Non-vitamin K Antagonist Oral Anticoagulants Research Articles

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.

Implementation of an atrial fibrillation better care (ABC) pathway management strategy: Findings from the Iranian registry of atrial fibrillation

IntroductionThe Atrial Fibrillation Better Care (ABC) pathway is such an integrated care approach, recommended in guidelines. The aim of this service evaluation study was to evaluate the impact of implementing the ABC pathway in Iranian population. MethodsIn this prospective longitudinal cohort study, consecutive patients with a diagnosis of AF were initially evaluated. Patients at baseline were evaluated in hence of adherence to ABC pathway strategy. After study enrolment, first and second follow-up service evaluations were conducted at 6 and 12 months, respectively. ResultsThe use of vitamin K antagonists (VKA) decreased from 25.1 % at enrolment to 13.8 % at follow-up; instead, non-VKA oral anticoagulants (NOAC) utilization increased from 40.0 % to 86.1 %, while antiplatelet treatment decreased from 34.9 % to 0 %. Use of antihypertensive drugs, ARBs, diuretics, and statins increased after implementation of the ABC pathway. Implementation of the ABC pathway approach led to a decrease in the occurrence of stroke/TIA (from 6.3 % to 2.2 %, p = 0.002), systemic thromboembolism (from 1.4 % to 0.0 %, p = 0.04), nose bleeds (from 0.8 % to 0.6 %, p = 0.04), skin bruising (from 1.2 % to 0.0 %, p = 0.002), and heart failure (from 7.7 % to 4.7 %, p = 0.04). The proportion of patients in EHRA Class I-II increased from 93.3 % at enrolment to 98.1 % at follow-up. ConclusionIn this first study from a Middle East population, compliance with ABC pathway strategy in the management of AF was associated with optimization of management and general improvements in patient outcomes during follow-up.

Association between antithrombotic drug regimen changes and clinical outcomes after stroke in atrial fibrillation

BackgroundThe impact of post-stroke antithrombotic regimen in atrial fibrillation is uncertain. ObjectiveThis study aimed to describe antithrombotic therapy prescribing patterns after ischemic stroke and the impact on outcomes. MethodsA total of 23,165 patients with atrial fibrillation experiencing ischemic stroke were identified. Subsequent post-stroke events included recurrent ischemic stroke, intracranial hemorrhage, major bleeding, mortality, and composite outcomes. ResultsOf those who were nonanticoagulated before a stroke, 33.5% remained nonanticoagulated and 39.2% were prescribed only antiplatelet agents (APs) after a stroke. Compared with non–vitamin K antagonist oral anticoagulants (NOACs) after stroke, there was a significant increase in ischemic stroke and mortality in nonanticoagulated patients (adjusted hazard ratio [aHR], 2.09 and 3.92) and AP users (aHR, 1.32 and 1.28). Post-stroke warfarin was associated with a significantly increased risk of major bleeding compared with NOACs (aHR, 1.23). Of 769 patients receiving NOACs before stroke and continuing NOACs after stroke, those switching to a different NOAC were associated with significantly higher risk of ischemic stroke (aHR, 2.07) and composite outcomes (aHR, 1.36–1.85) with no difference in intracranial hemorrhage, major bleeding, or mortality compared with those receiving the same NOAC after stroke. Of patients receiving NOACs before stroke, the risks of clinical events were similar between patients taking NOACs alone and those taking NOAC plus AP after stroke. ConclusionNOAC alone after stroke was associated with a better clinical outcome compared with nonanticoagulation, AP, or warfarin. Of patients already taking NOACs before stroke, the addition of AP did not confer additional benefits compared with NOACs alone. A change of NOAC types after stroke was associated with a 2-fold higher risk of ischemic stroke and composite outcomes.

Non-vitamin K versus vitamin K antagonist oral anticoagulants in surgical mitral valve repair or bioprosthetic valve replacement in the first three months after surgery

Introduction and ObjectivesOral anticoagulation (OAC) with non-vitamin K antagonist oral anticoagulants (NOACs) after surgical mitral valve repair (MVR) or bioprosthetic valve replacement (BVR) in mitral position remains a controversial topic among the cardiovascular community, in particular in the early postoperative period. This study aimed to evaluate the efficacy and safety of NOACs in the first three months after MVR or mitral BVR compared to vitamin K antagonists (VKAs). MethodsThis was a single-center retrospective study with prospectively collected peri-intervention outcomes between 2020 and 2021. Records were retrieved and all participants were contacted by telephone. Patients were divided into groups according to OAC strategy. The primary outcome was a composite of death, rehospitalization, myocardial infarction, stroke or transient ischemic attack, systemic embolism, mitral thrombosis, or bleeding during the first three months after surgery. ResultsA total of 148 patients were enrolled, with a mean age of 65.5±12.2 years, 56.8% male. On discharge, 98 (66.2%) patients were on VKAs and 50 (33.8%) were on DOACs for at least three months. The primary outcome occurred in 22 (22.4%) patients in the VKA group and in three (6%) in the NOAC group (p=0.012), mainly driven by more bleeding events in the former. Independent predictors of the primary outcome were smoking (p=0.028) and OAC with VKAs at discharge, the latter predicting three times more events (p=0.046, OR 3.72, 95% CI 1.02–13.5). ConclusionsNOACs were associated with fewer events, supporting their efficacy and safety during the first three months after surgical MVR or mitral BVR.

Safety and efficacy of concomitant treatment with non-vitamin K antagonist oral anticoagulants and antiseizure medications: A propensity score matching cohort study.

Research on cerebrovascular events in atrial fibrillation (AF) patients taking non-vitamin K antagonist oral anticoagulants (NOACs) with antiseizure medications (ASMs) is limited, highlighting a significant gap in literature. We assessed thrombotic and hemorrhagic risks in patients on NOACs and ASMs versus those on NOACs or ASMs alone. We analyzed a retrospective cohort from five centers, including AF and epilepsy patients on both medications (n = 188), AF patients on NOACs (n = 298), and epilepsy patients on ASMs (n = 50), with a 3-year follow-up. Propensity score matching adjusted for cardiovascular risk differences. The primary outcomes were ischemic stroke, transient ischemic attack, and major bleeding. Results showed the ASM+NOAC group had a higher risk of primary outcomes compared to the NOAC-only group (5.68% vs. 1.18%, hazard ratio = 5.72, 95% confidence interval = 2.22-14.73), with no events in the ASM-only group. This suggests an increased risk for patients on combined NOAC and ASM therapy, underlining the need for careful drug interaction consideration.

Employing Real-World Evidence for the Economic Evaluation of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation in Thailand.

This study aimed to assess the cost-effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) in comparison with warfarin using data from real practice based on the perspective of the health care system in Thailand. A four-state Markov model encompassing well-controlled atrial fibrillation (AF), stroke and systemic embolism, major bleeding and death was utilised to forecast clinical and economic outcomes. Transitional probabilities, direct medical costs and utilities were derived from the real-world data of the 'COOL-AF Thailand' registry, Thailand's largest nationwide registry spanning 27 hospitals. The cohort comprised AF patients. The primary outcomes assessed were total costs, life years, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio. All costs and outcomes were subject to an annual discount rate of 3.0%. A spectrum of sensitivity analyses was conducted. The mean age of the cohort was 68.8±10.7 years. The NOACs group incurred a marginally lower total lifetime cost than the warfarin group (247,857 Thai baht [THB] vs 253,654 THB or 7137 USD vs 7304 USD) and experienced gains of 0.045 life years and 0.043 QALYs over the warfarin group. Given the lower cost and higher benefits associated with NOACs, this implies that NOAC treatment is a dominant strategy compared to warfarin for AF patients. At a ceiling ratio of 160,000 THB (4607 USD) per QALY, NOACs presented a 61.2% probability of being cost effective. Non-vitamin K antagonist oral anticoagulants represent a cost-saving alternative to warfarin in the real clinical practice. However, with a probability of being cost effective below 65%, it suggests some parameter uncertainty regarding their overall cost effectiveness compared to warfarin.

Patient-reported treatment burden: comparison between vitamin-K antagonist and non-vitamin K antagonist oral anticoagulants

Abstract Introduction Treatment burden (TB) is defined as the overall workload that maintenance or improvement of their functioning and well-being poses on patients with chronic medical conditions. A high patient-reported TB has been associated with lower adherence to treatment and increased risk of major adverse events including death. We explored the differences in patient-reported TB value and prevalence of unacceptably high TB score (≥59 points) between patients receiving vitamin K antagonist oral anticoagulants (VKA) and non-vitamin K antagonist oral anticoagulants (NOAC). Furthermore, we explored contributory factors associated with TB and the relationship between TB and quality of life (QoL) in these patients. Methods A single-centre study included consecutive adult in- and outpatients on long-term oral anticoagulation, seen at a university clinical centre a from April to June 2019, who were willing to complete the Treatment Burden Questionnaire encompassing 13 items assessing the TB associated with taking medicine, self-monitoring, laboratory assessments, medical consultations, organisational and administrative requirements, adherence to dietary and physical activity recommendations, as well as the social repercussions of the treatment. Results Of 320 enroled patients, 206 (64.4%) were taking a VKA. Atrial fibrillation was the most common indication for long-term oral anticoagulation (n=299, 93.4%). The mean TB score was significantly higher in patients on VKA versus those taking a NOAC (48.8 ±26.5 vs. 41.8 ±19.7, P= 0.014), mostly owing to significantly higher TB values for questions related to self-monitoring, including the International Normalized Ratio (INR) control (3.85±3.32 vs. 1.62±1.38, P<0.001) and diet restrictions (3.98±3.43 vs. 2.48±2.49, P<0.001) in patients taking VKA (Figure 1). In addition, these patients significantly more often reported an unacceptably high TB of ≥59 points compared with those taking NOAC (30.1% vs 18.4%, P= 0.024). Multivariable regression analysis of predictors of TB in patients taking a VKA or NOAC are presented in Table 1. Conclusion In our study, patients receiving a VKA reported significantly higher TB compared to those using NOAC, especially regarding the questions about self-monitoring (including INR control) and diet restrictions. An unacceptably high TB was also more prevalent among patients receiving a VKA. Our findings suggest that prescribing NOACs in preference to VKAs could help in decreasing the self-reported TB in patients who need oral anticoagulant therapy.

Predicting bleeding risk in frail older patients with atrial fibrillation using data from the FRAIL-AF trial

Abstract Background Bleeding remains an important complication in anticoagulated patients with atrial fibrillation (AF). Hereto, multiple scores have been developed to predict bleeding risk and subsequently identify a subset of patients in whom additional effort may be warranted to lower the risk of bleeding. Bleeding risk is particularly high in frail older individuals with AF. Yet to what extent existing scores can accurately identify patients at high risk in this population is unknown. Purpose To validate existing bleeding risk scores for predicting bleeding in frail older AF patients using oral anticoagulants. Methods We used data from the FRAIL-AF trial that randomized frail AF patients ≥75 years of age between continuing vitamin K antagonist (VKA) treatment or switching to non-VKA oral anticoagulant (NOAC) treatment. The outcome was major or clinically relevant non-major bleeding. We validated 4 existing bleeding risk scores: ORBIT, ATRIA, AF-BLEED and (the recently derived) DOAC-score. We used cause specific cox proportional hazard models with all-cause mortality as a competing risk, with the number of points on each score as a univariate variable to calculate discrimination by means of the c-statistic for each score. Next, to assess clinical utility, we estimated the incidence bleeding rates for patients classified as low-risk and high-risk by each respective score. Results In total 661 patients continued VKA treatment, and 663 switched to any NOAC. An additional 66 patients, originally excluded from randomization due to an estimated glomerular filtration rate (eGFR) ≤30 ml/min/1.73 m2 but followed observationally were included in the current analysis. The median age was 82.3 years (interquartile range (IQR) 78.7 – 86.6), 61.4% were male. Median eGFR was 61 (IQR 49 – 57), 54% had hypertension, 14% a previous bleeding, and 1.2% liver disease. In total 172 first bleedings occurred. Discrimination of all risk scores was poor, both in VKA and in NOAC users. Table 1 shows the c-statistics across the different risk scores; ranging from 0.54 to 0.56. The observed risk of bleeding in the low-risk category varied widely, see Table 2. Conclusion Existing bleeding risk scores are unable to accurately predict the bleeding risk in frail older patients with AF. Novel risk tools are needed for this growing population of vulnerable AF patients at high risk of bleeding.

Outcomes of on-label reduced-dose edoxaban in octogenarian patients with atrial fibrillation

Abstract Background Non-vitamin K antagonist oral anticoagulants (NOACs) are effective in preventing thromboembolisms and reduce the risk of bleeding compared with warfarin. There are few reports on the outcomes of on-label reduced-dose NOACs. Purpose The aim of this study was to assess the safety and efficacy of on-label reduced-dose edoxaban in octogenarian patients with atrial fibrillation (AF). Methods This study is a multi-center, prospective, non-interventional study to evaluate the safety and efficacy of on-label reduced-dose edoxaban in patients with AF. We evaluated outcomes of major bleeding, stroke or systemic embolism, all-cause death, and composite clinical outcomes. Results A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study. 932 patients (38.1%) were octogenarians. Major bleeding events occurred at a rate of 1.69%/yr in octogenarian patients and 0.9%/yr in non-octogenarian patients. The event rate of strokes and systemic embolisms was 1.93%/yr in octogenarian patients and 0.66%/yr in non-octogenarian patients The overall net clinical outcomes occurred at a rate of 5.45%/yr in octogenarian patients and 2.24%/yr in non-octogenarian patients. Conclusions Reduced-dose edoxaban can be used safely in Asian patients with very elderly patients. Older age was associated with a higher risk of ischemic stroke and composite adverse events.

Quality of life when switching from a vitamin K antagonist to non-vitamin K antagonist oral anticoagulation in frail older patients with atrial fibrillation

Abstract Background Many older patients with atrial fibrillation (AF) are frail, putting them at high risk of adverse outcomes including mortality, hospitalization, functional decline, and dependency on others. In this special population, management strategies – such as anticoagulation for stroke prevention – need special consideration. To what extent the type of anticoagulation influences the quality of life (QoL) in frail patients with AF is unclear. Purpose To assess QoL in frail older patients with AF switching from a vitamin K antagonist (VKA) to a non-VKA oral anticoagulant (NOAC), as compared to patients continuing a VKA. Methods We used data from the FRAIL-AF trial that randomized frail older AF patients between continuing VKA treatment or switching to any NOAC. At baseline, after six months and twelve months of follow-up, QoL was assessed using the EQ-5D-5L questionnaire. For every timepoint, the mean EQ-5D-5L score was calculated with corresponding 95% confidence intervals (CI), missing data were imputed using ten-fold multiple imputation. Absolute differences in EQ-5D-5L score were calculated between patients switching to a NOAC and patients continuing with a VKA, with corresponding 95% CI. The distribution of the scores on each domain of the EQ-5D-5L was compared using a chi-square test. Results In total 661 patients continued VKA treatment, and 663 switched to a NOAC. The median age was 82.2 years (interquartile range (IQR) 78.7 – 86.5), 61.3% were male. Major bleeding or clinically relevant non-major bleeding occurred in 101 patients (17.8 per 100 person-years) switching to NOAC therapy, and 62 patients (10.5 events per 100 person-years) continuing with a VKA (hazard ratio 1.69, 95% confidence interval 1.23 – 2.32). Mortality occurred in 44 and 46 patients, respectively. In 25 patients data was missing. Table 1 shows the mean EQ-5D-5L scores at baseline, at 6 months follow-up and at 12 months follow-up. Scores were similar between patients switching to NOAC treatment or continuing with a VKA and did not change significantly during 12 months follow-up. Table 2 shows the distribution of the scores on all domains of the EQ-5D-5L, with no significant differences between groups. Conclusion Switching from a VKA to a NOAC in frail older patients with AF was associated with an increased risk of bleeding, yet without any effect on overall and different domains of QoL.

#1279 Efficacy and safety of non-vitamin K antagonist oral anticoagulants in renal transplant recipients with atrial fibrillation

Abstract Background and Aims Atrial fibrillation (AF) is associated with increased stroke and bleeding risk in patients with chronic kidney disease (CKD) including renal transplant recipients (RTRs). Little is known about the real-life use of non-vitamin K antagonist oral anticoagulants (NOACs) in RTRs. Method In a retrospective cohort study conducted in one academic transplant center, we enrolled consecutive 168 RTRs with AF on NOACs including 139 (82.7%) subjects on apixaban 5 or 10 mg/day, 18 (10.7%) on rivaroxaban 15 or 20 mg/day, 6 (3.6%) subjects on edoxaban 30 mg/day and 5 patients (3.0%) firstly treated with rivaroxaban and then switched to apixaban. Thromboembolic (stroke, transient ischemic attack, systolic embolism) and bleeding events (major and clinically relevant non-major bleeding) were recorded during a median follow-up of 21.2 months. There were no significant differences in demographic, clinical, and laboratory variables at baseline between the 3 treatment groups (Fig. 1). Results During follow-up, arterial thromboembolic events occurred in 9 (6.3%) subjects on apixaban and 4 (18.2%) on rivaroxaban. Patients treated with rivaroxaban did not have a significantly higher hazard of arterial thromboembolic events when compared with those on apixaban (hazard ratio [HR] 2.04; 95% CI: 0.68-6.12, p=0.21). Major bleeding or clinically relevant non-major bleeding occurred in 17 (11.8%) patients receiving apixaban (one experienced both events), 3 (13.0%) patients on rivaroxaban, and 2 (33.3%) on edoxaban. When compared to apixaban, the other NOACs did not significantly differ in the hazard of bleeding [rivaroxaban: HR 0.79 (95% CI: 0.24-2.58; p=0.69); edoxaban: HR 1.90 (95% CI: 0.35-10.27; p=0.46)]. Conclusion The study suggests that RTRs with AF receiving apixaban and rivaroxaban have a similar risk of thromboembolism and bleeding in the everyday practice of the academic transplantation center. Edoxaban was rarely chosen in this group of patients, therefore evidence is uncertain.

Perioperative Management in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Minor Bleeding Risk Procedure: Rationale and Protocol for the PERIXa Study.

While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks. This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk. This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events. This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk. Clinicaltrials.gov: NCT05801068.

Oral anticoagulants and cognitive impairment in patients with atrial fibrillation: A systematic review with meta-analysis and trial sequential analysis

BackgroundThis systematic review assesses the likelihood of developing dementia and cognitive impairment in patients with atrial fibrillation (AF) receiving non-vitamin K antagonist oral anticoagulants (NOACs) as opposed to vitamin K antagonists (VKAs). MethodsWe performed a systematic review with meta-analysis and trial sequential analysis (TSA), which encompassed both randomized controlled trials (RCTs) and observational studies. The objective was to assess the impact of NOACs and VKAs on the incidence of dementia in individuals diagnosed with AF. ResultsOut of 1914 studies that were screened, 31 studies were included in the final analysis, which consisted of nine RCTs or their subsequent post-hoc analyses, in addition to 22 observational studies. The meta-analysis shows that NOACs were associated with a decreased probability of developing dementia of any cause [Rate Ratio (RR): 0.88; 95 % confidence interval (95 % CI): 0.82–0.94], especially in patients below the age of 75 (RR: 0.78; 95 % CI: 0.73–0.84). Consistent patterns were observed across all forms of dementia and cognitive function decline. The overall evidence indicates notable variability in the outcome with a moderate-to-low degree of certainty. The TSA suggests that the total sample size of the included trials (155,647 patients) was significantly smaller than the required information size of 784,692 patients to discern the true effect of NOAC versus VKA in terms of reducing dementia risk. ConclusionNOACs may reduce the likelihood of developing dementia in patients with AF, particularly in those under the age of 75. This review highlights the urgent necessity for thorough research to determine the efficacy of NOACs in safeguarding cognitive health.

Clinical Care Pathway and Management of Major Bleeding Associated with Nonvitamin K Antagonist Oral Anticoagulants: A Modified Delphi Consensus from Saudi Arabia and UAE.

The nonvitamin K antagonist oral anticoagulants (NOACs) have become the mainstay anticoagulation therapy for patients requiring oral anticoagulants (OACs) in the Gulf Council Cooperation (GCC) countries. The frequency of NOAC-associated major bleeding is expected to increase in the Emergency Department (ED). Nonetheless, we still lack local guidelines and recommendations for bleeding management in the region. The present Delphi-based consensus aims to establish a standardized and evidence-based clinical care pathway for managing NOAC-associated major bleeding in the Kingdom of Saudi Arabia (KSA) and the United Arab Emirates (UAE). We adopted a three-step modified Delphi method to develop evidence-based recommendations through two voting rounds and an advisory meeting between the two rounds. A panel of 11 experts from the KSA and UAE participated in the consensus development. Twenty-eight statements reached the consensus level. These statements addressed key aspects of managing major bleeding events associated with NOACs, including the increased use of NOAC in clinical practice, clinical care pathways, and treatment options. The present Delphi consensus provides evidence-based recommendations and protocols for the management of NOAC-associated bleeding in the region. Patients with major DOAC-induced bleeding should be referred to a well-equipped ED with standardized management protocols. A multidisciplinary approach is recommended for establishing the association between NOAC use and major bleeding. Treating physicians should have prompt access to specific reversal agents to optimize patient outcomes. Real-world evidence and national guidelines are needed to aid all stakeholders involved in NOAC-induced bleeding management.

Effectiveness of Anticoagulants in Reducing Stroke Risk Among Patients With Atrial Fibrillation.

Atrial fibrillation (AF) is a type of cardiac arrhythmia causing shortness of breath, lightheadedness, and palpitations. It may go unrecognized and asymptomatic among many patients. AF is not a potentially fatal arrhythmia; its hemodynamic, structural, and hemocoagulative effects have a significant impact on the standard of life, which can lead to various complications such as stroke.A stroke caused by AF leads to additional burdens on both patients and the global economy.Patients with AF can prevent strokes with oral anticoagulants; however, ensuring diligent adherence to medication is crucial for maximizing treatment efficacy. Since they have a lighter treatment load than warfarin, non-vitamin K antagonist oral anticoagulants (NOACs) are also recommended with better hope for medication adherence. Various anticoagulants such as warfarin and ximelagatran, among many more, are prescribed to patients who have the potential to reduce the incidence of stroke as well as alleviate their likelihood of developing other thromboembolic events that can decrease their quality of life. Economic and psychological burdens associated with diminished functionality can be prevented by anticoagulant therapy among AF patients, therefore reducing their economic and social burden. This is due to the negative association between stroke among AF patients and anticoagulation consumption.

Appropriateness of prescribing profiles and intake adherence to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: analysis of a retrospective longitudinal study using real-world data from Northern Portugal (AF-React Study)

ObjectivesThis study aimed to assess the appropriateness of prescribing profiles and intake adherence to non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF).DesignRetrospective longitudinal study.SettingThe study was...

Ex Vivo Antiplatelet Effects of Oral Anticoagulants.

The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on platelet function is still unclear. We conducted a comprehensive ex vivo study aimed at assessing the effect of the four currently marketed NOACs on platelet function. We incubated blood samples from healthy donors with concentrations of NOACs (50, 150 and 250 ng/mL), in the range of those achieved in the plasma of patients during therapy. We evaluated generation of thrombin; light transmittance platelet aggregation (LTA) in response to adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), human γ-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; and expression of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. All NOACs concentration-dependently reduced thrombin generation compared with control. THR-induced LTA was suppressed by the addition of dabigatran at any concentration, while TF-induced LTA was reduced by factor-Xa inhibitors. ADP- and TRAP-induced LTA was not modified by NOACs. TXB2 generation was reduced by all NOACs, particularly at the highest concentrations. We found a concentration-dependent increase in PAR-1 expression after incubation with dabigatran, mainly at the highest concentrations, but not with FXa inhibitors; P-selectin expression was not changed by any drugs. Treatment with the NOACs is associated with measurable ex vivo changes in platelet function, arguing for antiplatelet effects beyond the well-known anticoagulant activities of these drugs. There are differences, however, among the NOACs, especially between dabigatran and the FXa inhibitors.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis—a nationwide cohort study

BackgroundIn post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies.MethodsThis study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone.ResultsThe risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052–1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454—0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529—0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478—0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231—1.880), ICH (aHR 2.045, 95% CI 1.329—3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB.ConclusionsFor post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Gender Differences in Patients with Atrial Fibrillation Receiving Oral Anticoagulants.

Gender is a well-recognized risk factor in atrial fibrillation (AF)-related ischemic stroke. The association of gender with the use of oral anticoagulants (OACs) and prognosis remains unknown. The National Health Insurance Research Database in Taiwan identified 203,775 patients with AF aged 20 years from 2012 to 2018, with 55.4% of males. Our main study cohort included 67,426 patients using OACs. The study endpoints include death, ischemic stroke, intracranial hemorrhage, major bleeding, and composite adverse events. Significant differences were found in baseline characteristics between sexes. Female patients with AF were older and had higher -VASc and HAS-BLED scores. Non-vitamin K antagonist oral anticoagulant (NOAC) use was more prominent in females while the use of warfarin was similar in both sexes. The distribution of baseline characteristics between the warfarin and NOAC groups in both sexes was much alike. Among the whole study cohort, NOAC was associated with a decreased risk of clinical endpoints compared to warfarin, which remained the same in subgroup analyses of both sexes. Additionally, a greater risk reduction of ischemic stroke with NOAC was observed in female patients compared to male patients (adjusted hazard ratio: 0.517 in males, 0.425 in females, interaction p = 0.040). This nationwide cohort demonstrated the differences between male and female patients with AF, including baseline characteristics, risk profiles, and medication use. Despite great differences in baseline demographic data, NOAC was associated with better clinical outcomes compared to warfarin in both sexes, and females benefited more than males in preventing ischemic stroke using NOACs.

Current Anticoagulation Statuses among Older Chinese People with Nonvalvular Atrial Fibrillation.

The reported anticoagulation rate may be overestimated among Chinese patients with atrial fibrillation (AF). Therefore, we aimed to understand the current status and time trends of anticoagulation among older people in the Chinese community. Data were obtained from the physical examination program for the elderly (aged 65 years) in Guangzhou. During 2017-2020, a total of 31,829, 58,573, 55,483, and 54,845 older people underwent annual physical examinations, respectively, where their general information, AF-related medical history, and use of oral anticoagulants (OACs) were collected for analysis. From 2017 to 2020, the estimated annual prevalence of older people with nonvalvular atrial fibrillation (NVAF) in Guangzhou was 0.99%, 0.92%, 1.05%, and 1.14%, respectively. In patients with high stroke risk (CHA2DS2-VASc score 2 for males or 3 for females), the annual anticoagulation rates were 2.83%, 2.05%, 5.29%, and 5.82%, respectively. The proportion of NVAF patients prescribed non-vitamin K antagonist oral anticoagulants (NOACs) increased gradually over the same period (p = 0.004). Males (odds ratios (OR), 1.797; 95% confidence interval (CI), 1.169-2.763; p = 0.008), ages over 75 (OR, 1.858; 95% CI, 1.212-2.849; p = 0.005), low education levels (OR, 1.737; 95% CI, 1.132-2.665; p = 0.011), and lacking the ability for self-care (OR, 4.432; 95% CI, 1.067-18.418; p = 0.041) were less likely to receive OAC therapy. The low anticoagulation rate of older people with NVAF in the Chinese community has not significantly improved in recent years, with only 5.82% of patients with high stroke risk being prescribed OACs. Therefore, it is necessary to establish an appropriate mode of anticoagulant management to improve the current situation.