Effect of the Clopidogrel–Proton Pump Inhibitor Drug Interaction on Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome

Abstract

Study Objective This study examined the effect of clopidogrel and proton pump inhibitors (PPIs) interaction on subsequent acute coronary syndrome (ACS)-related inpatient and emergency room (ER) visits. Design Population based, retrospective cohort study. Data Source IMS LifeLink Health Plan administrative claims database containing a large nationally dispersed group of commercially insured subjects between 2001 and 2008. Patients Subjects age ≥18 years with a diagnosis of ACS and at least one clopidogrel prescription within 90 days after the diagnosis were included. Exposed group was defined as having overlapping clopidogrel-PPI prescriptions. Subjects were followed from their first clopidogrel prescription until they experienced an adverse cardiovascular event (re-hospitalization or errors visit due to ACS), were disenrolled or reached the end of study period. Measurements and Main Results The clopidogrel plus PPIs group was matched 1:1 with the clopidogrel alone group using the propensity scoring method. Exposure to overlapping clopidogrel-PPI prescriptions was modeled as a time dependent covariate. Cox hazards regression was used to estimate the risk of an adverse cardiovascular event for those having overlapping clopidogrel-PPI prescriptions versus those having clopidogrel alone. Propensity score matching resulted in 2,674 patient pairs. The mean age was 61.30 years with a mean follow-up of 268 days and 70.04% were male. Clopidogrel use co-medicated with PPIs was associated with a significantly increased risk of cardiovascular adverse events (HR=1.438; 95% CI, 1.237-1.671), as compared to clopidogrel use not co-medicated with PPIs. Conclusion Concurrent use of clopidogrel plus PPIs was associated with a significant increase in risk of adverse cardiovascular events for ACS patients.

Connections between nutritional status and proton pump inhibitor therapy in patients scheduled for cardiovascular rehabilitation after treatment for ischaemic and valvular heart disease

“…Less invasive treatments were related with no change, or minimal increase in platelets counts, conversely to the significant increase seen after surgical treatments. The latter might, in part, explain the confounding results of earlier studies of interactions with clopidogrel [24]. Interestingly, the operated patients exhibited the least number of pharmaceuticals in chronic therapy, despite the fact that they had an equal background of ischaemic heart disease.…”

Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients

“…However, evidence from mechanistic studies has indicated that the anti-platelet effect of clopidogrel is reduced in the presence of PPIs because PPIs inhibit CYP2C19, an enzyme responsible for the conversion of clopidogrel to its active metabolite [6][7][8] . Moreover, several observational studies have shown that concomitant use of clopidogrel and PPIs increases the risk of adverse cardiovascular events [9][10][11][12][13][14][15] . In response to growing concerns over combined use of clopidogrel and PPIs, the US Food and Drug Administration (FDA) issued a public advisory in 2009 advising physicians to re-evaluate the need of PPI use in patients receiving clopidogrel and subsequently a 'black box' warning was added to all clopidogrel (Plavix*) labels in 2011 advising physicians to avoid prescribing clopidogrel and PPIs, namely omeprazole and esomeprazole, simultaneously 16 .…”

Current Perspectives in NSAID-Induced Gastropathy

“…Clopidogrel is a prodrug that is transformed in vivo to an active metabolite by the cytochrome P450 enzyme system [74]. However, some reports have suggested that PPIs interfere with clopidogrel to impair platelet function [23, 24, 75]. PPIs possibly inhibit hepatic cytochrome P450 2C19 (CYP2C19) isoenzyme preventing the conversion of clopidogrel into its active metabolite.…”