Non-vitamin K Antagonist Oral Anticoagulants Research Articles

Ex Vivo Antiplatelet Effects of Oral Anticoagulants

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Effect of drug interactions with non-vitamin-K oral anticoagulants on thromboembolic events in patients with nonvalvular atrial fibrillation

Introduction: Few real-world studies have investigated drug-drug interactions (DDIs) involving non-vitamin-K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). The interactions encompass drugs inducing or inhibiting cytochrome P450 3A4 and permeability glycoprotein. These agents potentially modulate the breakdown and elimination of NOACs. This study investigated the impact of DDIs on thromboembolism in this clinical scenario. Method: Patients who had NVAF and were treated with NOACs were selected as the study cohort from the National Health Insurance Research Database of Taiwan. Cases were defined as patients hospitalised for a thromboembolic event and who underwent a relevant imaging study within 7 days before hospitalisa-tion or during hospitalisation. Each case was matched with up to 4 controls by using the incidence density sampling method. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer or inhibitor or both with NOACs was identified. The effects of these interactions on the risk of thromboembolic events were examined with univariate and multivariate conditional logistic regressions. Results: The study cohort comprised 60,726 eligible patients. Among them, 1288 patients with a thromboembolic event and 5144 matched control patients were selected for analysis. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer resulted in a higher risk of thromboembolic events (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.004–1.51). Conclusion: For patients with NVAF receiving NOACs, the concurrent use of cytochrome P450 3A4/ permeability glycoprotein inducers increases the risk of thromboembolic events.

Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial

BackgroundBoth anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. MethodsThe ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. ConclusionsThe ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. Clinical trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT04250116.

Use of acenocoumarol in cardioembolic stroke: an evidence-based review

Stroke is the leading cause of long-term disability and the second most common cause of death worldwide. Nearly two-thirds of all strokes represent cerebral ischemia, of which about 15%-30% are of cardioembolic origin. Atrial fibrillation accounts for about 60% of all cardioembolic strokes. Current clinical evidence suggests that oral anticoagulant therapy can prevent around 70% of strokes in patients with atrial fibrillation. Oral anticoagulation therapy is preferred over antiplatelet therapy in patients with cardioembolic stroke. Vitamin K antagonists (VKAs) and nonvitamin K antagonist oral anticoagulants (NOACs) are routinely prescribed oral anticoagulants in patients at risk of stroke; however, there are specific indications where VKA use surpasses NOAC use or there are conditions where NOACs are contraindicated. A group of experts revisited the role of oral anticoagulants in the management of cardioembolic stroke in India with emphasis on VKA, specifically acenocoumarol. This article discusses various aspects of anticoagulation therapy, including the timing of initiation and patient monitoring, in patients with cardioembolic stroke with reference to current clinical evidence and expert opinion based on Indian clinical experience.

Effect of China national centralized drug procurement policy on anticoagulation selection and hemorrhage events in patients with AF in Suining.

Background: Launched in March 2019, the National Centralized Drug Procurement (NCDP) initiative aimed to optimize the drug utilization framework in public healthcare facilities. Following the integration of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) into the procurement catalog, healthcare establishments in Suining swiftly transitioned to the widespread adoption of NOACs, beginning 1 March 2020. Objective: This study aims to comprehensively assess the impact of the NCDP policy on the efficacy of anticoagulation therapy, patient medication adherence, and the incidence of hemorrhagic events in individuals with non-valvular atrial fibrillation (NVAF) residing in Suining. The analysis seeks to elucidate the broader impacts of the NCDP policy on this patient demographic. Methods: This study analyzed patient hospitalization records from the Department of Cardiology at Suining County People's Hospital, spanning 1 January 2017, to 30 June 2022. The dataset included demographic details (age, sex), type of health insurance, year of admission, hospitalization expenses, and comprehensive information on anticoagulant therapy utilization. The CHA2DS2-VASc scoring system, an established risk assessment tool, was used to evaluate stroke risk in NVAF patients. Patients with a CHA2DS2-VASc score of 2 or higher were categorized as high-risk, while those with scores below 2 were considered medium or low-risk. Results: 1. Treatment Cost Analysis: The study included 3,986 patients diagnosed with NVAF. Following the implementation of the NCDP policy, a significant increase in the average treatment cost for hospitalized patients was observed, rising from 8,900.57 ± 9,023.02 CNY to 9,829.99 ± 10,886.87 CNY (p < 0.001). 2. Oral Anticoagulant Utilization: Overall, oral anticoagulant use increased from 40.02% to 61.33% post-NCDP (p < 0.001). Specifically, NOAC utilization among patients dramatically rose from 15.41% to 90.99% (p < 0.001). 3. Hemorrhagic Events: There was a significant decrease in hemorrhagic events following the NCDP policy, from 1.88% to 0.66% (p = 0.01). Hypertension [OR = 1.979, 95% CI (1.132, 3.462), p = 0.017], history of stroke [OR = 1.375, 95% CI (1.023, 1.847), p = 0.035], age ≥65years [OR = 0.339, 95% CI (0.188, 0.612), p < 0.001], combination therapy of anticoagulants and antiplatelets [OR = 3.620, 95% CI (1.752, 7.480), p < 0.001], hepatic and renal insufficiency [OR = 4.294, 95% CI (2.28, 8.084), p < 0.001], and the NCDP policy [OR = 0.295, 95% CI (0.115, 0.753), p = 0.011] are significant risk factors for bleeding in patients with atrial fibrillation. 4. Re-hospitalization and Anticoagulant Use: Among the 219 patients requiring re-hospitalization, there was a notable increase in anticoagulant usage post-NCDP, from 36.07% to 59.82% (p < 0.001). NOACs, in particular, saw a substantial rise in usage among these patients, from 11.39% to 80.92% (p < 0.001). 5. Anticoagulant Type Change: The NCDP policy [OR = 28.223, 95% CI (13.148, 60.585), p < 0.001] and bleeding events [OR = 27.772, 95% CI (3.213, 240.026), p = 0.003] were significant factors influencing the alteration of anticoagulant medications in patients. Conclusion: The NCDP policy has markedly improved anticoagulation management in patients with AF. This policy has played a crucial role in enhancing medication adherence and significantly reducing the incidence of hemorrhagic events among these patients. Additionally, the NCDP policy has proven to be a key factor in guiding the selection and modification of anticoagulant therapies in the AF patient population.

Altered fibrin clot properties are associated with the progression of chronic kidney disease in atrial fibrillation

IntroductionFormation of denser and resistant to lysis fibrin clot networks has been shown in chronic kidney disease (CKD) and atrial fibrillation (AF). We investigated whether such prothrombotic fibrin clot properties are associated with faster progression of CKD in AF patients. Material and methodsWe recruited 265 AF patients (men 49.1 %, median age of 64.0 years, median estimated glomerular filtration rate [eGFR] of 77.0 ml/min/1.73 m2), including 137 patients on non-vitamin K antagonist oral anticoagulants (NOACs) (51.7 %) and 109 patients (41.1 %) on vitamin K antagonists (VKAs). At baseline while off anticoagulation, we determined fibrin clot permeability (Ks), and clot lysis time (CLT), along with plasminogen activator inhibitor-1 (PAI-1), endogenous thrombin potential (ETP), and von Willebrand factor (vWF). The kidney function was assessed at baseline and after a median follow-up of 50.0 months. ResultsDuring follow-up, a median eGFR decreased by 8.0 (5.0–11.0) ml/min/1.73 m2, 1.8 ml/min/1.73 m2/year and this change correlated with age (R = 0.19, P = 0.002), Ks (R = 0.46, P < 0.0001), and CLT (R = -0.17, P = 0.005), but not ETP, fibrinogen, PAI-1 or vWF. A decrease in eGFR was lower in patients who used NOACs at baseline but not in those who started NOACs during follow-up (n = 101) as compared to the remaining patients. On multiple linear regression analysis, adjusted for age and fibrinogen, baseline Ks, eGFR, hypertension, and NOACs use independently predicted a decrease in eGFR. ConclusionsThis study is the first to show that more compact fibrin clot networks may contribute to faster progression of CKD in AF, indicating novel kidney-related harmful effects of prothrombotic clot properties in humans.

The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation.

The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. After up to 5years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

Thromboembolic and bleeding events after valvular intervention in patients with atrial fibrillation

AimTo assess outcomes after cardiac surgery with biological valve replacement, valve repair or transcatheter aortic valve implantation (TAVI) in patients with atrial fibrillation (AF) in accordance with oral anticoagulant (OAC)...

The safety and efficacy of nonvitamin K antagonist oral anticoagulants in morbidly obese patients with atrial fibrillation: a meta-analysis

Background and aimAtrial fibrillation (AF) is the most frequently observed cardiac arrhythmia in clinical settings. Obesity can influence the efficacy of the treatment administered, which requires a larger dose and more time to accomplish therapeutic targets due to altered pathophysiology. Our study aimed to assess the overall efficacy and safety of nonvitamin K antagonist oral anticoagulants (NOACs) versus warfarin in AF patients with morbid obesity (BMI > 40 kg/m2 and/or weight > 120 kg) to prevent complications.MethodsWe conducted a literature search on PubMed, Web of Science, the Cochrane Library, and Scopus till October 2022 for articles addressing the efficacy and safety of NOACs versus warfarin for the treatment of AF in morbidly obese patients. We performed the meta-analysis with RevMan software version 5.4 and Open Meta Analyst. The main outcomes assessed were stroke, major bleeding, and minor bleeding after anticoagulation, as did the history of comorbidities and risk factors in morbidly obese patients. Quality assessment was performed using Cochrane’s ROB-2 tool and the Newcastle–Ottawa scale.ResultsRegarding major bleeding events, pooled data showed that patients taking NOACs had a significantly lower risk than patients taking warfarin (OR = 0.54, 95% CI: [0.41–0.70]; p < 0.00001). However, for minor bleeding, there was a nonsignificant effect of NOACs on reducing the risk of bleeding (OR = 0.72, 95% CI = 0.47–1.09; p = 0.12), which became highly significant in favor of NOACs after sensitivity analysis (OR = 0.55, 95% CI = 0.49–0.61]; p < 0.00001). There was a significant difference in the incidence of stroke between the NOAC group and the warfarin group (OR = 0.69, 95% CI = 0.60–0.80]; p < 0.00001). According to the results of the single-arm study analysis, the overall effect of all the outcomes was associated with a high risk of disease development in patients receiving NOACs.ConclusionOur meta-analysis showed a favorable effect of NOACs vs warfarin in morbidly obese patients. Some outcomes were not significantly different, which calls for future research to better assess their safety and efficacy in this particular weight group.Trial registrationThe study was registered with PROSPERO under registration number CRD42022362493 on October 2022.

Non-vitamin-K-antagonist oral anticoagulants (NOACs) after acute myocardial infarction: a network meta-analysis.

Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The potential of non-vitamin K antagonist oral anticoagulants (NOACs) to prevent ischaemic cardiovascular events is promising, but the evidence remains limited. To evaluate the efficacy and safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in addition to background antiplatelet therapy, compared with placebo, antiplatelet therapy, or both, after acute myocardial infarction (AMI) in people without an indication for anticoagulation (i.e. atrial fibrillation or venous thromboembolism). We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science, and two clinical trial registers in September 2022 with no language restrictions. We checked the reference lists of included studies for any additional trials. We searched for randomised controlled trials (RCTs) that evaluated NOACs plus antiplatelet therapy versus placebo, antiplatelet therapy, or both, in people without an indication for anticoagulation after an AMI. Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects pairwise analyses using Review Manager Web, and network meta-analysis using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons and allow ranking of treatments on a continuous 0-to-1 scale. We identified seven eligible RCTs, including an ongoing trial that we could not include in the analysis. Of the six RCTs involving 33,039 participants, three RCTs compared rivaroxaban with placebo, two RCTs compared apixaban with placebo, and one RCT compared dabigatran with placebo. All participants in the six RCTs received concomitant antiplatelet therapy. The available evidence suggests that rivaroxaban compared with placebo reduces the rate of all-cause mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.69 to 0.98; number needed to treat for an additional beneficial outcome (NNTB) 250; 3 studies, 21,870 participants; high certainty) and probably reduces cardiovascular mortality (RR 0.83, 95% CI 0.69 to 1.01; NNTB 250; 3 studies, 21,870 participants; moderate certainty). There is probably little or no difference between apixaban and placebo in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35; number needed to treat for an additional harmful outcome (NNTH) 334; 2 studies, 8638 participants; moderate certainty) and cardiovascular mortality (RR 0.99, 95% CI 0.77 to 1.27; number needed to treat not applicable; 2 studies, 8638 participants; moderate certainty). Dabigatran may reduce the rate of all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06; NNTB 63; 1 study, 1861 participants; low certainty). Dabigatran compared with placebo may have little or no effect on cardiovascular mortality, although the point estimate suggests benefit (RR 0.72, 95% CI 0.34 to 1.52; NNTB 143; 1 study, 1861 participants; low certainty). Two of the investigated NOACs were associated with an increased risk of major bleeding compared to placebo: apixaban (RR 2.41, 95% CI 1.44 to 4.06; NNTH 143; 2 studies, 8544 participants; high certainty) and rivaroxaban (RR 3.31, 95% CI 1.12 to 9.77; NNTH 125; 3 studies, 21,870 participants; high certainty). There may be little or no difference between dabigatran and placebo in the risk of major bleeding (RR 1.74, 95% CI 0.22 to 14.12; NNTH 500; 1 study, 1861 participants; low certainty). The results of the network meta-analysis were inconclusive between the different NOACs at all individual doses for all primary outcomes. However, low-certainty evidence suggests that apixaban (combined dose) may be less effective than rivaroxaban and dabigatran for preventing all-cause mortality after AMI in people without an indication for anticoagulation. Compared with placebo, rivaroxaban reduces all-cause mortality and probably reduces cardiovascular mortality after AMI in people without an indication for anticoagulation. Dabigatran may reduce the rate of all-cause mortality and may have little or no effect on cardiovascular mortality. There is probably no meaningful difference in the rate of all-cause mortality and cardiovascular mortality between apixaban and placebo. Moreover, we found no meaningful benefit in efficacy outcomes for specific therapy doses of any investigated NOACs following AMI in people without an indication for anticoagulation. Evidence from the included studies suggests that rivaroxaban and apixaban increase the risk of major bleeding compared with placebo. There may be little or no difference between dabigatran and placebo in the risk of major bleeding. Network meta-analysis did not show any superiority of one NOAC over another for our prespecified primary outcomes. Although the evidence suggests that NOACs reduce mortality, the effect size or impact is small; moreover, NOACs may increase major bleeding. Head-to-head trials, comparing NOACs against each other, are required to provide more solid evidence.

Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation.

The efficacy and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain. We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m2 (n=598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m2. Among 58 464 patients, the median BMI was 28.3 (interquartile range, 25.2-32.2) kg/m2, and the median BW was 81.0 (interquartile range, 70.0-94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke/SEE overall (adjusted hazard ratio [HRadj], 0.80 [95% CI, 0.73-0.88]; P<0.001), with a generally consistent effect across BMI (Ptrend across HRs, 0.48). NOACs also reduced major bleeding overall (HRadj, 0.88 [95% CI, 0.82-0.94]; P<0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [Ptrend], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HRadj, 0.91 [95% CI, 0.87-0.95]; P<0.001; death, HRadj, 0.91 [95% CI, 0.86-0.97]; P=0.003), these benefits were attenuated at higher BMI (Ptrend, 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW. The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.

Delayed Prescribing of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) in Patients with Low Socioeconomic Status

Background/Objective: Atrial fibrillation (AF) and venous thromboembolism (VTE) are conditions with significant morbidity and mortality when left untreated. American Heart Association guidelines changed in 2019 to make non-vitamin K antagonist oral anticoagulants (NOACs) the preferred method for preventing stroke and systemic embolism in patients with AF or history of VTE. NOACs were first introduced to the United States in 2010 and now include dabigatran, apixaban, rivaroxaban, and edoxaban. There is a dearth of research concerning the speed with which new treatments are prescribed to those in different socioeconomic status (SES) groups. We hypothesized that patients with lower SES were prescribed NOACs later than higher SES counterparts following the introduction of NOACs in 2010.&#x0D; Methods: The IU Cardiovascular Research Consortium/Sidus Dataset was mined for AF and VTE patients prescribed a NOAC between 2010 and 2022. The SES groups were determined using 2020 U.S. Census income data that correlated to patients’ zip codes. The yearly number ofpatients in each SES group were compared to assess for proportional uptake of NOAC prescribing. The primary outcome was the proportion of low SES to high SES prescribing over each year between 2010 and 2022.&#x0D; Results: Low SES patients (n=101,945) were prescribed NOACs at an average of 0.65 times the rate of high SES patients (n= 89,130) from 2010 to 2012, the first three years of NOAC market availability. Prescribing rates equilibrated in 2013 and low SES prescribing has outpaced high SES prescribing since 2021.&#x0D; Conclusion/Impact: Low SES patients experienced a three year delay in receiving NOAC prescriptions at the same rate as their high SES counterparts. Systemic changes, like more frequent prescribing guideline updates and improved evidence-based education amongst providers in low-income areas, could prevent a similar delay when introducing similarly transformative treatments in the future.

Survey of Using Oral Anticoagulants in Patient with Non-valvular Atrial Fibrillation.

In Vietnam, there has been no survey conducted on the prescribing and monitoring practices of oral anticoagulants to ensure that patients with atrial fibrillation receive appropriate. Objective: Therefore, we conducted this research to clarify the aforementioned issue in our hospital. We carried out a cross-sectional study by reviewing outpatient electronic medical records at the University Medical Center in Ho Chi Minh City. Our study included 1087 patients aged 18 years or older diagnosed with non-valvular atrial fibrillation (NVAF), who visited the Cardiology clinic between January 1st, 2021, and June 30th, 2021. Among the 1087 patients with non-valvular atrial fibrillation (NVAF), 1036 were eligible for anticoagulant therapy. However, only 847 (81.8%) received prescriptions for either Vitamin K antagonists (VKAs) (n=129, 15.2%) or Non-Vitamin K antagonist oral anticoagulants (NOACs) (n=718, 84.8%). NOAC prescriptions were more commonly found in patients aged 75 or older (adjusted odds ratio [OR]=2), those with health insurance coverage (adjusted OR=2.9), and in individuals with a history of hypertension (adjusted OR=2). On the contrary, patients with a farming occupation were less likely to be prescribed NOACs (adjusted OR=0.4). About 75% of patients adhered to the guidelines recommending close monitoring during anticoagulant treatment. Notably, inappropriate prescriptions were identified in 27.7% of cases, especially among those with no recorded body weight (which is necessary for precise dosing based on creatinine clearance), those without health insurance, those with undocumented CHA2DS2-VASc scores, or those who were concurrently using antiplatelet agents. A discrepancy persists between clinical guidelines and the actual practice in diagnosing and managing patients with non-valvular atrial fibrillation (NVAF). It is crucial to prioritize the regular reevaluation of thromboembolic risk scores at follow-up appointments, ensure strict adherence to clinical monitoring standards, and align anticoagulant medication prescriptions with established guidelines.

Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.

Selection of Non-vitamin K Antagonist Oral Anticoagulant for Stroke Prevention in Atrial Fibrillation Based on Patient Profile: Perspectives from Vietnamese Experts. Part 1.

In Asia, especially Vietnam, AF is a common arrhythmia and is linked to a higher risk of stroke and systemic embolism. Anticoagulation therapy for stroke prevention in AF patients can result in bleeding complications. To effectively manage AF, adopting appropriate anticoagulation and addressing modifiable risk factors are crucial. Vietnamese clinicians are particularly interested in non-vitamin K antagonist oral anticoagulants (NOACs), a recent development in AF treatment. However, the lack of head-to-head trials comparing NOACs makes selecting a specific NOAC challenging. This review aims to provide a comprehensive overview of the available clinical evidence on NOACs for stroke prevention in AF to assist clinicians in making informed decisions and improving treatment outcomes in patients with AF. The first part of this review will present the current landscape of AF in Vietnam, focusing on AF prevalence and highlighting gaps in clinical practice. Furthermore, this part extensively discusses the anticoagulation strategy for both primary and secondary stroke prevention in AF.

Comparison of Non-Vitamin K Antagonist Oral Anticoagulants on Ischemic Stroke and Bleeding

Objective: Non-vitamin K antagonist oral anticoagulants (NOACs) have become widely utilized for various clinical indications, including non-valvular atrial fibrillation (NVAF), deep vein thrombosis (DVT), and apical thrombus. Despite their increasing popularity, limited comparative data exist on the clinical outcomes associated with different NOACs. This study aims to address this gap by directly comparing NOACs in terms of ischemic stroke, hemorrhagic stroke, and gastrointestinal bleeding. Materials and Methods: A retrospective search of the electronic database was conducted to identify patients using NOACs for NVAF, DVT, and apical thrombus. Clinical outcomes, including ischemic stroke, hemorrhagic stroke, and gastrointestinal bleeding, were directly compared among different NOACs. The chi-square test and Fisher's exact test were employed to assess the relative incidence of stroke and extracranial complications across four patient groups. Results: Among the 4,112 retrospectively analyzed patients, 55 were included in the study. Demographic and clinical profiles showed no significant differences among patients in the four different drug groups (p &gt; 0.05). Ischemic stroke was observed in 90.9% of the patients, hemorrhagic stroke in 5.8%, and gastrointestinal bleeding in 3.3%. A statistically significant difference was identified between drug doses and the rate of ischemic stroke (p &lt; 0.001). Conclusion: The findings of this retrospective study carry significant implications, especially considering the widespread global use of NOACs. The study revealed no discernible difference in the risk of ischemic stroke among patients using different NOACs. Notably, the risk of hemorrhagic stroke was dose-dependent in the dabigatran group, while rivaroxaban was associated with the highest risk of gastrointestinal bleeding. Given the elevated rate of thromboembolism in patients and the relatively short half-life of NOACs, the study concludes that further optimization of NOAC use is imperative.

Association of high-estimated glomerular filtration rate with the severity of ischemic stroke during non-vitamin K antagonist oral anticoagulants therapy: a nationwide cohort study.

While the relationship between impaired kidney function and non-vitamin K antagonist oral anticoagulants (NOACs) is well established, there is limited research exploring the association between an elevated estimated glomerular filtration rate (eGFR) and the efficacy of NOACs, especially concerning the outcomes of acute ischemic stroke (AIS). This study aimed to examine the association between higher-than-normal eGFR and the severity of AIS during the use of NOACs using a nationwide multicenter stroke registry in Korea. This study utilized data from the Korean Stroke Registry (KSR) database, examining information from 2,379 patients with AIS, who had atrial fibrillation (AF) and a history of utilizing NOACs prior to hospitalization due to incident stroke occurring between 2016 and 2021. Patients with a history involving two or more types of anticoagulants or one or more forms of antiplatelet agents were excluded. Baseline characteristics, medical history, medication usage, CHADS2-VASc score, and the anticoagulation and risk factors in atrial fibrillation (ATRIA) score were evaluated. Renal function was assessed using eGFR levels and calculated with the Cockcroft-Gault equation. The severity of stroke was measured by the National Institutes of Health Stroke Scale as an outcome. For sensitivity analysis, further evaluation was performed using eGFR levels according to the modification of diet in renal disease (MDRD) study equation. The mean age of subjects was 76.1 ± 8.9 years. The moderate-to-severe stroke severity group exhibited an elevation in creatinine levels. The eGFR of 60 to 89 mL/min/1.73 m2 group was associated with a decreased risk of moderate-to-severe stroke severity [hazard ratio (HR)] (0.77, 95% confidence interval (CI) [0.61, 0.98], p = 0.031) compared to the eGFR≥90 mL/min/1.73 m2 group. An increment of 10 units in eGFR was marginally associated with an increased risk of moderate-to-severe stroke severity (HR: 1.03, 95% CI [1.00, 1.07], p = 0.054). The study revealed that individuals with eGFR ≥ 90 mL/min/1.73 m2 had an association linked to an increased risk of moderate-to-severe stroke severity. Our study suggests that patients taking NOACs with higher-than-normal eGFR levels may have an increased severity of AIS.

Standardized community management on the diagnosis, treatment, and risk factors control for non-valvular atrial fibrillation in elderly patients

BackgroundBy investigating the knowledge, medication, occurrence of complications, and risks among elderly non-valvular atrial fibrillation (NVAF) patients in Shanghai communities, and providing standardized comprehensive management and follow-up, we aim to explore the impact of standardized community management on improving disease awareness, standardizing atrial fibrillation (AF) treatment, reducing the risk of complications occurrence, and addressing risk factors for AF patients.MethodsThis research selected elderly atrial fibrillation patients from Zhuanqiao Community Health Service Center, Minhang District, Shanghai from July 2020 to October 2022. Their personal health records and examination results were reviewed, and the incidence of AF, awareness, medication, and complications were investigated. Age-adjusted Charlson Comorbidity Index (aCCI), CHA2DS2-VASc score, and HAS-BLED score were used to evaluate disease burden, thromboembolic risk, and bleeding risk, respectively. The patients were subjected to standardized community management, and the compliance rate of disease awareness, treatment, resting heart rate, blood pressure, fasting blood glucose, and body mass index (BMI) were assessed at the baseline, 6 months and 1 year after management.ResultsA total of 243 NVAF patients were included, with an average aCCI score of (4.5 ± 1.1). Among them, 28% of the patients were aware of their AF, and 18.1% of the patients were aware of the hazards of AF. Of the patients, 11.9% used anticoagulant drugs, including 6.6% and 5.3% for warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), respectively. 7% of patients used antiplatelet drugs. 26.7% of the patients used heart rate control drugs. 10.3% of the patients experienced thromboembolic events, and 0.8% of the patients experienced bleeding events. 93.0% of the patients were at high risk of thromboembolism, and 24.7% of the patients were at high risk of bleeding. Compared with the baseline, there were significant statistical differences (P < 0.001) in disease awareness, awareness of the hazards of AF, use of anticoagulant drugs and heart rate control drugs, and control of risk factors among NVAF patients after standardized community management. Moreover, with the extension of management time, there was a linear increase in the awareness of NVAF, awareness of the hazards of AF, utilization rate of anticoagulant drugs, utilization rate of heart rate control drugs, blood pressure, blood glucose, and BMI compliance rate (P < 0.001).ConclusionCurrently, the awareness, treatment, and control of risk factors for AF in elderly NVAF patients in Shanghai community are not satisfactory. Standardized community management helps to improve the diagnosis, treatment, and control of risk factors in AF.

Risk of Bleeding Following Non–Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase

Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs). To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs. This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO. NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment. The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model. Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis. In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.