PURLs

PPIs With Warfarin Regimens: Balancing the Perks and Pitfalls

Clinician Reviews. 2017 December;27(12):17-18,20

References

1. 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.
2. Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2008;52:1502-1517.
3. Salas M, Ward A, Caro J. Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta analysis of randomized clinical trials. BMC Gastroenterol. 2002;2:17.
4. Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10:528-534.
5. Lanas A, García-Rodríguez LA, Arroyo MT, et al. Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol. 2007;102:507-515.
6. Lin KJ, Hernández-Díaz S, García Rodríguez LA. Acid suppressants reduce risk of gastrointestinal bleeding in patients on antithrombotic or anti-inflammatory therapy. Gastroenterology. 2011;141:71-79.
7. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl):160S-198S.
8. Schulman S, Beyth RJ, Kearon C, et al. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl):257S-298S.
9. Ament PW, Dicola DB, James ME. Reducing adverse effects of proton pump inhibitors. Am Fam Physician. 2012;86:66-70.
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11. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176:238-246.
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WHAT’S NEW

PPIs offer benefits, but not to warfarin-only patients

The statistically significant results in this large observational study suggest that PPI co-therapy is beneficial in reducing the risk for 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

Not a randomized controlled trial

This study was observational, not a randomized control trial (RCT). Therefore, unknown confounding variables may have skewed results. For example, patients could have taken OTC 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 for upper GI bleeds. We need RCTs to determine whether PPIs cause a risk reduction.

Don’t overlook the risks 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 increased risk for pneumonia, infection with Clostridium difficile, hip and spinal fractures, anemia, and possibly chronic kidney disease and dementia.^9-11 In addition, cost-analysis studies of PPI therapy are limited and their results are inconsistent.¹² Therefore, it’s best to make decisions regarding PPIs after discussing other risks and benefits.

What about DOACs? Another option is to prescribe a direct oral anticoagulant (DOAC; eg, 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 Compared to warfarin, rivaroxaban has been shown to result in fewer fatal bleeding events due to intracranial bleeds, although it is associated with more GI bleeding.¹³ Apixaban is associated with fewer GI bleeds and lower bleeding rates overall, compared with warfarin.¹³ Further research is warranted to determine if PPI therapy is beneficial to patients who are taking DOACs.

CHALLENGES TO IMPLEMENTATION

It’s still a balancing act

When long-term anticoagulation is necessary, providers and patients must attempt to prevent thrombotic events while minimizing the risk for 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.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[11]:694-696).

PPIs With Warfarin Regimens: Balancing the Perks and Pitfalls

References

WHAT’S NEW

PPIs offer benefits, but not to warfarin-only patients

CAVEATS

Not a randomized controlled trial

CHALLENGES TO IMPLEMENTATION

It’s still a balancing act

ACKNOWLEDGEMENT

Pages

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