Non-vitamin K Antagonist Oral Anticoagulants Group Research Articles

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.

Abstract 15764: Early versus Late Initiation of Non-Vitamin K Antagonist Anticoagulation After Ischemic Stroke in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis

Introduction: Atrial fibrillation (AF) is a common cause of acute ischemic stroke (AIS). Non-vitamin K antagonist oral anticoagulants (NOACs) are recommended for stroke prevention. However, presumed higher risk of hemorrhagic transformation in early (≤ 5 days) start of NOACs delays timing of anticoagulation initiation after AIS. This meta-analysis was conducted to evaluate granularity of data on the timing of initiation of NOACs after AIS in patients with AF. Methods: This meta-analysis followed the PRISMA guidelines and is registered in PROSPERO (CRD42023391198). PubMed, PubMed Central, Embase, and Scopus databases were searched for relevant articles from inception through May 2023. Title and abstract were screened by two independent authors, followed by full text review in Covidence platform. Pertinent data was extracted in Microsoft Excel. Data were analyzed using RevMan v5.4 with odds ratio as effect measure. Results: A total of 6326 studies were identified from database search. Five studies with 7442 patients were included. There was no significant difference between the groups in terms of recurrent stroke (OR 0.86, CI 0.62-1.20;), intracranial hemorrhage (OR 0.71, CI 0.26-1.93), major bleeding (OR 1.22, CI 0.66-2.26) or mortality (OR 0.75, CI 0.44-1.27). However, pooled results from two studies showed a statistically significant lower occurrence of hemorrhagic transformation in early NOAC group as compared to late NOAC group (OR 0.43, CI 0.32-0.60). Conclusions: Based on this meta-analysis, early NOAC initiation after AIS in patients with AF is a safe strategy in terms of efficacy (recurrent stroke) and safety (major bleeding, intracranial hemorrhage, mortality, and hemorrhagic transformation).

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation at low risk of stroke in japan: a retrospective cohort study.

Contemporary guidelines differ in their recommendations regarding initiating non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) at low risk of stroke. This study aimed to examine the effectiveness and safety of NOACs for low-risk AF in a Japanese cohort. In this retrospective cohort study based on the JMDC Claims Database extracted between April 2011 and November 2022, we identified 13 291 patients with AF at low risk of stroke. We performed inverse probability of treatment weighting Cox regression analyses to compare the embolization and bleeding risks between the nontreatment and NOAC groups. Net clinical benefit was defined as the annual incidence of ischaemic stroke events prevented by NOACs after subtracting intracranial haemorrhage (ICH) events attributable to NOACs, multiplied by a weighting factor. The incidences of stroke and ICH in the nontreatment group were 0.47 and 0.15 per 100 person-years, respectively. The NOAC group had higher incidences of ICH (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 0.75-4.00) and stroke (HR: 1.41, 95% CI: 0.84-2.36). The net clinical benefit of NOAC treatment was -0.35% per year (95% CI: -0.99-0.29%). Non-vitamin K antagonist oral anticoagulants treatment may be associated with a slightly high risk of ICH, and it yielded a neutral clinical benefit in the present Japanese population, which provides reassurance concerning the role of ethnicity in NOAC treatment for patients with AF and suggests a need to assess comprehensive weighting of the respective risk factors.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulant in the treatment of patients with morbid obesity or high body weight with venous thromboembolism: A meta-analysis.

Venous thromboembolism (VTE) poses a significant health risk to patients with morbid obesity or high body weight. Non-vitamin K antagonist oral anticoagulants (NOACs) are emerging treatments, but their effectiveness and safety compared with vitamin K antagonists (VKAs) in this population are yet to be thoroughly studied. We conducted a systematic review and meta-analysis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four electronic databases were searched for relevant studies comparing the efficacy and safety of NOACs and VKAs in treating patients with VTE with a body mass index > 40 kg/m2 or body weight > 120 kg. Eligible studies were scored for quality using the Newcastle-Ottawa Scale. Thirteen studies were included. The meta-analysis results showed that compared to VKAs, NOACs significantly decreased the risk of VTE occurrence (odds ratio = 0.72, 95% CI: 0.57-0.91, I2 = 0%, P < .001) and were associated with a lower risk of bleeding (odds ratio = 0.74, 95% CI: 0.58-0.95, I2 = 0%, P < .05). Subgroup analysis showed that in the cancer patient subgroup, both risks of VTE occurrence and bleeding were lower in the NOAC group than in the VKA group. In patients without cancer, the risk of VTE was significantly lower in the NOAC group. NOACs appear to be more effective and safer than VKAs in patients with morbid obesity or a high body weight with VTE. However, further large-scale randomized controlled trials are required to confirm these findings.

Non-vitamin K Antagonist Oral Anticoagulant, Warfarin, and ABC Pathway Adherence on Hierarchical Outcomes: Win Ratio Analysis of the COOL-AF Registry.

Atrial fibrillation (AF) Better Care (ABC) pathway adherence is associated with improved outcomes. Clinical trials have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are as least as effective as warfarin for stroke prevention in AF patients. The Win Ratio method, analyzing hierarchical composite outcomes considering event timing and severity, has limited data on its use in Asians. We aim to apply Win Ratio in a registry to access the comparative effectiveness of NOACs versus warfarin and ABC adherence versus nonadherence in Asian patients with AF. Our study included nonvalvular AF patients from the nationwide prospective COOL-AF registry in Thailand. The NOAC-treated group was compared with the warfarin-treated group using the Win Ratio, with the following order: all-cause death, intracranial hemorrhage (ICH), ischemic stroke/transient ischemic attack/systemic embolism, non-ICH major bleeding, and myocardial infarction or heart failure. ABC pathway adherence versus nonadherence was also compared. A Win Ratio greater than 1.00 indicating a better outcome. The analysis included 2,568 patients, with 228 in the NOAC group and 2,340 in the warfarin group. The NOAC group had more wins than the warfarin group, with an unmatched Win Ratio of 1.64 (95% confidence interval [CI]: 1.22-2.20; p < 0.001). When compared with nonadherence, ABC pathway adherence was associated with a Win Ratio of 1.57 (95% CI: 1.33-1.85; p < 0.001). This Win Ratio analysis demonstrates the significant benefits of NOACs over warfarin and ABC pathway adherence over nonadherence in reducing the composite outcome in patients with AF.

Oral anticoagulants and concurrent rifampin administration in tuberculosis patients with non-valvular atrial fibrillation

BackgroundEvidence and guidelines for Non-vitamin K antagonist oral anticoagulants (NOACs) use when prescribing concurrent rifampin for tuberculosis treatment in patients with non-valvular atrial fibrillation (NVAF) are limited.MethodsUsing the Korean National Health Insurance Service database from January 2009 to December 2018, we performed a population-based retrospective cohort study to assess the net adverse clinical events (NACE), a composite of ischemic stroke or systemic embolism and major bleeding, of NOACs compared with warfarin among NVAF patients taking concurrent rifampin administration for tuberculosis treatment. After a propensity matching score (PSM) analysis, Cox proportional hazards regression was performed in matched cohorts to investigate the clinical outcomes.ResultsOf the 735 consecutive patients selected, 465 (63.3%) received warfarin and 270 (36.7%) received NOACs. Among 254 pairs of patients after PSM, the crude incidence rate of NACE was 25.6 in NOAC group and 32.8 per 100 person-years in warfarin group. There was no significant difference between NOAC and warfarin use in NACE (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.48–1.14; P = 0.172). Major bleeding was the main driver of NACE, and NOAC use was associated with a statistically significantly lower risk of major bleeding than that with warfarin use (HR, 0.63; 95% CI, 0.40–1.00; P = 0.0499).ConclusionsIn our population-based study, there was no statically significant difference in the occurrence of NACE between NOAC and warfarin use. NOAC use may be associated with a lower risk of major bleeding than that with warfarin use.

Comparison of the real-life clinical outcomes of warfarin with effective time in therapeutic range and non-vitamin K antagonist oral anticoagulants: Insight from the AFTER-2 trial.

It is unclear whether warfarin treatment with high time in therapeutic range (TTR) is as effective and safe as non-vitamin K antagonist oral anticoagulants (NOACs). It is crucial to compare warfarin with effective TTR and NOACs to predict long-term adverse events in patients with atrial fibrillation. We aimed to compare the long-term follow-up results of patients with atrial fibrillation (AF) who use vitamin K antagonists (VKAs) with effective TTR and NOACs. A total of 1140 patients were followed at 35 different centers for five years. During the follow-up period, the international normalized ratio (INR) values were studied at least 4 times a year, and the TTR values were calculated according to the Roosendaal method. The effective TTR level was accepted as >60% as recommended by the guidelines. There were 254 patients in the effective TTR group and 886 patients in the NOAC group. Ischemic cerebrovascular disease/transient ischemic attack (CVD/TIA), intracranial bleeding, and mortality were considered primary endpoints based on one-year and five-year follow-ups. Ischemic CVD/TIA (3.9% vs. 6.2%; P = 0.17) and intracranial bleeding (0.4% vs. 0.5%; P = 0.69), the one-year mortality rate (7.1% vs. 8.1%; P = 0.59), the five-year mortality rate (24% vs. 26.3%; P = 0.46) were not different between the effective TTR and NOACs groups during the follow-up, respectively. The CHA2DS2-VASC score was similar between the warfarin with effective TTR group and the NOAC group (3 [2-4] vs. 3 [2-4]; P = 0.17, respectively). Additionally, survival free-time did not differ between the warfarin with effective TTR group and each NOAC in the Kaplan-Meier analysis (dabigatran; P = 0.59, rivaroxaban; P = 0.34, apixaban; P = 0.26, and edoxaban; P = 0.14). There was no significant difference in primary outcomes between the effective TTR and NOAC groups in AF patients.

Abstract 25: Safety And Outcomes Of Endovascular Thrombectomy In Acute Ischemic Stroke Patients With Recent Use Of Non-vitamin K Antagonist Oral Anticoagulants

Introduction: An increasing number of patients with acute ischemic stroke (AIS) have recently used non-vitamin K antagonist oral anticoagulants (NOACs). However, there are limited data on safety of endovascular therapy (EVT) in these patients. Methods: We performed a retrospective, observational, cohort study of patients treated with EVT within 6 hours of symptom onset in the American Heart Association’s “Get With The Guideline-Stroke Program” between October 2015 and March 2020 to compare safety and functional outcomes in patients who were or were not taking NOACs in the 7 days prior to stroke. Results: Of 33,355 patients (median age 72 years (60,81); 50.8% female), 3,727 (11.2%) were taking NOACs, and 29,628 (88.8%) were not taking any oral anticoagulants (OAC) prior to stroke. Compared with those not on OAC, patients taking NOACs were older (median age 75 vs. 71 years) and had a higher prevalence of comorbidities including cardiovascular risk factors, although stroke severity was similar between the groups (median NIHSS 18 vs. 17). After adjusting for baseline clinical factors including intravenous alteplase, patients taking NOACs were not at a significantly higher risk of sICH compared with patients not taking anticoagulants (4.9% vs 6.4%; aOR, 0.93 [95% CI, 0.75-1.14]) or in-hospital mortality (14.1% vs 13.1%; aOR, 0.90 [95% CI, 0.78-1.02]). Of the secondary discharge outcomes, 3 of 7 showed significant differences in favor of the NOAC group including ambulating independently (33.7% vs 38.7%; aOR, 1.15 [95% CI, 1.02-1.30]) and freedom from disability (modified Rankin Scale [mRS] 0-1, 13.0% vs 16.2%; aOR, 1.23 [95% CI, 1.04-1.46]) at discharge. In a subset of patients with documented time of last NOACs dose (n=213), sICH rate was 3.1% (6/196) with last dose ≤2 days and 0% (0/17) with &gt;2 days. Conclusions: Among patients with acute ischemic stroke treated with EVT within 6 hours, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of adverse events and was associated with better functional outcomes at discharge.

Long-term stroke and major bleeding risk in patients with non-valvular atrial fibrillation: A comparative analysis between non-vitamin K antagonist oral anticoagulants and warfarin using a clinical data warehouse.

Non-vitamin K antagonist oral anticoagulants (NOACs) has been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation (AF) since 2014. Many studies based on claim data revealed that NOACs had comparable effect to warfarin in preventing ischemic stroke with fewer hemorrhagic side effects. We analyzed the difference in clinical outcomes according to the drugs in patients with AF based on the clinical data warehouse (CDW). We extracted data of patients with AF from our hospital's CDW and obtained clinical information including test results. All claim data of the patients were extracted from National Health Insurance Service, and dataset was constructed by combining it with CDW data. Separately, another dataset was constructed with patients who could obtain sufficient clinical information from the CDW. The patients were divided NOAC and warfarin groups. The occurrence of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, and death were confirmed as clinical outcome. The factors influencing the risk of clinical outcomes were analyzed. The patients who were diagnosed AF between 2009 and 2020 were included in the dataset construction. In the combined dataset, 858 patients were treated with warfarin, 2,343 patients were treated with NOACs. After the diagnosis of AF, the incidence of ischemic stroke during follow-up was 199 (23.2%) in the warfarin group, 209 (8.9%) in the NOAC group. Intracranial hemorrhage occurred in 70 patients (8.2%) among the warfarin group, 61 (2.6%) of the NOAC group. Gastrointestinal bleeding occurred in 69 patients (8.0%) in the warfarin group, 78 patients (3.3%) in the NOAC group. NOAC's hazard ratio (HR) of ischemic stroke was 0.479 (95% CI 0.39-0.589, p < 0.0001), HR of intracranial hemorrhage was 0.453 (95% CI 0.31-0.664, p < 0.0001), and HR of gastrointestinal bleeding was 0.579 (95% CI 0.406-0.824, p = 0.0024). In the dataset constructed using only CDW, the NOAC group also had a lower risk of ischemic stroke and intracranial hemorrhage than warfarin group. In this CDW based study, NOACs are more effective and safer than warfarin in patients with AF even with long-term follow-up. NOACs should be used to prevent ischemic stroke in patients with AF.

Risk of heart failure in elderly patients with atrial fibrillation and diabetes taking different oral anticoagulants: a nationwide cohort study

BackgroundHeart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin.MethodsA nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models.ResultsThe study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74–0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80–0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74–0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68–0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60–0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings.ConclusionsThis nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.

Cardiovascular and renal protective effects of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation.

AimData on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in relation to the risk of cardiovascular (CV) disease and renal protection among patients with atrial fibrillation (AF), are relatively sparse. We aimed to compare the effectiveness and safety of NOACs with those of warfarin for vascular protection in a large-scale, nationwide Asian population with AF.Methods and resultsPatients with AF who were prescribed oral anticoagulants according to the Korean Health Insurance Review and Assessment database between 2014 and 2017 were analyzed. The warfarin and NOAC groups were balanced using propensity score weighting. Clinical outcomes included ischemic stroke, myocardial infarction, angina pectoris, peripheral artery disease, chronic kidney disease (CKD), end-stage renal disease (ESRD), CV death, and all-cause death. NOAC use was associated with a lower risk of angina pectoris (HR, 0.79 [95% CI, 0.69–0.89] p<0.001), CKD stage 4 (HR, 0.5 [95% CI, 0.28–0.89], p = 0.02), and ESRD (HR, 0.15[95% CI, 0.08–0.32], p<0.001) than warfarin use. NOACs and warfarin did not significantly differ with respect to stroke reduction (HR, 1.05 [95% CI, 0.88–1.25], p = 0.19). NOAC use was associated with a lower risk of intracranial hemorrhage (HR, 0.6 [95% CI, 0.44–0.83], p = 0.0019), CV death (HR, 0.55 [95% CI, 0.43–0.70], p<0.001), and all-cause death (HR, 0.6 [95% CI, 0.52–0.69], p<0.001) than warfarin use.ConclusionNOACs were associated with a significantly lower risk of adverse CV and renovascular outcomes than warfarin in patients with AF.

Evaluation of Fracture Risk Among Patients With Type 2 Diabetes and Nonvalvular Atrial Fibrillation Receiving Different Oral Anticoagulants.

Patients with type 2 diabetes are at higher risk for fracture risk because of attenuated bone turnover and impaired bone microarchitecture. The comparative effect of warfarin over non-vitamin K antagonist oral anticoagulants (NOACs) on incident fractures among patients with type 2 diabetes comorbid with atrial fibrillation (AF) remains to be elucidated. This was a retrospective, propensity score-weighted, population-based cohort study of adults with type 2 diabetes and AF who were started on warfarin or NOAC between 2005 and 2019 identified from an electronic database of the Hong Kong Hospital Authority. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, proximal humerus, and wrist). Hazard ratios (HRs) were calculated using Cox proportional hazards regression models. A total of 15,770 patients with type 2 diabetes comorbid with AF were included (9,288 on NOAC, 6,482 on warfarin). During a median follow-up of 20 months, 551 patients (3.5%) sustained major osteoporotic fractures (201 [2.2%] in the NOAC group, 350 [5.4%] in the warfarin group). The adjusted cumulative incidence was lower among NOAC users than warfarin users (HR 0.80; 95% CI 0.64, 0.99; P = 0.044). Subgroup analyses showed consistent protective effects against major osteoporotic fractures among NOAC users across sex, age, HbA1c, duration of diabetes, and history of severe hypoglycemia compared with warfarin users. NOAC use was associated with a lower risk of major osteoporotic fractures than warfarin use among patients with type 2 diabetes comorbid with AF. NOAC may be the preferred anticoagulant from the perspective of bone health.

Current Use of Oral Anticoagulation Therapy in Elderly Patients with Atrial Fibrillation: Results from an Italian Multicenter Prospective Study-The ISNEP Study.

Background: Atrial fibrillation (AF) is the most common heart arrhythmia, and its prevalence increases with age. Oral Anticoagulant Therapy (OAT) with non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) is essential to avoid thromboembolic events in AF. However, this treatment is associated with a high risk of bleeding and low adherence in elderly patients. Aim: The aim was to evaluate the real-world use of OAT in a population of patients aged ≥80 years in twenty-three Italian centers and to investigate the tolerance of and patient satisfaction with this therapy. Methods: The ISNEP Study is a multicenter cross-sectional study enrolling patients with AF and aged ≥80 years and treated with either NOACs or VKAs. A written questionnaire was administered to each patient to evaluate the adherence to and patient satisfaction with this therapy. Results: The study included 641 patients with a mean age of 85 (82–87) years. The use of NOACs was reported in 93.0% of cases, with the remaining 7.0% treated with VKAs. A history of stroke events was reported in five (11.1%) and one (0.2%) patients in the VKA and NOAC groups, respectively. The rate of referred ecchymosis/epistaxis was significantly higher in the VKA group compared to the NOAC group (p < 0.001). Patients receiving NOACs reported a substantial improvement in their quality of life compared to the VKA group. Conclusions: A small, but not negligible, proportion of elderly AF patients is still treated with VKAs. Patients treated with NOAC have a higher level of satisfaction with the therapy and complete adherence.

Risk of Ischemic Bowel Disease in Patients With Atrial Fibrillation Receiving Warfarin or Non-vitamin K Antagonist Oral Anticoagulants.

BackgroundAlthough atrial fibrillation (AF) is a risk factor for ischemic bowel disease, data regarding the incidence of ischemic bowel disease in patients with anticoagulated AF were limited.MethodsThe present study used the Taiwan NHIRD and included newly diagnosed patients with AF aged ≥ 20 years without ischemic bowel disease from 2012 to 2018. A total of 69,549 patients taking warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) constituted the final study group. We aimed to study the incidence of ischemic bowel disease in patients with AF receiving warfarin or NOACs. Secondary endpoints were also analyzed, including ischemic stroke, systemic embolism, myocardial infarction, mortality, intracranial hemorrhage (ICH), major bleeding, and composite adverse events (ischemic bowel disease or ICH or major bleeding).ResultsThere were 43,787 patients taking NOACs and 25,762 patients taking warfarin. The overall incidence rate of ischemic bowel disease was 0.036% per year and increased with the CHA2DS2-VASc scores [0.013% for patients with a CHA2DS2-VASc score of 0 (men) or 1 (women), 0.022% for those with a CHA2DS2-VASc score of 1 (men) or 2 (women), and 0.039% for those with a CHA2DS2-VASc score ≥ 2 (men) or ≥ 3 (women)]. The risk of ischemic bowel disease was similar between NOAC and warfarin groups (0.036%/year vs. 0.037%/year; adjusted hazard ratio 0.802, p = 0.430), whereas the NOAC group had a significantly lower risk of secondary endpoints compared to the warfarin group.ConclusionWe reported the incidence of ischemic bowel disease in patients with anticoagulated AF from a nationwide cohort database and observed a positive correlation between the increase of CHA2DS2-VASc scores and the incidence rate. Moreover, NOAC was as effective as warfarin for the risk of ischemic bowel disease.

Clinical Performance of Oral Anticoagulants in Elderly with Atrial Fibrillation and Low Body Weight: Insight into Italian Cohort of PREFER-AF and PREFER-AF Prolongation Registries.

Background: Elderly patients are at high risk of both ischaemic and bleeding events, and the low body weight is considered a risk factor for major bleeding in atrial fibrillation (AF) patients on anticoagulation therapy. The aim of our study was to compare the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus well-controlled vitamin-K antagonists (VKA) therapy among AF patients aged >75 years and with a body weight <60 kg in a prospective registry setting. Methods: Data for this study were sourced from the Italian cohorts of PREFER in AF and PREFER in AF PROLONGATION registries. The occurrence of a composite of stroke, transient ischemic attack and systemic embolism (thromboembolic events) was the primary effectiveness endpoint. The occurrence of major bleeding was the primary safety endpoint. All-cause hospitalizations and all-cause death were the secondary endpoints. The net clinical benefit (NCB) was calculated in order to obtain an integrated assessment of the anti-thromboembolic and pro-haemorrhagic effects of NOACs vs. VKA. Results: Overall, 522 patients were included; 225 were on treatment with NOACs and 317 patients with VKA. The NOAC group more frequently featured a higher BMI and a higher prevalence of history of stroke/TIA and insulin-requiring diabetes; conversely, heart failure and chronic liver disease were less frequent in the NAOC group. In the unmatched study population, 18 patients (3.6% in the NOAC vs. 3.2% in the VKA group, p = 0.79) experienced thromboembolic events; 19 patients (1.78% in the NOAC vs. 4.73% in the VKA group, p = 0.06) experienced major bleeding events; and 68 patients were hospitalized during the follow-up (9.3% vs. 14.8%, p = 0.06). After balancing for potential confounders by using the 1:1 propensity score matching technique, 426 patients (213 on NOAC and 213 on VKA) were selected. We found no significant differences in terms of thromboembolic events (3.76% vs. 4.69%, p = 0.63), major bleeding events (n: 1.88% vs. 4.22%, p = 0.15) and hospitalizations (9.9% vs. 16.9%, p = 0.06) between NOAC vs. VKA matched population. Based on these incidences, we found a positive net clinical benefit (+1.6) of NOACs vs. VKAs. Conclusions: These real-world data suggest the safety and effectiveness of using NOACs in elderly patients with low body weight.

A Meta-Analysis Comparing Different Oral Anticoagulation for the Treatment of Ventricular Thrombus

Background: Patients with ventricular thrombus (VT) require anticoagulation therapy and it remains unknown that whether non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) are more effective. Objective: We aimed to compare the effectiveness and safety of NOACs with VKAs on the rate of thrombus resolution and clinical outcomes. Methods: MEDLINE, PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database and Wanfang Database, were searched up to November 22, 2021. The primary outcome was the rate of thrombus resolution, and the secondary outcomes were bleeding, stroke or systemic embolism (SSE), stroke and all-cause death. Odds ratio (OR) and 95% confidential intervals (CI) were used for the pooled results. Results: Eighteen studies with 1755 participants (NOACs, n = 607; VKAs, n = 1148) were included. There were no significant differences in thrombus resolution (OR 0.92, 95% CI 0.68–1.23, p = 0.558), bleeding (OR 0.85, 95% CI 0.54–1.35, p = 0.496), SSE (OR 0.77, 95% CI 0.41–1.43, p = 0.401), stroke (OR 0.65, 95% CI 0.29–1.49, p = 0.312) or all-cause death (OR 1.02, 95% CI 0.63–1.67, p = 0.925) between NOACs and VKAs. Subgroup analyses showed a statistics difference in thrombus resolution between NOACs and VKAs among studies which enrolled patients with or without dabigatran (Yes: OR 0.80, 95% CI 0.59–1.08; No: OR 1.48, 95% CI 1.00–2.19; p = 0.01), while no significances were observed according to baseline characteristics. Conclusions: Our findings showed that NOACs were comparable to VKAs in thrombus resolution as well as clinical outcomes. In studies that enrolled patients without dabigatran, the thrombus resolution seemed to be greater in NOACs group than VKAs group. And in different proportion of baseline left ventricular ejection fraction, history of ischemic cardiomyopathy and combination with antiplatelet, the thrombus resolution among the two groups remained similar.

Gastrointestinal bleeding risk of non-vitamin K antagonist oral anticoagulants versus warfarin in general and after polypectomy: a population-based study with propensity score matching analysis.

Gastrointestinal bleeding (GIB) risk for non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin is largely unknown. We aimed to determine the risk of overall and post-polypectomy GIB for NOACs and warfarin. Using the Korean National Health Insurance database, we created a cohort of patients who were newly prescribed NOACs or warfarin between July 2015 and December 2017 using propensity score matching (PSM). Kaplan-Meier analysis with log-rank test was performed to compare the risk of overall and post-polypectomy GIB between NOACs (apixaban, dabigatran, and rivaroxaban) and warfarin. Post-polypectomy GIB was defined as bleeding within 1 month after gastrointestinal endoscopic polypectomy. Out of 234,206 patients taking anticoagulants (187,687 NOACs and 46,519 warfarin), we selected 39,764 pairs of NOACs and warfarin users after PSM. NOACs patients showed significantly lower risk of overall GIB than warfarin patients (log-rank P<0.001, hazard ratio, 0.86; 95% confidence interval, 0.78-0.94; P=0.001). Among NOACs, apixaban showed the lowest risk of GIB. In the subgroup of 7,525 patients who underwent gastrointestinal polypectomy (lower gastrointestinal polypectomy 93.1%), 1,546 pairs were chosen for each group after PSM. The NOACs group showed a high risk of post-polypectomy GIB compared with the warfarin group (log-rank P=0.001, hazard ratio, 1.97; 95% confidence interval, 1.16-3.33; P=0.012). This nationwide, population-based study demonstrates that risk of overall GIB is lower for NOACs than for warfarin, while risk of post-polypectomy GIB is higher for NOACs than for warfarin.

Association of Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase

Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants. A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines-Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry. Prestroke treatment with NOACs within 7 days prior to alteplase treatment. The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home. Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], -0.51% [95% CI, -1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, -1.20% [95% CI, -2.39% to -0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]). Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.

Real-world comparison of different periprocedural antithrombotic strategies for atrial fibrillation catheter ablation

Abstract Introduction Atrial Fibrillation (AF) catheter ablation carries high bleeding and thromboembolic risks, requiring a detailed assessment of overall risk-benefit profile regarding antithrombotic strategy. Vitamin K Anticoagulant (VKA) and Non-Vitamin K Antagonist Oral Anticoagulant (NOAC) have been used in the latest years in this setting, and with different interruption protocols periprocedural. Our goal was to evaluate the rate of acute adverse events (AAE) and compare them according to antithrombotic strategy used periprocedural, in a real-world basis. Methods A single-center retrospective study, including adult patients admitted to first AF catheter ablation, from 2004 to 2020. Different antithrombotic strategies (anticoagulation with VKA uninterrupted, anticoagulation with NOAC uninterrupted, no therapy or antiaggregation/interrupted ACO) were compared concerning the rate of any clinically relevant AAE; the composite of major AAE (hemopericardium and stroke/transient ischemic attack [TIA]) and minor AAE associated with vascular access. Descriptive statistics and logistic regression were used to compare groups according to the antithrombotic strategy with an alpha level of 0.05. Results Among the 868 patients included (mean age 59±12 yo, 67,5% [n=586] men), pulmonary vein isolation was performed under uninterrupted anticoagulation in 640 (73,7%), of which 595 patients with NOAC (68,5%) and 45 with VKA (5,2%). AF was paroxysmal, persistent and long-standing persistent in 63,4% (n=550), 21,4% (n=185) and 15,4% (n=133) patients, respectively. Mean CHADS-VASc score was 1,86±1,48. Over time there was a shift in the distribution of the type of antithrombotic therapy used, consistent with changes in recommendations (Graph 1). The composite outcome occurred in 6,8% (n=62), including hemopericardium in 1,8% (n=16), stroke/TIA in 0,7% (n=6) and events related to vascular access in 1,4% (n=13) [Table 1]. No anticoagulation therapy or antiaggregation/interrupted ACO was more associated to the outcome, driven by major AAE, although the difference did not meet statistical significance (p=0,06) [Table 1]. No difference was found between VKA and NOAC group. Additionally, there was no diference in the incidence of hemorrhagic AAE since the implementation of an uninterrupted anticoagulation strategy periprocedural. Conclusion In our population of patients submitted to AF catheter ablation, an uninterrupted anticoagulation strategy is associated with lower rate of AAE, either with VKA or NOAC. Our real-world results are reassuring of the benefit of an uninterrupted strategy, and consistent with recent controlled trials. Funding Acknowledgement Type of funding sources: None. Antithrombotic therapies over timeClinically relevant acute adverse events

Oral anticoagulation patterns and prognosis in octogenarian patients with atrial fibrillation.

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