The benefits—and limits—of PPIs with warfarin regimens
Patients on warfarin + antiplatelet/NSAID regimens are likely to benefit from the gastroprotective effect of PPIs. For patients taking warfarin alone, it’s a different story.
PRACTICE CHANGER
Prescribe a proton pump inhibitor for patients taking dual antiplatelet/antithrombotic therapy to reduce the risk of upper gastrointestinal bleeding.
STRENGTH OF RECOMMENDATION
B: Based on a cohort study
Ray WA, Chung CP, Murray KT, et al. Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology. 2016;151:1105-1112.1
WHAT’S NEW
PPIs offer benefits, but not to patients taking warfarin alone
The statistically significant results in this large observational study suggest that PPI co-therapy is beneficial in reducing the risk of upper GI bleeding in patients taking warfarin plus an antiplatelet agent/NSAID, but that PPI co-therapy provides no benefit to patients taking warfarin exclusively.
CAVEATS
Study was good, but it wasn’t a randomized controlled trial
This study is observational, and not a randomized control trial (RCT). Therefore, unknown confounding variables may have skewed results. For example, patients could have taken over-the-counter medications that influenced or obscured results, but were not included in the data analysis (misclassification bias).
At best, we can infer a correlation between PPIs and decreased risk of upper GI bleeds. We need RCTs to determine whether PPIs cause a lower risk.
Don’t overlook the risk of PPIs. This study assessed the ability of PPIs to prevent bleeds, but did not address the risks of long-term PPI therapy. Adverse effects of PPIs include an increased risk of pneumonia, infection with Clostridium difficile, hip and spine fractures, anemia, and possibly chronic kidney disease and dementia.9-11 In addition, cost-analysis studies of PPI therapy are limited and inconsistent.12 Therefore, it’s best to make decisions regarding PPIs after discussing other risks and benefits.
What about DOACs? Another consideration is the option to prescribe a direct oral anticoagulant (DOAC), such as dabigatran, rivaroxaban, or apixaban, instead of warfarin. DOACs are at least as effective as warfarin at preventing stroke in patients with atrial fibrillation and may even be safer.13 Dabigatran 110 mg causes fewer “major bleeding” events than warfarin.13 Rivaroxaban has been shown to result in fewer fatal bleeding events than warfarin due to fatal intracranial bleeds, although it is associated with more GI bleedding.13 Compared with warfarin, apixaban is associated with fewer GI bleeds and lower bleeding rates overall.13 Further research is warranted to determine if PPI therapy is beneficial to patients taking DOACs.
CHALLENGES TO IMPLEMENTATION
It’s still a balancing act
When chronic anticoagulation is necessary, physicians and patients must attempt to prevent thrombotic events while minimizing the risk of GI bleeds. PPIs may be beneficial in preventing upper GI bleeds in patients taking dual warfarin and antiplatelet therapy, but the long-term consequences of PPI therapy should not be ignored.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
