• NOTE: Information on metabolic pathways presented here is from the manufacurer's PI, FDA website, and a handful of published reviews. Other metabolic pathways may exist; therefore, the information is not meant to be all-inclusive.
Metabolism and clearance
Enzyme Clopidogrel Prasugrel Ticagrelor Ticlopidine
CYP1A2 Substrate - - Weak inhibitor
CYP2B6 Substrate
Weak inhibitor
Substrate (primary)
Weak inhibitor
- Weak inhibitor
CYP2C8 Strong inhibitor - - -
CYP2C19 Substrate (primary) Substrate - Strong inhibitor
CYP2C9 Substrate Substrate - -
CYP2D6 - - - Inhibitor
CYP3A4 Substrate Substrate (primary) Substrate (primary) -
P-glycoprotein - - Weak substrate

COGENT trial - Clopidogrel + Omeprazole vs Clopidogrel alone for Secondary Prevention of CVD, NEJM (2010) [PubMed abstract]
  • The COGENT trial enrolled 3873 patients who had an indication for 12 months of clopidogrel therapy
Main inclusion criteria
  • Anticipated therapy with aspirin and clopidogrel for 12 months including patients with acute coronary syndrome and/or stent placement
Main exclusion criteria
  • Medical need for PPI, H₂ antagonist, sucralfate, or misoprostol
  • Erosive esophagitis
  • Previous gastric surgery
  • Recent fibrinolysis
Baseline characteristics
  • Median age 68 years
  • Positive for H. Pylori - 48%
  • Using NSAIDs - 8.6%
  • PCI - 71%
  • MI - 29%
  • Stroke - 7.8%
  • History of GI bleed or ulcer - 4.1%
Randomized treatment groups
  • Group 1 (1876 patients) - Omeprazole 20 mg once daily + clopidogrel 75 mg once daily
  • Group 2 (1885 patients) - Placebo + clopidogrel 75 mg once daily
  • All patients also received enteric coated aspirin 75 - 325 mg once daily
Primary outcomes: The primary cardiovascular endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization (PCI or CABG), or ischemic stroke. The primary gastrointestinal (GI) outcome was a composite of upper GI clinical events (defined as bleeding, ulcer, pain with erosions, obstruction, or perforation)

Duration: Median of 106 days. The trial was stopped early due to loss of funding.
Outcome Omeprazole + clopidogrel Clopidogrel Comparisons
Primary outcome (CV events) 4.9% 5.7% p=0.96
Primary outcome (GI events) 1.1% 2.9% p<0.001

Findings: Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI.