Doses Of Oral Anticoagulants Research Articles

Dilemmas Related to Direct-Acting Oral Anticoagulant Administration in Patients With Extreme Obesity.

The objective of the study was to discuss the controversies surrounding the use and dosing of direct-acting oral anticoagulants (DOACs) in obese patients recognizing the limitations of the existing evidence base that preclude strong recommendations. A literature search of MEDLINE was performed (2020 to end August 2022) subsequent to recent guidelines using the following search terms: direct acting anticoagulants, obesity, rivaroxaban, apixaban, edoxaban, dabigatran, dabigatran etexilate, and clinical practice guidelines. English-language studies and those conducted in adults were selected. The available randomized studies evaluating DOACs had relatively small numbers of patients with more extreme forms of obesity (body mass index [BMI] > 40 kg/m2) and none of the larger studies had a specific focus on dosing DOACs in obese patients. Recent guidelines by the International Society on Thrombosis and Haemostasis (ISTH) have specific recommendations for dosing DOACs in obesity. There are pharmacokinetic/pharmacodynamic and observational studies published before and after the ISTH guidelines with a focus on DOAC dosing in obese patients that generally support the recommendations in the guidelines, but most involved small numbers of patients usually with BMIs <45 kg/m2. This review discusses DOAC dosing in obesity with important considerations for clinicians related to DOAC choice and dosing. Dosing alterations of DOACs do not appear to be necessary when used for either prophylaxis or treatment in patients with BMIs up to approximately 45 to 50 kg/m2, but research is needed for BMIs >50 kg/m2.

Safety of off-label dose reduction of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

To investigate the effects of off-label non-vitamin K oral anticoagulant (NOAC) dose reduction compared with on-label standard dosing in atrial fibrillation (AF) patients in routine care. Population-based cohort study using data from the United Kingdom Clinical Practice Research Datalink, comparing adults with non-valvular AF receiving an off-label reduced NOAC dose to patients receiving an on-label standard dose. Outcomes were ischaemic stroke, major/non-major bleeding and mortality. Inverse probability of treatment weighting and inverse probability of censoring weighting on the propensity score were applied to adjust for confounding and informative censoring. Off-label dose reduction occurred in 2466 patients (8.0%), compared with 18 108 (58.5%) on-label standard-dose users. Median age was 80 years (interquartile range [IQR] 73.0-86.0) versus 72 years (IQR 66-78), respectively. Incidence rates were higher in the off-label dose reduction group compared to the on-label standard dose group, for ischaemic stroke (0.94 vs 0.70 per 100 person years), major bleeding (1.48 vs 0.83), non-major bleeding (6.78 vs 6.16) and mortality (10.12 vs 3.72). Adjusted analyses resulted in a hazard ratio of 0.95 (95% confidence interval [CI] 0.57-1.60) for ischaemic stroke, 0.88 (95% CI 0.57-1.35) for major bleeding, 0.81 (95% CI 0.67-0.98) for non-major bleeding and 1.34 (95% CI 1.12-1.61) for mortality. In this large population-based study, the hazards for ischaemic stroke and major bleeding were low, and similar in AF patients receiving an off-label reduced NOAC dose compared with on-label standard dose users, while non-major bleeding risk appeared to be lower and mortality risk higher. Caution towards prescribing an off-label reduced NOAC dose is therefore required.

Prevalence and risk of inappropriate dosing of direct oral anticoagulants in two Swiss atrial fibrillation registries

BackgroundDirect oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring. Methods and resultsIn two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under- or overdosed DOACs, according to label. Primary outcome was a composite of major adverse clinical events (MACE), defined as cardiovascular death, myocardial infarction (MI), ischaemic stroke and systemic embolism. Secondary outcomes included major bleeding. Adjustment for confounding was performed. Median follow-up was 4 years.Of 3236 patients, 1875 (58%) were on VKAs and 1361 (42%) were on DOACs, of which 1137 (83%) were adequately-, 134 (10%) over- and 90 (7%) under-dosed. Compared to adequately dosed individuals, overdosed patients were more likely to be older and female. Underdosing correlated with concomitant aspirin therapy and coronary artery disease. Both groups had higher CHA2DS2-VASc scores. Patients on overdosed DOACs had higher incidence of MACE (HR 1.75; CI 1.10–2.79; adjusted-HR: 1.22) and major bleeding (HR 1.99; CI 1.14–3.48; adjusted-HR: 1.51). Underdosing was not associated with a higher incidence of MACE (HR 0.94; CI 0.46–1.92; adjusted-HR 0.61) or major bleeding (HR 1.07; CI 0.46–2.46; adjusted-HR 0.82). After adjustment, all CIs crossed 1.0. ConclusionInappropriate DOAC-dosing was more prevalent in multimorbid patients, but did not correlate with higher risks of adverse events after adjusting for confounders. DOAC prescription should follow label.

Complexity and clinical significance of drug-drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT).

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug–drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncology drugs are extensively used, more attention should be given to monitoring potential DDIs to minimize risks. Recognition of DDIs is of utmost importance in an era of rapid developments in cancer treatments and introduction of novel treatments and protocols. When managing cancer-associated thrombosis (CAT), the concomitant use of a DOAC and a moderate or strong modulator (inhibitor or inducer) of CYP3A4 or a P-glycoprotein (P-gp) is most likely to be associated with significant DDIs. Therefore, LMWHs remain the first-line option for the long-term management of CAT under these circumstances and physicians must consider utilizing LMWHs as first line. This review describes the risk of DDIs and their potential impact and outcomes in patients with cancer associated thrombosis (CAT) receiving anticoagulation.

A call to action for anticoagulation stewardship

A call to action for anticoagulation stewardship

Stroke, Thrombosis, Bleeding and Addiction to Anticoagulants in the Context of Course Therapy: A Pharmacologic Perspective.

After reading with great interest the article entitled: "Non-vitamin K antagonist oral anticoagulants (NOACs) do not increase the risk of hepatic impairment in patients with non-valvular atrial fibrillation: insights from multi-source medical data" authored by Zhi-Chun Gu et al. and published by Reviews in Cardiovascular Medicine, we would like to add the following thoughts. Oral anticoagulants are generally accepted in patients with non-valvular atrial fibrillation to prevent thrombosis and stroke. Since anticoagulants are taken daily for many months in these patients, we cannot rule out chronic poisoning and the development of liver failure. But another complication is just as likely, that being bleeding. Thus, the determining risk factor for the health of patients with a prolonged course of oral anticoagulants is hypofunctional activity of the blood coagulation system, which remains at the same level throughout the course of treatment. At the same time, it is the activity of the blood coagulation system that is an important and very sensitive link of adaptation to various external and internal factors, including anticoagulants. The fact is that regular and prolonged oral use of anticoagulants is likely to develop and tolerance to them. That is why it is necessary to carefully study the relationship between the dose of oral anticoagulants, the duration of pharmacotherapy and the development of thrombosis (bleeding) in patients with non-valvular atrial fibrillation.

Direct Oral Anticoagulants in Long-term Care Facilities: Rates of FDA-Approved Dosing.

Objective To determine rates of compliance with Food & Drug Administration (FDA)-approved dosing of direct oral anticoagulants (DOACs) in long-term care residents. Design A retrospective chart review of 90 patients, utilizing an electronic health record, and a longterm care pharmacy's dispensing record. Patient electronic health records were reviewed to collect the following data: prescribed DOAC, dose, therapy duration, diagnosis, age, height, weight, and serum creatinine. This information was used to determine the FDA-recommended DOAC dose and recommended duration, which was compared with the prescribed dose and duration. Main Outcome Measure The rate of incorrect DOAC doses, defined as a discrepancy from the FDA-recommended dose, based on patient characteristics. Setting Two chains of long-term care facilities in Michigan, Ohio, North Carolina, Tennessee, and Virginia serviced by a long-term care pharmacy. PATIENTS: Patients prescribed one of three targeted DOACs (apixaban, rivaroxaban, or dabigatran) between August and October 2019. Patients had to be a resident within two long-term care chains. Results Thirty-three out of 90 residents were treated with an incorrect DOAC dose. This broke down into 20% of patients on a dose that was too low and 17% of patients on a dose that was too high. Conclusion The results of the study identify the need for pharmacists to closely review the dosing of DOACs and recommend therapeutic changes based on treatment guidelines.

Effectiveness and Safety of Reduced and Standard Daily Doses of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation: A Cohort Study Using National Database Representing the Japanese Population.

PurposeTo compare the effectiveness and safety of reduced or standard daily doses of direct oral anticoagulants (DOACs) with warfarin in Japanese patients with nonvalvular atrial fibrillation (NVAF). We used post-hoc analyses to identify patient groups that could benefit from reduced-dose DOACs.Patients and MethodsUsing the National Database of Health Insurance Claims and Specific Health Checkups of Japan, we identified 944,776 patients with NVAF who had started an oral anticoagulant after at least one year of non-use between April 2011 and March 2016. We matched patients taking any, reduced, or standard doses of DOACs 1:1 with those taking warfarin. We measured treatment effectiveness based on admission due to stroke or systemic embolism (S/SE) and safety based on admission due to any bleeding (defined as major bleeding, MB). We compared both outcomes between DOACs and warfarin using the Cox proportional hazards model. We used post-hoc analysis to match patients receiving reduced-dose DOACs to those receiving standard-dose DOACs and compared treatment effectiveness and safety.ResultsMore than half of patients receiving DOACs used a reduced dose. The occurrences of S/SE and MB in patients receiving any, reduced, or standard doses of DOACs were equal to or lower than those receiving warfarin. In the post-hoc analysis, the risk of S/SE and MB was similar between reduced and standard doses of DOACs except for those with a history of cerebral infarction and CHA2DS2-VASc score ≥3, where the risk of S/SE was lower for reduced doses of any and individual DOACs.ConclusionFindings from the current study are consistent with recent Asian and global studies but different from most studies conducted in North America and Europe, where patients receiving a reduced dose of DOACs had an increased risk of S/SE. Future studies should test the reproducibility of results from the current study.

Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation.

AimsTo evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients.Methods and resultsIn the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01–1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92–0.98), lower weight (OR: 0.98 per kg, 0.97–1.00), active malignancy (OR: 2.46, 1.19–5.09), anaemia (OR: 1.73, 1.08–2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57–9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88–0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96–1.00).ConclusionIn newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation

PurposeOlder age is associated with inappropriate dose prescription of direct oral anticoagulants. The aim of our study was to describe the prevalence and the clinical predictors of inappropriate DOACs dosage among octogenarians in real-world setting.MethodsData for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation (AF) Research Database (NCT03760874). Of the AF patients aged ≥ 80 who received DOACs treatment, 253 patients were selected. Participants were categorized as appropriate dosage, overdosage, or underdosage. Underdosage and overdosage were, respectively, defined as administration of a lower or higher DOAC dose than recommended in the EHRA consensus.ResultsA total of 178 patients (71%) received appropriate DOACs dose and 75 patients (29%) inappropriate DOACs dose; among them, 19 patients (25.6%) were overdosed and 56 (74.4%) were underdosed. Subgroup analysis demonstrated that underdosage was independently associated with male gender [OR = 3.15 (95% IC; 1.45–6.83); p < 0.001], coronary artery disease [OR = 3.60 (95% IC 1.45–9.10); p < 0.001] and body mass index [OR = 1.27 (1.14–1.41); p < 0.001]. Overdosage was independently associated with diabetes mellitus [OR = 18 (3.36–96); p < 0.001], with age [OR = 0.76 (95% IC; 0.61–0.96; p = 0.045], BMI [OR = 0.77 (95% IC; 0.62–0.97; p = 0.043] and with previous bleedings [OR = 6.40 (0.7; 1.43–28); p = 0.039]. There wasn’t significant difference in thromboembolic, major bleeding events and mortality among different subgroups. Underdosage group showed a significatively lower survival compared with appropriate dose group (p < 0.001).ConclusionIn our analysis, nearly one-third of octogenarians with AF received an inappropriate dose of DOAC. Several clinical factors were associated with DOACs’ overdosage (diabetes mellitus type II, previous bleeding) or underdosage (male gender, coronary artery disease, and higher body mass index). Octogenarians with inappropriate DOACs underdosage showed less survival.

Expert Recommendations on the Usage of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) from India: Current Perspective and Future Direction.

Non-vitamin K antagonist oral anticoagulants (NOACs) are a new class of anticoagulant drugs used in the prevention and treatment of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulation requires the integration of the correct type and dose of oral anticoagulants based on patient characteristic, and therefore therapy needs to be individualized for each patient. Growing scientific evidence from studies on NOACs has led to a better understanding of their benefits and safety. A large amount of available data creates a necessity for an adaptable practical document for the usage of NOACs in India. The current consensus, developed by experts from India, aims to give recommendations on various frequently raised clinical questions with regards to NOACs and its usage. This practical document provides a platform upon which future guidelines, policies, training, and education for the use of NOACs can be tailored.

Different Renal Function Equations and Dosing of Direct Oral Anticoagulants in Atrial Fibrillation.

Randomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs. The authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes. Medical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively. At the cutoff values of eGFR of<15, 15-50, and >50mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of<50kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as "on label" based on MDRD or CKD-EPI, only those whose dosages were "truly on label" based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95%CI: 0.26-0.45) compared to warfarin. The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equationshould be used as the gold standard to calculate eGFRs and guide the DOAC dosages.

Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study

Background and purposePrescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. MethodsWe assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. Results322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17–6.00; P = 0.0186). ConclusionsSelecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Haemorrhagic complications following cataract and vitreoretinal surgery with sub-Tenon’s block in patients receiving non–vitamin K oral anticoagulant agents: A prospective audit

There is a lack of data to support either continuation or interruption of non-vitamin K oral anticoagulants for cataract and vitreoretinal surgery. A prospective audit was undertaken of 291 patients undergoing cataract surgery or vitreoretinal surgery, predominantly under sub-Tenon's block, while continuing these agents. The median time from last non-vitamin K oral anticoagulant dose to the insertion of sub-Tenon's block was five hours. No patient required emergency reversal of anticoagulation. There were no sight-threatening complications in the immediate perioperative period, although two vitreoretinal patients (3.8%) had a moderate haemorrhagic complication on day five, and two cataract patients (0.8%) had a minor haemorrhagic complication on days one and 14 postoperatively. Despite continuing their non-vitamin K oral anticoagulants, three (1%) cataract patients had a moderate thromboembolic complication within the 30-day postoperative period. The risk of haemorrhagic complications associated with continuation of anticoagulation with non-vitamin K oral anticoagulants for cataract and vitreoretinal surgery is low, and this audit supports the continuation of non-vitamin K oral anticoagulants for our patients having cataract and vitreoretinal surgery.

Direktni oralni antikoagulansi i periferna arterijska bolest

Peripheral arterial disease (PAD) is a disease of the arteries of the lower extremities and represents a global health problem with an increasing prevalence rate. Evidence for the use of standard anticoagulant therapy in patients with PAB is limited. Direct oral anticoagulants are selective inhibitors of activated coagulation factor X and thrombin, thereby blocking the common pathway of the coagulation cascade and preventing fibrin formation. In addition to their procoagulant role, these drugs potentially participate in the regulation of the process of inflammation and tissue fibrosis, which may inhibit the progression of atherosclerotic plaque. The first large study examining the effects of DOAC in patients with atherosclerosis was COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies). This study showed the first encouraging results, although the design was not adapted exclusively to patients with PAD. The VOYAGER PAD (Vascular Outcomes of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) study laid the groundwork for the use of low doses of direct oral anticoagulants in patients with PAB after revascularization. The applicability of the results of the COMPASS and VOYAGER PAD studies in everyday practice is still questionable. There is clear evidence that the use of direct oral anticoagulants in patients with the peripheral arterial disease may play an important role in the secondary prevention of adverse cardiovascular events, with an acceptable risk of hemorrhagic complications. Additional studies are needed to clarify which groups of patients these drugs have the greatest effect on, in everyday practice.

Prevalence and Risk of Inappropriate Dosing of Direct Oral Anticoagulants in Two Swiss Atrial Fibrillation Registries

Prevalence and Risk of Inappropriate Dosing of Direct Oral Anticoagulants in Two Swiss Atrial Fibrillation Registries

Predicting Drug-Drug Interaction with Physiologically Based Pharmacokinetic/Pharmacodynamic Modelling and Optimal Dosing of Oral Anti-Coagulants with Dronedarone Co-Administration

Predicting Drug-Drug Interaction with Physiologically Based Pharmacokinetic/Pharmacodynamic Modelling and Optimal Dosing of Oral Anti-Coagulants with Dronedarone Co-Administration

Efficacy and Safety of Non-recommended Dose of New Oral Anticoagulants in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis

Introduction: The real-world treatment of atrial fibrillation (AF) often involves the prescription of new oral anticoagulants (NOACs) using dosing both lower and higher than recommended guidelines. Our study aimed to evaluate the efficacy and safety of non-recommended dosage of NOACs in AF patients.Methods: A systematic search was performed for relevant studies across multiple electronic databases (PubMed, Embase, Cochrane Library, Clinical Trials Registry) from inception to May 1, 2021. Multicenter randomized trials and observational studies were selected with key reporting measures for inclusion involved efficacy outcomes including stroke or systemic thromboembolism along with safety endpoints assessing major or clinically relevant bleeding events.Results: A total of 11 eligible studies were included involving 48,648 patients receiving recommended dose of NOACs and 50,116 patients receiving non-recommended dosage. Compared to AF patients treated with recommended dose regimens, administration of low dose of NOACs was associated with higher risk of stroke/systemic embolism (RR = 1.24, 95% CI 1.14–1.35, P < 0.00001), but without reducing bleeding risk (RR = 1.18, 95% CI 0.91–1.53, P = 0.21) and a higher risk of all-cause mortality (RR = 1.58, 95% CI 1.25–1.99, P = 0.0001). Moreover, high dose of NOACs was associated with higher risk of stroke and systemic embolism efficacy (RR = 1.71, 95% CI 1.06–2.76, P = 0.03) and a non-significant trend to a greater risk of major or clinically relevant bleeding (RR = 1.57, 95% CI 0.96–2.58, P = 0.07).Conclusions: AF patients treated with low dose of NOACs showed equivalent safety but with worse efficacy compared with recommended dose. High dose of NOACs was not superior to recommended dose regimens in preventing stroke/systemic embolism outcomes in AF patients.

284 Worsening renal function as an outcome predictor in patients with new onset atrial fibrillation on direct oral anticoagulant

Abstract Aims In patients with atrial fibrillation (AF), baseline kidney function is used to guide oral anticoagulant (OA) selection and dosing, and chronic kidney disease (CKD) is a significant outcome predictor. However, the incidence of worsening renal function (WRF) and its prognostic role during treatment with direct oral anticoagulants (DOACS) has been poorly explored. To assess the prognostic role of WRF in terms of bleedings and major adverse cardiovascular events (MACEs) in a cohort of patients with newly diagnosed non-valvular AF (NVAF) treated with DOACs. Methods and results Between January 2017 and March 2019, we enrolled all the patients with newly diagnosed NVAF and OA indication, treated with DOACs. Renal function was assessed using the mean value of the estimated glomerular filtration rates (eGFR) calculated using Cockcroft–Gault (CG), modification of diet in renal disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. CHA2DS2-VASc and HAS-BLED scores were used at baseline to estimate the ischaemic and haemorrhagic risk, respectively. At follow-up, WRF was identified as a decrease in eGFR of at least 20% while bleedings were classified according to the international society of thrombosis and haemostasis (ISTH) criteria. Finally, we defined AF progression as the transition from paroxysmal to persistent or permanent AF or from persistent to permanent AF. 1009 patients with newly diagnosed NVAF started on DOAC were enrolled. They were followed-up for 21.6 ± 9.5 months. Overall, WRF was observed in 181 cases (18%). Patients with WRF had higher rates of progression of AF (18.5% vs. 11.8%, P = 0.02), MACEs (20.4% vs. 12.9%, P = 0.09) and major bleedings (MBs) (9.4% vs. 4.7%, P = 0.013). WRF did not correlate with all bleedings, stroke, or acute coronary syndrome (ACS). However, those who presented WRF using CKD-EPI formula had higher ACS incidence (6.1% vs. 2.5%, P = 0.015), and generally better-predicted MACEs. At multivariate analysis adjusted for age, hypertension, baseline HAS-BLED score and WRF, the latter emerged as an independent predictor of MB (OR: 1.9, 95% CI: 1.059–3.51). Conclusions In patients with newly diagnosed NVAF treated with DOACs, WRF is associated with AF progression and MACEs, and emerged as an independent predictor of major bleedings. WRF evaluated with CKD-EPI formula better predicted MACEs.

244 Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation

Abstract Aims Older age is associated with inappropriate dose prescription of direct oral anticoagulants. The aim of our study was to describe the prevalence and the clinical predictors of inappropriate DOACs dosage among octogenarians in real-world setting. Methods Data for this study were sourced from the multicentre prospectively maintained Atrial Fibrillation (AF) Research Database (NCT03760874). AF patients aged ≥80 who received DOACs treatment 253 patients were selected. Participants were categorized as appropriate dosage, overdosage, or underdosage. Underdosage and overdosage were respectively defined as administration of a lower or higher DOAC dose than recommended in the EHRA consensus. Results A total of 178 patients (71%) received appropriate DOACs dose and 75 patients (29%) inappropriate DOACs dose; among them 19 patients (25.6%) were overdosed and 56 (74.4%) were underdosed. Subgroup analysis demonstrated that underdosage was independently associated with male gender [OR = 3.15 (95% IC 1.45–6.83); P &amp;lt; 0.01], coronary artery disease [OR = 3.6 (95% IC 1.41–9.1); P&amp;lt; 0.01] and body mass index [OR = 1.27 (1.14–1.41); P &amp;lt; 0.01]. Overdosage was independently associated with diabetes mellitus [OR = 18 (3.36–96); P &amp;lt; 0.01], with age [OR = 0.76 (95% IC; 0.61–0.96); P &amp;lt; 0.05], BMI [OR = 0.77 (0.11; 0.62–0.97); P &amp;lt; 0.05] and with previous bleedings [OR = 6.4 (0.7; 1.43–28) P &amp;lt; 0.05]. There wasn’t significant difference in thromboembolic, major bleeding events and mortality among different subgroups. Underdosage group showed a significatively lower survival compared with appropriate dose group (P &amp;lt; 0.001). Conclusion In our analysis, nearly one-third of octogenarians with AF received an inappropriate dose of DOAC. Several clinical factors increased the risk of DOACs’ overdosage (diabetes mellitus Type II) or underdosage (male gender, coronary artery disease and higher body mass index). Octogenarians with inappropriate DOACs underdosage showed less survival.