Risk of Adverse Cardiovascular Events Following a Myocardial Infarction in Patients Receiving Combined Clopidogrel and Proton Pump Inhibitor Treatment: A Nested Case–Control Study

BACKGROUND: The clinical implications of potential interactions between proton pump inhibitors (PPIs) and clopidogrel have been debated for over a decade. OBJECTIVE: We assessed the association between combined clopidogrel–PPI treatment and the risk of recurrent myocardial infarction (MI) and three secondary outcomes. PATIENTS AND METHODS: A nested case–control study was conducted within Cerner Corporation’s Health Facts(®) database. A retrospective cohort of patients who experienced a first MI and started clopidogrel treatment was created. Within this cohort, patients experiencing a second MI (cases) were matched with up to five controls. Logistic regression was used to estimate adjusted odds ratios (aORs). Findings were compared with those obtained from models with three negative control exposure drugs: H(2) receptor antagonists, prasugrel, and ticagrelor. RESULTS: In total, 2890 recurrent MI cases were identified within 12 months following entry into the cohort of clopidogrel users (N = 52,006). aOR for PPI use versus non-use among clopidogrel users was 1.08 [95% confidence interval (CI) 0.95–1.23]. Similar ORs were obtained for secondary endpoints. A positive association between combined use of clopidogrel/PPIs and increased risk of MI was seen in the group aged 80–89 years (aOR 1.26; 95% CI 1.05–1.51). No associations with MI were observed for (1) H2 receptor antagonist use versus non-use among clopidogrel users or (2) PPI use versus non-use among prasugrel users or among ticagrelor users. CONCLUSIONS: Overall, our findings do not support a significant adverse clinical impact of concomitant clopidogrel/PPI use by patients with MI. Nonetheless, investigation of the possible association seen in those aged 80–89 years may be warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40801-020-00204-9) contains supplementary material, which is available to authorized users.