Non-vitamin K Antagonist Oral Anticoagulants Dosing Research Articles

Antithrombotic Therapy in Chronic Kidney Disease

Abstract Chronic kidney disease (CKD) affects over 10% of the global population and is more prevalent in the elderly, females, patients with diabetes or hypertension, and certain racial minorities. CKD is a leading cause of mortality, especially in CKD stage G5 and End-Stage Renal Disease (ESRD). Left ventricular hypertrophy (LVH) is common in CKD patients, predicting mortality even in early stages. CKD patients face a higher risk of bleeding, with a 3.5 times higher risk in hemodialysis patients. Atrial fibrillation (AF) and acute coronary syndrome are more prevalent in patients with eGFR <60 ml/min, and the risk of pulmonary embolism increases by 25-30% regardless of CKD stage. Antithrombotic treatment is crucial for CKD patients with cardiovascular diseases. In early stages (G1-G3), both warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) can be used, with NOACs preferred due to their safety profile. In advanced stages (G4-G5) and ESRD (G5D), warfarin is commonly used, with reduced NOAC doses as an option. NOACs require careful monitoring of renal function, and hemodialysis can remove a significant portion of plasma dabigatran. Monitoring renal function is vital for CKD patients receiving NOACs. Some studies suggest NOACs may have a lower risk of cardiovascular events compared to warfarin, but conflicting data exist regarding bleeding risk. Individualized treatment decisions should consider the patient's renal function.

Pharmacokinetic relevance of glomerular hyperfiltration for drug dosing.

In chronic kidney disease (CKD) patients, hypofiltration may lead to the accumulation of drugs that are cleared mainly by the kidney and, vice versa, hyperfiltration may cause augmented renal excretion of the same drugs. In this review we mainly focus on the issue of whether hyperfiltration significantly impacts the renal clearance of drugs and whether the same alteration may demand an up-titration of the doses applied in clinical practice. About half of severely ill, septic patients and patients with burns show glomerular hyperfiltration and this may lead to enhanced removal of drugs such as hydrophilic antibiotics and a higher risk of antibiotic treatment failure. In general, hyperfiltering obese individuals show higher absolute drug clearances than non-obese control subjects, but this depends on the body size descriptor adopted to adjust for fat excess. Several mechanisms influence pharmacokinetics in type 2 diabetes, including renal hyperfiltration, reduced tubular reabsorption and augmented tubular excretion. However, no consistent pharmacokinetic alteration has been identified in hyperfiltering obese subjects and type 2 diabetics. Non-vitamin K antagonist oral anticoagulants (NOACs) have exhibited lower plasma concentrations in hyperfiltering patients in some studies in patients with atrial fibrillation, but a recent systematic review failed to document any excess risk for stroke and systemic embolism in these patients. Hyperfiltration is common among severely ill patients in intensive care units and drug levels should be measured whenever possible in these high-risk patients to prevent underdosing and treatment failure. Hyperfiltration is also common in patients with obesity or type 2 diabetes, but no consistent pharmacokinetic alteration has been described in these patients. No NOAC dose adjustment is indicated in patients with atrial fibrillation being treated with these drugs.

Use of Direct Acting Oral Anticoagulants in Elderly Patients with Atrial Fibrillation: A Multicenter, Cross-Sectional Study in Spain.

Non-vitamin K antagonist oral anticoagulants (NOACs) have substantially improved anticoagulation. However, data on NOAC use among elderly patients are scarce. We sought to describe NOAC use among elderly AF patients in Spain. We performed a non-interventional, multicenter, multispecialty, cross-sectional study in elderly (≥75 years) AF patients treated with NOACs for stroke prevention. Patients' characteristics by NOAC treatment were compared using standardized differences (SDD). NOAC dosing was classified according to the Spanish summary of products characteristics (SmPC) into appropriate (recommended dose) and inappropriate (under and overdosed). Multivariate logistic regression analyses were used to explore factors associated with inappropriate dosing. 500 patients were included. Mean (SD) age was 81.5 (4.7) years, and 50% were women. Mean (SD) creatinine clearance was 57.4 mL/min (18.8), and 23.6% were frail. Dabigatran treatment totaled 38.4%, rivaroxaban 15.2%, apixaban 33.2%, and edoxaban 13.2%. Almost one-fourth of elderly patients treated with NOACs in Spain were inappropriately dosed (underdosing 14.4% and overdosing 9.6%). Underdosing was significantly associated with weight (OR = 1.03, 95%CI = 1.0-1.1), while higher a EHRA score decreased the risk of underdosing (OR = 0.47, 95%CI = 0.2-1.0). Overdosing was significantly associated with a history of ischemic stroke (OR = 2.95, 95%CI = 1.1-7.7). Addressing incorrect dosing among elderly AF patients is relevant to improve patient outcomes.

Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study.

Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs. Methods: AF patients initiating anticoagulation between 2013-2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose. Results: Among 254,478AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64-0.72)), all-cause mortality (HR 0.76, 95%CI (0.74-0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91-0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66-0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83-0.90); HR 0.86, 95%CI (0.83-0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83-0.99); HR 0.86, 95%CI (0.81-0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80-0.92)) and edoxaban (HR 0.79, 95%CI (0.72-0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively. Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran.

Abstract 25: Safety And Outcomes Of Endovascular Thrombectomy In Acute Ischemic Stroke Patients With Recent Use Of Non-vitamin K Antagonist Oral Anticoagulants

Introduction: An increasing number of patients with acute ischemic stroke (AIS) have recently used non-vitamin K antagonist oral anticoagulants (NOACs). However, there are limited data on safety of endovascular therapy (EVT) in these patients. Methods: We performed a retrospective, observational, cohort study of patients treated with EVT within 6 hours of symptom onset in the American Heart Association’s “Get With The Guideline-Stroke Program” between October 2015 and March 2020 to compare safety and functional outcomes in patients who were or were not taking NOACs in the 7 days prior to stroke. Results: Of 33,355 patients (median age 72 years (60,81); 50.8% female), 3,727 (11.2%) were taking NOACs, and 29,628 (88.8%) were not taking any oral anticoagulants (OAC) prior to stroke. Compared with those not on OAC, patients taking NOACs were older (median age 75 vs. 71 years) and had a higher prevalence of comorbidities including cardiovascular risk factors, although stroke severity was similar between the groups (median NIHSS 18 vs. 17). After adjusting for baseline clinical factors including intravenous alteplase, patients taking NOACs were not at a significantly higher risk of sICH compared with patients not taking anticoagulants (4.9% vs 6.4%; aOR, 0.93 [95% CI, 0.75-1.14]) or in-hospital mortality (14.1% vs 13.1%; aOR, 0.90 [95% CI, 0.78-1.02]). Of the secondary discharge outcomes, 3 of 7 showed significant differences in favor of the NOAC group including ambulating independently (33.7% vs 38.7%; aOR, 1.15 [95% CI, 1.02-1.30]) and freedom from disability (modified Rankin Scale [mRS] 0-1, 13.0% vs 16.2%; aOR, 1.23 [95% CI, 1.04-1.46]) at discharge. In a subset of patients with documented time of last NOACs dose (n=213), sICH rate was 3.1% (6/196) with last dose ≤2 days and 0% (0/17) with >2 days. Conclusions: Among patients with acute ischemic stroke treated with EVT within 6 hours, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of adverse events and was associated with better functional outcomes at discharge.

Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis

ObjectiveThere has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation (AF). This review identified and systematically...

Do Patients with Atrial Fibrillation and a History of Ischemic Stroke Overuse Reduced Doses of NOACs?-Results of the Polish Atrial Fibrillation (POL-AF) Registry.

Background: The aim of our study was to assess if patients with AF (atrial fibrillation) and a history of ischemic stroke (IS) excessively receive reduced doses of NOACs (non-vitamin K antagonist oral anticoagulants). Methods: The Polish AF (POL-AF) registry is a prospective, observational, multicenter study, including patients with AF from 10 cardiology hospital centers. In this study we focused on patients with IS in their past. Results: Among 3999 patients enrolled in the POL-AF registry, 479 (12%) had a previous history of IS. Compared to patients without IS history, post-stroke subjects had a higher CHA2DS2-VASc score (median score 7 vs. 4, p < 0.05). Of these subjects, 439 (92%) had anticoagulation therapy, 83 (18.9%) were treated with a vitamin K antagonist (VKA), 135 (30.8%) with rivaroxaban, 112 (25.5%) with dabigatran, and 109 (24.8%) with apixaban. There were a significant number of patients after IS with reduced doses of NOACs (48.9% for rivaroxaban, 45.5% for dabigatran, and 36.7% for apixaban). In many cases, patients were prescribed reduced doses of NOACs without any indication for reduction (28.8% of rivaroxaban use, 56.9% of dabigatran use, and 60.0% of apixaban use—out of reduced dosage groups, p = 0.06). Conclusions: A significant proportion of AF patients received reduced doses of NOAC after ischemic stroke in a sizeable number of cases, without indication for dose reduction.

Risk of left atrial appendage thrombus in patients with atrial fibrillation and chronic kidney disease.

BackgroundAtrial fibrillation (AF) and chronic kidney disease (CKD) are associated with an increased risk of ischemic stroke. The aim of this study was to compare the clinical characteristics, the incidence of left atrial appendage (LAA) thrombus and its predictors, and spontaneous echo contrast (SEC) in a population of patients with AF depending on estimated glomerular filtration rate (eGFR) values.MethodsThis study included 1962 patients who underwent transesophageal echocardiographic examination prior to cardioversion or ablation in the years 2014–2018 in three cardiac centers.ResultsMore than a quarter of AF patients had decreased eGFR (< 60 mL/min/1.73 m2) and were characterized as a high-risk population, with more comorbidities, higher thromboembolic and bleeding risk compared to those with normal renal function. Oral anticoagulation (OAC) was prescribed in 97% and 93% of patients with decreased and normal eGFR, respectively, with a higher prevalence of prescribed non-vitamin K antagonist oral anticoagulants (NOACs). The incidence of LAA thrombus (24%, 9% and 4%) and SEC (25%, 25% and 19%) increases simultaneously with a decrease in eGFR (< 30, 30–59 and ≥ 60 mL/min/1.73 m2, respectively). Among patients prescribed reduced doses of NOAC, those with decreased eGFR were more often observed with LAA thrombus (10% vs. 2.5%). Non-paroxysmal AF, heart failure and previous bleeding were predictors of LAA thrombus, irrespective of eGFR value. CKD was the predictor of LAA thrombus in all patients including those with non-paroxysmal AF, males, without diabetes, without hypertension and with CHA2DS2-VASc < 2.ConclusionsDespite OAC, patients with concomitant AF and CKD remain at high risk for LAA thrombus formation.

The Safety and Efficacy of Standard-Dose versus Low-Dose Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Left Atrial Appendage Thrombus.

Background Data comparing different doses of non-vitamin K antagonist oral anticoagulants (NOACs) regarding resolution of left atrial appendage thrombus (LAAT) in patients with nonvalvular atrial fibrillation (AF) are scarce. This study aimed to investigate the safety and efficacy of standard-dose versus low-dose NOACs in patients with nonvalvular AF and LAAT. Methods Patients with nonvalvular AF who underwent transesophageal echocardiography (TEE) before interventional procedures for the detection of LAAT and treated with NOACs from October 2014 to September 2020 in Ningbo First Hospital were retrospectively screened. The study population was divided into two groups according to the doses of NOACs: standard-dose group (dabigatran 150 mg, twice daily; rivaroxaban 20 mg, once daily) and low-dose group (aged ≥75 years, body weight <50 kg, or creatinine clearance <50 mL/min; dabigatran 110 mg, twice daily; rivaroxaban 15 mg, once daily). Repeated TEE was performed 1, 2, and 3 months later. The rate of LAAT completely resolved and incidence of thromboembolic and major bleeding events were compared between the two groups. Results A total of 24 patients were included, 14 patients in the standard-dose group and 10 in the low-dose group. After 3 months, LAAT was completely resolved in 12 out of 14 (85.7%) and 8 out of 10 (80%) patients treated with standard- and low-dose NOACs, respectively. The rate of LAAT completely resolved was comparable between groups. No thromboembolic or major bleeding events occurred during the follow-up. Conclusion Low-dose NOACs are a safe and effective option for the treatment of LAAT in some special subset patients. However, the results warrant validation in a prospective study.

Factors associated with inappropriate reduced doses of non-vita-min K antagonist oral anticoagulants in patients with atrial fibrillation

The objective was to study the factors associated with inappropriate reduced doses of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) in real outpatient practice.Methods and materials. 10663 case histories of patients hospitalized to the therapeutic clinic of the university for 5 years (2014 — 2018) were studied, 1307/10663 (12,3 %) case histories of patients with AF were selected. Factors associated with inappropriate low doses of anticoagulant therapy (ACT) with NOACs at prehospital treatment were studied.Results. NOACs received 57.7 % (384/665) of patients with AF at the outpatient stage: rivaroxaban — 180/384 (46.9 %) patients, dabigatran etexilate — 110/384 (28.6 %) patients, apixaban — 94/384 (24.5 %) patients. Inappropriate reduced doses of NOACs were revealed in 68/384 (17.7 %) patients: apixaban — 22/94 (23.4 %), dabigatran — 18/110 (16,4 %) and rivaroxaban — 28/180 (15.6 %) (p&gt;0,05). Patients who received inappropriate reduced doses of NOACs as compared to those who received standard doses of NOACs had higher frequency of major bleedings in the past (7.4 and 1.0 %; p=0.014) and had higher risk of bleedings (HAS-BLED 1.7±1,1 and 1.2±1.0; p = 0.0002). Proportion of patients who had HAS-BLED≥3 in these groups were 19.1 % and 8.6 % (p=0.033). All patients who received inappropriate reduced doses of NOACs had modifiable risk factors of bleedings. 85.3 % of patients with AF who received inappropriate reduced doses of NOACs had high risk of stroke according to CHA2DS2-VASc scale.Conclusion. In real outpatient practice, NOACs were recommended to 57.7 % of patients with AF. 17.7 % of patients received NOACs s in inappropriate reduced doses. Frequency of major bleedings in the past and bleeding risk in AF patients with inappropriate reduced doses was higher than in patients with standard doses.

Are low doses of non-vitamin K antagonists effective in Chinese patients with atrial fibrillation? A report from the Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry.

Suboptimal low dosages of non-vitamin K antagonist oral anticoagulants (NOACs) are often inappropriately used due to a fear of bleeding, particularly among elderly patients. Such practice is common in Asia, and we aimed to evaluate the use of low-dose NOACs and their impact on clinical outcomes among Chinese patients with atrial fibrillation. The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry was a prospective, multicenter study conducted in China from October 2014 to December 2018. For this report, we included NOAC-treated patients with available data on NOAC dosage and one-year follow-up. Logistic regression analysis assessed the association (adjusted for age, sex, prior ischemic stroke, prior major bleeding, heart failure, coronary artery disease, hypertension, diabetes mellitus, chronic kidney disease, liver disease, current anemia) between the low doses and study outcomes among NOAC-treated patients, as well as comparisons with non-anticoagulated patients. The eligible cohort included 1310 NOAC-treated patients (mean age of 72.1 ± 10.9; 38.9% female), of whom 341 (26.0%) received a low "off-label" dose. The use of low-dose NOACs was independently associated with higher odds of the composite outcome (OR: 2.51; 95% CI: 1.11-5.71) and thromboembolism (OR: 4.73; 95% CI: 1.11-20.01). Compared with non-anticoagulated patients, lower rates of the composite outcome (7.3% vs. 11.3%; p = 0.025) and all-cause death (5.3% vs. 9.7%; p = 0.007) were seen in the low-dose group (ORs 0.50; 95% CI: 0.32-0.78, and 0.42; 95% CI: 0.26-0.70, respectively). Low doses of NOACs should not be recommended as a part of standard therapy among Chinese patients with atrial fibrillation as their use was associated with a higher odds ratio of the composite outcome and thromboembolic events compared with standard dose NOAC regimens. Compared to non-treatment, the use of low-dose NOAC may result in a survival benefit (but not thromboembolic reduction) among high-risk patients.

The Importance of Appropriate Dosing of Nonvitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation

Preventing thromboembolic events, while minimizing bleeding risks, remains challenging when managing patients with atrial fibrillation (AF). Several factors contribute to current dosing patterns of nonvitamin K antagonist oral anticoagulants (NOACs), including patient characteristics, comorbidities, and physician judgment. Application of NOAC doses inconsistent with the drug labels may cause patients to receive either subtherapeutic (increasing stroke risk) or supratherapeutic (increasing bleeding risk) anticoagulant levels. In clinical practice, under- or over-dosing of NOACs in patients with AF is not uncommon. This analysis of prospective and retrospective registry and database studies on NOAC use in patients with AF (with at least 250 patients in each treatment arm) showed that under-dosing may be associated with reduced effectiveness for stroke prevention, with similar or even increased bleeding than with the standard dose. This may reflect underlying conditions and patient factors that increase bleeding despite NOAC dose reduction. Such factors could drive the observed overuse of reduced NOAC dosages, often making the prescription of reduced-dose NOAC an intentional label deviation. In contrast, over-dosing more likely occurs accidentally; instead of providing benefits, it may be associated with worse safety outcomes than the standard dose, including increased bleeding risk and higher all-cause mortality rates. This review summarizes the main findings on NOAC doses usually prescribed to patients with AF in clinical practice.

Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation

ObjectivesTo assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population.MethodsWe identified...

Clinical outcomes of patients who received a lower dose of non-vitamin K antagonist oral anticoagulants for the medical management of acute pulmonary embolism

Background Non-vitamin K antagonist oral anticoagulants (NOACs) are used to treat acute pulmonary embolism (PE). However, lower NOAC doses are often prescribed because of increased risk of NOAC complications. Objective We sought to determine the incidence and clinical outcomes of patients with acute provoked PE receiving lower NOAC doses. Method 140 patients with acute PE with only NOACs used for medical management was enrolled and were followed up for 6 months. The composite primary endpoint was all-cause death, venous thromboembolism recurrence, and residual thrombus on follow-up computed tomography. Results Of the 140 patients, 99 (70.7%) received the standard NOAC dose and 41 (29.3%) received the lower dose. The crude incidences of the primary endpoint were 19 (19.2%) in patients who received the standard NOAC dose and 13 (31.7%) in those who received the lower dose. Compared with patients who received the standard dose, those who received the lower dose had no differences in the rate of primary endpoints (hazard ratio 1.140, 95% confidence interval 0.536–2.423, p = 0.733) during a median of 185 days. Conclusion We found that up to 30% of patients received the lower dose of NOACs for acute PE in clinical practice. Clinical outcomes with appropriate underdoing of NOAC treated in acute PE might not increase compared to the standard NOAC doses.

Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

[Figure: see text].

ANTICOAGULATION BEFORE AND AFTER CARDIOVERSION OR ABLATION. CHALLENGES, PROBLEMS AND MISTAKES

Background: Limited data exists addressing the daily use of anticoagulants for atrial fibrillation (AF) and atrial flutter (AFL) patients before and after electrical cardioversion (ECV) or catheter ablation procedures. The purpose of the study was to evaluate the appropriateness of anticoagulant therapy. Methods: We evaluated the prescribed dosage of anticoagulant therapy for 257 non-valvular AF and AFL patients scheduled for ECV or catheter ablation and the appropriateness of periprocedural anticoagulation according to European Society of Cardiology (ESC) AF Guidelines. The statistical analysis was performed using IBM SPSS Statistics software (v.26.0). Results: The majority of the patients (84%) used nonvitamin K antagonist oral anticoagulants (NOACs) for pre-procedural anticoagulation. An intervention was not performed for 12.2% of warfarin users because of insufficient hypocoagulation, while anamnesis of patients’ missed doses with a possibility of inadequate hypocoagulation occurred only in 1.9% of patients on NOACs. The odds of having insufficient pre-procedural hypocoagulation were 7.4 times higher for warfarin users compared to the NOACs group (p=0.001, OR=7.4). An incorrect NOAC dose was assigned to 22 (8.6%) patients. Rivaroxaban was the most prescribed NOAC and this group of patients had the highest percentage of incorrect dosage according to the ESC guidelines. Conclusions: Mistakes of prescribing the dosage of anticoagulant therapy are common. The majority of the patients in the study were prescribed with NOACs before and after ECV or catheter ablation procedures. Warfarin users had higher odds of the intervention not being performed and not reaching sufficient hypocoagulation prior to the procedure compared to NOACs users.

Non-vitamin K antagonist oral anticoagulant use at doses inappropriately lower than recommended in outpatient older adults: a real-life data

There has been a rapid increase in the use of non-vitaminK-antagonist oral anticoagulants (NOAC). Current guidelines recommend dose adjustments be made in accordance with certain criteria for each NOAC. This study is aimed at determining whether or not NOAC were prescribed for non-valvular atrial fibrillation (AF) in guideline-recommended doses in community-dwelling older adults. Older adults taking NOAC for non-valvular AF presenting to a cardiology outpatient clinic for the first time were included in the study. The NOAC dose for each patient was assessed based on the recommendations of the European Society of Cardiology and were categorized as appropriate or inappropriate (low or high dose). The patients were also evaluated for demographic data, diseases, CHA2DS2-VASc score, HASBLED score, frailty and falls in the previous year. A total of 302 older adults were included in the study, with a mean age of 75.5 ± 7.5years. One hundred eighty-four patients (60.9%) were found to be on appropriate doses of NOAC, while 109 (36.1%) were on inappropriately low doses and nine (2.98%) were on inappropriately high doses. Accordingly, 39.1% of the AF patients were found to be on inappropriate doses of NOAC, 92.4% of which were inappropriately low. A multivariate logistic regression analysis revealed that the only factor associated with inappropriate low-dose NOAC use was patient age (OR = 1.061, 95% CI = 1.009-1.116, p = 0.022). Our study suggests that the inappropriate use of lower dose NOAC may emerge as a significant problem in outpatient older adults. This inappropriate practice seems to be associated with older age rather than the diseases, CHA2DS2-VASc/HASBLED scores, frailty and presence of falls.

Concurrent use of P-glycoprotein or Cytochrome 3A4 drugs and non-vitamin K antagonist oral anticoagulants in non-valvular atrial fibrillation.

To determine the concurrent use of P-glycoprotein (P-gp) or Cytochrome (CYP) 3A4 drugs and non-vitamin K antagonist oral anticoagulants (NOACs) among non-valvular AF (NVAF) patients in clinical practice. Administrative databases identified all adults (≥18 years) with incident or prevalent NVAF who initiated a NOAC in an outpatient or inpatient setting, between July 2012 and March 2019 in Alberta, Canada. Concurrent use was defined as a P-gp or CYP3A4 dispensation in the 100 days prior to and overlapping NOAC dispensation. The P-gp and CYP3A4 drugs were categorized into three groups and drug-drug interactions classified according to the 2018 European Heart Rhythm Association practical guide. Time-varying Cox models calculated the crude hazard ratio (HR) of outcomes at 1-year. A total of 642 255 NOAC dispensations occurred for 36 566 NVAF patients. Of these, 71 643 (11.2%) had a concurrent dispensation of an interacting P-gp or CYP3A4 drug. Overall, the drug-drug interaction was defined as contraindicated in 2.5%, avoid/caution in 2.3%, and for another 6.7% should require a dose adjustment. When all drug-drug interactions were considered, inappropriate NOAC prescribing occurred in 63% (n = 45 080) of dispensations. There was a significantly higher risk of death (HR 1.58, 1.47-1.70) for a drug-drug interaction but not for stroke (P = 0.89) or major bleeding risk (P = 0.13). The concurrent use of P-gp or CYP3A4 drugs and NOACs was uncommon but important since almost two-thirds of patients with drug-drug interactions had inappropriate NOAC dosing and a higher risk of death. More attention to this issue is needed.

Trends in the Prescription of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation: Results of the Polish Atrial Fibrillation (POL-AF) Registry.

Background: Current guidelines do not suggest in which groups of patients with atrial fibrillation (AF) individual non-vitamin K antagonist oral anticoagulants (NOACs) should be used for the prevention of thromboembolic complications. The aim of this study was to evaluate the frequency of use of apixaban, dabigatran, and rivaroxaban, and attempt to identify factors predisposing their administration. Methods: The Polish Atrial Fibrillation (POL-AF) registry is a prospective, non-interventional study, including consecutive patients with AF hospitalized in ten Polish cardiology centers during the period ranging from January to December 2019. In this study, all patients were treated with NOACs. Results: Among the 2971 patients included in the analysis, 40.4% were treated with rivaroxaban, 32% with apixaban, and 27.6% with dabigatran. The mean age of the total population was 72 ± 11.5 years and 43% were female. A reduced dose of NOAC was used in 35% of patients treated with apixaban, 39.7% of patients treated with dabigatran, and 34.4% of patients treated with rivaroxaban. Independent predictors of the use of apixaban were previous bleeding (OR 2.37, CI 1.67–3.38), GFR < 60 mL/min (OR 1.38, CI 1.25–1.64), heart failure (OR 1.38, CI 1.14–1.67) and age (per 5 years) (OR 1.14, CI 1.09–1.19). GFR < 60 mL/min (OR 0.79, CI 0.66–0.95), female (OR 0.8, CI 0.67–0.96) and age (per 5 years) (OR 0.95, CI 0.91–0.99) diminished the chance of using dabigatran. Previous bleeding (OR 0.43, CI 0.28–0.64), vascular disease (OR 0.84, CI 0.70–0.99), and age (per 5 years) (OR 0.94, CI 0.90–0.97) diminished the chance of choosing rivaroxaban. Conclusions: In hospitalized patients with AF, the most frequently chosen NOAC was rivaroxaban. Apixaban was chosen more often in patients after bleeding, and in those who were advanced in years, with heart failure and impaired renal function. Impaired renal function and female gender were factors that diminished the chance of using dabigatran. Previous bleeding and vascular disease was the factor that diminished the chance of using rivaroxaban. Dabigatran and rivaroxaban have been used less frequently in elderly patients.

Inappropriate dose of nonvitamin-K antagonist oral anticoagulants: prevalence and impact on clinical outcome in patients with nonvalvular atrial fibrillation.

Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs). To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription. Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions. Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.