There are conflicting data on the potential adverse interaction between the effects on clinical events of the P2Y12 inhibitor clopidogrel and proton pump inhibitors (PPIs), while the importance of such an interaction with other P2Y12 inhibitors is less investigated. Ticagrelor is a directly acting P2Y12 inhibitor with no known interaction with PPIs. In view of the ongoing debate on the clinical significance of the interaction between clopidogrel and PPIs, researchers examined the relationship between PPI use and cardiovascular (CV) outcomes in ACS patients randomised to clopidogrel or ticagrelor in a pre-specified, non-randomised subgroup analysis of the PLATelet inhibition and patient Outcomes (PLATO) trial.

The following findings were reported:

• The primary endpoint rates were higher for individuals on a PPI (n=6539) vs. those not on a PPI (n=12060) at randomisation in both the clopidogrel (13.0% vs. 10.9%, adjusted hazard ratio 1.20, 95% CI, 1.04 to 1.38) and ticagrelor (11.0% vs. 9.2%; 1.24, 1.07 to 1.45) groups.

• Patients on non-PPI gastrointestinal (GI) drugs had similar primary endpoint rates compared to those on a PPI (PPI vs. non-PPI GI treatment: clopidogrel, 0.98; 0.79 to 1.23; ticagrelor; 0.89; 0.73 to 1.10).

• Patients on no gastric therapy had a significantly lower primary endpoint rate (PPI vs. no GI treatment: clopidogrel, 1.29; 1.12 to 1.49; ticagrelor 1.30, 1.14 to 1.49).

The researchers conclude that “the use of a PPI was independently associated with a higher rate of CV events in ACS patients receiving clopidogrel. However, a similar association was observed between CV events and PPI use during ticagrelor treatment and with other non-PPI GI treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of CV events.” They acknowledge the inherent limitations of non randomised comparisons, but suggest that their findings do not support the need to avoid concomitant PPI use with clopidogrel or ticagrelor.