Inappropriate Direct Oral Anticoagulants Research Articles

Appropriateness of direct oral anticoagulant dosing in patients with atrial fibrillation at a tertiary care hospital in Thailand

BackgroundAppropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical efficacy and safety. Several studies have shown that DOAC dosing are often inconsistent with guideline recommendations. Little is known about this issue in Thailand. This study aimed to evaluate the appropriateness of DOAC dosing in Thai hospitalized patients with atrial fibrillation (AF). MethodThis was a retrospective descriptive study conducted on hospitalized patients at Rajavithi Hospital, a tertiary care hospital in Thailand. Inpatients diagnosed with AF and treated with DOACs between February 2021 and February 2023 were enrolled in the study. The appropriate dosing of DOACs was assessed according to the recommendation of the 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (EHRA). Descriptive statistics were used to analyze the data; median (interquartile range) for continuous variables, and numbers and percentages for categorical variables. ResultsA total of 120 patients with AF were evaluated for dosing. The patients received rivaroxaban in 47 cases (39.2 %), apixaban in 32 cases (26.7 %), edoxaban in 31 cases (25.8 %), and dabigatran in 10 cases (8.3 %). Most of the patients were elderly, with a median age of 77.5 (68–84) years. Females were predominant (57.5 %). Our findings indicate that the prevalence of appropriate dosing of DOACs was 63.3 %. However, approximately one-third of patients received inappropriate dosing, with 24 (20.0 %) being overdosed, and 20 (16.7 %) being underdosed. The highest overdosing and underdosing rates were seen in dabigatran (90.0 %) and apixaban (21.9 %), respectively. ConclusionInappropriate dosing of DOACs according to the 2021 EHRA recommendations was high in 36.7 %, with overdosing mostly occurring in 20.0 %. The high number of inappropriate dosing highlights the need for implementation of optimal strategies to select the appropriate dose of DOACs in Thai hospitalized patients with AF.

Inappropriate Underdosing of Direct Oral Anticoagulants in Atrial Fibrillation Patients: Results from the START2-AF Registry.

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.

Predictors of Plasma Levels of Direct Oral Anticoagulants Among Patients with Atrial Fibrillation in Need of Elective Cardiac Procedures.

The withdrawal timing of direct oral anticoagulants (DOACs) among patients in need of elective invasive surgery is based on DOAC pharmacokinetics in order to perform the procedure out of the DOAC peak plasma concentration. We aimed to investigate the prevalence and predictors of plasma levels of DOACs out of trough range in patients with atrial fibrillation (AF) in need of elective cardiac procedure. We evaluated all consecutive AF patients on DOAC therapy in need of elective cardiac procedure, admitted to our division from January 2022 to March 2022. All patients underwent DOAC plasma dosing the morning of procedure day. They were categorized as in range, above range, and below range, according to the DOAC reference range at the downstream point. The timing of discontinuation of DOAC therapy was considered as appropriate or not, according to the current recommendations. The clinical predictors of out-of-range DOAC plasma levels have been evaluated. We included 90 consecutive AF patients (56.6% male, mean age 72.95 ± 10.12years); 74 patients (82.22%) showed DOAC concentration out of the expected reference range. In half of them (n, 37), the DOAC plasma concentration was below the trough reference range. Of the study population, 17.7% received inappropriate DOAC dosages (10% overdosing, 7% underdosing), and 35.5% had incorrect timing of DOAC withdrawal (26% prolonged, 9.5% shortened). At multivariable analysis, inappropriate longer DOAC withdrawal period (OR 10.13; P ≤ 0.0001) and increased creatinine clearance (OR 1.01; P = 0.0095) were the independent predictors of plasma DOAC levels below the therapeutic trough range. In contrast, diabetes mellitus (OR 4.57; P = 0.001) was the only independent predictor of DOAC plasma level above the therapeutic trough range. Increased creatinine clearance and inappropriate longer drug withdrawal period are the only independent predictors of DOAC plasma levels below the reference range; in contrast, diabetes is significantly correlated with DOAC plasma levels above the reference.

Pharmacist-led interventions in optimising the use of oral anticoagulants in patients with atrial fibrillation in general practice in England: a retrospective observational study.

Oral anticoagulation (OAC) is the mainstay of treatment for the prevention of strokes in patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) account for increasing OAC in patients with AF. However, prescribing DOACs for patients with established AF poses various challenges and general practice pharmacists may have an important role in supporting their management. To investigate the effectiveness of pharmacist-led interventions in general practice in optimising the use of OAC therapies in AF. A retrospective observational study in general practices in Bradford. The data were collected retrospectively from 1 November 2018-31 December 2019 using electronic health record data. The data were analysed: 1) to identify patients with AF not on OAC; 2) to describe inappropriate DOAC prescriptions; and 3) to calculate HAS-BLED scores. Overall, 76.3% (n = 470) of patients with AF received OAC therapy, and of these, 63.4% received DOACs. Pharmacist-led interventions increased DOAC prescribing by 6.0% (P = 0.03). Inappropriate DOAC use was identified in 24.5% of patients with AF, with underdosed and overdosed identified in 9.7% and 14.8%, respectively. Post-intervention, inappropriate prescribing was reduced to 1.7%. The mean HAS-BLED score decreased from 3.00 to 2.22 (P<0.01). Successful transition from vitamin K antagonist (VKA) therapy to DOACs was achieved in 25.7% of patients. Pharmacist-led interventions have successfully improved the use of OAC therapies in patients with AF, and effectively managed the bleeding risks and transition from VKA to DOAC therapy, in line with guidelines.

Inappropriate dosing of direct oral anticoagulants: findings from a clinical vignette study and physician survey

ABSTRACT Objective Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%. This study explores specific patient and physician factors associated with prescribing inappropriate DOAC underdoses. Methods DOAC-prescribing physicians within the UK completed both a clinical vignette survey, which contained 12 hypothetical patient profiles designed to replicate DOAC prescribing scenarios, and a physician survey to capture sociodemographic, clinical experience, and prescriber-related beliefs and motivations related to DOAC prescribing. Eight patient factors based on a literature search and an expert consultation process were varied within the vignettes. Associations between the prescribers’ dosing choices and patient factors were explored via multilevel logistic regression. The analysis is focused on the most frequently selected DOACs, apixaban and rivaroxaban, both of which have different dosing guidelines. Results In all, 336 prescribers (69% male; 233/336) completed the survey, mostly general physicians (GPs) (45%) or cardiology specialists (36%) with a mean of 17.9 years’ experience. Most prescribers (73%; 244/336) inappropriately underdosed at least once; rates between GPs and specialists were nearly identical. Patient factors most strongly associated with apixaban inappropriate underdosing included a history of major bleeding and falls. For rivaroxaban, these were major bleeding and severe frailty. Only 32% (106/335) of prescribers reported DOAC dosing guidelines as the sole influence on their prescribing behaviour. Among prescribers who did not inappropriately underdose, greater prescribing confidence was aligned to increased perception of inappropriate underdose risk. Conclusions Overall, patient factors such as major bleeding and severe frailty were found to be associated with inappropriate underdosing of apixaban and rivaroxaban. Furthermore, prescribers who were more confident in DOAC prescribing, and were more worried about the risk of stroke, were significantly less likely to inappropriately underdose. These findings suggest that all prescribers, regardless of speciality, may benefit from education and training to raise awareness of the risks associated with inappropriate DOAC underdosing.

Characteristics of patients with atrial fibrillation treated with direct oral anticoagulants and new insights into inappropriate dosing: results from the French National Prospective Registry: PAFF.

Since the introduction of direct oral anticoagulant (DOAC) for atrial fibrillation (AF) therapy, inappropriate and/or underdosing of these drugs has been a major clinical challenge. We evaluated the characteristics of patients with AF treated with inappropriate and low-dose DOACs. Patients with AF treated with inappropriate and low-dose DOACs from October 2021 to December 2021 were evaluated from the French National Prospective Registry (PAFF). We evaluated 1890 patients with AF receiving DOACs (apixaban 55%, dabigatran 7%, and rivaroxaban 38%). Inappropriate dosing was noted in 18% of the population. Patients with appropriate dosing had less comorbidities: younger age (75 ± 10 vs. 82 ± 8 years old, P < 0.0001), reduced chronic renal failure (26 vs. 61%, P < 0.0001), and lower CHA2DS2VASc and HASBLED scores (3 ± 2 vs. 4 ± 3, P < 0.0001; 2 ±1 vs. 2 ± 2, P < 0.0001), respectively. In multivariate analysis, older age (P < 0.0001) and a higher CHA2DS2VASc score (P = 0.0056) were independently associated with inappropriate DOAC dosing. Among 472 patients (27%) treated with low-dose rivaroxaban or apixaban, 46% were inappropriately underdosed. Patients inappropriately underdosed were younger (82.3 ± 8.4 vs. 85.9 ± 5.9 years, P < 0.0001) with less chronic renal disease (47 vs. 98%, P < 0.0001). However, these patients had higher rates of prior haemorrhagic events (18 vs. 10%, P = 0.01), clopidogrel use (11 vs. 3%, P = 0.0002), and apixaban prescription (74 vs. 50%, P < 0.0001). Within this large registry, DOACs were associated with inappropriate dosing in 18% of cases. Independent predictors of inappropriate dosing were high CHA2DS2VASc scores and older age. Moreover, 46% of patients treated with low-dose DOACs were inappropriately underdosed and more frequently in patients treated with apixaban.

Direct Oral Anticoagulants and Non-valvular Atrial Fibrillation: Compliance with Dose Level Guidelines in Patients Aged 80Years and Over.

Direct oral anticoagulants (DOACs) are currently recommended as first-line or (after vitamin K antagonists) second-line therapy for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation. In patients aged 80 years and over, however, the fear of DOAC-associated bleeding and the complexity of DOAC dosing regimes may prompt physicians to prescribe inappropriate dose levels. The objective of this study was to determine compliance with French and European guidelines of doses of three DOACs (apixaban, dabigatran and rivaroxaban) prescribed to patients aged over 80years in an indication of non-valvular atrial fibrillation, and to identify factors associated with poor compliance. We performed a retrospective single-centre study of patients aged over 80 years routinely treated with a DOAC (apixaban, dabigatran or rivaroxaban) for non-valvular atrial fibrillation at Valenciennes General Hospital (Valenciennes, France) between 1 January, 2016 and 31 December, 2017. We determined compliance with French and European guidelines of DOAC doses as a function of each patient's clinical and laboratory parameters, and thus classified the regime as being appropriately dosed, overdosed or underdosed. A total of 703 patients (371 taking apixaban, 92 taking dabigatran and 240 taking rivaroxaban) were included in the study. We found that 274 patients (39%) had been prescribed an inappropriate DOAC regime, with underdosing in 241 cases (34%) and overdosing in 33 cases (5%). Underdosing mainly concerned the two most widely prescribed DOACs, i.e. apixaban (39% of all apixaban prescriptions were underdosed) and rivaroxaban (40%). Concomitant treatment with an antidepressant was associated with underdosing of rivaroxaban or apixaban (p=0.0339). In contrast, initial management in a neurology department was associated with appropriate dosing (p=0.000146) for both these DOACs. Among patients with non-valvular atrial fibrillation aged 80 years and over, about 40% of DOAC prescriptions feature inappropriate dose levels. It might be possible to reduce inappropriate dosing by raising awareness among hospital-based and private-practice prescribers, providing prescription support tools for DOACs, and performing medication reconciliations and reviews at hospital and in private practice.

Determinants for under- and overdosing of direct oral anticoagulants and physicians' implementation of clinical pharmacists' recommendations.

To analyse the appropriateness of direct oral anticoagulant (DOAC) dosing and determinants for under-and overdosing as well as acceptance and implementation rates of pharmacists' interventions. Cross-sectional study in a tertiary hospital in hospitalized patients with atrial fibrillation on DOACs in 2019 (n =1688). Primary outcome was the proportion of patients with inappropriate DOAC prescribing with identification of determinants for under-and overdosing. Secondary outcomes included acceptance and implementation rates of pharmacists' recommendations and determination of reasons for nonacceptance/nonimplementation. Inappropriate prescribing was observed in 16.9% of patients (n =286) with underdosing (9.7%) being more prevalent than overdosing (6.9%). For all DOACs considered together, body weight<60 kg (odds ratio [OR] 0.46 [0.27-0.77]), edoxaban use (OR 0.42 [0.24-0.74]), undergoing surgery (OR 0.57 [0.37-0.87]) and being DOAC naïve (OR 0.45 [0.29-0.71]) were associated with significantly lower odds of underdosing. Bleeding history (OR 1.86 [1.24-2.80]) and narcotic use (OR 1.67 [1.13-2.46]) were associated with significantly higher odds for underdosing. Determinants with a significantly higher odds of overdosing were renal impairment (OR 11.29 [6.23-20.45]) and body weight<60 kg (OR 2.34 [1.42-3.85]), whereas dabigatran use (OR 0.24 [0.08-0.71]) and apixaban (OR 0.18 [0.10-0.32]) were associated with a significantly lower odds of overdosing compared to rivaroxaban. Physicians accepted the pharmacists' advice in 179 cases (79.2%) consisting of 92 (51.4%) recommendations for underdosing, 82 (45.8%) for overdosing and 5 (2.8%) for contraindications. Inappropriate DOAC prescribing remains common, although there is a slight improvement compared to our study of 2016. Clinical services led by pharmacists help physicians to reduce the number of inadequate prescriptions for high-risk medications such as DOACs.

A Survey of the Use of Direct Oral Anticoagulants in Patients' Possession at the Time of Hospitalization

The dose of direct oral anticoagulants (DOACs) must be determined based on package insert recommendations. There are reports on the rate of inappropriate DOAC dose usage defined as a dose deviating from the approved dose in the package insert but no reports on factors that led to such deviations. Thus, patients who were admitted to the Suzuka Kaisei Hospital between 1 April 2016 and 31 March 2017 were chosen as subjects. Moreover, the factors that during hospitalization led to dose deviation from the package-insert DOAC dose were retrospectively examined. The characteristics of patients administered doses deviating from the package insert were compared with those of patients in the appropriate-dose group. The finding was that the proportion concomitantly administered antiplatelet agents was higher in the underdose group. In contrast, deviations from the recommended dose did not occur when DOACs were combined with CYP3A4 inhibitors or P-glycoprotein (P-gp) inhibitors. It was suggested that increase in the risk of hemorrhage by antiplatelet agents in combination with oral anticoagulants could explain deviations from the stipulated DOAC dose. In addition, a higher proportion of patients in the overdose group showed depressed Ccr, and gastrointestinal bleeding. In future, it will be necessary to propose principle-based dose changes for patients administered doses deviating from the package insert. If an underdose is administered, it is important to make a dose change that takes the concomitant drugs into consideration.

Appropriateness of inpatient dosing of direct oral anticoagulants for atrial fibrillation.

Direct oral anticoagulant (DOAC) use for stroke prevention in atrial fibrillation (AF) has dose reduction criteria including age, weight, serum creatinine, and creatinine clearance. There is a paucity of data for rates of inappropriate inpatient DOAC dosing in Australia. The objective was to determine the rates of inappropriate inpatient DOAC dosing in AF and identifying its associated underlying factors. We conducted a retrospective cross-sectional study from December 2013 to November 2019 across six South Australian public hospitals utilising a centralised electronic health record. Multivariate analysis was used to identify factors associated with underdosing of patients prescribed apixaban. Of 1882 inpatients, 544 (28.9 %) were inappropriately dosed. Underdosing was the most common form of inappropriate dosing with rates of 22.9 % (n = 295), 7.1 % (n = 7), and 25.1 % (n = 124) for apixaban, dabigatran, and rivaroxaban, respectively. Independent factors predictive of apixaban underdosing included higher age (adjusted odds ratio (aOR) 1.63 [95 % Confidence Interval (CI): 1.47-1.81]), higher serum creatinine (aOR 1.13 [95 % CI: 1.08-1.19]), higher total number of drugs on discharge (aOR 1.08 [95 % CI: 1.04-1.11]), and being already prescribed a DOAC on admission (aOR 1.63 [95 % CI: 1.12-2.38]). Nearly one quarter of all apixaban prescribing was inappropriately underdosed. Older patients with multimorbidity, frailty and polypharmacy present a challenge for clinicians in balancing risks of thromboembolism and bleeding. It is likely prescribers are more conservative in their apixaban dosing in this population. Clinicians should consider alternative drug regimens to avoid DOAC use at inappropriate doses at unknown safety and efficacy.

Oral Anticoagulant Dosing, Administration, and Storage: A Cross-Sectional Survey of Canadian Health Care Providers

Background: Direct oral anticoagulant (DOAC) use is increasing worldwide. However, if not taken or prescribed correctly, DOACs have serious side effects. It is crucial that healthcare providers (HCPs) provide patients with accurate information and counselling around DOACs, to optimize safe and effective use.Aims: To assess HCPs' knowledge about oral anticoagulant indication, dosing, storage, and administration.Methods: An electronic survey was distributed to HCPs across Canada from June to July 2017, with 18 questions on oral anticoagulant practical use.Results: A total of 73 responses were received: 27 (37%) from Hematologists, 4 (5.4%) from Thrombosis Medicine specialists, 17 (23.3%) from nurse practitioners, 17 (23.3%) from pharmacists, and 8 (11%) from residents and fellows in Hematology training programs across Canada. The median duration of practice was 7 years (range 0.5 to 41). The majority of respondents (64 of 73; 88%) worked in the outpatient setting. Only 18 (25%) of the respondents correctly identified all the approved indications for warfarin and 4 DOACs including dabigatran, rivaroxaban, apixaban, and edoxaban. Most of the respondents (54 of 73; 74%) correctly identified that DOACs are not approved for treatment of heparin induced thrombocytopenia, cerebral sinus venous thrombosis, or mechanical prosthetic valves. However, 11 (15%) cited one or more of the above indications incorrectly; 7 of 11 (9.5%) alarmingly chose mechanical prosthetic valves as an indication for DOACs. Most of the respondents (51 of 73; 70%) felt comfortable or very comfortable prescribing oral anticoagulants. When counselling patients, 69 (95%) discussed the indication and bleeding side effects, 62 (85%) discussed when/how to take the drug, and only 37 (51%) discussed adherence and administration strategies. About two thirds of the respondents (63%) knew that dabigatran should not be crushed, however only 38 (52%) knew that it should not be exposed to moisture. Forty-five of the respondents (62%) knew that higher dose rivaroxaban should be taken with food. While 45 (62%) correctly adjusted the dose of apixaban based on age, only 35 (48%) did the same for dabigatran. 80%, 77%, 70%, and 45% correctly adjusted rivaroxaban, apixaban, dabigatran, and edoxaban, respectively for renal function.Conclusions: Although the majority of respondents expressed comfort with oral anticoagulants, there are important knowledge gaps around HCPs' practical understanding of oral anticoagulants, particularly in correctly identifying approved indications and counselling patients on adherence and administration. These knowledge gaps (e.g., inappropriate DOAC use in patients with mechanical valves) may lead to significant patient harm in the form of thrombosis or bleeding. Future research should focus on educational interventions to improve HCPs' knowledge around oral anticoagulants, with the goal of enhancing patient safety.Figure 1. What do health care providers counsel patients about when prescribing oral anticoagulants? [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Adverse outcomes associated with inappropriate direct oral anticoagulant starter pack prescription among patients with atrial fibrillation: a retrospective claims-based study.

Direct oral anticoagulant (DOAC) starter packs are designed for unique treatment dosing for acute venous thromboembolism (VTE). Inappropriate use of 30-day DOAC starter packs in patients with atrial fibrillation (AF) may increase the risk for bleeding events given higher dosing in the first 1-3weeks of treatment. A retrospective analysis of medical and outpatient pharmacy claims data from 2015 to 2018 in Optum's De-identified Clinformatics® Data Mart was performed.Patients greater than 18years of age with AF and a new prescription of apixaban or rivaroxaban were included. Patients with an acute VTE were excluded. The main outcome of interest was adverse events (emergency department [ED] visits, hospitalizations, and deaths within 90days after prescription fill date) associated with inappropriate DOAC starter pack prescription. A total of 90,950 DOAC-treated patients with AF were identified. The mean age was 74.5years (SD 10.0) and 42,717 (47.0%) were female. Inappropriate starter packs were used by 117 (0.1%) patients, who were younger than non-starter pack patients (71.3years vs. 74.5years). Patients who received an inappropriate DOAC prescription were more likely to identify as Black (12.0% vs. 8.8%). Rates of ED visits, hospitalizations, and deaths overall were numerically lower in patients with starter pack compared to non-starter pack DOAC prescriptions. In contrast, rates ofED visits and hospitalizationsrelated to significant bleeding were numerically higherin patients with starter pack compared to non-starter pack DOAC prescriptions. Among patients with AF but no VTE, those who received an inappropriate DOAC starter pack had numerically higher rates of severe bleeding leading to ED visits and hospitalizations compared to those prescribed an appropriate non-starter pack DOAC anticoagulant.

Evaluation of Direct Oral Anticoagulant Prescribing in Patients With Moderate to Severe Renal Impairment.

Patients with renal impairment require dose adjustments for direct oral anticoagulants (DOACs), though there is uncertainty regarding their use in severe chronic kidney disease. Inappropriately dosed DOACs may increase risk of ischemic events when under-dosed, or risk of bleeding when over-dosed. The purpose of this study was to describe DOAC selection, dosing strategies, and associated clinical outcomes in patients with moderate to severe renal impairment at our institution. This was a single-center retrospective analysis of adult outpatients with moderate to severe renal impairment (estimated creatinine clearance <50 mL/min, including need for hemodialysis) who were prescribed a DOAC by a cardiologist between June 1, 2015 and December 1, 2018. Outcomes evaluated included the percentage of patients who received appropriate and inappropriate DOAC dosing, prescriber reasons for inappropriate DOAC dosing if documented, and incidence of thrombotic and bleeding events. A total of 207 patients were included. Overall, 61 (29.5%) patients received inappropriate dosing, with 43 (70.5%) being under-dosed and 18 (29.5%) being over-dosed as compared to FDA-labeled dosing recommendations for atrial fibrillation or venous thromboembolism (VTE). By a median follow-up duration of 20 months, stroke occurred in 6 (3.3%) patients receiving DOACs for atrial fibrillation, and VTE occurred in 1 (4.3%) patient receiving a DOAC for VTE. International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding occurred in 25 (12.1%) patients. Direct oral anticoagulants were frequently prescribed at off-label doses in patients with moderate to severe renal impairment, with a tendency toward under-dosing.

Inappropriate Dosing of Direct Oral Anticoagulants in Patients with Atrial Fibrillation

Direct Oral Anticoagulants (DOACs) require dose adjustment based on specific patient characteristics, making them prone to incorrect dosing. The current study aimed to evaluate the prevalence of inappropriate DOAC dosing, its predictors, and corresponding outcomes in a single-center cohort of atrial fibrillation (AF) patients. We reviewed all patients with AF treated at Mayo Clinic with a DOAC (Apixaban, Rivaroxaban, or Dabigatran) between 2010 and 2017. Outcomes examined were ischemic stroke /transient ischemic attack (TIA)/embolism and bleeding. 8,576 patients (mean age 69.5 ± 11.9 years, 35.1 % female, CHA2DS2-VASc 3.0±1.8) received a DOAC (38.6% apixaban, 35.8% rivaroxaban, 25.6% dabigatran). DOAC dosing was inappropriate in 1,273 (14.8%) with 1071 (12.4%) receiving an inappropriately low dose, and 202(2.4%) an inappropriately high dose. Patients prescribed inappropriate doses were older (72.4 ± 11.7 vs 69.0 ± 11.8, p <0.0001), more likely to be female (43.1% vs 33.7%, p <0.0001), had a higher CHA2DS2-VASc score (3.4 ± 1.8 vs 2.9 ± 1.8, p <0.0001) and a greater Charlson co-morbidity index (3.5 ± 3.3 vs 2.9 ± 3.2, p<0.0001). Over 1.2 ±1.6 years (median 0.5 years) follow up; there was no significant difference in the incidence of stroke and/or TIA and/or embolism and bleeding between patients who were inappropriately dosed versus appropriately dosed. In conclusion, DOAC dosing was not in compliance with current recommendations in 15% of AF patients. Patients at higher risk of stroke and/or TIA based on older age, female gender, and higher CHA2DS2-VASc score were more likely to be underdosed, but there was no significant difference in outcomes including stroke/TIA/embolism and bleeding.

Appropriateness of the Direct Oral Anticoagulants Dosing in the Middle East Gulf Region.

Direct oral anticoagulants (DOACs) have proven efficacy to prevent cardioembolic strokes. Data are scarce about the appropriateness of DOAC dosing in the Middle East. We investigated the prevalence of inappropriate DOAC dosing in the region. A cross-sectional study was conducted at our hospital between April 2015 and February 2019 of patients receiving 1 of the 3 available DOACs. Patients with incomplete data sets, those prescribed DOACs for indications other than atrial fibrillation, on DOACs for <30 days, and dialysis patients were excluded. A total of 608 met the inclusion criteria. The mean age was 65.2 ± 13.9 years, and most were men (58.6%). The mean CHA2DS2-VASc score was 3.8 ± 2.0. There were 346 (56.9%) on apixaban, 123 (20.2%) on dabigatran, and 139 (22.9%) on rivaroxaban. The logistic regression model showed that for the 3 agents together, age, eGFR, major bleeding history, and history of prior stroke were significantly associated with the decision to inappropriately underdose (P < 0.05). Fifteen patients had an ischemic stroke after apixaban initiation (5 underdosed and 3 overdosed). Among patients with at least one follow-up encounter, major bleeding occurred in 13 patients (11.7%) with inappropriate dosing compared with 29 patients (6.0%) with appropriate dosing (P = 0.04). Ischemic stroke occurred in 11 patients (9.9%) with inappropriate dosing compared with 15 patients (3.1%) with appropriate dosing (P < 0.01). We concluded that inappropriate DOAC underdosing is common in our region, particularly with apixaban and rivaroxaban. It is associated with increased risk of stroke and bleeding. More education targeting prescribers is needed to encourage adherence to standard dosing criteria.

Quality of clinical direct oral anticoagulant prescribing and identification of risk factors for inappropriate prescriptions.

Even though the use of direct oral anticoagulants (DOACs) is safe based on clinical outcomes, drug safety also depends on appropriateness of drug prescription, which is challenging for DOACs since many patient factors need to be considered. The aim of this study was to assess the appropriateness of DOAC prescriptions and to identify risk factors of determinants for inappropriate DOAC prescriptions. A retrospective study in a nonuniversity teaching hospital was performed of hospitalized patients (≥18 years) who received an initial DOAC prescription between February and August 2018. Appropriateness of prescribing was evaluated on 8 criteria by using a modified version of the medication appropriateness index. A total of 770 initial DOAC prescriptions of inpatients were evaluated: 267 patients (34.6%) had at least met 1 inappropriate criterion for a DOAC prescription. The most frequent inappropriate criterion was dosage (17.4%). Of the 4 DOACs, dabigatran (21.6%) and apixaban (21.2%) were mostly inappropriate dosed. In a multivariable analysis, reduced renal function (estimated glomerular filtration rate <50 mL/min; odds ratio [OR] = 2.35; P < .001), a diagnosis of atrial fibrillation (OR = 1.87; P = .004), and 'prescribed by surgeons' (OR = 1.9; P = .013) were independently associated with inappropriateness of prescribing. This study has highlighted a high degree of inappropriate prescribing of DOACs. These results underline the need for targeted interventions to improve DOAC prescribing.

Inappropriate direct oral anticoagulant dosing in atrial fibrillation patients is associated with prescriptions for outpatients rather than inpatients: a single-center retrospective cohort study

BackgroundInappropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical safety and efficacy; however, little is known about clinical data associated with an inappropriate DOAC dosing in Japan. In addition, there is no report in which the appropriateness of DOAC dosing between prescription for inpatients and for outpatients was examined. In this study, we aimed to investigate the prevalence and factors associated in the inappropriate dosing of DOACs in patients with atrial fibrillation (AF).MethodsThe retrospective cohort study was conducted at a single Japanese university hospital. Both inpatients and outpatients, who were diagnosed with AF and for whom treatment with either dabigatran, rivaroxaban, apixaban, or edoxaban was initiated between April 1, 2014 and March 31, 2018, were enrolled in the study. Appropriateness of DOAC dosing was assessed according to the manufacturer’s labeling recommendations (dose reduction criteria) of each DOAC. Inappropriate reduced dose, namely, underdosing, was defined as prescription of a reduced dose of DOAC despite the patient not meeting the dose reduction criteria. Inappropriate standard dose, namely, overdosing, was defined as prescription of a standard dose of DOAC despite the patient meeting the dose reduction criteria. Inappropriate DOAC dosing was defined as a deviation of the recommended dose (both underdosing and overdosing).ResultsA total of 316 patients (dabigatran, 28; rivaroxaban, 107; apixaban, 116; and edoxaban, 65) were included, with a median (interquartile range) age of 75 (66–81) years and 62.3% male. DOACs were prescribed at an appropriate standard dose in 39.2% of patients, an appropriate reduced dose in 36.7%, an inappropriate standard dose in 2.5%, and an inappropriate reduced dose in 19.3%. Multivariate analysis revealed that the inappropriate dosing of DOACs was significantly associated with prescriptions for outpatients (vs. inpatients; odds ratio [OR] 2.87, 95% confidence interval [CI] 1.53–5.62, p < 0.001) and those with higher HAS-BLED scores (OR 1.87, 95% CI 1.42–2.51, p < 0.001).ConclusionsOur results demonstrated that the inappropriate dosing of DOACs occurred in approximately 20% of AF patients, and was more frequent in outpatients (vs. inpatients) and in those with a higher risk of bleeding. It is recommended that pharmacists play a greater role in assisting in the prescription process to help physicians make better decisions.

Burden of Inappropriate Prescription of Direct Oral Anticoagulants at Hospital Admission and Discharge in the Elderly: A Prospective Observational Multicenter Study.

Direct oral anticoagulants (DOACs) were developed to overcome some of the limitations associated with vitamin K antagonists (VKAs), such as interindividual variability or the need for therapeutic drug monitoring. However, the complexity of DOAC dose regimens can still lead to dosing errors and potential bleeding-related or thromboembolic adverse events, especially in the elderly. Our objective was to evaluate the rate of inappropriate preadmission DOAC prescriptions at hospital and to evaluate the ability of hospitals to correct them. An observational prospective study was conducted in elderly patients (aged ≥ 65years) hospitalized in six acute units of three Parisian university hospitals between February and July 2018. DOAC prescriptions prior to admission and at discharge were analyzed according to the guidelines in the summaries of product characteristics. A total of 157 patients were included in the study, with a median age of 84years (interquartile range [IQR] 77-89). The median glomerular filtration rate, determined with the Cockcroft-Gault equation, was 48mL/min (IQR 35-61). Apixaban was the most frequently prescribed drug, mainly for atrial fibrillation. Overall, 48 (30.6%) and 34 (22.4%) prescriptions were inappropriate prior to admission and at discharge, respectively, showing a significant decrease (p < 0.001). Hospitals significantly corrected more inappropriate prescriptions (37.5%) than they generated (4.6%) (p < 0.05). The nature of the inappropriate prescribing was underdosing (68.8% and 76.5% prior to admission and at discharge, respectively), followed by overdosing (stable rate at almost 20%) and indication errors. No risk factors for inappropriate use were identified by our analysis. One-third of DOAC preadmission prescriptions for elderly patients were inappropriate, indicating that a need remains to strengthen DOAC prescribing guidelines in ambulatory clinical practice. However, the rate of inappropriate prescriptions decreased at patient discharge. Future studies are needed to test actions to promote the proper use of DOACs.

Abstract 242: Comparison of Pharmacist-Managed Initial Dosing of Direct Oral Anticoagulants with Non-Pharmacist Practitioner Prescribing Patterns

Background: There is currently a lack of data regarding pharmacist-managed DOAC (direct oral anticoagulant) therapy. The objective of this study was to assess the impact of pharmacist-managed initial dosing of apixaban and rivaroxaban utilizing a Pharmacy and Therapeutics Committee approved guideline when compared with general practitioner/cardiologist practitioner prescribing practices for patients with Non-Valvular Atrial Fibrillation (NVAF). Methods: A retrospective, chart review was performed during the period of January 2015 to January 2018 and included adults 18-95 years old, who were prescribed apixaban or rivaroxaban for documented NVAF. Patients eligible for this study were split up into two cohorts: a pharmacist-managed cohort and a non-pharmacist-managed cohort. The primary endpoint of the study was the percentage of patients who received appropriate initial apixaban or rivaroxaban dosing. Any incorrect initial doses of apixaban or rivaroxaban were then analyzed to determine the reason for error. The secondary endpoints included thromboembolic and hemorrhagic adverse events. Exploratory analyses included: provider follow up-time, inappropriate DOAC use in valvular atrial fibrillation (VAF), and correct transition from warfarin to DOAC. Results: For the primary endpoint, the pharmacist practitioner was significantly more accurate when initially dosing apixaban and rivaroxaban compared to non-pharmacist practitioners (97% [63 out of 65] vs. 74% [48 out of 65] correct prescriptions, p=0.001). When evaluating the reason for error in prescribing, non-pharmacist providers were significantly less likely to dose the patient appropriately based on renal function or drug interactions (p=0.003). For the secondary endpoint of hemorrhagic or thromboembolic events, there were no statistically significant differences among the two provider types. The exploratory analyses revealed that 3% (2 out of 65) of the patients in the non-pharmacist managed cohort had VAF and received a DOAC for antithrombotic therapy. The patients in the pharmacist managed cohort had zero patients receive a DOAC for VAF. The pharmacist was also significantly better at transitioning patients from warfarin to DOACs correctly compared to non-pharmacist practitioner (100% [12 out of 12] vs. 50% [3 out of 6], p=0.025) and following up with patients within a four-month time frame compared to non-pharmacist practitioners (100% [65 out of 65] vs. 82% [53 out of 65], p=0.001). Conclusion: Additional research is required to evaluate the benefits of pharmacist-managed anticoagulation; however, based on the results of this study, pharmacists are significantly better equipped to initiate DOAC therapy for patients with NVAF. Based on the findings of the study results, pharmacist-managed DOAC services may be transferrable to a variety of different disease states requiring anticoagulation therapy.

Appropriateness of DOAC Prescribing Before and During Hospital Admission and Analysis of Determinants for Inappropriate Prescribing.

Background and Objectives: Appropriate dosing of direct oral anticoagulants (DOACs) is required to avoid under- and overdosing that may precipitate strokes or thromboembolic events and bleedings, respectively. Our objective was to analyze the appropriateness of DOAC dosing according to the summaries of product characteristics (SmPC). Furthermore, determinants for inappropriate prescribing were investigated.Methodology: Retrospective cohort study of hospitalized patients aged ≥60 years with at least one DOAC intake during hospital stay. Descriptive analyses were used to summarize the characteristics of the study population. Chi-square test was used to evaluate differences between DOACs. Binary logistic regression analysis was performed to assess determinants for inappropriate prescribing.Results: For the 772 included patients, inappropriate dosing occurred in 25.0% of hospitalizations with 23.4, 21.9, and 29.7% for dabigatran, rivaroxaban, and apixaban, respectively (p = 0.084). Underdosing was most prevalent for apixaban (24.5%) compared to dabigatran (14.0%) and rivaroxaban (12.8%), p < 0.001. In 67.1% (apixaban), 26.7% (dabigatran), and 51.2% (rivaroxaban) of underdosed DOAC cases according to the SmPC, the dose would be considered appropriate according to the European Heart Rhytm Association (EHRA) guidelines. Overdosing was observed in 4.5% (apixaban), 4.7% (dabigatran), and 7.7% (rivaroxaban) of patients. For all DOACs, our analysis showed an age ≥80 years (p = 0.036), use of apixaban (p = 0.026), DOAC use before hospitalization (p = 0.001), intermediate renal function (p = 0.014), and use of narcotic analgesics (p = 0.019) to be associated with a higher rate of inappropriate prescribing. Undergoing surgery was associated with a lower odds of inappropriate prescribing (p = 0.012). For rivaroxaban, use of medication for hypothyroidism (p = 0.027) and the reduced dose (p < 0.001) were determinants for inappropriate prescribing. Treatment of venous thromboembolism was associated with less errors (p = 0.002). For apixaban, severe renal insufficiency (p < 0.001) and initiation in hospital (p = 0.016) were associated with less and the reduced dose (p < 0.001) with more inappropriate prescribing. No determinants were found in the dabigatran subgroup.Conclusions: Inappropriate DOAC prescribing is frequent with underdosing being the most common drug related problem when using the SmPC as reference. More appropriate prescriptions were found when taking the EHRA guidelines into account. Analysis of determinants of inappropriate prescribing yielded insights in the risk factors associated with inappropriate DOAC prescriptions.