Challenges of Acute Ischemic Stroke Treatment in Orally Anticoagulated Patients via Telemedicine

Anticoagulation has revolutionized stroke prevention in patients with atrial fibrillation either with vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs). However, a substantial number of patients may experience acute ischemic stroke (AIS) because of inadequate anticoagulation, noncardioembolic stroke pathogenesis, or true treatment failure and can present to the emergency room within the time window for intravenous thrombolysis (IVT).1 In a series of AIS patients potentially eligible for IVT, 8.7% were pretreated with oral anticoagulants.2 Because of the increased bleeding risk in patients pretreated with VKA, IVT is formally contraindicated if international normalized ratio on hospital admission is >1.7 in patients presenting within 3 hours from symptom onset and in all AIS patients regardless of international normalized ratio during the time window of 3 to 4.5 hours,3 whereas IVT is contraindicated if a patient takes oral anticoagulants regardless of international normalized ratio according to the European license of intravenous (IV) tissue-type plasminogen activator (tPA).4 The use of point-of-care international normalized ratio devices has simplified the management of IVT in AIS patients pretreated with VKAs. On the contrary, because NOAC-specific coagulation assays are more complex with limited availability, this specific subgroup of patients is often excluded from IVT. These treatment recommendations regarding the use of IV-tPA in AIS patients pretreated with NOACs aim to prevent severe bleeding complications, in particular, symptomatic intracranial hemorrhage (sICH). However, because they are based on expert opinion, they could result in withholding IVT in otherwise eligible patients who may eventually benefit from timely tPA administration. Because NOAC use increases exponentially in clinical practice worldwide, there are a growing number of reports of patients on NOACs who receive IVT for …

AimsSwitching between oral anticoagulants and treatment discontinuation are common events related to therapy with non-vitamin K antagonist oral anticoagulants (NOACs). However, knowledge on the reasons leading to these treatment changes is scarce. The aim of this study was to identify clinical events preceding anticoagulant switching and NOAC discontinuation during oral anticoagulant therapy in patients with atrial fibrillation.Methods and resultsWe performed a nationwide register-based study including Danish atrial fibrillation patients initiating a NOAC between August 2011 and February 2016 (n = 50 623). We explored potential reasons leading to changes in anticoagulant treatment by identifying clinical events preceding switches from vitamin K antagonists (VKA) to NOAC, switches from NOAC to VKA, and discontinuations of NOACs. Among 23 531 anticoagulant users changing treatment, we identified 13 295 switches from VKA to NOAC, 5206 switches from NOAC to VKA, and 8995 discontinuations of NOACs. Approximately half of all treatment changes were preceded by a hospitalization. A relevant specific clinical event or procedure was identified prior to 18.3% of switches from VKA to NOAC, prior to 23.0% of switches from NOAC to VKA, and prior to 26.6% of discontinuations. Switches from VKA to NOAC were most often preceded by thromboembolic events (7.0%), whereas cardioversion was the most common specific event prior to a switch from NOAC to VKA (11.4%). Discontinuations were most often preceded by bleeding events (7.6%).ConclusionFor about one in five patients, treatment changes during anticoagulant therapy were preceded by a major clinical event. However, the majority of patients changed treatment for reasons not recorded in health registries.

The relationship between oral anticoagulants (OACs) and prognosis in elderly patients with atrial fibrillation (AF)has not been adequately explored. In this retrospective cohort study, we identified subjects aged over 80 from a database of 1140 AF patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018. We examined the OAC treatment of octogenarian patients at discharge [VKA (vitamin K antagonist), NOAC (non-vitamin K antagonist oral anticoagulant), no OAC treatment]. We analyzed follow-up data of patients on OAC at discharge. The primary endpoint was all-cause death. The secondary endpoint was the incidence of stroke and major bleeding. The association of NOAC versus VKA treatment with these endpoints was assessed with multivariable Cox regression, using the VKA group as reference. A total of 330 octogenarian patients with AF were included with a mean (± SD) age of 83.9 ± 3.5years. At discharge, 53.3% received a NOAC, 30% a VKA, and 16.7% no OAC. Patients on OAC were followed-up over a median of 2.6-years . The adjusted risk of all-cause death was not different in the NOAC group, compared with the VKA group (hazard ratio [HR], 0.72; 95% confidence intervals [CI] 0.50-1.03; P = 0.07). The risk of stroke or major bleeding was not different either (all P > 0.05). In conclusion,in this cohort of post-discharge octogenarian patients with AF, the risk for all-cause death was similar in NOAC versus VKA users, after adjustment for baseline covariates. No differences in stroke and major bleeding events among these treatment groups were revealed.

Introduction: Clinical trials and subsequent meta-analyses showed advantages of non-vitamin K antagonists oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation. The impact of preadmission anticoagulation in acute ischaemic stroke (AIS) has not been established. Objective: To compare functional outcome of patients with AIS with preadmission NOACs vs. VKAs. Methods: A retrospective analysis was conducted on consecutive AIS patients under oral anticoagulation (VKAs or NOACs) admitted in 4 Portuguese hospitals within a period of 30 months. Two primary outcomes were defined and compared between VKA and NOAC groups: symptomatic intracerebral hemorrhage transformation (sICH) and modified Rankin Scale (mRS) at 3 months. Results: Four hundred sixty-nine patients were included, of whom 332 (70.8%) were treated with VKA and 137 (29.2%) with NOAC. Patients’ median age was 78.0 and 234 (49.9%) were male. NOAC-treated patients had a higher median CHA2DS2-VASc score than those under VKA (5.0 vs. 4.0, p = 0.023). The two primary outcomes showed no statistical differences between the VKAs’ group and the NOACs’ group (sICH: 5.4 vs. 5.4% [p = 0.911]; mRS at 3 months: 3.0 vs. 3.0 [p = 0.646], respectively). Conclusion: Preadmission anticoagulation with NOACs in AIS has a functional impact similar to that of VKAs.

Background and Purpose: In Japan, four non-vitamin K antagonist oral anticoagulants (NOACs) became available in clinical use for prevention of stroke in patients with non-valvular atrial fibrillation (NVAF) between 2011 through 2014. The aim of this study is to determine underlying characteristics and ischemic stroke/TIA features of patients taking NOACs or warfarin, a vitamin K antagonist (VKA) prior to stroke/TIA. Methods: We enrolled oral anticoagulant (OAC) users for NVAF, who were admitted to our stroke center for acute ischemic stroke/TIA between March 2011 and June 2015 (ClinicalTrials.gov Identifier: NCT02251665). Results: 381 OAC users who developed stroke/TIA were studied. Of these, 63 patients took NOACs [23 women, 77±9 years, dabigatran in 33 (7 taking higher dosage between two official ones), rivaroxaban in 22 (5), apixaban in 8 (3), edoxaban in none] and 318 took VKA (143 women, 79±8 years). There were no significant differences between NOACs users and VKA users in sex, age, CHADS2 score (median 3[IQR 2-4] vs. 3 [2-4]), history of ischemic stroke/TIA (57% vs. 51%) and prior antiplatelet use (25% vs. 24%). Admission NIHSS score tended to be lower (3 [1-15] vs. 7 [2-20], p=0.076) and discharge NIHSS score was lower (1[0-5] vs 3[1-13], p=0.032) in NOACs users. Discharge mRS (2 [1-4] vs. 3 [1-4]) and mortality during hospitalization (5% vs. 4%) were similar between two groups. A different point was timing of stroke/TIA after initiating OAC ; 6% of NOAC users developed events within 14 days and 32% within 3 months, whereas 4% and 7% of VKA users did, respectively (p<0.001). Congestive heart failure tended to be more common in NOACs users developing events within 3 months than those developing events later (43% vs. 19%, p=0.070). Conclusions: NOACs users tended to show milder neurological deficits than VKA users during acute hospitalization of ischemic stroke/TIA, although discharge mRS was similar. NOACs users often developed stroke/TIA within the initial 3 months after initiating OAC, particularly between 14 days and 3 months. One would take special care of ischemic events during early months after initiating NOACs.

ABSTRACTBackground:Non-vitamin K antagonist oral anticoagulants (NOACs) reduce the risk of stroke in patients with non-valvular atrial fibrillation (NVAF) and have better safety profile than vitamin K antagonists (VKAs). However, there is a dearth of quality, real-world, patient data on the use of these drugs to guide healthcare policies in United Arab Emirates (UAE).Aims and Objectives:The aim is to address the knowledge gap in demographic and clinical profiles of NVAF patients on NOACs (apixaban, rivaroxaban, and dabigatran) and warfarin in UAE.Materials and Methods:This retrospective cohort analysis utilized the Dubai Real-World Claims Database to extract anonymized longitudinal data on NVAF patients with at least one NOAC or warfarin claim between January 2015 and March 2019. Data examined included comorbidities, healthcare resource utilization (HCRU), treatment adherence, and clinical events.Results:From 11,086 NVAF patients in the database, 940 patients on oral anticoagulant treatment were selected with mean age of 58.6 ± 14.7 years and 73.7% men. At baseline, the mean CHA2DS2-VASc risk score was 2.4, and the mean Deyo–Charlson comorbidity index (CCI) score was 1.6. Most patients (71%) started oral anticoagulation treatment on a standard index dose. High medication possession ratio (MPR) and proportion of days covered (PDC) were observed in 86.8% and 43.1% of the overall cohort. The mean number of HCRU claims and cost during the 180-day follow-up period was 18.5 and 9,747 USD, respectively. Warfarin users accounted for both the highest number of claims and cost, whereas apixaban accounted for the lowest figures. Time to first major bleeding was shorter for warfarin users compared with patients on NOACs. Longer times to first stroke/systemic embolism (SE) were observed for rivaroxaban and warfarin.Conclusion:This study provides important comparative insights about comorbidities, adherence, HCRU, and outcome events among NOAC and warfarin users from real-world clinical practice settings.

Introduction: Oral anticoagulants (OAC) are under-utilised in atrial fibrillation (AF). Even patients prescribed an OAC may stop taking the drug soon after treatment initiation, particularly with Vitamin K Antagonists (VKA). The Non-VKA OAC (NOAC) drugs offer greater ease of use, and persistence is likely to be higher. Aim: To determine persistence on treatment in the first year after inception of NOACs and VKA in incident AF in real-world clinical practice. Methods: We studied 24,467 OAC-naïve patients with incident non-valvular AF diagnosed between Jan 2011-Feb 2014, mean age 73.9 ± 12.5, 45.6% female, in a very large UK primary care database (Clinical Practice Research Datalink, CRPD), with full linkage to medication use. Follow up was for a mean of 1.2 ± 0.9 years. The proportion of OAC initiation in the 90 days after first-time AF and of those remaining on OAC one year after initiation were estimated using competing risk survival analyses censoring for use of alternative OAC. Results: NOAC drugs prescribed included Rivaroxaban, Dabigatran and Apixaban. Overall, 12,579 (51.4%) were commenced on an OAC: 11,888 on VKA and 691 on NOAC, within 90 days after incident AF. Amongst all OAC users, the proportion taking NOAC increased from 0.3% in 2011 to 12.3% in 2014. Persistence, defined as the proportion still taking the OAC after one year, declined over the 12 months to 54.3% for VKA and 80.7% for NOAC (Table). Persistence was significantly greater for NOAC than VKA at all time points. Conclusions: There is a progressive fall in VKA use amongst OAC naïve patients with AF in real-world practice to only 54% at 1 year. This contributes to under-utilisation of anticoagulation in AF and would result in an increased rate of stroke. Persistence was significantly improved with NOACs compared to VKA, and this factor alone could lead to reduced stroke burden with increasing uptake of the NOACs.

Background/Introduction Osteoporotic fractures are associated with high mortality and reduced life quality in an elderly population. Several studies report an increased risk of fractures among patients treated with oral anticoagulants (OAC), however, only sparse research has been made to clarify the difference between treatment with vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOACs) regarding the risk of osteoporotic fractures. Purpose The purpose of this study was to evaluate the risk of osteoporotic fractures among patients with atrial fibrillation (AF) in long-term VKA or NOAC treatment. Methods Patients with AF were identified using Danish national registries and were included when they had undergone 180 days OAC treatment, and only if they had no prior use of osteoporosis medication. The study period was from 1 January 2013 until 30 June 2017, and patients were followed for 2 years, or until death, outcome or emigration. Outcomes were hip fracture, major osteoporotic fracture, any fracture, initiation of osteoporosis medication, and a combined endpoint. G-formula was used to determine standardized absolute risk, and multiple covariate adjusted Cox regressions were used to calculate hazard ratios (HR). Results Overall, 37,350 patients with AF were included; 32.6% received VKA treatment (median age 72 years, 61.8% men) and 67.4% received NOAC treatment (median age 73 years, 55.9% men). The standardized absolute 2-year risk of any fracture was low among NOAC treated patients (3.1%; 95% CI: 2.9% to 3.3%), and among VKA treated patients (3.8%; 95% CI: 3.4% to 4.2%). NOAC was associated with a significantly lower relative risk of any fracture (HR: 0.85; 95% CI: 0.74 to 0.97), of major osteoporotic fractures (HR: 0.85; 95% CI: 0.72 to 0.99), and of initiating osteoporotic medication (HR: 0.82; 95% CI: 0.71 to 0.95). A combined endpoint showed that patients treated with NOAC had a significantly lower risk of suffering from any fracture or initiating osteoporosis medication (HR: 0.84; 95% CI: 0.76 to 0.93). Adjusted relative two-year risks Conclusion In a nationwide population, the absolute risk of osteoporotic fractures was low among AF patients on OAC, but NOAC was associated with a significantly lower risk of osteoporotic fractures compared to VKA. Acknowledgement/Funding Scholarship from The Copenhagen University Hospital Herlev and Gentofte

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly preferred over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management. However, differences in oral anticoagulant (OAC) prescribing according to patient's age, sex and physician's specialty may be present. Therefore, incident and prevalent use of OACs, NOACs and VKAs, stratified by age, sex and prescriber, and factors associated with the choice of OAC were investigated. Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 OAC prescription claim between 2013 and 2019 were identified. OAC use was investigated per half-year. Factors influencing NOAC vs. VKA initiation were identified by multivariable logistic regression. Among 448 661 included OAC-treated AF patients, 297 818 were newly treated. Incident OAC use ranged from 45-49 to 42-44 users/10 000 persons between 2013 and 2019, whereas prevalent OAC use increased from 337 to 435 users/10 000 persons. Incident and prevalent NOAC use exceeded VKA use since 2013 and 2015, respectively, and NOACs represented 92% of incident and 81% of prevalent OAC users in 2019. Apixaban was the most frequently used NOAC since 2016. NOACs were significantly more prescribed by cardiologists and to older patients, whereas VKAs were more initiated in patients with cardiovascular, renal and hepatic comorbidities. Prevalent OAC use increased less in women than men (25.3% vs. 33.0% between 2013 and 2019) and female subjects had 5% significantly lower odds of NOAC vs. VKA initiation than men. Since 2013, prevalent anticoagulant use increased almost one third in Belgium, while incident use was stable. Potential (N)OAC underuse in women requires further exploration.

For many years, vitamin K antagonists have been the only oral anticoagulant drugs available for the prevention and treatment of thromboembolic diseases and, thanks to several studies which have consistently documented their high effectiveness, they are still currently used by millions of patients worldwide1. Vitamin K antagonists do, however, have numerous drawbacks, such as delayed onset and offset of action, a narrow therapeutic window, genetic variations of metabolism and interactions with food and drugs that necessitate frequent monitoring of the International Normalised Ratio and dose adjustments1–3. To overcome these limitations, a new class of non-vitamin K antagonist oral anticoagulants (NOA) has been developed in the last decade4. Two types of NOA are currently available: the factor Xa inhibitors apixaban, rivaroxaban and edoxaban and the thrombin inhibitor dabigatran5. In contrast to vitamin K antagonists, which block the formation of multiple active vitamin K-dependent coagulation factors (factors II, VII, IX and X), the NOA block the activity of one single step in coagulation (see Table I for the main characteristics of NOA). The results of several randomised trials and meta-analyses have clearly demonstrated the efficacy of these novel antithrombotic agents in the prevention and treatment of thromboembolism4,6. Table I Main characteristics of novel oral anticoagulants. There are currently two different attitudes to the prescription of NOA, a more permissive one according to which NOA are prescribed to the majority of patients with venous thromboembolism with very few exceptions (i.e., patients with severe renal impairment and patients with cancer) and a more restrictive attitude, which suggests particular caution in the use of NOA mainly because of the lack of antidotes and of comparative efficacy long-term studies (against warfarin) and real-world safety data. These different positions are well represented in the two debates published by Prandoni7 and Riva and Ageno8 in this issue of Blood Transfusion. These papers were presented orally at the last meeting of the Italian Society for the Study of Hemostasis and Thormbosis (SISET) held in Livorno.

Introduction: Atrial Fibrillation (AF) is the most common arrhythmia, with an increased risk of ischaemic stroke and subsequent morbidity and mortality. Oral anticoagulants such as Vitamin K Antagonists (VKAs) and non VKA Oral Anticoagulants (NOACs) are effective stroke prevention treatments, when used properly. The CHA2 DS2 -VASc and HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly (age >65 years), and Drugs/ alcohol) scores are utilised to guide clinical decision-making in stroke prevention and bleeding risk management for patients with AF. However, real-world evidence on anticoagulation strategies and their effectiveness in rural Indian populations remains limited. Aim: To evaluate the clinical outcomes of NOACs versus VKAs in Non Valvular Atrial Fibrillation (NVAF) patients in a rural tertiary care hospital in India. Materials and Methods: An ambidirectional cohort study, conducted from January 2014 to December 2024, evaluated baseline demographic and clinical characteristics and anticoagulation therapy (NOACs or VKAs) in NVAF patients. Clinical outcomes evaluated encompass major (example: ischaemic or haemorrhagic stroke) and minor bleeding, and allcause mortality. Fisher’s exact test was used to compare patient and clinical characteristics between the NOAC and VKA groups. The log-rank test and Cox proportional hazards analysis were used to compare bleeding risk and mortality between NOAC and VKA groups. Results: Among the 347 patients with NVAF, those prescribed NOACs were significantly older (median age 74 vs. 58 years, p-value <0.0001) and had higher CHA2DS2-VASc scores (median 4 vs. 3, p-value <0.0001) than VKA users. NOAC users also had a higher prevalence of hypertension, diabetes, ischaemic heart disease, prior stroke and chronic kidney disease (p-value <0.0001). Major bleeding was slightly more common in NOAC patients (2.9 vs. 2.1 events per 1,000 person-months, p-value=0.40). The log-rank test showed no significant difference in major bleeding event between NOAC and VKA groups (p-value=0.10). However, all-cause mortality was higher in NOAC users (11.6 vs. 7.7 per 1,000 personmonths). Conclusion: Although NOACs are generally favoured in AF management, this study found higher mortality and bleeding risks among NOAC users in a rural Indian cohort. Older age, higher burden of co-morbidities, being underweight and higher stroke and thromboembolic risk can contribute to adverse outcomes among NOAC users. These findings highlight the need for individualised anticoagulation strategies, particularly in resource-limited settings.

The first-line drugs for the treatment of non-valvular atrial fibrillation (AF) are non-vitamin K antagonist oral anticoagulants (NOACs), which are preferred over vitamin K antagonists (VKAs). There is some evidence that there are dis-crepancies between everyday clinical practice and the guidelines. The study aimed to compare the characteristics of patients on VKAs, dabigatran, and rivaroxaban in everyday practice (i.e. baseline characteristics, drug doses, risk factors for bleeding and thromboembolic events). Additionally, we assessed the frequency of prescription of different oral anticoagulants (OACs) in recent years. This study consisted of data from the multicentre CRAFT (MultiCentre expeRience in AFib patients Treated with OAC) study (NCT02987062). This was a retrospective analysis of hospital records of AF patients (hospitalised in the years 2011-2016) treated with VKAs (acenocoumarol, warfarin) and NOACs (dabigatran, rivaroxaban). A total of 3528 patients with non-valvular AF were enrolled in the CRAFT study. The total cohort consisted of 1973 patients on VKA, 504 patients on dabigatran, and 1051 patients on rivaroxaban. Patients on rivaroxaban were older (70.5 ± 13.1 years) and more often female (47.9%), compared with those on VKAs (67.0 ± 12.8 years, p < 0.001; 35.5%, p < 0.001) and on dabigatran (66.0 ± 13.9 years, p < 0.001; 38.9%, p = 0.001). Among NOACs, patients with persistent and permanent AF were more likely to receive rivaroxaban (54.7% and 73.4%, re-spectively) than dabigatran (45.3%, p < 0.001 and 26.6%, p = 0.002, respectively). Patients on rivaroxaban had higher risk of thromboembolic events (CHA2DS2VASc 3.9 ± 2.0, CHADS2 2.2 ± 1.4) than those on VKAs (3.3 ± 2.0, 1.9 ± 1.3) and on dabigatran (3.1 ± 2.0, 1.8 ± 1.3). Patients on rivaroxaban had also a higher rate of prior major bleeding (11.2%) than those on VKAs (6.7%, p < 0.001) and on dabigatran (7.3%, p = 0.02). Patients on lower doses of dabigatran and rivaroxaban had a significantly higher risk of thromboembolic and bleeding events. Use of VKAs in the year 2011 was reported in over 96% of patients on OACs, but this proportion decreased to 34.6% in 2016. In the last analysed year (2016) AF patients were treated mainly with NOACs - dabigatran (24.2%) and rivaroxaban (41.3%). The prescription of VKAs declined significantly after the introduction of NOACs. Patients treated with different OACs demonstrated a distinct baseline clinical profile. The highest risk of thromboembolic events and incidence of major bleedings was observed in patients on rivaroxaban, in comparison to patients on VKAs and dabigatran. Among NOACs, patients treated with lower doses of dabigatran and rivaroxaban were older and had a significantly higher risk of thromboembolic and bleeding events.

Introduction Following the first gastrointestinal bleeding in a patient with atrial fibrillation (AF) on oral anticoagulant treatment, apprehension of a reoccurrence may prevent clinicians from resuming anticoagulant treatment. However, risk of stroke and thromboembolism in these patients remains substantial. Limited literature exists on resumption patterns of vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOACs), as well as risks of outcomes associated with treatment compared to discontinuation. Purpose We investigated time trends of resumption of NOACs and VKA, and second, risks of recurrent gastrointestinal bleeding, stroke/thromboembolism and all-cause mortality associated with resumption of NOACs and VKA compared with non-resumption. Methods This study was based on a nationwide cohort study using Danish registries, from 1st January 2005 to 31st July 2017. All patients diagnosed with AF and receiving oral anticoagulants prior to admission to hospital with gastrointestinal bleeding were included. Follow-up began 90 days post discharge and patients were categorised in groups of non-resumption, resumption of NOAC, or resumption of VKA. Trends from 2005 to 2017 of resumption of oral anticoagulants were tested using Cochran-Armitage trend tests. Outcomes of interest included recurrent gastrointestinal bleeding, stroke/thromboembolism, and all-cause mortality, measured in terms of multiple-adjusted hazard ratios (HR) and standardised absolute risks. Results The study included 4842 patients with AF receiving oral anticoagulants, discharged from hospital after a gastrointestinal bleeding. Time trends showed a decline in non-resumption from 35.2% in 2006 to 16.5% in 2016. Within 90 days following discharge, 16.3% resumed NOACs, 57,9% resumed VKA, and 25,8% did not resume either anticoagulant treatment. Compared with non-resumption, resumption of was associated with lower hazard of all-cause mortality [HR 0.63 (0.54–0.75) and 0.68 (0.56–0.83), respectively] and lower, but not significant, hazard of stroke/thromboembolism [HR of 0.79 (0.52–1.19) and 0.78 (0.48–1.28), respectively]. There is similar hazard of recurrent gastrointestinal bleeding [HR 0.98 (0.75–1.28) and 0.82 (0.59–1.13), respectively]. The figure shows the standardised absolute risk of recurrent gastrointestinal bleeding and stroke/thromboembolism. Standardised Absolute Risks Conclusion(s) The number of patients not resuming anticoagulant treatment has approximately halved over 10 years between 2006 and 2016. Resumption of NOACs and VKA subsequent to gastrointestinal bleeding in patients with AF was associated with lower hazard of all-cause mortality. There is lower, but not significant, hazard of stroke/thromboembolism and similar hazard of recurrent gastrointestinal bleeding with resumption of VKA and NOACs compared to non-resumption, which suggests that apprehension of recurrent gastrointestinal bleeding is insufficient to justify discontinuation of treatment.

BackgroundIn 2012, around 400.000 patients in the Netherlands were treated with Vitamin K Antagonists (VKA) for thromboembolic diseases. Since 2011, non-VKA oral anticoagulants (NOACs) are available. NOACs do not require frequent INR monitoring which benefits patients, but also imposes a risk of reduced therapy adherence. The objective of this study is to describe uptake and patient adherence of NOACs in The Netherlands until October 2016.MethodsPrescription data for 247.927 patients across 560 pharmacies were used to describe patient profiles, uptake of NOACs among new naive patients and switch between VKA and NOACs, and calculate therapy adherence as the Proportion of Days Covered (PDC).ResultsDuring the studied period the share of NOACs in oral anticoagulants has grown to 57% of prescriptions to new patients. More than 70% of new NOAC users were new naive patients and around 26% switched from VKA. The overall share of NOACs among starters is largest in the group of patients of 50-80 years. Calculated compliance rate for NOAC patients shows that 88% of all users are adherent with a PDC higher than 80%.ConclusionsNOAC have overtaken VKA as the major treatment prescribed to new oral anticoagulant patients, and the number of starters on VKA is decreasing. Patients are generally adherent to NOACs during the implementation phase, the period that the medication is used. Fear for inadherence by itself does not need to be a reason for not prescribing NOACs instead of VKA.

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs.