/SCAI Coronary Revascularization Guideline: Key Perspectives (Lawton JS et al., J Am Coll Cardiol 2022;79:e21–e129) · Merck Manual Professional — Percutaneous Coronary Interventions (PCI) · Cohn SL. 2024 ACC/AHA guideline on perioperative cardiovascular management before noncardiac surgery: What's new? Cleve Clin J Med 2025;92(4):213 · Society for the Advancement of Patient Blood Management — Management of antiplatelet agents (platelet recovery: clopidogrel 5–7 d, ticagrelor 3–5 d, prasugrel 7–10 d) · Cleveland Clinic Consult QD — New guideline on acute coronary syndromes: key takeaways (ticagrelor monotherapy after 1 month = Class 1) · CardioNerds — Decipher the Guidelines: 2025 ACC/AHA ACS Guideline (clopidogrel with fibrinolysis, sections 4.3.2 and 4.4) · Greenberg SM et al. 2022 AHA/ASA Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage. Stroke 2022;53:e282–e361 (full-text PDF copy) · emDocs — 2026 Guideline Update: Early Management of Acute Ischemic Stroke (Jan 2026) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).