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

• 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