Abstract 6241: Proton Pump Inhibitors May Attenuate the Benefits of Clopidogrel among ACS Patients: Empirical Evidence from 3,311 ACS Patients
Background: A prior report showed omeprazole decreases platelet inhibitory effects of clopidogrel (clopid). However, the clinical impact of these findings is unknown. We studied outcomes of patients taking clopid alone versus clopid and proton-pump inhibitor (PPI) after acute coronary syndrome (ACS) in a national VA registry.
Methods: This was a retrospective cohort study of 3,311 ACS patients discharged from 127 VA hospitals on either clopid alone or clopid+PPI based on pharmacy dispensing data. The main outcome was AMI/death. Cox proportional hazards regression models assessed the association between drug use as a time varying covariate and outcomes. Mean follow-up was >1 year. During follow-up, patients could have gaps in their treatment and thus could be categorized as “no drugs” or “PPI-only” for short durations.
Results: At discharge, 34% were prescribed clopid alone and 66% clopid+PPI. Baseline characteristics were quite similar (e.g. mean age 68.1 yrs for clopid vs 68.3 yrs for clopid+PPI) except clopid+PPI patients had less diabetes and more renal insufficiency. In multivariable analyses, clopid+PPI was associated with a higher risk of AMI/death risk compared to clopid alone (HR 1.28; 95% CI 1.07–1.53) (Figure⇓). Findings were consistent excluding patients with bleeding event during follow-up and using a nested case-control study design.
Conclusion: Concomitant use of clopidogrel and PPI after ACS is associated with higher risk of adverse outcomes than clopidogrel use without PPI. These findings, coupled with the prior mechanistic study, suggest that concomitant PPI use attenuates the benefits of clopidogrel after ACS.