Non-vitamin K Oral Anticoagulants Research Articles

Safety of Non-vitamin K Antagonist Oral Anticoagulants on Outcomes After Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis.

The existing evidence on the use of non-vitamin K oral anticoagulants (NOACs) after transcatheter aortic valve replacement (TAVR) surgery is inconclusive and contradictory. Likewise, major society guidelines remain ambivalent about NOAC use around the time of TAVR. The objective of our meta-analysis was to assess the efficacy of NOACs in comparison to vitamin K antagonists (VKAs) in lowering complications following TAVR. An electronic literature search was conducted using MEDLINE, EMBASE, the international clinical trials database, and Cochrane Library. The primary endpoint was all-cause mortality, and the secondary endpoints included cardiovascular-related death, myocardial infarction, all-cause stroke, and various bleeding events. Forest plots were constructed for the pooled analysis of data. Subgroup and sensitivity analyses were also performed. No significant difference was noted between the NOAC and VKA groups with respect to the risk of all-cause mortality (14.14% vs. 20.28%; risk ratio (RR): 0.82; 95% confidence interval (CI): 0.61 to 1.10; p = 0.18), cardiovascular-related deaths (6.10% vs. 8.55%; RR: 1.02; 95% CI: 0.78 to 1.33; p = 0.91), myocardial infarction (1.52% vs. 2.51%; RR: 1.13; 95% CI: 0.50 to 2.56; p = 0.77), all-cause stroke (2.74% vs. 2.68%; RR: 1.02; 95% CI: 0.75 to 1.39; p = 0.89), major bleeding (7.74% vs. 9.62%; RR: 0.97; 95% CI: 0.58 to 1.61; p = 0.90), minor clinically relevant bleeding (14.33% vs. 13.73%; RR: 0.91; 95% CI: 0.67 to 1.24; p = 0.55), and other bleeding events. The risk of intracranial hemorrhage was lower in the NOAC group than in the VKA group (0.45% vs. 0.67%; RR: 0.61; 95% CI: 0.42 to 0.88; p = 0.008). Our study found NOACs to be non-inferior to VKAs in several outcomes, such as all-cause mortality, cardiovascular-related deaths, myocardial infarction, all-cause stroke, and bleeding events. In fact, NOACs were favored over VKAs, as the VKA group had a higher risk of developing intracranial hemorrhage.

Long‐term cognitive function changes with non‐vitamin K oral anticoagulants in older patients with atrial fibrillation. A multicenter cohort study

AbstractBackgroundAtrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non‐vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time.MethodsNine hundred and eighty‐three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between‐arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group‐based trajectory model analyses.ResultsIn the whole multicenter observational study, after a long follow‐up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow‐up (−0.3 ± 0.03 vs.−1.7 ± 0.1, p < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times).ConclusionIn older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities.

Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling.

Non-vitamin K oral anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs-apixaban, rivaroxaban, edoxaban, and dabigatran-not only as anticoagulants, but also as modulators of inflammation via protease-activated receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as factor Xa (FXa) and thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles, but also paves the way for future research and clinical applications in inflammation and cardiovascular health.

Oral anticoagulation with Edoxaban for stroke prevention in patients with atrial fibrillation: Analysis of 1-year follow-up data of routine clinical practice in Germany, Austria and Switzerland (DACH) from the ETNA-AF registry

Non-vitamin-K oral anticoagulants (NOACs) are safe and effective for stroke prevention in patients with atrial fibrillation (AF). Data on the safety and efficacy of Edoxaban in routine care in Germany, Austria and Switzerland (DACH) are limited. We report one-year outcomes in patients with AF treated with Edoxaban in routine care. The ETNA-AF-Europe study (Clinicaltrials.gov:NCT02 944 019) is a multicenter, prospective, observational study that enrolled 13 092 patients with AF treated with Edoxaban from 852 sites across 10 European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Switzerland, and the United Kingdom). The DACH-cohort consists of 5457 (41,7 %) patients of sites in Germany, Austria and Switzerland. Patients had a mean age of 74 years (2384 [44 %]women) and a mean CHA2DS2-VASc-score of 3.2 ± 1.4. A label-conform dosing of Edoxaban was administered to 4309 patients (78,9 %). At the one-year-follow-up a stroke or systemic embolism occurred in 42 patients (0,8 %/year), and severe bleeding was reported in 36 patients (0,7 %/year). Ten patients (0,2 %/year) suffered intracranial and 13 patients (0,3 %/year)gastrointestinal bleeding. Numbers of death from all causes and cardiovascular death occurred in 179 patients (3,4 %/year) and 85 patients (1,6 %/year), respectively. Age > 75 years, frailty and a CHA2DS2-VASc score ≥ 4 were associated with a higher all-cause mortality - and those patients were more likely to suffer a stroke or a major bleeding event. In Germany, Austria and Switzerland in patients with AF on Edoxaban therapy for stroke prevention the number of stroke and major bleeding events is low. Increasing morbidity is associated with a higher number of important clinical events.

Left atrial appendage thrombus in patients with atrial fibrillation who underwent oral anticoagulation.

Electric cardioversion of atrial fibrillation (AF) is associated with an increased risk of embolism, with embolic material existing in the heart cavities. The initiation of oral anticoagulation therapy reduces the risk of thromboembolic events. The aims of this study were to evaluate the prevalence of left atrial appendage (LAA) thrombi in non-valvular AF, to compare vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) with respect to thrombus prevalence, and to evaluate the rate of LAA thrombus persistence on repeat transesophageal echocardiography (TEE) after treatment change. We enrolled 160 consecutive AF patients who presented with an AF duration > 48 h and had undergone TEE before cardioversion. Left atrial appendage thrombus was observed in 12 (7.5%) patients, and spontaneous echo contrast 4 was observed in 19 (11.8%) patients; the incidence was similar between the NOAC and VKA groups (8.9% vs. 3.6% and 12.4% vs. 18.5 %, respectively). Among patients on NOAC, thrombus prevalence was detected in 8.4% of users of rivaroxaban, 8% of users of dabigatran, and 12.5% of users of apixaban. The LAA thrombus developed in 7.5% of patients despite anticoagulation therapy, demonstrating similar prevalence rates among patients either on NOAC or VKA. Lower mean LAA flow velocity and a history of vascular disease were independent predictors of embolic material in the LAA. It seems that in the case of embolic materials in LAA under NOAC treatment, switching to VKA provides additional clinical benefit to the patients.

Time trends in stroke risk management among high-risk patients with non-valvular atrial fibrillation in Australia between 2011–2019

BackgroundAtrial fibrillation (AF) is associated with stroke. Major changes to AF management recommendations in 2016–2018 advised that: 1. Stroke risk be estimated using the CHA2DS2-VA score; 2. Antiplatelet agents (APAs) do not effectively mitigate stroke risk; 3. Anticoagulation is prioritised above bleeding risk among high-risk patients; and 4. Non-vitamin K oral anticoagulants (NOACs) are used as first-line anticoagulants. AimTo examine trends in stroke risk management among high-risk patients with non-valvular AF in Australia between 2011–2019. MethodDe-identified data of patients were obtained from 164 separate general practices. Data included information on patient demographics, diagnoses, health risk factors and recent prescriptions. Patients with a diagnosis of non-valvular AF were identified and stroke risk was calculated by CHA2DS2-VA score. High risk patients (i.e. CHA2DS2-VA ≥ 2) were categorised as being managed by oral anticoagulants (OACs, i.e., warfarin or NOACs), APAs only, or neither (i.e., no OACs or APAs) and time trends in prescribing were examined. Multivariate analyses examined the characteristics of patients receiving the guideline recommended OAC management. ResultsData were available for 337,964 patients; 8696 (2.6 %) had AF. Most patients with AF (85.8 %, n = 7116) had high stroke risk. The proportion of high-risk patients managed on OACs increased from 56.7 % in 2011 to 73.7 % in 2019, while the proportion prescribed APAs declined from 31.1 % to 14.0 %. Those receiving neither treatment remained steady (around 12 %). Overall, 26.3 % of patients were inadequately anticoagulated at the end of the study period. There were no age or gender differences in receiving the guideline-recommended therapy, and patients with comorbidities associated with increased stroke risk were more likely to receive OAC therapy. ConclusionsStroke risk management among patients with AF has improved between 2011–2019, however there is still scope for further gains as many high-risk patients remain inadequately anticoagulated. Better stroke risk assessment by clinicians coupled with addressing practitioner concerns about bleeding risk may improve management of high-risk patients.

Thromboembolic and bleeding complications after elective cardioversion of atrial fibrillation: a nationwide cohort study.

Elective cardioversion (ECV) is routinely used in atrial fibrillation (AF) to restore sinus rhythm. However, it includes a risk of thromboembolism even during adequate oral anticoagulation treatment. The aim of this study was to evaluate the risk of thromboembolic and bleeding complications after ECV in a real-life setting utilizing data from a large AF population. This nationwide register-based study included all (n = 9625) Finnish AF patients undergoing their first-ever ECV between 2012 and 2018. The thromboembolic and bleeding complications within 30 days after ECV were analysed. The mean age of the patients was 67.7 ± 9.9 years, 61.2% were men, and the mean CHA2DS2-VASc score was 2.6 ± 1.6. Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants (NOACs) in 3380 (35.1%) cardioversions. Fifty-two (0.5%) thromboembolic complications occurred, of which 62% were ischaemic strokes, 25% transient ischaemic attacks, and 13% other systemic embolisms. Thromboembolic events occurred in 14 (0.4%) NOAC-treated patients and in 38 (0.6%) warfarin-treated patients (odds ratio 0.77; confidence interval: 0.42-1.39). The median time from ECV to the thromboembolic event was 2 days, and 78% of the events occurred within 10 days. Age and alcohol abuse were significant predictors of thromboembolic events. Among warfarin users, thromboembolic complications were more common with international normalized ratio (INR) <2.5 than INR ≥2.5 (0.9% vs. 0.4%, P = 0.026). Overall, 27 (0.3%) bleeding events occurred. The rate of thromboembolic and bleeding complications related to ECV was low without significant difference between NOAC- and warfarin-treated patients. With warfarin, INR ≥2.5 at the time of cardioversion reduced the risk of thromboembolic complications.

Outcomes of non-vitamin K oral anticoagulants for secondary prevention in ischemic stroke with atrial fibrillation

Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78–0.95), ischemic stroke (aHR 0.89; 95% CI 0.81–0.99), major bleeding (aHR 0.78; 95% CI 0.68–0.89), and all-cause death (aHR 0.87; 95% CI 0.81–0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.

Risk of bleeding during flapless immediate implant placement after tooth extraction in patients taking antithrombotics

AbstractObjectivesTo assess postoperative bleeding in patients undergoing immediate implant placement after tooth extraction without discontinuing or adjusting the dosage of oral antithrombotic drugs.Materials and methodsPatients from February 2020 to August 2022 were selected who had undergone flapless immediate implant placements after tooth extraction and were on antithrombotics. A total of 27 patients were included. The patients were on different types of anticoagulants: vitamin K antagonists (one patient), non‐vitamin K oral anticoagulants (NOACs) (five), antiplatelet agents (15), dual antiplatelet therapy (five), and combination of anticoagulant and antiplatelet agents (one).ResultsOne patient taking an anticoagulant (NOACs: apixaban) and antiplatelet agent (clopidogrel) showed mild bleeding at the implant placement site in the lower right canine area, and gauze compression was applied to control the bleeding. No special treatment was required for the other patients. There were no implant failures after surgery.ConclusionsThis study shows that the flapless immediate implant placements after tooth extraction for patients taking antithrombotics can be safely executed under adequate hemostasis without medication cessation. However, when anticoagulants and antiplatelets are taken together, it is speculated that surgeons may need careful hemorrhage management. Future research should include larger patient cohorts to yield more comprehensive evidence.

Non-vitamin K oral anticoagulants versus warfarin for the treatment of left ventricular thrombus.

Left ventricular thrombus (LVT) is associated with significant morbidity and mortality. Conventional treatment comprises warfarin-mediated anticoagulation; it is unclear whether non-vitamin K oral anticoagulants (NOACs) exhibit comparable efficacy and safety. Limited data are available for Asian patients. This study compared NOACs with warfarin in terms of clinical efficacy and safety for managing LVT. Clinical and echocardiographic records were retrieved for all adult patients with echocardiography-confirmed LVT at a major regional centre in Hong Kong from January 2011 to January 2020. Discontinuation of anticoagulation by 1 year was recorded. Outcomes were compared between patients receiving NOACs and those receiving warfarin. Primary outcomes were cumulative mortality and net adverse clinical events (NACEs). Secondary outcomes were complete LVT resolution and percentage reduction in LVT size at 3 months. Forty-three patients were included; 28 received warfarin and 15 received NOACs, with follow-up periods (mean ± standard deviation) of 20 ± 12 months and 22 ± 9 months, respectively (P=0.522). Use of NOACs was associated with significantly lower NACE risk (hazard ratio [HR]=0.111, 95% confidence interval [CI]=0.012-0.994; P=0.049) and a tendency towards lower cumulative mortality (HR=0.184, 95% CI=0.032-1.059; P=0.058). There were no significant differences in secondary outcomes. Considering LVT resolution, discontinuation of anticoagulation by 1 year was not significantly associated with different outcomes. Non-vitamin K oral anticoagulants may be an efficacious and safe alternative to warfarin for LVT management. Future studies should explore the safety and efficacy of anticoagulation discontinuation by 1 year as an overall strategy.

Appropriate vs inappropriate dosing of non-vitamin K oral anticoagulants (NOACS) in older persons with atrial fibrillation: Characteristics and outcomes

Appropriate vs inappropriate dosing of non-vitamin K oral anticoagulants (NOACS) in older persons with atrial fibrillation: Characteristics and outcomes

Global Research Hotspots in Venous Thromboembolism Anticoagulation: A Knowledge-Map Analysis from 2012 to 2021.

Venous thromboembolism (VTE) is a common cardiovascular disease that seriously threatens human lives. Anticoagulant therapy is considered to be the cornerstone of VTE treatment. An increasing number of studies has been updated in the VTE anticoagulation field. However, no bibliometric analyses have assessed these publications comprehensively. Therefore, our study aimed to analyze the global status, hotspots, and trends of anticoagulant therapy for VTE. The relevant literature on VTE anticoagulation published between 2012 and 2021 was retrieved and collected from the Web of Science Core Collection database. VOSviewer, Cooccurrence Matrix Builder, gCLUTO, and some online visualization tools were adopted for bibliometric analysis. A total of 15,152 related articles were retrieved. In recent years, the research output of VTE anticoagulation gradually increased. The United States was the most productive country. International cooperation is concentrated in North America and Europe; the most influential documents, journals, authors, and organizations were also from these two continents. Research hotspots mainly focus on clinical guidelines, VTE in special populations, non-vitamin K oral anticoagulants (NOACs), and parenteral anticoagulation. The research frontiers and trends include the assessment of NOACs and the antithrombotic management of VTE complicated with coronavirus disease 2019 (COVID-19). This bibliometric analysis provides a systematic overview of the VTE anticoagulation research, which will facilitate researchers to better understand the situation of VTE anticoagulation. Future studies should be dedicated to NOACs application and VTE-combined COVID-19 patients.

Anticoagulation therapy in patients with atrial fibrillation and active cancer

Abstract Background Atrial fibrillation (AF) is common among cancer patients. Oral anticoagulation therapy (OAT) is important to prevent stroke in AF patients, but active cancer may also predispose to bleeding. Current knowledge on the use of OAT among AF patients with active cancer is scarce. Purpose To assess the influence of active cancer on the initiation of OAT in patients with AF and to explore cancer features predicting withholding OAT. Methods The nationwide FinACAF registry linked data from several registries covering all levels of care as well as drug purchases and included all 123 618 patients diagnosed with incident AF in Finland during 2011- 2018 with an indication for OAT (≥1 non-sex CHA2DS2-VASc point). Patients were considered to have active cancer if they had received a new cancer diagnosis or treatment for cancer during the preceding year from AF diagnosis. The primary outcome was the initiation of OAT (including non-vitamin K oral anticoagulants (NOAC) and warfarin) and the secondary outcome the initiation of any anticoagulation therapy (AAT; including OAT and low molecular-weight heparin) during the first year from AF diagnosis. Results The mean age of the patients was 73.9 (standard deviation 11.5) years and 62 955 (50.9%) of them were women. Altogether, 7015 (5.7%) patients had active cancer at AF diagnosis. The median CHA2DS2-VASc (3 [interquartile range 2-4] for both groups) and HAS-BLED (2 [interquartile range 2-3] for both groups) scores were similar in patients with active cancer and those without cancer history. Patients with active cancer, compared to those without cancer history, less often initiated OAT (47.7% vs. 70.5 %) or AAT (61.8% vs. 71.8%) (Figure). In Fine-Gray regression analyses with all-cause mortality as a competing risk, after adjusting for confounding factors, active cancer remained associated with lower likelihood of OAT (adjusted subdistribution hazard ratio (aSHR 0.501) (95% confidence interval (CI): 0.485-0.518), p&amp;lt;0.001) as well as AAT (aSHR 0.745 (95%-CI 0.723-0.769, p&amp;lt;0.001) initiation. Among cancer patients, metastases, gastrointestinal cancer and radiotherapy were associated with lower likelihood of OAT initiation, while only metastases predicted lower likelihood of AAT initiation (Table). Among patients initiating OAT, active cancer was associated with lesser likelihood of choosing a NOAC over warfarin compared to those without cancer (36.0% vs. 39.2%; adjusted hazard ratio 0.712 (95%-CI: 0.640-0.792), p&amp;lt;0.001). Conclusion AF patients with active cancer are less likely to initiate anticoagulation therapy, and those starting OAT are less likely to initiate with NOACs, compared to patients without cancer history. Metastases are the most important predictor of withholding anticoagulation therapy among AF patients with cancer.

Safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: a prospective cohort study with historical control comparison

Abstract Introduction In adults with congenital heart disease (ACHD), atrial arrhythmias (AA) confer an increased risk of thromboembolic events. Data regarding treatment with non-vitamin K oral anticoagulants (NOACs) of patients with ACHD and AA are limited. Methods A prospective, multicenter, observational study of ACHD patients with AA (atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia) treated with apixaban from 2019 to 2022 was performed (PROTECT-AR, NCT03854149). Comparisons were made with a historical vitamin-K antagonist (VKA) treatment cohort from 2002 to 2014. The primary efficacy endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. Results The apixaban-treated cohort consisted of 215 patients (median follow-up 28 months) and the historical VKA-treated ­cohort consisted of 229 patients with ACHD and AA (median follow-up 48 months). The burden of age and comorbidities was higher in the apixaban versus the VKA treatment group (Table). Comparing the apixaban with the VKA treatment group yielded no significant differences in the annualized rate of stroke or thromboembolism (1.2% vs. 1.4%, respectively; p=0.24) and major bleeding (1.2% vs. 4.4%, respectively; p=0.08) (Figure). Conclusion In ACHD patients with AA treated with apixaban as part of routine care, the risk of major thromboembolic and bleeding events was low. This risk was comparable with historical cohort data on VKA. Prospective studies directly comparing NOAC and VKA-treated patients are needed.

Abstract 15341: A Prospective Study on the Safety and Effectiveness of Apixaban for the Prevention of Thromboembolism in Adults With Congenital Heart Disease and Atrial Arrhythmias: The PROTECT-AR Study

Introduction: In adults with congenital heart disease (ACHD), atrial arrhythmias (AA) confer an increased risk of thromboembolic events. Limited data exist on non-vitamin K oral anticoagulant (NOAC) treatment for ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. Methods: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia, who were routinely treated with apixaban, were included. The primary efficacy endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. Patients who were previously on vitamin K antagonists (VKAs) before transitioning to apixaban served as a historical control group. Results: In total, 218 patients with ACHD and AA on apixaban (previous VKA users 34.9%) were included (mean age 51±17 years; 45.9% male; predominantly moderate complexity). Over a mean follow-up of 2.4±1.3 years, the rate of stroke or thromboembolism was 0.57% [95% confidence interval (CI): 0.15-1.55] and the rate of major bleeding was 1.52% [95%CI: 0.71-2.88] per patient-year, respectively. In the subset of patients who were previously on VKA, the risk of the primary endpoints did not differ significantly between apixaban and VKA-treatment periods (Figure). Conclusion In ACHD patients with AA on routine apixaban treatment, the risk of major thromboembolic and bleeding events was low. Among prior VKA users, the risk of adverse events during the apixaban-treatment period was comparable to that during the VKA-treatment period. Prospective studies directly comparing NOAC and VKA-treated patients are needed.

Treatment Satisfaction and Convenience for Patients With Atrial Fibrillation on Edoxaban or Vitamin K Antagonists After Transcatheter Aortic Valve Replacement: A Post Hoc Analysis from the ENVISAGE-TAVI AF Trial

ENVISAGE-TAVI AF (Edoxaban versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation-Atrial Fibrillation; NCT02943785) was a prospective, randomized, open-label trial comparing non-vitamin K oral anticoagulant (NOAC) edoxaban with vitamin K antagonists (VKAs) in patients with atrial fibrillation after successful transcatheter aortic valve replacement (TAVR). The effect of edoxaban- or VKA-based therapy on patient-reported outcomes remains unknown, as most studies focus on efficacy and safety. Pre-TAVR patient-reported expectations and post-TAVR Treatment Satisfaction and Convenience with edoxaban or VKA treatment (at months 3 and 12) were analyzed using the Perception of Anticoagulation Treatment Questionnaire (PACT-Q). This analysis included randomized and dosed patients with an evaluable PACT-Q1 assessment at baseline and ≥1 postbaseline assessment (PACT-Q2). Subanalyses included patients stratified by pre-TAVR anticoagulant (NOAC, VKA, no NOAC/VKA). Edoxaban- (n = 585) and VKA-treated (n = 522) patients had similar baseline characteristics and treatment expectations. Pre-TAVR anticoagulant use did not affect treatment expectations. After TAVR, edoxaban-treated patients had significantly higher Treatment Satisfaction and Convenience scores compared with VKA-treated patients at all time points (p <0.001 for all). Among edoxaban-treated patients, those who received VKAs pre-TAVR were significantly more satisfied with treatment than those who received NOACs (p <0.001) or no NOACs/VKAs (p = 0.003); however, there was no significant difference in the perception of convenience (p = 0.927 and p = 0.092, respectively). Conversely, among VKA-treated patients, the type of anticoagulant used pre-TAVR did not affect Treatment Satisfaction or Convenience scores post-TAVR. In conclusion, patients with atrial fibrillation who received edoxaban post-TAVR reported significantly higher Treatment Satisfaction and Convenience scores compared with those who received VKAs, resulting in a clinically meaningful difference between treatment groups.

Clinical Outcomes in Older Patients with Atrial Fibrillation: Insights from the GARFIELD-AF Registry

BackgroundOral anticoagulants (OAC) are underutilized in older patients with atrial fibrillation, despite proven clinical benefits. Our objective was to investigate baseline characteristics, treatment patterns, and impact of anticoagulation upon clinical outcomes with respect to age. MethodsAdults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed up for 24 months. Adjusted hazard ratios (HR) were obtained via Cox proportional-hazards models with applied weights, to quantify the association of age with clinical outcomes. Comparative effectiveness of OAC vs No OAC and non-vitamin K oral anticoagulants (NOAC) vs vitamin K antagonists (VKA) were assessed using a propensity score with an overlap weighting scheme. ResultsOf 52,018 patients, 32.6% were 65-74 years of age, 29.3% were 75-84 years, and 7.9% were ≥85 years. OAC treatment was associated with a numerical reduction in all-cause mortality among those aged 65-74 years (HR; 95% confidence interval) (0.86; 0.69-1.06) and aged 75-84 years (0.89; 0.75-1.05) and a significant reduction in patients ≥85 years (0.77; 0.63-0.95) vs no OAC. Similarly, OACs were associated with a decrease in stroke: 65-74 (0.51; 0.35-0.76) and ≥85 years (0.58; 0.34-0.99) and a numerical decrease in 75-84 years (0.84; 0.59-1.18). No increase in major bleeding was observed in patients aged ≥85 treated with OACs. Compared with VKA, NOACs were associated with a significant reduction in all-cause mortality in patients aged <65 and 65-74, with numerical reductions in those aged 75-84 and ≥85 years. ConclusionsOlder patients using OACs saw lower all-cause mortality and stroke risk; NOACs had less mortality and major bleeding compared with VKAs.

Early or late initiation of dabigatran versus vitamin-K-antagonists in acute ischemic stroke or TIA: The PRODAST study.

The optimal timing of initiating or resuming anticoagulation after acute ischemic stroke (AIS) or transient ischemic attack (TIA) in patients with atrial fibrillation (AF) is debated. Dabigatran, a non-vitamin K oral anticoagulant (NOAC), has shown superiority against vitamin K antagonists (VKA) regarding hemorrhagic complications. In this registry study, we investigated the initiation of dabigatran in the early phase after AIS or TIA. PRODAST (Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA) is a prospective, multicenter, observational, post-authorization safety study. We recruited 10,039 patients at 86 German stroke units between July 2015 and November 2020. A total of 3,312 patients were treated with dabigatran or VKA and were eligible for the analysis that investigates risks for major hemorrhagic events within 3 months after early (⩽ 7 days) or late (> 7 days) initiation of dabigatran or VKA initiated at any time. Further endpoints were recurrent stroke, ischemic stroke, TIA, systemic embolism, myocardial infarction, death, and a composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. Major bleeding event rates per 10,000 treatment days ranged from 1.9 for late administered dabigatran to 4.9 for VKA. Early or late initiation of dabigatran was associated with a lower hazard for major hemorrhages as compared to VKA use. The difference was pronounced for intracranial hemorrhages with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval (CI): 0.10-2.21) for early dabigatran use versus VKA use and an adjusted HR of 0.09 (95% CI: 0.00-13.11) for late dabigatran use versus VKA use. No differences were found between early initiation of dabigatran versus VKA use regarding ischemic endpoints. The early application of dabigatran appears to be safer than VKA administered at any time point with regards to the risk of hemorrhagic complications and in particular for intracranial hemorrhage. This result, however, must be interpreted with caution in view of the low precision of the estimate.

Prescriptive behavior of non-vitamin K oral anticoagulants in patients affected by atrial fibrillation in general practice

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and in recent years the pharmacological approach has been strongly implemented; in Italy, the prescription of the non-vitamin K oral anticoagulants (NOAC) was also extended to General Practitioners (GPs) since 2020. The aim of the present study was to investigate the GPs prescribing behaviour of NOACs. An observational study was performed by using the computerized medical record of 14 GPs in Sicily: patients affected by AF were selected and stratified according to the prescribed antithrombotic drugs. Patients were considered inadequately managed if antithrombotic treatment was not adherent to recent ESC guidelines. A total of 467 (2.7 %) patients were affected by AF, 276 (59.1 %) were treated with an oral anticoagulant (OAC) regardless the high stroke risk (OR 1.64; 95 %CI 0.74–3.62; p = 0.226). The NOAC users were 236 patients as follow: Rivaroxaban 33.5 %, Apixaban 33,1 %, Dabigatran 17,4 %, Edoxaban 16.1 %. In 7 patients an inappropriate NOAC treatment was observed. Among Vitamin-K antagonist users, 25.0 % were considered inappropriate. Patients not treated with OAC were 191, of them 81.7 % were at high stroke risk and did not receive any OAC despite the indication to treat. In addition, the probability to be not properly managed significantly increased in older and in patients with atherosclerosis. Conversely, patients with at least one reported cardiology counselling significantly reduced the likelihood to be not properly managed (OR 0.38, 95 %CI 0.25–0.58; p 0.01). Our results suggest the need to optimize the management of real-life AF patients by improving prescribing adherence to ESC guidelines.

Non-vitamin k oral antagonists versus aspirin for primary thromboprophylaxis in patients with multiple myeloma on outpatient chemotherapy: A systematic review and meta-analysis.

e20041 Background: Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased in patients receiving immunomodulatory drugs (IMiDs). Current guidelines suggest that non-vitamin K oral anticoagulants (NOACs) may be an alternative to low-dose aspirin (ASA) for primary thromboprophylaxis in this population. However, there is limited data comparing these two antithrombotic therapies among MM patients undergoing treatment with IMiDs. Methods: We performed a systematic review and meta-analysis to compare NOACs with ASA for primary thromboprophylaxis in individuals with newly-diagnosed or relapsed/refractory MM undergoing outpatient chemotherapy with an IMiD-based regimen. PubMed, Cochrane, and EMBASE were systematically searched from inception to January 2023. Observational studies and randomized controlled trials were included when comparing NOACs versus aspirin for thrombotic and hemorrhagic outcomes. Statistical analysis was performed with Review Manager 5.4.1. Results: We included 10 randomized controlled trials and observational studies comprising 1026 MM patients who underwent primary thromboprophylaxis with NOACs (33%) or ASA (67%). Thromboprophylaxis with NOACs was associated with a significantly lower incidence of VTE compared with ASA (OR, 0.33; 95% CI, 0.16-0.68; p &lt; 0.001; I² = 0%). Each group had one major bleeding event, with no statistically significant difference between NOACs and ASA (OR, 1.35; 95% CI, 0.05-35.51; p = 0.86; I² = 51%). Similarly, clinically relevant non-major bleeding (OR, 0.56; 95% CI, 0.12-2.70; p = 0.47; I² = 0%) and minor bleeding (OR 1.48; 95% CI: 0.42-5.24; p = 0.54; I² = 0%) event rates did not differ significantly between groups. Conclusions: These findings suggest that NOACs may be superior to ASA for VTE prophylaxis among MM patients receiving IMiD-based chemotherapy, with no significant difference in the overall bleeding risk between the two groups.