The interaction between the use of a proton pump inhibitor (PPI) and clopidogrel has raised many concerns recently although the clinical significance of this interaction remains uncertain.1 Goodman and colleagues, from the Platelet Inhibition and Patient Outcomes (PLATO) trial group, published a non-randomized subgroup analysis of Acute Coronary Syndrome (ACS) patients from the PLATO trial to determine the clinical significance of this interaction.2 The authors also looked to see if there is any clinical impact of the interaction between PPI use and ticagrelor, the new oral antiplatelet agent, and clopidogrel on the primary endpoints of the PLATO trial (the 12-month composite of cardiovascular death, MI, or stroke). Secondary end points such as all-cause mortality; cardiovascular death or nonfatal MI, any MI, stent thrombosis, and major non-coronary artery bypass grafting bleeding were included as well.
The use of a PPI before randomization was associated with higher rate of the composite primary end point at 30 days in both the clopidogrel and ticagrelor groups. The primary end point rates were higher for individuals on a PPI (n=6539) compared with those not on a PPI (n=12060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR] 1.20; 95% confidence interval [CI], 1.04-1.38) and ticagrelor (11.0% versus 9.2%; HR 1.24; 95% CI, 1.07-1.45) groups.
Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, (HR 0.98; 95% CI, 0.79-1.23; ticagrelor, HR 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49).
This study provides some information about the interaction between PPIs and clopidogrel and ticagrelor. However, given a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment, the authors concluded that there is no sufficient evidence to change the practice of prescribing PPIs to high risk patients since the risk of bleeding is well established. The practice should remain the same until randomized clinical trial is established.
1. Kastrati A, von Beckerath N, et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost. 2009;101:607–609.
2. Goodman SG, Clare R, Pieper KS, et al. Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes with Clopidogrel and Ticagrelor: Insights From the Platelet Inhibition and Patient Outcomes Trial. Circulation 2012;125(8):978-986.