Pharmacology · Cardiovascular

Antiplatelet Therapy

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

Platelets are activated through four major surface receptors that are each pharmacological targets: COX-1 generates TXA2 (blocked irreversibly by aspirin for the platelet's entire 7 to 10 day lifespan); P2Y12 sustains ADP-driven aggregation (blocked by clopidogrel, prasugrel, ticagrelor, or cangrelor); GP IIb/IIIa is the final common pathway binding fibrinogen (blocked by abciximab, eptifibatide, or tirofiban); and PAR-1 responds to thrombin (blocked by vorapaxar).
Among P2Y12 inhibitors, the critical pharmacokinetic distinction is activation pathway: clopidogrel requires CYP2C19 metabolism and has variable response including functional loss-of-function in poor metabolizers; prasugrel requires less CYP activation and is more potent but contraindicated after stroke or TIA; ticagrelor is a direct-acting reversible agent with faster onset and offset, preferred in most ACS patients; cangrelor is IV with a 60 to 90 minute offset, used when oral loading is not feasible before PCI.
DAPT duration is the central management decision after coronary stenting: 12 months minimum after ACS with drug-eluting stent; 6 months for elective PCI with drug-eluting stent in standard-risk patients; 1 to 3 months acceptable in high bleeding risk with new-generation stents; the TWILIGHT trial supports de-escalation to ticagrelor monotherapy (dropping aspirin) after 3 months in high-risk PCI patients.
GP IIb/IIIa inhibitors represent the most potent antiplatelet option but carry the highest bleeding risk — reserved for high-risk PCI and acute coronary syndrome scenarios where their intravenous, reversible profile (eptifibatide, tirofiban) or sustained effect (abciximab) justifies the risk; they are not used in chronic oral antiplatelet regimens.
Perioperative management requires knowing reversal timelines: aspirin 7 to 10 days; clopidogrel 5 days; prasugrel 7 days; ticagrelor 5 days; cangrelor 1 hour — and in patients with recent coronary stents, the risk of stopping P2Y12 inhibitors early must always be weighed against surgical bleeding risk, with cardiology input before elective procedures.

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

Suggested References

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