-Author name in bold denotes the presenting author
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5129 Outcomes of Oral Anticoagulation with Concomitant NSAID Use: A Registry Based Cohort Study

Program: Oral and Poster Abstracts
Session: 904. Outcomes Research—Non-Malignant Conditions: Poster III
Hematology Disease Topics & Pathways:
Research, Anticoagulant Drugs, adult, Clinical Practice (Health Services and Quality), Non-Biological therapies, health outcomes research, Clinical Research, Combination therapy, Therapies, real-world evidence, registries, Adverse Events, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Jordan K Schaefer, MD1, Josh Errickson, PhD2*, Xiaowen Kong, MA3*, Mona A Ali, PharmD4*, Naina Chipalkatti, MD5, Paul Dorby, PharmD6,7*, Christopher Giuliano, PharmD, MPH6,7*, Brian Haymart, RN, MS3*, Scott Kaatz, DO, MSc8*, Jacob E Kurlander, MD, MS9*, Gregory D Krol, MD10*, Sahana Shankar, BS11*, Suman L Sood, MD, MSCE1, James Froehlich, MD, MPH3* and Geoffrey D. Barnes, MD, MSc3*

1Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
2Consulting for Statistics, Computing, & Analytics Research, University of Michigan, Ann Arbor, MI, University of Michigan, Ann Arbor, MI
3Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
4Department of Heart and Vascular Services, Corewell Health William Beaumont University Hospital, Royal Oak, MI
5Department of Internal Medicine, University of Michigan, Ann Arbor, MI
6Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Science, Wayne State University, Detroit, MI
7Ascension St. John Hospital, Detroit, MI
8Division of Hospital Medicine, Henry Ford Health, Detroit, MI
9Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
10Department of Internal Medicine, Henry Ford Health, Detroit, MI
11Oakland University William Beaumont School of Medicine, Rochester, MI


Nonsteroidal anti-inflammatory drugs (NSAIDs), available without a prescription, are some of the most commonly used drugs in the United States. For patients on oral anticoagulation (OAC), concomitant NSAID use can increase the risk of bleeding. Patients are often advised to avoid this drug combination, or else consider adding a proton pump inhibitor (PPI) or H2 receptor antagonists (H2RA) for gastroprotection when both NSAIDs and OAC are used. However, there are limited data on how NSAID use impacts thrombotic and hemorrhagic outcomes. Available data may be biased due to selection bias, confounding, misclassification, and variable NSAID exposure. We sought to determine the frequency of NSAID use among patients on OAC, the impact on clinical outcomes, and if gastroprotection may mitigate bleeding risk. We hypothesized that NSAIDs would increase bleeding risk without impacting thrombotic risk. We did not anticipate gastroprotection would mitigate this risk.


We conducted a retrospective registry-based cohort study of adults starting a direct oral anticoagulant (DOAC) or warfarin therapy for the indications of venous thromboembolism and/or non-valvular atrial fibrillation between June 2011 and June 2023. As part of the Michigan Anticoagulation Quality Improvement Initiative (MAQI2), warfarin-treated patients were followed by six anticoagulation clinics, and four of the six clinics contributed data for patients on DOACs. Patients were excluded if they had a history of valvular AF, less than 3 months of follow-up, or on more than one antiplatelet drug. Two propensity matched cohorts (OAC alone vs. OAC+NSAID) of patients were analyzed based on NSAID use at the time of study enrollment, using a 4:1 matching ratio. Both prescribed and over the counter NSAIDs were included, potentially with the former being more frequently captured in the study registry. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or venous thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room visits, hospitalizations, transfusions, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression.


Of 12,083 patients on OAC, 449 (3.7%) were on concomitant NSAIDs. After propensity matching, we compared 1,796 patients on OAC to 449 patients on OAC+NSAIDs. Patient demographics, co-morbidities, indication for anticoagulation, history of bleeding or clotting, medications, and duration of follow-up were well-balanced after matching. Patients were followed for an average of 30 months (standard deviation 34.2 months). For patients on OAC alone vs. OAC+NSAIDs, bleeding event rates were similar: 25.1 (95% confidence interval [CI] 23.7-26.6) versus 24.3 (95% CI 21.4-27.3) bleeds per 100 patient years (P=0.56). Rates of non-major, major, life-threatening, central nervous system, and fatal bleeding were also similar. Furthermore, rates of thrombosis, emergency room visits, hospitalizations, transfusion, and death were similar. A pre-defined subgroup analysis comparing patients on OAC+NSAIDs with gastrointestinal prophylaxis (PPIs or H2RAs, N=179) to patients on OAC+NSAIDs without gastrointestinal prophylaxis (N=270) also showed similar rates of bleeding and healthcare utilization.


Nearly 4% of patients were taking NSAIDs with OAC and outcomes were similar to patients on OAC alone. Study limitations include NSAIDs and gastroprotection were only reliably known at time of enrollment. In addition, the potential for unmeasured or unadjusted confounding inherent to observational studies. Further research is needed to determine if there is a “safe” level of NSAID use for patients on OAC and to better define the role of gastrointestinal prophylaxis.

Disclosures: Schaefer: Pfizer: Consultancy. Kaatz: AC Forum: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Gilead: Honoraria; PhaseBio: Honoraria; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Osmosis Research: Research Funding; National Blood Clot Alliance: Membership on an entity's Board of Directors or advisory committees; PERT Consortium: Membership on an entity's Board of Directors or advisory committees. Froehlich: Pfizer: Honoraria; Merck: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Boehringer Ingelheim: Honoraria. Barnes: National Certification Board of Anticoagulation Providers: Membership on an entity's Board of Directors or advisory committees; AC Forum: Membership on an entity's Board of Directors or advisory committees; Connected Health: Honoraria; Boston Scientific: Honoraria; Abbott Vascular: Honoraria; Acelis: Honoraria; Janssen: Honoraria; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria.

*signifies non-member of ASH