Prevalence, contributory factors and severity of medication errors associated with direct-acting oral anticoagulants in adult patients: a systematic review and meta-analysis

Purpose This study aimed to estimate the prevalence, contributory factors, and severity of medication errors associated with direct acting oral anticoagulants (DOACs). Methods A systematic review and meta-analysis were undertaken by searching 11 databases including Medline, Embase, and CINHAL between January 2008 and September 2020. The pooled prevalence of errors and predictive intervals were estimated using random-effects models using Stata software. Data related to error causation were synthesised according to Reason’s accident causation model. Results From the 5205 titles screened, 32 studies were included which were mostly based in hospitals and included DOAC treatment for thromboembolism and atrial fibrillation. The proportion of study population who experienced either prescription, administration, or dispensing error ranged from 5.3 to 37.3%. The pooled percentage of patients experiencing prescribing error was 20% (95% CI 15–25%; I2 = 96%; 95% PrI 4–43%). Prescribing error constituted the majority of all error types with a pooled estimate of 78% (95%CI 73–82%; I2 = 0) of all errors. The common reported causes were active failures including wrong drug, and dose for the indication. Mistakes such as non-consideration of renal function, and error-provoking conditions such as lack of knowledge were common contributing factors. Adverse events such as potentially fatal intracranial haemorrhage or patient deaths were linked to the errors but causality assessments were often missing. Conclusions Despite their favourable safety profile, DOAC medication errors are common. There is a need to promote multidisciplinary working, guideline-adherence, training, and education of healthcare professionals, and the use of theory-based and technology-facilitated interventions to minimise errors and maximise the benefits of DOACs usage in all settings. Protocol A protocol developed as per PRISMA-P guideline is registered under PROSPERO ID = CRD42019122996

Guideline-discordant dosing of direct-acting oral anticoagulants in the veterans health administration

Background Clear guidelines exist to guide the dosing of direct-acting oral anticoagulants (DOACs). It is not known how consistently these guidelines are followed in practice. Methods We studied patients from the Veterans Health Administration (VA) with non-valvular atrial fibrillation who received DOACs (dabigatran, rivaroxaban, apixaban) between 2010 and 2016. We used patient characteristics (age, creatinine, body mass) to identify which patients met guideline recommendations for low-dose therapy and which for full-dose therapy. We examined how often patient dosing was concordant with these recommendations. We examined variation in guideline-concordant dosing by site of care and over time. We examined patient-level predictors of guideline-concordant dosing using multivariable logistic models. Results A total of 73,672 patients who were prescribed DOACS were included. Of 5837 patients who were recommended to receive low-dose therapy, 1331 (23%) received full-dose therapy instead. Of 67,935 patients recommended to receive full-dose therapy, 4079 (6%) received low-dose therapy instead. Sites varied widely on guideline discordant dosing; on inappropriate low-dose therapy, sites varied from 0 to 15%, while on inappropriate high-dose therapy, from 0 to 41%. Guideline discordant therapy decreased by about 20% in a relative sense over time, but its absolute numbers grew as DOAC therapy became more common. The most important patient-level predictors of receiving guideline-discordant therapy were older age and creatinine function being near the cutoff value. Conclusions A substantial portion of DOAC prescriptions in the VA system are dosed contrary to clinical guidelines. This phenomenon varies widely across sites of care and has persisted over time.

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