Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from...

Area of Science:

• Cardiology
• Pharmacology

Background:

• The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) is not well understood.
• Previous studies have suggested a potential link between PPI use and adverse cardiovascular outcomes in patients treated with antiplatelet agents.

Purpose of the Study:

• To investigate the relationship between proton pump inhibitor (PPI) use and 1-year cardiovascular events in patients with acute coronary syndrome (ACS).
• To compare the incidence of cardiovascular events in patients receiving clopidogrel versus ticagrelor, stratified by PPI use.

Main Methods:

• A subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial was conducted.
• Patients with ACS randomized to clopidogrel or ticagrelor were assessed for PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke).
• Outcomes were compared between patients using PPIs, non-PPI gastrointestinal drugs, and no gastric therapy.

Main Results:

• Patients on PPIs had higher rates of 1-year cardiovascular events compared to those not on PPIs, regardless of whether they received clopidogrel or ticagrelor.
• The adjusted hazard ratio for cardiovascular events in PPI users versus non-users was 1.20 for clopidogrel and 1.24 for ticagrelor.
• Patients on no gastric therapy had significantly lower event rates compared to PPI users, suggesting confounding factors may influence the observed association.

Conclusions:

• Proton pump inhibitor (PPI) use was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel.
• A similar association was observed with ticagrelor and other non-PPI gastrointestinal treatments, suggesting PPI use may be a marker for higher-risk patients rather than a direct cause.
• The findings suggest that confounding by indication may explain the observed association between PPI use and adverse cardiovascular events in the PLATO trial.