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
- large number
- discrete end points
- stratified permuted blocks used (based on Helicobacter serology and used of NSAIDS)
Weaknesses
- not completed due to loss of sponsor funding (loss of power)
- 94% of patients were white
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