Systemic Embolic Events Research Articles

Safety and efficacy of direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation electrical cardioversion: An update systematic review and meta-analysis

BackgroundA systematic evaluation focused on efficacy and safety for electrical cardioversion of atrial fibrillation (AF) among different Direct Oral Anticoagulants (DOACs) has not been previously performed. In this setting, we conducted a meta-analysis of studies evaluating DOACs vs vitamin K antagonists (VKA) as common comparator. MethodsWe searched Cochrane Library, Pubmed, Web Of Science and Scopus databases for all English-only articles concerning studies that have estimated the effect of DOACs and VKA on stroke, transient ischemic attack or systemic embolism (SSE) and major bleeding (MB) events in AF patients undergoing electrical cardioversion. We selected 22 articles comprising 66 cohorts and 24,322 procedures (12,612 with VKA). ResultsDuring follow-up (studies' median 42 days), 135 SSE (52 DOACs and 83 VKA) and 165 MB (60 DOACs and 105 VKA) were recorded. The overall pooled effects, DOACs vs VKA, was estimated by an univariate Odds Ratio of 0.92 (0.63–1.33; p = 0.645) for SSE and 0.58 (0.41–0.82; p = 0.002) for MB; at bivariate evaluation, adjusting for study type, were respectively 0.94 (0.55–1.63; p = 0.834) and 0.63 (0.43–0.92, p = 0.016). Each single DOAC showed similar and non statistically different results in outcome occurrence compared to VKA as well as when Apixaban, Dabigatran, Edoxaban and Rivaroxaban were indirectly compared to each other. ConclusionsIn patients undergoing electrical cardioversion, compared to VKA, DOACs have similar thromboembolic protection with lower major bleeding incidence. Single molecule does not show difference in event rate compared to each other. Our findings, provide useful information about safety and efficacy profile of DOACs and VKA.

Descriptive Analysis of Rheumatic Heart Disease Related Complications in Pediatric Patients at Tertiary Hospital, Addis Ababa, Ethiopia.

Rheumatic heart disease continues to be a public health problem worldwide. In developing countries such as Ethiopia where rheumatic heart disease is endemic, most of the patients present with complaints related to complications including heart failure, arrhythmias, pulmonary hypertension, stroke, systemic embolic events and infective endocarditis. To identify the types and magnitude of complications in pediatric patients with rheumatic heart disease. Hospital-based cross-sectional study was conducted at Saint Paul Hospital Millennium Medical College, pediatric and child health department. All pediatric cardiac patients with rheumatic heart disease seen from January 1, 2018 to December 30, 2021 were included in the study. The majority of patients presented to our health facility with complications which implies the need for action at the community level to detect the disease at early stage. We recommend a similar large-scale study to be conducted at the national level and introduce a national RHD registry to better understand the magnitude of the problem, based on which necessary action will be undertaken. There is also a need to assess the proper implementation of screening and preventive RHD programmes.

Embolic myocardial infarction associated with patent foramen ovale: a case series

A patent foramen ovale (PFO) is a fairly common mild cardiac defect that causes a shunting across the atrial septum. PFO is also a known risk factor for cryptogenic stroke. Much less frequently, PFO is associated with non-cerebral systemic embolic events. The article describes a case series of paradoxical embolism of the coronary arteries (CA), which caused myocardial infarction (MI). The presence of PFO was confirmed by imaging techniques. Subsequently, the patients underwent successful endovascular closure of the PFO. Thus, paradoxical CA embolism is a rare and underdiagnosed cause of acute MI. It should be considered in patients with MI and a low risk of atherosclerotic coronary artery disease. However, in most cases, it is not possible to verify the source of the embolism. The significance of occluder implantation as one of the treatment tactics requires further clarification.

Edoxaban Anticoagulation in Atrial Fibrillation: Real-World Data and Evidence.

Atrial fibrillation (AF) and stroke are two prevalent health conditions with many shared risk factors. Over the past two decades, non-vitamin K antagonist oral anticoagulants (NOACs) have emerged as important alternatives to vitamin K antagonists, owing to their efficacy, safety profile, and the absence of a need for frequent international normalized ratio monitoring. Introduced as the most recent NOAC, edoxaban has been approved for stroke prevention in non-valvular AF in numerous countries since 2014. The pivotal phase III Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial demonstrated that edoxaban is as efficacious as warfarin in preventing strokes and systemic embolic events. Furthermore, it is linked to reduced rates of major, life-threatening, intracranial, major, or clinically relevant non-major bleeding events and decreased cardiovascular mortality in AF when compared to warfarin. Growing data highlights the utilization of edoxaban in treating AF patients in clinical settings. This article provides an overview of real-world evidence regarding edoxaban's use in preventing stroke and systemic embolic events in AF patients, emphasizing the concerns that physicians factor into their clinical decision-making.

Residual stroke risk despite oral anticoagulation in patients with atrial fibrillation.

Oral anticoagulation (OAC) reduces the risk of thromboembolic events in patients with atrial fibrillation (AF); however, thromboembolism (TE) still can occur despite OAC. Factors associated with residual risk for stroke, systemic embolism, or transient ischemic attack events despite OAC have not been well described. The purpose of this study was to evaluate the residual risk of thromboembolic events in patients with AF despite OAC. A total of 18,955 patients were analyzed in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF I and II) using multivariable Cox proportional hazard modeling. Mean age was 72 ± 10.7, and 42% were women. There were 451 outcome events. The risk of TE despite OAC increased with CHA2DS2-VASc score: 0.76 (95% confidence interval [CI] 0.63-0.92) events per 100 patient-years for CHA2DS2-VASc score <4 vs 2.01 (95% CI 1.81-2.24) events per 100-patient years for CHA2DS2-VASc score >4. Factors associated with increased risk were previous stroke or transient ischemic attack (hazard ratio [HR] 2.87; 95% CI 2.30-3.59; P <.001), female sex (HR 1.52; 95% CI 1.24-1.86; P <.001), hypertension (HR 1.50; 95% CI 1.09-2.06; P = .01), and permanent AF (HR 1.47; 95% CI 1.12-1.94; P = .001). When transient ischemic attack was excluded, the results were similar, but permanent AF was no longer significantly associated with thromboembolic events. Patients with AF have a residual risk of TE with increasing CHA2DS2-VASc score despite OAC. Key risk markers include previous stroke/transient ischemic attack, female sex, hypertension, and permanent AF.

When to set anticoagulant therapy in asymptomatic AF? looking for a cut-off duration.

The incidence of atrial fibrillation (AF) is progressively increasing, in line with the aging of the population and with the increase in chronic diseases. The care burden of the disease and above all to its consequences (i.e. ischaemic stroke and heart failure) significantly impacts the various health systems with forecasts of exponential increase in the near future. Clinical forms of AF, i.e. those diagnosed with electrocardiogram, have a clear correlation with systemic embolic events and also with a reduction in survival. Thromboembolic prophylaxis in these patients, with anticoagulant drugs, has in fact been shown to greatly reduce the incidence of ischaemic stroke and improve survival. In recent decades, the widespread use of therapeutic intra-cardiac devices, which allow constant and continuous monitoring of myocardial electrical activity, is bringing to light a large number of atrial high rate episodes (AHREs), which are not associated with clinical manifestation. The incidence of these findings grows linearly with the duration of the observation. More independent studies have shown that AHREs are associated with a risk of stroke that is higher (about double) than controls but significantly lower than in patients with manifest AF. However, taking into consideration patients with ischaemic stroke and wearers of implantable devices, no temporal correlation emerged between the incidence of the ischaemic episode and arrhythmia. The presence of AHRE is associated with an approximately six-fold increase in the incidence of clinical AF but only a minority of these patients meet the criteria for prescribing anticoagulation. Pending the publication of the studies still in progress, the European Society of Cardiology guidelines for the treatment of AF recommend considering the initiation of anticoagulant therapy in patients with long-lasting AHRE (> 24 h) associated with a high embolic risk. In patients with episodes of shorter duration (1-24 h), especially if with high burden, anticoagulant therapy can be considered in case of very high embolic risk (e.g. secondary prevention, CHADVASc ≥ 3).

Abstract 10984: Alert-Based Computerized Decision Support for High-Risk Ambulatory Clinic Patients With Atrial Fibrillation Not Prescribed Anticoagulation: A Randomized, Controlled Trial (AF-Alert2)

Introduction: Despite widely available risk stratification tools, safe and effective anticoagulants, and guideline recommendations, antithrombotic therapy for stroke prevention in atrial fibrillation (AF) is under-prescribed in ambulatory clinic patients. Hypothesis: We hypothesized that alert-based computerized decision support (CDS) would increase anticoagulation prescription in ambulatory clinic patients with AF and high-risk for stroke. Methods: We enrolled 798 patients (CHA 2 DS 2- VASc score≥2) with AF who were not prescribed anticoagulant therapy and had an ambulatory clinic visit at Brigham and Women’s Hospital. Patients were randomly allocated, according to Attending Physician of record, to intervention (alert-based CDS) versus control (no notification). The primary efficacy outcome was the frequency of anticoagulant prescription. Results: The CDS tool assigned 395 and 403 patients to the alert and control groups, respectively. Patients in the alert group were more likely to be prescribed anticoagulation within 48 hours of the clinic visit (15.4% vs. 7.7%, p&lt;0.001) and at 90 days (17.2% vs. 9.9%, p&lt;0.01). Direct oral anticoagulants (DOACs) comprised the majority of increased prescriptions of anticoagulation at 48 hours and 90 days. No differences in stroke, TIA, or systemic embolic events (0% vs. 0.8%, p=0.09), symptomatic VTE (0.5% vs. 1%, p=0.43), CV mortality (0.5% vs. 0.7%, p=0.99), or a composite of major adverse cardiovascular events (2.8% vs. 2.5%, p=0.79) were observed at 90 days ( Figure ). Conclusions: An alert-based CDS strategy increased anticoagulation in ambulatory clinic patients with AF and high-risk for stroke who were not receiving anticoagulation at the time of the office visit. ClinicalTrials.gov Identifier: NCT02958943

Incidence of stroke, systemic embolism and bleeding events in patients without anticoagulation based on real-world data in Japan: a retrospective cohort study

ObjectivesTo examine the incidence of stroke or systemic embolic events (SSEs) and bleeding events in untreated patients with non-valvular atrial fibrillation (NVAF) after widespread use of direct oral anticoagulant agents...

The Electrocardiogram in the Diagnosis and Management of Patients With Left Ventricular Non-Compaction.

Left ventricular non-compaction (LVNC) is characterised by prominent left ventricular trabeculae and deep inter-trabecular recesses. Although considered a distinct cardiomyopathy, prominent trabeculations may also be found in other cardiomyopathies, in athletes or during pregnancy. Clinical presentation includes heart failure symptoms, systemic embolic events, arrhythmias and sudden cardiac death. Currently, LVNC diagnosis relies on imaging criteria, and clinicians face several challenges in the assessment of patients with prominent trabeculations. In this review, we summarise the available information on the role of the ECG in the diagnosis and management of LVNC. ECG abnormalities have been reported in 75-94% of adults and children with LVNC. The lack of specificity of these ECG abnormalities does not allow (in isolation) to diagnose the condition. However, when considered in a set of diagnostic criteria including family history, clinical information, and imaging features, the ECG may differentiate between physiological and pathological findings or may provide clues raising the possibility of specific underlying conditions. Finally, some ECG features in LVNC constitute ominous signs that require a stricter patient surveillance or specific therapeutic measures. The ECG remains a cornerstone in the diagnosis and management of patients with cardiomyopathies, including LVNC.

Perceived frailty and clinical outcomes in men and women with atrial fibrillation treated with edoxaban: insights from the 2-year follow-up of ETNA-AF-Europe

Abstract Background/Introduction Many clinicians estimate the frailty of patients solely using their clinical expertise instead of validated scores. Previous reports show that women are more often perceived as frail than men. It is uncertain whether the same trend is observed in patients with atrial fibrillation (AF) and if the association between perceived frailty and adverse clinical outcomes is affected by sex. Purpose To assess whether sex affects the association between frailty status and adverse clinical outcomes in patients with AF. Methods ETNA-AF-Europe is an ongoing, post-authorisation, prospective cohort study conducted in 825 centres enrolling patients with AF treated with edoxaban in 10 European countries. In this substudy on the first 2-years of follow-up, patients were categorised in four subgroups based on sex and clinician-perceived frailty at baseline. We calculated incidence rates (per 100 patient-years) of the composite endpoint of any stroke or systemic embolic event (SEE), of major bleeding, and of all-cause death for the four subgroups; and determined the unadjusted association between perceived frailty (frail vs non-frail) and each outcome, stratified by sex, using Cox proportional hazards models. To assess for consistency in our findings, we tested the same associations by sex category but using objective risk factors: age (&amp;gt;74 vs &amp;lt;65 years) and CHA2DS2-VASc score (≥4 vs &amp;lt;4). Results Information about frailty-status was recorded for 12,254 (93.3%) patients, of whom 8.5% of men and 15.4% of women were perceived as frail by their clinician (p&amp;lt;0.0001) (Table 1). For both sex categories calculated separately, the risk of any stroke or SEE, major bleeding, or all-cause death was higher in the frail than in the non-frail patients (Figure 1A). However, the difference in risks of stroke or SEE between frail and non-frail patients was greater for men (HR 3.77, 95% confidence interval [CI] 2.25–6.31) than for women (HR 2.18, 95% CI 1.34–3.55) and a similar trend toward a greater risk-difference for men was seen for the risk of all-cause death (HR 4.58, 95% CI 3.76–5.59 vs HR 3.63, 95% CI 2.94–4.49). There was no marked difference between sex categories in the association between frailty-status and major bleeding (HR 2.86, 95% CI 1.81–4.50 vs HR 2.56, 95% CI 1.68–3.90) (Figure 1A). The association of age or CHA2DS2-VASc subgroups with clinical outcomes were either similar between sexes or suggested a possible lower risk-difference for men (Figure 1B and 1C). Conclusion In our cohort, differences in the risks of clinical outcomes between those who were perceived as frail and those who were not is more pronounced for men than women. Because we did not observe similar trends in the associations between age or CHA2DS2-VASc score subgroups and clinical outcomes, our results indicate that clinicians perceive the extent of frailty differently in men than in women. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was funded by Daiichi Sankyo Europe.

Comparing direct oral anticoagulants versus vitamin K antagonist in patients with atrial fibrillation after transcatheter aortic valve replacement: an updated meta-analysis

Abstract Background Oral anticoagulation therapy is indicated for patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant or new onset atrial fibrillation (AF). However the data on optimal anticoagulation regimen in this population remains unclear. Purpose To compare efficacy and safety outcomes of direct oral anticoagulants (DOACs) versus Vitamin K antagonists (VKA) in patients with AF post TAVR. Methods We searched electronic databases (PubMed, Embase, Scopus, Cochrane) from inception to February28th, 2022 using MeSH terms and keywords for DOACs, AF or TAVR. Primary outcome of interest was all-cause stroke or systemic embolic event. Secondary safety outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effects model. Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis were performed using RevMan 5.4.1 software. Results We identified five eligible studies (1RCT, 4 observational) including 3694 patients (DOAC n=1581, VKA n=2113). The mean age was 81.4±0.9 years. The mean follow-up was 12.4±14.3 months. Type of DOACs included apixaban (n=394, 24.9%), rivaroxaban (n=354, 22.4%), dabigatran (n=119, 7.5%) and edoxaban (n=714, 45.2%).There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.93; CI: 0.65–1.33; p&amp;gt;0.05; I2=5%), or in secondary outcomes of major bleeding (RR: 1.02; CI: 0.78–1.34; p&amp;gt;0.05; I2=44%) and all-cause mortality (RR: 0.87; CI: 0.59–1.27; p&amp;gt;0.05; I2=56%) between DOACs and VKA groups. Conclusion This meta-analysis shows anticoagulation therapy with DOACs has similar safety and efficacy outcomes compared to VKA in patients with AF undergoing TAVR. Funding Acknowledgement Type of funding sources: None.

To compare efficacy and safety of direct oral anticoagulants in patients with concurrent atrial fibrillation and bioprosthetic heart valve repair or replacement: a systematic review and meta-analysis

Abstract Background Use of direct oral anticoagulants (DOACs) is contraindicated in patients with mechanical valves. However data on their use in patients with atrial fibrillation (AF) and bioprosthetic valves (BV) is still limited. Purpose To assess the safety and efficacy of DOACs versus Vitamin K antagonist (VKA) in patients with AF after BV repair or replacement. Methods We performed a comprehensive review of electronic databases (PubMed, Embase, Scopus, Cochrane) using MeSH terms and keywords for DOACs, AF and BVs from inception through December 2021. Randomized clinical trials (RCT) or observational studies that reported clinical outcomes comparing DOACs versus VKA in patients with AF and BVs were eligible for inclusion. Ten articles were reviewed for full text. Primary outcome was a composite of all cause stroke or systemic embolic event. Secondary outcomes included major bleeding and all-cause mortality. Subgroup analysis stratified by study design was performed. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using Mantel-Haenszel method with DerSimonian-Laird estimator for tau2 for random effects model. Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis was performed using RevMan 5.4.1 software. Results Ten studies (5 RCTs, 5 observational studies) with a total of 5,333 patients (DOACs n=2434; VKA n=2899) were included. Aortic, mitral and mixed BV repair or replacement were 74.2%, 25.6% and 0.02% respectively. The mean age was 72.6±11.9 years. The mean follow-up was 15.7±12.9 months. Type of DOACs included apixaban (n=553, 22.7%), rivaroxaban (n=893, 36.7%), dabigatran (n=151, 6.2%) and edoxaban (n=837, 34.4%). There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.79; CI: 0.56–1.11; p&amp;gt;0.05; I2=12%) or secondary outcomes of major bleeding (RR: 0.84; CI: 0.64–1.11; p&amp;gt;0.05; I2=45%), and all-cause mortality (RR: 0.84; CI: 0.64–1.11; p&amp;gt;0.05; I2=29%) between DOACs compared with VKA. Conclusion In patients with AF and BV, DOACs are non-inferior to VKA for risk of stroke or systemic embolism, major bleeding, and all-cause mortality. Thus, DOACs can serve as a viable alternative to VKAs which have a narrow therapeutic index, multiple drug interactions, and require frequent monitoring. Funding Acknowledgement Type of funding sources: None.

Two-year outcomes of patients with atrial fibrillation and heart failure: the ETNA-AF-Europe registry

Abstract Background Heart failure (HF) is an established risk factor for stroke and systemic embolic events (SEE) in subjects with atrial fibrillation (AF), but it is debated whether this risk varies according to left ventricular ejection fraction (LVEF). Methods We investigated the impact of HF in the ETNA-AF-Europe registry, a prospective, multi-centre, post-authorisation, observational study enrolling patients treated with edoxaban for AF in 825 sites from 10 European countries. This 2-year follow-up analysis is based on a data snapshot from 26 October 2020. HF was defined as a) history of HF or b) ischaemic cardiomyopathy or c) EF &amp;lt;40% or d) dyspnoea not due to chronic obstructive pulmonary disease together with ≥1 of the following: ischaemic heart disease, valvular heart disease, or hypertension treated with ≥3 drugs. Patients' characteristics are summarised descriptively and clinical outcomes are reported as annualised event rates. The hazard ratio (HR) with 95% confidence intervals (CI) for the association of HF with the outcomes was assessed in Cox regression models with stepwise variable selection. Results Of the 13,133 patients, 1,854 (14.1%) had HF; LVEF was available for 1,489 (80.3%), and was &amp;lt;40% in 671 (43.9%) and ≥40% in 857 (56.1%). Patients with HF were more often men and slightly older than those without (Table 1). As expected, they also had more cardiovascular (CV) comorbidities and higher CHA2DS2-VASC and, to a lesser extent, HAS-BLED scores (Table 1). At the end of the 2-year follow-up, the rates of ischaemic stroke/transient ischaemic attack (TIA)/SEE, major bleeding, intracranial haemorrhage (ICH), CV death, and all-cause death were higher in patients with than without HF (Figure 1). When patients with HF were categorized according to LVEF, ischaemic stroke/TIA/SEE was more frequent in those with LVEF ≥40% vs those with LVEF &amp;lt;40%. By contrast, more patients with LVEF &amp;lt;40% died due to any as well as CV causes. The rates of major bleeding and ICH were comparable between the two subgroups (Figure 1). Univariable Cox regression analysis confirmed the association of HF with major bleeding (HR 2.01, 95% CI [1.49–2.71]) and all-cause death (2.62 [2.28–3.02]), but not with ischaemic stroke/TIA/SEE (1.06 [0.72–1.55]). The results were consistent when LVEF was taken into account: the HRs for LVEF &amp;lt;40% or LVEF ≥40%, respectively, were 1.60 (0.99–2.60) and 1.55 (1.02–2.38) for major bleeding, 2.11 (1.69–2.63) and 1.59 (1.28–1.97) for all-cause death, and 0.66 (0.31–1.41) and 1.19 (0.71–1.98) for ischaemic stroke/TIA/SEE. Conclusions In this real-world, large cohort of patients with AF on edoxaban, those with HF at baseline faced more ischaemic, bleeding, and death events, and having HF increased the risk of major bleeding and death, with no differences according to LVEF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was funded by Daiichi Sankyo Europe.

The association between dyslipidaemia treatment and the risk of clinical events in edoxaban-treated patients with atrial fibrillation: insights from the 2-year follow-up of ETNA-AF-Europe

Abstract Background/Introduction Dyslipidaemia is a major risk factor for cardiovascular (CV) events. This increased risk can be attenuated with lipid-lowering therapies (LLT), such as statins, which are associated with a relative risk reduction of CV events of 22% for each 1 mmol/L reduction in low-density lipoprotein cholesterol. Purpose To explore the association between use of LLT and clinical outcomes in routine practice patients with atrial fibrillation (AF) receiving edoxaban. Methods ETNA-AF-Europe is a prospective, multi-centre, post-authorisation, observational cohort study conducted in 825 centres, enrolling routine practice patients with AF treated with edoxaban in 10 European countries. This registry is still ongoing and patients are to be followed-up annually for 4 years after enrollment. In the current sub-study, on the now available first 2 years of follow-up, patients were categorised by use of LLT at baseline. We used Cox proportional hazards models to determine the associations between LLT use and adverse clinical events, including the composite of any stroke and systemic embolic events (SEE), major bleeding, and death, after adjusting for confounding factors at baseline. Results Of 13,133 patients with AF, 36.3% (n=4761) used LLT at baseline. Among those receiving LLT, 90.7% received statins only and 3.6% received combination therapy with a statin. Most patients in both treatment groups were 65 years or older and had one or more CV-risk factors aside from a history of AF. Patients receiving LLT were older and had a higher prevalence of CV co-morbidities (including diabetes, hypertension, peripheral artery disease and coronary heart disease) than those who did not receive LLT (Table 1). After correction for confounders, treatment with LLT was associated with a significantly lower rate of any stroke or SEE (HR: 0.61; 95% CI: 0.42–0.88), ischaemic stroke (HR: 0.54; 95% CI: 0.35–0.83), all-cause death (HR: 0.73; 95% CI: 0.63–0.85) and CV-death (HR: 0.73; 95% CI: 0.60–0.90), but not with bleeding events or myocardial infarction (Figure 1). Conclusion These findings suggest a protective effect of LLT on the risk of stroke in anticoagulated patients with AF, although an overall better CV risk management in these patients probably contributed to this reduced risk. Notably, both mono- and combination-LLT were seemingly underused in our cohort, highlighting the potential for further reductions of CV risks in the AF patients seen in our clinics. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This research was funded by Daiichi Sankyo Europe.

Variables associated with bleeding and thrombotic outcomes among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomised clinical trial

Abstract Background In the ACTION trial, therapeutic anticoagulation did not show benefit on mortality, days of hospitalization and oxygens therapy at 30 days among patients with COVID19. However, this strategy was associated with higher rate of bleeding and a potential reduction in the rate of clinical thrombotic events. The current analysis evaluated which variables were independently associated with both outcomes in order to help the identification of the risk for thrombotic and hemorrhagic events among patients with COVID19. Methods A total of 615 patients hospitalized with COVID-19 and elevated D-dimer levels were randomly assigned to prophylactic anticoagulation (mainly in-hospital heparin) or a therapeutic strategy that used in-hospital rivaroxaban 20 mg daily for stable patients, or enoxaparin 1 mg/kg twice daily for unstable patients, followed by rivaroxaban through 30 days. One patient withdrew consent and was not included in the analysis. The current analysis tested baseline clinical characteristics and laboratorial exams one by one with independent logistic regressions for the composite of bleeding (major bleeding and clinically relevant nonmajor bleeding) and thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, and major adverse limb events). Significant variables (p&amp;lt;0.05) were selected to adjust several multiple logistic models. Final models were chosen based on Akaike information criterion and therapeutic anticoagulation was included in the final model based on the primary results of the trial. Results The model for bleeding events showed an accuracy of area under the curve (AUC) of 0.635 (table 1) while the model for thrombotic events had an AUC of 0.725 (table 2). Level of respiratory support (especially invasive ventilation) was associated with both outcomes in the multivariable analysis (tables 1 and 2). Beyond respiratory support, level of creatinine and history of coronary disease were also independently associated to the risk of thrombotic events. When the utilization of therapeutic anticoagulation (mainly with rivaroxaban) was included in the multivariable analysis, this variable was strongly associated with higher risk of bleeding (model AUC of 0.718) but was not associated with lower rate of thrombotic events (Tables 1 and 2). Conclusion Since the variables associated with higher risk of thrombotic events are similar to the variables associated to bleeding complications, the selection of patients with better balance of risk vs. benefit to use therapeutic anticoagulation in COVID-19 still a challenging decision. Coronary disease and creatine may help to identify patients at higher risk of thrombotic complications while the use of therapeutic dose of direct oral anticoagulant increased the risk of bleeding in almost 4 times among patients hospitalized due to COVID19. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Investigator initiated research with financial support of Bayer

Direct Oral Anticoagulants versus Vitamin K Antagonists for the Treatment of Left Ventricular Thrombosis: A Meta-Analysis.

Vitamin K antagonists (VKAs) have been recommended as first-line anticoagulants for patients with left ventricular thrombosis (LVT). Direct oral anticoagulants (DOACs) are used as an alternative to the standard of care in anticoagulation. The aim of this meta-analysis was to compare the efficacy and safety of VKAs and DOACs in the treatment of patients with LVT. Studies were identified by searching the PubMed, Web of Science, and Embase. The main outcomes included stroke or systemic embolism (SSE), thrombus resolution, and bleeding events. The pooled risk ratio (RR) with 95% confidence intervals (CIs) was estimated with fixed effect or random effect models. Seventeen studies were included. Pooled estimate showed that DOACs had comparable efficacy in prevention of SSE (RR = 0.96, 95% CI: 0.80, 1.16; p = 0.677) and thrombus resolution as compared with VKAs (RR = 1.07, 95% CI: 0.97, 1.18; p = 0.193). DOACs significantly decreased the risk of stroke in patients with LVT (RR = 0.68, 95% CI: 0.47, 1.00; p = 0.048). However, this effect was not observed in the sensitive analysis by high-quality studies (RR = 0.69, 95% CI: 0.47, 1.02; p = 0.06). In terms of safety outcomes, DOACs had similar risk of bleeding events (RR = 1.12, 95% CI: 0.80, 1.57; p = 0.386) and clinically relevant bleeding events (RR = 0.49, 95% CI: 0.23, 1.03; p = 0.060). Meta-regression analysis demonstrated that none of the variables (study design, concomitant antiplatelet medication, duration of follow-up, primary cause of LVT, sample size, types of DOACs) had an impact on the risk of SSE, thrombus resolution and bleeding events. Subgroup analysis based on the use of antiplatelet and treatment switching revealed that there were no significant differences among patients with different treatment regimens. Based on the present evidence, both DOACs and VKA offered similar effective and safe outcomes in patients with LVT.

Risk Factors and Outcomes of AKI after LAAC Operation: A Single-Center Observational Study from Mainland China.

This study aimed to investigate the predictors and prognosis of acute kidney injury (AKI) occurrence among Chinese patients following left atrial appendage closure (LAAC). We retrospectively enrolled 512 consecutive patients who underwent LAAC between January 2014 and December 2019. AKI was clinically defined according to the Kidney Disease Improving Global Outcomes serum creatinine criteria. Major adverse cardiovascular events were defined as the composite of all-cause mortality, readmission due to heart failure, cardiac surgery, systemic embolism, or bleeding events. The incidence of AKI was 5.3% and was highest in patients with chronic kidney disease (CKD) stages 4-5 (25.0%), followed by those with CKD stages 3a-3b (9.1%), and those with CKD stages 1-2 or without CKD (3.9% only). Multivariate logistic regression showed that lower body mass index (odds ratio [OR] = 0.889; 95% confidence interval [CI], 0.803-0.986; p = 0.017), hypertension (OR = 5.577; 95% CI, 1.267-24.558; p = 0.023), and CKD stages 4-5 (OR = 6.729; 95% CI, 1.566-28.923; p = 0.010) were independent risk factors for AKI development after LAAC. AKI after LAAC was associated with 3-year major adverse cardiovascular events (33.3% vs. 7.5%, p 0.001) and all-cause mortality (11.1% vs. 0.9%, p 0.001) compared to that in the non-AKI group. AKI is relatively common after LAAC in patients with a baseline impaired glomerular filtration rate. Moreover, AKI after LAAC is mainly related to increased midterm mortality and morbidity, which require more strategies for prevention and treatment.

Risk Levels and Adverse Clinical Outcomes Among Patients With Nonvalvular Atrial Fibrillation Receiving Oral Anticoagulants

The CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata. To evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA2DS2-VASc risk score range, thromboembolic event history, and age group. This cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019. Initiation of oral anticoagulants. We observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA2DS2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes. We identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA2DS2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 events per 100 person-years [95% CI, 1.06-1.41 events]; high risk 2, 10.67 events per 100 person-years [95% CI, 10.26-11.48 events]). The 12-month cumulative incidence proportions for stroke and systemic embolism, major bleeding, and composite outcomes progressed alongside risk score strata (stroke or systemic embolism, 0.30%-1.85%; major bleeding, 0.55%-5.55%; composite, 1.05%-8.23%). Age subgroup analysis followed similar trends. The observed incidence of stroke or systemic embolism and major bleeding events generally conformed to an expected increasing incidence by risk score, adding insight into the importance of specific risk score range, thromboembolic event history, and age group strata. These results can help inform clinical decision-making, research, and policy.

Comparison of the Efficacy and Safety of Apixaban and Warfarin in the Prevention of Stroke in Patients With Non-valvular Atrial Fibrillation: A Meta-Analysis.

Atrial fibrillation is an irregular heart rhythm, and it is one of the most common cardiac arrhythmias. It is associated with a five times increase in the risk of stroke. Anti-coagulants are prescribed routinely to prevent strokes, especially in patients with atrial fibrillation for many years decreasing the risk of stroke among patients with atrial fibrillation. Non-vitamin K oral anticoagulants especially apixaban and rivaroxaban are frequently used and they are considered to be safe and more effective than warfarin. The aim of this meta-analysis is to compare the efficacy and safety of apixaban and warfarin in preventing stroke among patients with non-valvular arterial fibrillation. The current meta-analysis was conducted using the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search was done using databases, including PubMed, EMBASE, and Cochrane Library, with no restrictions on language and year of publication. The current meta-analysis included randomized control trials and non-randomized control trials (prospective and retrospective cohort studies) comparing the efficacy and safety of apixaban and warfarin in preventing stroke in patients with non-valvular atrial fibrillation. The primary efficacy outcome was stroke or systemic embolism while the primary safety outcome was major bleeding events. Overall, nine articles were included in the current meta-analysis with a pooled sample size of 267998 patients with non-valvular atrial fibrillation. The administration of apixaban was associated with a significant decrease in stroke or systemic embolism (RR: 0.77, 95% CI: 0.67-0.90) and major bleeding events (RR=0.63, 95% CI: 0.58-0.68) as compared to warfarin. However, no significant difference was reported in all-cause mortality (RR=0.80, 95% CI: 0.30-2.14) between the two groups. The current meta-analysis concluded that apixaban, compared to warfarin in patients with non-valvular atrial fibrillation showed a reduction in stroke and systemic embolism. Apixaban has also a better safety profile in terms of reduction in overall major bleeding events.

One-Year Incidences of Venous Thromboembolism, Bleeding, and Death in Patients With Lung Cancer (Cancer-VTE Subanalysis)

IntroductionThis subanalysis aimed to provide real-world data on venous thromboembolism (VTE) from patients with lung cancer in the Cancer-VTE Registry. MethodsThe primary outcome was the number of baseline VTE events in patients with lung cancer. The 1-year cumulative incidences of symptomatic VTE; composite VTE (symptomatic and incidental VTE requiring treatment); bleeding; cerebral infarction, transient ischemic attack, and systemic embolic events; and all-cause death were calculated. Clinical trial registration: UMIN000024942. ResultsThe study enrolled a total of 2377 patients with lung cancer; of these, 119 (5.0%) had VTE (six [0.3%], symptomatic, and 113 [4.8%], asymptomatic) and 14 (0.6%) had pulmonary embolism at baseline. During the follow-up period (mean, 337.7 d), the incidence was 0.6% for symptomatic VTE, 1.8% for composite VTE, 1.5% for bleeding events, 1.3% for cerebral infarction, transient ischemic attack, and systemic embolism, and 19.1% for all-cause death. Composite VTE frequency did not vary by anticancer drug type. Patients with (versus without) VTE at baseline had higher hazard ratios (HRs) for composite VTE (unadjusted HR: 5.29; Gray test p < 0.001) and symptomatic VTE (unadjusted HR: 4.89; Gray test p = 0.007). Patients with VTE at baseline had higher HRs for bleeding events (unadjusted HR: 3.27; Gray test p = 0.010) and all-cause death (unadjusted HR: 2.73; log-rank test p < 0.001) than patients without. In multivariable analysis, patients with baseline VTE prevalence and Eastern Cooperative Oncology Group Performance Status of 2 had increased composite VTE risk during cancer therapy. There were no other risk factors for composite VTE. ConclusionsOur findings emphasize the importance of VTE screening at cancer diagnosis.