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Open Access Research article

Prognosis of concomitant users of clopidogrel and proton-pump inhibitors in a high-risk population for upper gastrointestinal bleeding

Qing Wang1, Rickard Ljung12, Jesper Lagergren13 and Yunxia Lu14*

Author Affiliations

1 Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden

2 Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

3 Division of Cancer Studies, King’s College London, London, United Kingdom

4 Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom

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BMC Pharmacology and Toxicology 2014, 15:22  doi:10.1186/2050-6511-15-22

Published: 15 April 2014



It is unclear whether concomitant use of clopidogrel and proton-pump inhibitors (PPIs) increases the risk of recurrence of cardiovascular disease or death in patients at high risk of upper gastrointestinal (GI) bleeding.


Based on the Swedish Patient Register, a cohort of cardiovascular disease (including acute myocardial infarction, stroke and angina, from 2006 to 2008) was selected from a population with any diagnosis of upper GI bleeding. Data on drug prescription was retrieved from the Prescribed Drug Register. Patients entered into the cohort after their first discharge for cardiovascular disease and were followed up to death, recurrence of cardiovascular disease, or 90 days. A Cox regression model was conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to evaluate the risks among users of different drug prescriptions.


Patients who were current users of only PPIs (HR 2.02, 95% CI 1.19-3.44), only clopidogrel (HR 1.14, 95% CI 0.53-2.45) and nonusers of both (HR 2.36, 95% CI 1.39-4.00) were at a higher risk of death compared with patients with a concomitant use. Results were similar among 1779 patients who had any history of upper GI bleeding (HR 2.05, 95% CI 1.18-3.54; HR 1.25, 95% CI 0.57-2.72; HR 2.30, 95% CI 1.33-3.98, respectively).


Among patients at high risk of upper GI bleeding, those with a concomitant use of PPIs and clopidogrel were at a decreased risk of mortality, and possibly also a decreased risk of recurrence of cardiovascular disease.

Clopidogrel; Proton-pump inhibitors; Gastrointestinal bleeding; Cardiovascular disease