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

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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