Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants

Abstract

ObjectiveGastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.MethodsThis is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012–2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case–control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.Results98 376 patients on NOACs (median age: 75 years (IQR: 68–82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).ConclusionsConcomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.

Risk of gastrointestinal bleeding with concomitant NOAC and glucocorticoid treatment

“…A nationwide nested case–control study assessed the incidence of GI bleeding in people aged ≥18 years with atrial fibrillation (AF) who were prescribed a NOAC and an oral glucocorticoid. It used Danish registry data from 2012 to 2018 to identify people with AF who had received their first NOAC prescription 1. Cases were defined as all first-time GI bleeds within the study period and were matched with five controls from the study cohort.…”

“…A sample of 24 680 controls were compared with 914 who had been exposed to oral glucocorticoids 1. There was an increased hazard ratio (HR) for GI bleeding in patients exposed to glucocorticoids compared with the non-exposed group, and a dose–response relationship: <20 mg glucocorticoid dose HR 1.54 (95% CI 1.29 to 1.84) and for ≥20 mg glucocorticoid dose HR 2.19 (95% CI 1.81 to 2.65).…”

“…To estimate 60-day absolute risk (AR), 15 971 patients who received a glucocorticoid were matched with 47 837 controls 1. The 60-day AR of GI bleeding was modestly increased in those treated with glucocorticoids compared with the unexposed group (AR 0.71%[95% CI% 0.58 to 0.85%] vs 0.38% [95% CI 0.32% to 0.43%]) with a risk ratio of 1.89 (95% CI 1.43 to 2.36).…”

“…In people with atrial fibrillation, concomitant use of a NOAC and an oral glucocorticoid was associated with a higher rate and risk of GI bleeding than use of a NOAC alone 1…”

Non-vitamin K Antagonist Oral Anticoagulants and Drug-Food Interactions: Implications for Clinical Practice and Potential Role of Probiotics and Prebiotics

“…It is well known that NOACs have a lower propensity for drug and food interactions compared to vitamin K antagonists (VKAs), due to their individual coagulation proteins target and to the administration in fixed-dose without requiring routine coagulation monitoring (4). Even though, variations in NOACs concentration may occur with the concomitant use of inducers or inhibitors of P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4, thus increasing thrombotic and bleeding risk, respectively (5)(6)(7)(8).…”