Summary
Some pharmacokinetic studies have reported that proton pump inhibitors (PPIs) reduce
the activity of clopidogrel, but the results of studies assessing clinical outcomes
in patients receiving both drugs are inconsistent. We have therefore carried out a
population-based cohort study with nested case–control analysis, in order to evaluate
changes in the risk of cardiovascular and peptic ulcer bleeding (PUB) events associated
with PPI use in patients receiving clopidogrel. A total of 42,542 patients aged 50–84
years in 2000–2007 who survived an acute coronary event were identified in two UK-based
primary care databases (The Health Improvement Network and the General Practice Research
Database). Individuals were followed up to identify incident cases of non-fatal myocardial
infarction/coronary death (n = 2,546) and PUB (n = 194). Controls were frequency matched
to cases by age, sex and calendar year. Compared with PPI non-use, current continuous
PPI use was not associated with a significant change in risk of non-fatal myocardial
infarction/coronary death among current continuous users of clopidogrel monotherapy
(relative risk [RR], 1.06; 95% confidence interval [95% CI], 0.47 to 2.36) or dual
antiplatelet therapy (DAT; RR, 0.80; 95% CI, 0.47 to 1.37) who initiated their antiplatelet
therapy shortly after their coronary event. Among patients prescribed DAT at the start
date, the RR of PUB events associated with current PPI use initiated at the start
date was 0.66 (95% CI, 0.27 to 1.60).
Keywords
Clopidogrel - proton pump inhibitors - drug interactions