Over the past few years physicians have grown increasingly concerned about possible negative consequences when clopidogrel is given to people taking PPIs. Last November the FDA added a warning to the clopidogrel label and issued a public health advisory on the interaction between clopidogrel and omeprazole. Now a new study lends fresh support to concerns, and provides the first substantial evidence that another PPI, pantoprazole, may also be a problem.
Researchers at Prescription Solutions and the University of Washington reviewed data from patients enrolled in a multistate private and Medicare insurance plan who were taking clopidogrel and a PPI and compared them with matched patients (using propensity scoring) with patients taking clopidogrel alone. In their report in Archives of Internal Medicine, Karen Stockl and colleagues found that when compared to patients on clopidogrel alone, patients also taking a PPI had a 93% higher risk of rehospitalization for MI (adjusted HR = 1.93, CI 1.05–3.54, p=0.03) and a 64% higher risk of rehospitalization for MI or stent implantation (adjusted HR = 1.64, CI 1.16–2.32, p=0.05).
Previous interaction studies included few subjects who were taking pantoprazole. Nearly two-thirds (63.8%) of patients in this study were taking pantoprazole. The authors note that their finding raises questions about the potential mechanism of the proposed interaction between PPIs and clopidogrel, because laboratory studies have so far found little evidence for an inhibitory effect of pantoprazole on clopidogrel’s antiplatelet effect.
According to the researchers, the study is more representative of the general population than previous studies because it included more women and elderly patients than previous studies.
The authors conclude that their study “provides additional information supporting a potentially higher risk of adverse clinical outcomes in patients receiving clopidogrel with a PPI. These findings highlight the need for additional prospective randomized clinical studies to further evaluate clinical outcomes associated with a potential drug-drug interaction between clopidogrel and PPIs.”
Previous coverage of this topic on CardioBrief:
- More adverse events seen in patients on PPIs after DES (February 5, 2010)
- FDA issues public health advisory on interaction between clopidogrel and omeprazole (November 17, 2009)
- New warnings added to Plavix (clopidogrel) label (November 16, 2009)
- TCT: COGENT provides reassurance on use of PPIs with clopidogrel (September 24, 2009)
- ESC: TIMI study offers reassurance on concomitant use of PPIs and antiplatelets (August 31, 2009)
- Medco study: PPIs reduce clopidogrel efficacy post-stenting (May 6, 2009)