Clopidogrel + PPI

[Yariko]

Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis
J. M. Siller-Matula1, B. Jilma1, K. Schrör2, G. Christ3, K. Huber4

Objective: To investigate whether proton pump inhibitors (PPIs) negatively affect clinical outcome in patients treated with clopidogrel.
Methods: Systematic review and meta-analysis. Outcomes evaluated were combined major adverse cardiac events (MACE), myocardial infarction, stent thrombosis, death and gastrointestinal bleeding. Studies included were randomised trials or post-hoc analyses of randomised trials and observational studies reporting adjusted effect estimates.
Results: Twenty five studies met the selection criteria and included 159,138 patients. Administration of PPIs together with clopidogrel corresponded to a 29% increased risk of combined major cardiovascular events (risk ratio RR=1.29, 95%CI=1.15-1.45) and a 31% increased risk of myocardial infarction (RR=1.31, 95%CI=1.12-1.53). In contrast, PPI use did not negatively influence the mortality (RR=1.04, 95%CI=0.93-1.16), whereas the risk to develop a gastrointestinal bleeding under PPI treatment decreased by 50% (RR=0.50, 95%CI=0.37-0.69). The presence of a significant heterogeneity might indicate that the evidence is biased, confounded or inconsistent. The sensitivity analysis, however, yielded that the direction of the effect remained unchanged irrespective of the publication type, study quality, study size or risk to develop an event. Two studies indicate that PPIs have a negative effect irrespective of clopidogrel exposure.
Conclusions: Concomitant PPI use might be associated with an increased risk of cardiovascular events but does not influence the risk of death. Prospective randomised trials are required to investigate whether a cause-and-effect relationship truly exists and to explore whether different PPIs worsen clinical outcome in clopidogrel treated patients as the PPI-clopidogrel drug-drug interaction seems not to be a class effect.
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