Lorenzo Villa Zapata1, Philip D Hansten2, Jennifer Panic3, John R Horn4, Richard D Boyce5, Sheila Gephart6, Vignesh Subbian7, Andrew Romero8, Daniel C Malone9. 1. Skaggs School of Pharmacy and Pharmaceutical Sciences, Center for Pharmaceutical Outcomes Research, University of Colorado, Denver, Colorado, United States. 2. School of Pharmacy, University of Washington, Seattle, Washington, United States. 3. Marshfield Clinic Health System, Marshfield, Wisconsin, United States. 4. Department of Pharmacy Practice, School of Pharmacy, Pharmacy Services UW Medicine, University of Washington, Seattle, Washington, United States. 5. Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States. 6. Community and Health Systems Science, College of Nursing, The University of Arizona, Tucson, Arizona, United States. 7. Department of Biomedical Engineering, College of Engineering, The University of Arizona, Tucson, Arizona, United States. 8. Department of Pharmacy, Banner-University Medical Center Tucson, Tucson, Arizona, United States. 9. College of Pharmacy, L. S. Skaggs Research Institute, University of Utah, Salt Lake City, Utah, United States.
Abstract
BACKGROUND: Warfarin use can trigger the occurrence of bleeding independently or as a result of a drug-drug interaction when used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: This article examines the risk of bleeding in individuals exposed to concomitant warfarin and NSAID compared with those taking warfarin alone (Prospero Registry ID 145237). METHODS: PubMed, EMBASE, Scopus, and Web of Science were searched. The primary outcome of interest was gastrointestinal bleeding and general bleeding. Summary effects were calculated to estimate average treatment effect using random effects models. Heterogeneity was assessed using Cochran's Q and I 2. Risk of bias was also assessed using the Agency for Healthcare Research and Quality bias assessment tool. RESULTS: A total of 651 studies were identified, of which 11 studies met inclusion criteria for meta-analysis. The odds ratio (OR) for gastrointestinal bleeding when exposed to warfarin and an NSAID was 1.98 (95% confidence interval [CI]: 1.55-2.53). The risk of gastrointestinal bleeding was also significantly elevated with exposure to a COX-2 inhibitor and warfarin relative to warfarin alone (OR = 1.90, 95% CI: 1.46-2.46). There was an increased risk of general bleeding with the combination of warfarin with NSAIDs (OR = 1.58, 95% CI: 1.18-2.12) or COX-2 inhibitors (OR = 1.54, 95% CI: 0.86-2.78) compared with warfarin alone. CONCLUSION: Risk of bleeding is significantly increased among persons taking warfarin and a NSAID or COX-2 inhibitor together as compared with taking warfarin alone. It is important to caution patients about taking these medications in combination. Georg Thieme Verlag KG Stuttgart · New York.
BACKGROUND:Warfarin use can trigger the occurrence of bleeding independently or as a result of a drug-drug interaction when used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: This article examines the risk of bleeding in individuals exposed to concomitant warfarin and NSAID compared with those taking warfarin alone (Prospero Registry ID 145237). METHODS: PubMed, EMBASE, Scopus, and Web of Science were searched. The primary outcome of interest was gastrointestinal bleeding and general bleeding. Summary effects were calculated to estimate average treatment effect using random effects models. Heterogeneity was assessed using Cochran's Q and I 2. Risk of bias was also assessed using the Agency for Healthcare Research and Quality bias assessment tool. RESULTS: A total of 651 studies were identified, of which 11 studies met inclusion criteria for meta-analysis. The odds ratio (OR) for gastrointestinal bleeding when exposed to warfarin and an NSAID was 1.98 (95% confidence interval [CI]: 1.55-2.53). The risk of gastrointestinal bleeding was also significantly elevated with exposure to a COX-2 inhibitor and warfarin relative to warfarin alone (OR = 1.90, 95% CI: 1.46-2.46). There was an increased risk of general bleeding with the combination of warfarin with NSAIDs (OR = 1.58, 95% CI: 1.18-2.12) or COX-2 inhibitors (OR = 1.54, 95% CI: 0.86-2.78) compared with warfarin alone. CONCLUSION: Risk of bleeding is significantly increased among persons taking warfarin and a NSAID or COX-2 inhibitor together as compared with taking warfarin alone. It is important to caution patients about taking these medications in combination. Georg Thieme Verlag KG Stuttgart · New York.
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