Clopidogrel and proton pump inhibitors - where do we stand in 2012?

Table 3 Summary of studies reporting on adverse bleeding events

Study	Observed adverse event	Ascertainment	Results
Bhatt et al[25]	Composite of upper gastrointestinal bleeding (of known and unknown origin): overt bleeding, ulcers, symptomatic erosions, obstruction, perforation or decrease in hemoglobin of 2 g/dL	Endoscopic and radiologic confirmation (in known origin subgroup)	Significative reduction of upper gastrointestinal bleeding in the omeprazole treated group (1.1% against 2.9% under placebo; HR 0.34, 95% CI: 0.18-0.63)
Ray et al[27]	Hospitalization for bleeding at a gastroduodenal site (excluding angiodysplasia) or other gastrointestinal and non-gastrointestinal sites	Validated diagnostic codes with PPV of 91%	Adjusted 50% reduction of hospitalization in the PPI treated group (HR 0.50, 95% CI: 0.39-0.65), no significant difference concerning bleeding at other sites
van Boxel et al[14]	Occurence of complicated or non complicated peptic ulcer disease	ICD-9 diagnostic codes	Low incidence (0.7% with PPI against 0.2%) but significant increase of peptic ulcer disease in the PPI treated group even after multivariable adjusting (HR 4.76, 95% CI: 1.18-19.17)
Charlot et al[28]	Hospitalization for gastrointestinal bleeding	ICD-9 diagnostic codes	No reduction between the clopidogrel with PPI and clopidogrel alone group
Harjai et al[29]	TIMI major bleeding: intracranial hemorrage or a ≥ 5 g/dL decrease in hemoglobine TIMI minor bleeding: observed blood loss with decrease ≥ 3 g/dL in hemoglobine	Guthrie Health System database	No significant difference between the clopidogrel with PPI and clopidogrel alone group
Simon et al[30]	In-hospital major bleeding (not specified) or need for blood transfusion	FAST-MI registry	No significant difference between the clopidogrel with PPI and clopidogrel alone group

HR: Hazard ratio; CI: Confidence interval; PPV: Positive predictive value; PPI: Proton pump inhibitor; ICD-9: International classification of disease-9th revision; FAST-MI: French registry of acute-ST-elevation and non-ST-elevation myocardial infarction.