Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients with atrial fibrillation on direct-acting oral anticoagulants

Background Oral glucocorticoids and direct-acting oral anticoagulants (DOAC) have both been associated with a risk of gastrointestinal (GI) bleeding. However, drug safety, especially regarding the risk of bleeding, in relation to concomitant treatment with oral glucocorticoids and DOACs is insufficiently explored. Purpose We aimed to investigate the short-term risk of GI bleeding in patients with atrial fibrillation (AF) following concomitant treatment with DOACs and oral glucocorticoids. Methods Register-based, retrospective and nationwide Danish study including patients with AF and on DOAC treatment during 2012–2018. Patients were defined as exposed to oral glucocorticoids from the date of a redeemed prescription and 60 days forward. We associated concomitant treatment with GI bleeding and reported hazard ratios (HR) via a nested case-control design and standardized 60-day absolute risk adjusted for comorbidities using a cohort design. In both analyses, exposed were compared to non-exposed controls matched on age, sex, calendar year, follow-up time and DOAC agent. Results We included 98,376 patients (age [interquartile range]: 75 [68– 82], 44% females) with AF on DOAC treatment. The use of oral glucocorticoids among included patients was widespread with 16% redeeming at least one prescription within three years, 4% redeeming at least five (Figure 1A). Lung disease was the most frequent indication (Figure 1B). Concomitant treatment with DOACs and oral glucocorticoids was associated with an increased incidence of GI bleeding (total n=4,946) compared with only DOAC treatment, including a dose-response trend (<20mg daily dose, HR [95% confidence interval (CI)]: 1.64 [1.38–1.95]; ≥20mg daily dose, HR [95% CI]: 2.29 [1.90–2.77]). Likewise, the standardized 60-day absolute risk of GI bleeding from first oral glucocorticoid exposure was increased compared with non-exposed (Figure 2). Conclusion Caution should be exercised when prescribing even short-term oral glucocorticoid treatment for DOAC treated patients, most notably in high doses and for patients with elevated bleeding risk. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Ib Mogens Kristiansens Almene FondandHelsefonden

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

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.

Propylthiouracil-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis after COVID-19 Vaccination

We report the case of a patient who developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after receiving the coronavirus disease 2019 (COVID-19) vaccine BNT162b (Pfizer–BioNTech). A 37-year-old Japanese woman had been taking propylthiouracil for Graves’ disease. She had erythema on her forearm on the 12th day after receiving the first dose of the vaccine, fever on the 13th day, and redness and swelling of her left auricle on the 25th day. Her serum myeloperoxidase-ANCA and proteinase 3-ANCA levels, which were negative before the Graves’ disease treatment, were elevated. She had unilateral auricular symptoms but no other typical relapsing polychondritis findings. She was diagnosed with propylthiouracil-induced AAV. She was treated with oral glucocorticoids, and her symptoms improved. Propylthiouracil is considered to be the main cause of the onset of AAV in this case, but it cannot be ruled out that BNT162b may have had some effect on the onset of the disease. Although the development of propylthiouracil-induced AAV in this case may have been incidental and unrelated to the vaccination, this report provides important data for evaluating the safety of the vaccine.

Delayed leukoencephalopathy from suspected polymer embolism after neuroendovascular procedures

As the neurointervention field grows, a new side effect emerges. Delayed leukoencephalopathy (DL) is believed to be an inflammatory or allergic reaction to polymer material that is shed from catheters during endovascular procedures. We present four cases of DL after aneurysm treatment in two patients, endovascular stroke treatment and diagnostic arteriography. We present our diagnostic process, including biopsy results in two patients, our anti-inflammatory treatment and outcomes together with a review of the literature. In our series, prognosis was variable with ongoing seizures in two patients. Our literature review reveals that asymptomatic shedding of polymer material is common, occurring in a third of endovascular stroke procedures, whereas symptomatic DL occurs in <0.5% of therapeutic neuroendovascular procedures. Clinicians should be aware of this rare complication, and oral glucocorticoids seem to be a reasonable first-line treatment strategy.