3057 — Proton Pump Inhibitors May Attenuate the Benefits of Clopidogrel among ACS Patients: Using Registry Data to Address Medication Effectiveness

Ho PM (IHD-QUERI), Maddox TM (IHD-QUERI), Wang L (IHD-QUERI), Fihn SD (IHD-QUERI), Jesse RL (IHD-QUERI), Rumsfeld JS (IHD-QUERI)

Objectives:
A prior mechanistic study showed that omeprazole decreases platelet inhibitory effects of clopidogrel (clopid). However, the clinical impact of these findings is unknown. We used the Cardiac Care Follow-up Clinical Study (CCFCS), a registry of ACS patients discharged from all VHA hospitals starting in 2003, developed jointly by IHD-QUERI and the Office of Quality and Performance (OQP) to assess the outcomes of patients taking clopid alone versus clopid and proton-pump inhibitor (PPI) after acute coronary syndrome (ACS).

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 compared to clopid alone (HR 1.28; 95% CI 1.07-1.53). Findings were consistent excluding patients with bleeding event during follow-up and using a nested case-control study design.

Implications:
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. The results have important clinical implications given how common both medications are prescribed after ACS hospitalization and also highlight the uses of registry data to address longitudinal medication effectiveness questions.

Impacts:
This study utilized the CCFCS registry developed jointly by IHD-QUERI and OQP, providing a resource to assess the effectiveness of medications in routine practice, and information that may have important clinical implications.