Clopidogrel

CLASS

anti-platelet agent

MECHANISM OF ACTION

inhibition of the ADP platelet receptor and subsequent ADP-mediated activation of the glycoprotein IIb/IIIa complex -> inhibits platelet aggregation

PHARMACEUTICS

PO tablet
prodrug

DOSE

load: 300mg
maintenance: 75mg
paediatrics: 1.5mg/kg

INDICATIONS

ACS
post PCI’s
prophylaxis of vascular ischaemic events (post stenting)

ADVERSE EFFECTS

bleeding (stop for 5 days prior to surgery)
TTP
neutropenia
liver dysfunction

PHARMACOKINETICS

Absorption –
Distribution
Metabolism – hepatic to active drug
Elimination

EVIDENCE

-> in patients with TIA or CVA – combination of aspirin and clopidogrel -> increases bleeding risk and doesn’t change risk of recurrence (CAPRIE and CURE trials)

Deepak, L. et al (2010) “Clopidogrel with or without Omeprazole in Coronary Artery Disease” NEJM, 363:1909-17

PPI’s are purported to decrease the risk of GIH with anti-platelet therapy but may decrease efficacy of clopidogrel.
MRCT – double-blind, double-dummy, placebo-controlled, parallel-group
n = 3761
dual anti-platelet therapy with clopidogrel vs clopidogrel + omeprazole
primary gastrointestinal end-point: GIH, symptomatic GU, erosions, obstruction or perforation
primary cardiovascular end-point: composite death from cardiovascular causes, MI, revascularisation or CVA.

-> GI event rate was 1.1% with omeprazole and 3% without @ 180 days (P<0.001)
-> no significant difference in cardiovascular event rate

Strengths