Non-vitamin K Antagonist Oral Anticoagulants Research Articles

Use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation across five stages of chronic kidney diseases

Abstract Background Although non-vitamin K antagonist oral anticoagulants (NOACs) were more and more commonly prescribed in the daily practice, data about the use of NOACs in atrial fibrillation (AF) patients with stage 4 and 5 chronic kidney diseases (CKD) are limited. In the present study, we compared the clinical outcomes of AF patients receiving NOACs and those receiving warfarin or non-OACs in different stages of CKD. Methods A total of 39217 AF patients aged >20 years whose data about creatinine clearance (CCr) were available were identified from the electronic health record database of a multi-center healthcare system in Taiwan. Patients were categorized into stage 1 to stage 5 CKDs, and the composite risks of ischemic stroke/systemic embolism, major bleeding and mortality were compared between non-OACs, warfarin and NOACs. Results Around 12.7% and 9.4% of study patients had a stage 4 and stage 5 CKD, respectively. Compared to non-OACs, the use of OACs (either warfarin or NOACs) were consistently associated with a lower risk of composite events from stage 1 to stage 4 CKD, but not for stage 5 CKD (warfarin: aHR 0.912, 95%CI 0.742-1.121; NOACs: aHR 0.993, 95%CI 0.653-1.537)(Figure 1). Compared to warfarin, NOACs were associated with a lower risk of adverse events for patients with stage 2 (aHR 0.630), stage 3 (aHR 0.712) and stage 4 CKD (aHR 0.749). However, the risk did not differ between warfarin and NOACs for stage 1 and stage 5 CKD (Figure 2). Conclusions Although data of the clinical trials for AF patients with stage 4 CKD were relatively lacking, NOACs should still be considered for this AF population. More data are necessary to guide optimal stroke prevention strategy for patients with stage 5 CKD.

Atrial fibrillation-related complications following short-term use of antibiotics in patients receiving NOAC or warfarin

Abstract Introduction To study the association of antibiotics with ischaemic stroke/systemic embolism (IS/SE) in patients with atrial fibrillation (AF) receiving anticoagulants. Methods This retrospective population-based cohort study applied electronic health data from a territory-wide medical database. Data were collected for patients with AF who were prescribed non-vitamin K antagonist oral anticoagulants (NOAC) or warfarin between Jan 1, 2010 and Dec 31, 2018. We further identify the patients with and without use antibiotics (any classification of antibiotics with prescription period within 7 days) during the NOAC/warfarin treatment period. The primary outcome is IS/SE and the secondary outcomes including hemorrhagic stroke (HS) and all-cause mortality. Patients were followed up for a median of 3.7 years. A self-control case crossover design was adopted to compare the short-term association between use of antibiotics and outcomes of interest among NOAC and warfarin group. Results This study included 40221 patients, consisted of 30617 NOAC users and 9826 warfarin users, while 9604 patients in NOAC group and 3325 patients in warfarin group had concurrent antibiotics use. At baseline, 46.1% of patients in NOAC group were male and the mean (SD) age was 77.4 (9.8) years, and 56.2% of patients in warfarin group were male and the mean (SD) age was 73.8 (11.3) years. Short-term use of antibiotics is associated with increased risk of IS/SE, HS and all-cause mortality in both NOAC and warfarin groups (NOAC vs. warfarin group: IS/SE: hazard ratio [HR]:3.41 [95%CI, 2.78-4.18]; HR: 2.51 [95%CI, 2.00-3.14]; HS: HR: 2.22 [95%CI, 1.78-2.78]; HR: 2.53 [95%CI, 1.86-3.43]; mortality: HR: 1.96 [95%CI, 1.85-2.08]; HR: 1.87 [95%CI, 1.73-2.02]; all P < 0.001). Conclusion The findings of the present study suggest that the short-term antibiotics use was associated with an increased risk of IS/SE, HS and all-cause mortality among patients in both NOAC and warfarin group. These findings further suggest that use of antibiotics may indicate a higher risk of IS/SE, HS and death for patients with AF, even when receiving NOAC/warfarin and that further investigation is warranted.The study design.The odds ratios of different outcomes.

Temporal trends of prescription rates, dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation

Abstract Background The launch of non-vitamin K antagonist oral anticoagulant (NOAC) has revolutionized the landscape of stroke prevention in atrial fibrillation (AF). We aimed to analyze the temporal trends of prescription rates of oral anticoagulants (OACs), NOAC dosing, clinical outcomes and in patients with AF. Methods This was a retrospective study using the Taiwan National Health Insurance Research Database. During 2011 to 2020, A total of 249,107 patients aged ≥30 years with newly diagnosed AF were identified. We analyzed the 1-year risks of ischemic stroke, intracranial hemorrhage (ICH), and all-cause mortality for overall population and specifically for NOAC users. Results The prescription rate of OAC increased from 22.1% in year 2011 to 57.7% in 2020 (P<0.001) with NOAC accounting for 91.0% of overall OAC prescriptions. Compared to patients with incident AF diagnosed in 2011, there were increasing trends for a greater decrease in the risks of ischemic stroke (adjusted hazard ratios [aHRs] 0.914 in 2012, 0.879 in 2013, 0.925 in 2014, 0.822 in 2015, 0.754 in 2016, 0.763 in 2017, 0.769 in 2018, 0.713 in 2019 and 0.707 in 2020; all P<0.05) and mortality (aHRs 0.903 in 2014, 0.899 in 2015, 0.830 in 2016, 0.808 in 2017, 0.788 in 2018, 0.810 in 2019, 0.788 in 2020; all P<0.05), while the risk of ICH did not change significantly (Figure 1). For NOAC users, the percentages of high-dose NOACs increased from 11.04% in year 2012 to 44.29% in year 2019 to 2020. The increasing trend in the use of high-dose NOACs was temporally associated with a lower risk of ischemic stroke observed for patients receiving NOACs in year 2015 to 2017 (aHR 0.794) and year 2018 to 2020 (aHR 0.688) compared to those in year 2012 to 2014 (Figure 2). Conclusion In this nationwide cohort study, there was an increasing trend of OAC prescription, temporally associated with a decline of the risk of ischemic stroke and mortality. Even among NOACs users, the risk of ischemic stroke declined gradually, partly explained by the increasing prescriptions of high-dose NOACs.

Persistence and predictors for non-persistence to edoxaban therapy in patients with atrial fibrillation: 4-year follow-up data from the ETNA-AF-Europe study

Abstract Background Non-persistence to non-vitamin K antagonist oral anticoagulants (NOACs) is associated with increased stroke risk in atrial fibrillation (AF) patients. To date, most NOAC persistence studies have been retrospective and often did not include patients receiving edoxaban. Identifying predictors for non-persistence may be useful when considering the design of future studies and help develop strategies to reduce non-persistence in clinical practice. Purpose To define and describe patients who did not reach the end of the study period and were non-persistent to edoxaban during the 4-year follow-up of ETNA-AF-Europe. Methods ETNA-AF-Europe was a prospective, observational study conducted in AF patients receiving edoxaban. In this subanalysis, patients not reaching the end of the study period and patients who were non-persistent (defined as permanent discontinuation of edoxaban) after 4 years of treatment were examined, including patients switching to other NOACs and reasons for discontinuation. Baseline predictors for not reaching the end of the study period and baseline predictors for non-persistence with edoxaban treatment during 4 years of follow-up were also examined. Persistent patients may have missed dose/interruption. Results Overall, 13,164 patients were included in the analysis. During the whole study period, 14.3% died. At the end of the study, 27.3% of patients prematurely terminated the study and 71.5% were classified as completing the study. Of patients who left the study (n=3598), 30.2% were lost-to-follow-up, 6.9% withdrew consent, and 5.9% transferred to another institution. Of patients who completed the study (n=9417), 87.4% were classified as persistent within the 4 years. Only 6.2% permanently discontinued edoxaban without switching to another NOAC (Table). Following backwards elimination, baseline characteristics associated with premature study termination (excluding death) were male sex, low body mass index, low renal function, chronic hepatic disease, long standing persistent/permanent AF, smoking, low compliance as judged by investigator, vitamin K antagonist-naïve, and no rate/rhythm control drug at baseline. Characteristics associated with non-persistence were increasing age, male sex, body weight extremes, low renal function, heart failure, vascular disease, chronic hepatic disease, alcohol use, perceived frailty, chronic obstructive pulmonary disease, smoking, current AF symptoms, and ablation (Figure). The criterion for backward elimination was p=0.05. Conclusions Most patients in ETNA-AF-Europe reached the end of the study. Less than a quarter were classified as non-persistent during the 4-year follow-up. The majority of patients who were non-persistent switched to another NOAC with a small number completely stopping anticoagulant therapy. Male sex, low renal function, chronic hepatic disease, and smoking were associated with both treatment discontinuation and non-persistence.Termination and persistence

Rivaroxaban or warfarin in atrial fibrillation and coronary stent implantation in real-world patients involving chronic kidney disease (REWRAPS): 5-year follow-up study

Abstract Background Recent guidelines recommended either non vitamin K antagonist oral anticoagulants (NOAC) or vitamin K oral anticoagulant (VKA) one year after coronary stenting in patients with atrial-fibrillation (AF). However, whether NOAC is still superior to VKA at 5-years in patients involving chronic kidney disease (CKD) with AF and coronary stenting >1-year remains unclear. Methods In a multicenter, prospective, non-randomized registry, 493 patients were treated with either rivaroxaban or warfarin, while the majority (66.3%) of them had CKD. The primary efficacy endpoint was major adverse cardiac and cerebral events (MACCE). The primary safety endpoint was major bleeding (Bleeding Academic Research Consortium [BARC] 3 and 5). Net adverse clinical events (NACE) were defined as the composite of all-cause mortality and major bleeding. Both crude and propensity score matched (PSM) analyses were performed. P <0.05 was considered as statistically significant. Results At a median follow-up of 4.8 years MACCE rates did not differ between rivaroxaban and warfarin in 486 patients with crude-analysis (23.0% versus 29.0%, hazard-ratio [HR], 0.79; 95% confidence interval [CI], 0.55 to 1.11; P=0.17), while in 316 patients with PSM-analysis rivaroxaban met non-inferiority criteria to warfarin (HR, 0.86; 95% CI, 0.56 to 1.33; p=0.020 for non-inferiority). Rivaroxaban was associated with lower major bleeding risk compared with warfarin (6.5% versus 12.6%; HR, 0.50; 95% CI, 0.27 to 0.91; P=0.025) at crude analyses, which was no longer significant at PSM analyses (5.7% versus 10.8%; HR, 0.53; 95% CI, 0.24 to 1.19; P=0.12). However, NACE rates were significantly lower in rivaroxaban compared to warfarin at both crude (19.0% versus 35.7%; HR, 0.50; 95% CI, 0.35 to 0.72; P=0.0002) and PSM-analyses (19.6% versus 31.0%; HR, 0.63; 95% CI, 0.40 to 0.98; P=0.043), respectively. Conclusions Rivaroxaban did not differ from warfarin for efficacy endpoints of MACCE but was associated with lower NACE rates (i.e. all-cause mortality and major bleeding) in AF and coronary stent in real-world patients having CKD at 5-year follow-up (NCT02024230).

Implications of renal function on adverse clinical events in patients with atrial fibrillation: a comparative analysis of VKA and NOAC therapy - Insights from the GLORIA-AF Registry Phase III

Abstract Background Renal function, as assessed by creatinine clearance (CrCl), plays a crucial role in determining the efficacy and safety of oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF). Purpose To investigate the relationships between CrCl and the risk of clinical adverse events in patients with AF receiving OAC therapy, comparing the safety profiles of vitamin K antagonists (VKA) and non-vitamin K antagonist oral anticoagulants (NOACs). Methods Anticoagulated AF patients from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry Phase III were studied. CrCl was calculated for renal function, according to Cockcroft-Gault equation. Restricted cubic spline (RCS) were used to explore the nonlinear association between adverse end events and CrCl, comparing VKA and NOAC therapy. Cox regression models were used to analysis the associations between adverse end events and OAC therapy in patients with different CrCl levels, adjusted by clinical features and previous disease. Patients were followed up for the composite outcome (all-cause death, thromboembolism and major bleeding), all-cause death, cardiovascular disease (CVD), major bleeding, myocardial infarction (MI) and stroke. Results In 10,594 AF patients (mean age 70.35 ± 9.92 years; 55% male; 73% on NOAC), RCS analysis revealed decreased risks of all cause death, composite outcomes and CVD with increasing CrCl in patients with CrCl < 80 mL/min. Multivariate Cox models indicated that NOAC therapy associated with lower risk of all cause death (HR 0.68, 95% CI 0.58-0.78), composite outcomes (HR 0.77, 95% CI 0.68-0.86), CVD (HR 0.7, 95% CI 0.56-0.87), major bleeding (HR 0.74, 95% CI 0.61-0.91) in AF patients. For CrCl > 95 mL/min, a lower risk of all cause death (HR 0.56, 95% CI 0.38-0.82), composite outcomes (HR 0.68, 95% CI 0.51-0.91) and major bleeding (HR 0.54, 95% CI 0.35-0.85) were associated with NOAC therapy, vs. VKA. For CrCl < 30 mL/min, a lower risk of all cause death (HR 0.47, 95% CI 0.28-0.81), composite outcomes (HR 0.56, 95% CI 0.35-0.89) and CVD (HR 0.43, 95% CI 0.20-0.90) were related to NOAC therapy. No significant difference in outcomes between VKA and NOAC were found in patients with moderate CrCl. Conclusion Increasing CrCl were associated with decreased risk of adverse clinical events, including all-cause death and CVD in anticoagulated AF patients. For patients with CrCl >= 95 and < 30, NOAC therapy, was associated with lower risks of adverse outcomes.Figure 1Figure 2

Anticoagulation status and left atrial appendage occlusion indications in hospitalized cardiology patients with atrial fibrillation: a Hellenic Cardiorenal Morbidity Snapshot (HECMOS) sub-study

Abstract Background Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (NVAF) patients. Left atrial appendage occlusion (LAAC) may be considered for stroke prevention in patients with NVAF and contraindications for long-term anticoagulant treatment. Purpose We aimed to assess the anticoagulation status and LAAC indications in patients with NVAF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Methods HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with poor adherence to anticoagulants, high bleeding risk, previous major bleeding, and previous stroke were considered candidates for LAAC. Results Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA 2 DS 2 - VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA 2 DS 2 -VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA 2 DS 2 -VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA 2 DS 2 -VASc > 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 77 patients with NVAF (53 had only one risk factor, while 22 had two and 2 patients had three concurrent risk factors). In detail, 15 reported poor or no adherence to the anticoagulant therapy, 17 patients had a history of major bleeding, 36 had a prior stroke and 35 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusion Αnticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. Three out of ten AF patients should be screened for LAAC.Anticoagulation by thrombotic riskPotential LAAC candidates

Dynamic recommendation for anticoagulant treatment in patients with atrial fibrillation using deep reinforcement learning method

Abstract Background Recent evidence suggests that the guideline-directed anticoagulant therapy for atrial fibrillation (AF) remains controversial. Widely-used CHA2DS2-VASc score is solely based on limited traditional cardiovascular risk factors, omitting AF characteristics and other markers of thromboembolic risk. A more efficient, safer and more personalized anticoagulant approach is warranted. Purpose To develop a data-driven deep reinforcement learning (DRL) model for guiding dynamic anticoagulant treatment in AF patients to improve cardiovascular outcomes. Methods Participants of this study were enrolled from the multicentred China Atrial Fibrillation (China-AF) Registry between August 2011 and December 2022, who were with regular follow-up every 6 months. We excluded patients on warfarin at baseline due to its declining usage trend in non-valvular AF patients in China. The DRL model was trained in 70% randomly selected patients for optimal dynamic decision-making, and then subsequently tested in the remaining 30%. Data of sociodemographic characteristics, AF characteristics, medical history, lifestyle factors, laboratory examination, and medications were input for model training. Concordance rate between DRL model’s recommendations and physicians’ actual decisions of non-vitamin-K-antagonist oral anticoagulant (NOAC) prescription among all visits before censoring was calculated for each patient. Primary outcome was the composite of cardiovascular death, ischemic stroke, transient ischemic attack or systemic embolism (SSE), and major bleeding. Shapley additive explanation analysis ranked the most important factors affecting decision-making of the DRL model. Results A total of 20068 patients (mean age: 63.0±12.0 years; 36.2% female) were randomly divided into a training cohort of 14050 patients and a testing cohort of 6018 patients. The model’s NOAC recommendations were mostly affected by age, prior NOAC prescription, body mass index, hypertension history and prior statin prescription (Figure 1). Patients with concordance rates of 50.1%-75% and 75.1%-100% had significant risk reductions for the primary outcome (adjusted HR =0.63; 95% CI, 0.46-0.85; P = 0.003 and adjusted HR =0.59; 95% CI, 0.46-0.75; P <0.001, respectively), compared to those with a concordance rate of 0-25%. Similar results were observed for all-cause death, cardiovascular death and SSE outcomes, that patients with the highest concordance rate had a significant lower risk, compared to those with the lowest concordance rate. There was a nonsignificant but similar trend with regard to major bleeding events (Figure 2). Conclusions This modelling study suggests that a data-driven DRL model might provide more efficient, safer and more personalized anticoagulant suggestions, potentially assisting physicians in clinical practice.

Prevention of mechanical valve thrombosis with a combination of the factor Xa inhibitor edoxaban plus aspirin in swine: intermediate results from the EdoValves project

Abstract Background Patients with an implanted mechanical heart valve (MHV) currently have a contraindication to the use of non-vitamin K antagonist oral anticoagulants (NOACs) based on the unfavorable results of the RE-ALIGN trial with dabigatran. We hypothesized that the combination of a Factor Xa inhibitor, acting upstream of thrombin generation, plus aspirin, may effectively prevent valve thrombosis, providing a much more friendly and viable alternative to vitamin K antagonists for such patients. We tested this in a swine model with a recently implanted mechanical valve prosthesis in the mitral position, combining the most unfavorable conditions promoting mechanical valve thrombosis, based on (a) the implanting position; (b) recent surgery; (c) the high thrombogenicity of the animal model. The study was approved by the Animal Ethics Committee of the University of Pisa and the Italian Ministry of Health and conducted according to Good Clinical Practices for Animal Experiments. Methods 17 farm male pigs, weighing ≈30 kg at the beginning, underwent cardiac surgery under general anesthesia and with extracorporeal circulation to receive a 25 mm or 27 mm bileaflet Corcym Bicarbon mechanical heart valve replacement in the mitral position. Pigs were given 1 mg/kg enoxaparin immediately after surgery and started with the oral daily administration of edoxaban 1 mg/kg (30 mg, then escalated to 60 mg with the animal growth) + aspirin 100 mg, both given as crushed tablets with a food pellet since the animal awakening from anesthesia. An initially planned warfarin control group was quickly abandoned because of the extreme difficulty of controlling warfarin activity. Animals were submitted to blood sampling and transthoracic echocardiography at least twice in the follow-up when uneventful for up to three months or in case of health deterioration. The autopsy was performed by a certified pathologist after each spontaneous death or procured sacrifice. Results (Figure 1): Excluding 5 peri-operative deaths, 12 animals survived surgery. Of those, 6 died within the second month: pulmonary edema occurred in 3 cases, due to prosthesis-mismatch in the growing animals; pulmonary infection occurred in 1 subject; heart failure due to valve thrombosis occurred in 2 cases. Six swine were full-term survivors in good health status up to the 3-month planned observational time. No hemorrhagic events were ever documented. Conclusion The combination of edoxaban + aspirin effectively avoided valve thrombosis events in 10 out of 12 (83%) analyzable animals and was safe from bleeding complications. The study is ongoing up to a predicted sample size of ≥20 animals. If further confirmed, these data may open the possibility of an alternative to vitamin K antagonists in humans with the fixed-dose drug combination here used, without the need for continuous anticoagulation monitoring and with expected greater safety.Figure 1

Comparison of ََQuality of Life and Treatment Satisfaction among Sample of Iraqi Patients Using Anticoagulant Therapy (Warfarin or Non-Vitamin K Antagonist Oral Anticoagulants)

Background: Oral anticoagulation medication, warfarin and non-vitamin k antagonist oral anticoagulants (NOAC) may require long term use which may affect patients’ satisfaction with their treatment and their quality of life (QOL). Objective: To compare the quality of life and treatment satisfaction among groups of patients using different anticoagulant therapies (warfarin and NOAC). Patients and methods: A cross-sectional study was performed at Ibn Al-Bitar Hospital for cardiac surgery in Baghdad in the period between December 2022 to May 2023. The study population included a convenient sample of patients receiving either warfarin or non-vitamin k antagonist oral anticoagulants treatment. The Arabic version of the short form 12 (SF-12) questionnaire and the Anti-Coagulant Treatment Satisfaction Scale (ACTS) questionnaire were used to assess the quality of life and satisfaction with treatment respectively. Results: The study included 181 patients in total. The mean physical and mental quality of life scores for study participants were 42.3±9.92 and 52.6±10.36 respectively. There was no significant difference in the QOL between patients taking warfarin and those on non-vitamin k antagonist oral anticoagulants treatment. The mean total satisfaction score was 65.4±6.73. Patients receiving non-vitamin k antagonist oral anticoagulants had significantly higher satisfaction compared to those receiving warfarin (P=0.000). The physical score correlated significantly with gender, educational level, employment status, number of chronic medications and number of chronic diseases. The total satisfaction score correlated significantly with gender, number of chronic medications, number of side effects and duration of anticoagulation. There was a significant correlation between the QOL and treatment satisfaction (P=0.000). Conclusion: Treatment with non-vitamin k antagonist oral anticoagulants showed comparable QOL and higher treatment satisfaction than that of warfarin. Better treatment satisfaction can improve patients’ QOL which may ultimately enhance their adherence to treatment.

Preparation and Characterization of Isradipine as Surfactant-Free Dry Emulsion

Background: Oral anticoagulation medication, warfarin, and non-vitamin K antagonist oral anticoagulants (NOAC) may require long-term use which may affect patients’ satisfaction with their treatment and their quality of life (QOL). Objective: To compare the quality of life and treatment satisfaction among groups of patients using different anticoagulant therapies (warfarin and NOAC). Methods: A cross-sectional study was performed at Ibn Al-Bitar Hospital for cardiac surgery in Baghdad in the period from December 2022 to May 2023. The study population included a convenient sample of patients receiving either warfarin or non-vitamin k antagonist oral anticoagulants treatment. The Arabic version of the short form 12 (SF-12) questionnaire and the Anti-Coagulant Treatment Satisfaction Scale (ACTS) questionnaire were used to assess the quality of life and satisfaction with treatment respectively. Results: The study included 181 patients in total. The mean physical and mental quality of life scores for study participants were 42.3±9.92 and 52.6±10.36 respectively. There was no significant difference in the QOL between patients taking warfarin and those on non-vitamin k antagonist oral anticoagulant treatment. The mean total satisfaction score was 65.4±6.73. Patients receiving non-vitamin k antagonist oral anticoagulants had significantly higher satisfaction compared to those receiving warfarin. The physical score correlated significantly with gender, educational level, employment status, number of chronic medications, and number of chronic diseases. The total satisfaction score correlated significantly with gender, number of chronic medications, number of side effects, and duration of anticoagulation. There was a significant correlation between the QOL and treatment satisfaction. Conclusion: Treatment with non-vitamin K antagonist oral anticoagulants showed comparable QOL and higher treatment satisfaction than that of warfarin. Better treatment satisfaction can improve patients’ QOL which may ultimately enhance their adherence to treatment.

Patent Foramen Ovale and Other Cardiopathies as Causes of Embolic Stroke With Unknown Source.

In patients with stroke caused by cardiac embolism, the responsible heart diseases include atrial fibrillation, acute myocardial infarction, sick sinus syndrome, valvular disease, and significant heart failure. When there is no clear source of the embolism, the condition is referred to as "embolic stroke with unknown source (ESUS)." Recent studies have shown that the most common cause of ESUS is a right-to-left cardiac shunt through a patent foramen ovale (PFO). However, considering that PFOs are found in up to 25% of the general population, their presence does not necessarily indicate causality. In patients with ESUS associated with a PFO, either anticoagulants or antiplatelets are used for the prevention of future strokes or transient ischemic attacks. However, it currently remains unclear which treatment is superior. Nevertheless, recent randomized clinical trials have shown that percutaneous closure of the PFO more effectively reduces the incidence of recurrent strokes compared to medical therapy alone in patients with PFO-related strokes. This benefit is especially significant when the PFO carries high-risk features, such as a large shunt or the presence of an atrial septal aneurysm. Furthermore, the effectiveness of PFO closure has been well documented in young patients (<60 years) with a high-risk PFO development. In other cases, the therapeutic decision should be made through discussion among neurologists, cardiologists, and patients. Notably, in ESUS patients without a PFO, the underlying heart condition itself may be the source of embolism, with left atrial enlargement being the most important factor. Theoretically, anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) would be an effective therapy in these cases. However, recent trials have failed to show that NOACs are superior to antiplatelets in preventing further strokes in these patients. This may be due to the still uncertain definition of emboligenic cardiopathy and the presence of other potential embolic sources, such as mild but emboligenic arterial diseases. Overall, further research is needed to elucidate the source of embolism and to determine an effective management strategy for patients with ESUS.

Apixaban, edoxaban and rivaroxaban but not dabigatran are associated with higher mortality compared to vitamin-K antagonists: A retrospective German claims data analysis.

Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials. Using administrative data from a large German health insurance, we included all anticoagulation-naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding. Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching-cohort (PSM-cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all p<0.001) but not for dabigatran (p=0.13) compared to VKA. In this PSM-cohort, 5-year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all p<0.001) and 13.0% for dabigatran versus 12.8% for VKA (p=0.06). The observed effect was confirmed in sensitivity analyses using un-weighted and three different weighted Fine-Gray regression models on the basis of the entire cohort. In this large real-world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants Compared with Vitamin K Antagonists in Patients with Atrial Fibrillation and Type 2 Valvular Heart Disease: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and type 2 valvular heart disease (VHD). We searched the PubMed, LILACS, and MEDLINE databases to retrieve, randomized controlled trials (RCTs) comparing NOACs and VKAs in patients with AF and type 2 VHD, excluding mitral stenosis (moderate to severe, of rheumatic origin) or mechanical heart valves. The efficacy outcomes assessed were stroke and systemic embolism (SE), while safety outcomes included major bleeding and intracranial hemorrhage (ICH). Seven RCTs, including 16,070 patients with AF and type 2 VHD, were included. NOACs reduced the risk of stroke/SE (relative risk [RR], 0.75; 95% confidence interval [CI], 0.64-0.89; P = 0.0005), with no significant difference in major bleeding (RR, 0.88; 95% CI, 0.64-1.21; P = 0.43). The risk of ICH was reduced with NOACs (RR, 0.46; 95% CI, 0.27-0.77; P = 0.003). For patients with AF and bioprosthetic heart valve (five trials, 2805 patients), stroke/SE risks (RR, 0.65, 95% CI, 0.44-0.96) with NOACs were superior to VKAs. Major bleeding risks without ENVISAGE TAVI AF trial (RR, 0.53; 95% CI, 0.30-0.94; P = 0.03) with NOACs were superior to VKAs. The risks of ICH (RR, 0.61; 95% CI 0.34-1.09; P = 0.09) with NOACs were comparable to VKAs. NOACs demonstrate efficacy and safety in patients with AF and type 2 VHD and reduce the risk of stroke/SE and ICH when compared with those with VKAs.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in low-weight patients with atrial fibrillation.

It remains unclear whether non-vitamin K antagonist oral anticoagulants (NOACs) are more effective and safer than warfarin in low-weight patients with atrial fibrillation (AF). Here, we retrospectively compared the effectiveness and safety of NOACs with those of warfarin in low-weight patients with AF. We extracted the July 2011-September 2022 data of patients with AF treated with a NOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) or warfarin at a tertiary hospital. The patients were divided into low-weight (body weight ≤ 60 kg) and non-low-weight (body weight = 60-100 kg) groups. The primary outcomes were hospitalization for ischemic stroke (IS) or systemic embolism (SE) and major bleeding, whereas the secondary outcomes were any ischemic and bleeding events. We used the inverse probability of treatment weighting to balance the baseline characteristics between the groups. In total, 5,044 patients (mean age = 73.7 years, mean CHA2DS2-VASc score = 3.0, mean HAS-BLED score = 2.3) were enrolled and divided into low-weight and non-low-weight groups-containing 1,666 (1,406 NOAC users, 260 warfarin users) and 3,378 (2,978 NOAC users, 400 warfarin users) patients, respectively. NOACs were associated with a lower risk of any bleeding event in the low-weight group (adjusted hazard ratio = 0.61, 95% confidence interval = 0.51-0.73). The between-group differences in the risks of IS/SE, any ischemic event, major bleeding, and any bleeding event were nonsignificant. Thus, the use of NOACs (specifically dabigatran or edoxaban) is associated with a lower risk of any bleeding event than warfarin use in low-weight patients with AF.

Risk of gastrointestinal bleeding in Asian patients receiving oral anticoagulants for stroke prevention in atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in atrial fibrillation. At the Asia Pacific Advancing Patient care with EdoXaban 2023 meeting, experts shared insights on gastrointestinal bleeding with NOACs for stroke prevention in atrial fibrillation in Asian clinical practice, where NOACs have gained widespread acceptance due to their favourable profiles. Gastrointestinal bleeding risk varies amongst NOACs, emphasizing the importance of diligent patient assessment, dosage selection and vigilant monitoring. Edoxaban emerged as a viable option with a low gastrointestinal bleeding risk profile in Asian compared with non-Asian patients, supporting its continued clinical utilization for appropriate patients.

Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.

The use of non-vitamin K antagonist oral anticoagulants (NOACs) has brought a significant progress in the management of cardiovascular diseases, considered clinically superior to vitamin K antagonists (VKAs) particularly in the prevention and treatment of thromboembolic events. In addition, numerous advantages such as fixed dosing, lack of laboratory monitoring, and fewer food and drug-to-drug interactions make the use of NOACs superior to VKAs. While NOACs are synthetic drugs prescribed for specific conditions, nattokinase (NK) is a natural enzyme derived from food that has potential health benefits. Various experimental and clinical studies reported the positive effects of NK on the circulatory system, including the thinning of blood and the dissolution of blood clots. This enzyme showed not only fibrinolytic activity due to its ability to degrade fibrin, but also an affinity as a substrate for plasmin. Recent studies have shown that NK has additional cardioprotective effects, such as antihypertensive and anti-atherosclerotic effects. In this narrative review, we presented the cardioprotective properties of two different approaches that go beyond anticoagulation: NOACs and NK. By combining evidence from basic research with clinical findings, we aim to elucidate the comparative cardioprotective efficacy of these interventions and highlight their respective roles in modern cardiovascular care.

Atrial fibrillation fact sheet in Korea 2024: part 2—stroke prevention in Korean patients with atrial fibrillation

ObjectiveAtrial fibrillation (AF) increases the risk of thromboembolic events, making oral anticoagulants (OACs) essential for high-risk patients. This fact sheet provides nationwide statistics on AF management for stroke prevention in Korea. We aimed to evaluate current anticoagulation treatment trends and strategies in Korea.MethodThe Korean national health claims database from the National Health Insurance Service was used. AF patients aged ≥ 18 years from 2013 to 2022 were included. OAC use, including warfarin and non-vitamin K antagonist OACs (NOACs), was tracked through prescription data. The rates of OAC use were calculated based on continued use, considering prescription dates and amounts. For patients with multiple encounters, the last encounter was used for analysis.ResultsDuring the study, 20.4% of strokes were accompanied by AF, with AF diagnosed within 6 months before or after the stroke. The number of patients diagnosed with AF after a stroke increased from 4893 in 2013 to 6978 in 2022. Among newly diagnosed AF patients requiring OACs, 51% were not prescribed OACs within 6 months. OAC treatment rates for high-risk AF patients increased from 44.6% in 2013 to 77.5% in 2022, with NOAC prescriptions rising significantly after 2015. Regional variations in OAC prescription rates were observed, with lower rates in suburban/rural areas than in urban regions (76.0% vs. 79.6%, p < 0.001).ConclusionsConsiderable strokes could have been prevented with earlier AF detection and OAC treatment through more intensive electrocardiogram screening.

The use of non-vitamin K antagonist oral anticoagulants in chronic thromboembolic pulmonary hypertension: an updated meta-analysis.

Studies have demonstrated the beneficial effects of non-vitamin K antagonist oral anticoagulants (NOACs) for the treatment of atrial fibrillation and venous thromboembolism (VTE). The impact of NOACs on chronic thromboembolic pulmonary hypertension (CTEPH) remains controversial. This meta-analysis was conducted to investigate the effectiveness and safety of NOACs compared with vitamin K antagonists (VKAs) in patients with CTEPH. A comprehensive search of PubMed, Embase, and Cochrane Library was conducted for relevant studies, encompassing data from inception until November 2023. The data were pooled using a fixed-effects model if the I2 value was less than 50%; otherwise, a random-effects model was employed. Overall, two randomized controlled trials (RCTs) and eight observational studies involving 4556 patients with CTEPH were included. Patients receiving NOACs exhibited a significantly lower incidence of all-cause mortality (odds ratio [OR] = 0.52, 95% confidence interval [CI]: 0.36-0.76) and major bleeding (OR = 0.58, 95% CI: 0.36-0.92) compared to those with VKAs. There were no significant differences in the rate of VTE recurrence (OR = 1.07, 95% CI: 0.72-1.59), total bleeding (OR = 0.78, 95% CI: 0.60-1.01), and minor bleeding (OR = 1.11, 95% CI: 0.73-1.69) between the two studied groups. Similar results were found in the subgroup analysis and sensitivity analysis.This meta-analysis provided evidence that NOACs could be superior to VKAs for the treatment of CTEPH. NOACs might be safe and a convenient alternative to VKAs for thromboprophylaxis in patients with CTEPH.

Challenges, Recommendations, and Epidemiology of Pulmonary Embolism in India: A Narrative Review.

An embolized clot that travels to the lungs from the legs or, less commonly, other parts of the body (known as deep vein thrombosis or DVT) causes pulmonary embolism (PE), which is characterized by obstruction of blood flow to the pulmonary artery. As PE has the propensity to masquerade as various illnesses affecting both the cardiovascular (CV) and the respiratory system, it is crucial to identify PE at the earliest. Appropriate diagnosis of PE may lead to earlier treatment and improved patient outcomes. While pulmonary angiography remains the established gold standard for diagnosing PE, the contemporary standard of care for this condition is the computed tomography pulmonary angiogram (CTPA). Anticoagulation therapy is the fundamental strategy for managing PE, with the forefront of treatment being the use of novel and upcoming oral anticoagulants known as non-vitamin K antagonist oral anticoagulants (NOACs). The NOACs provide a practical single-drug treatment strategy, which does not hinder the patient's lifestyle and domestic responsibilities. Although PE may be fatal, early detection may lead to effective management. Despite that, mortality and morbidity associated with PE are very high in India. The awareness among Indian healthcare professionals about PE should be improved, and unified pan-country diagnostic and management guidelines should be formulated to tackle the country's PE burden.