Safety Of Oral Anticoagulants Research Articles

Current evidence on the effectiveness and safety of oral anticoagulants in superficial venous thrombosis: a systematic review and meta-analysis.

Previous studies suggest fondaparinux as an effective regimen for superficial venous thrombosis (SVT), but the inconvenience of prolonged parenteral injections has prompted investigations into oral anticoagulants (OACs). This study aims to evaluate the current evidence on the effectiveness and safety of OACs in the treatment of SVT. Following the PRISMA 2020 guidelines, we conducted a systematic review and meta-analysis registered in PROSPERO (CRD42024535625). A comprehensive literature search was performed across multiple databases up to April 2024. Studies were included if they involved adult patients diagnosed with SVT, treated with OACs, and reported relevant efficacy and safety outcomes. Both randomized controlled trials (RCTs) and observational studies were considered. Data extraction and risk of bias assessments were independently performed by two authors. The search identified 1531 studies, with six studies (three RCTs and three prospective cohort studies) meeting inclusion criteria. Meta-analysis for Rivaroxaban-treated group showed DVT occurrence was 1.30% (95% CI 0.17-3.07%), SVT extension was 0.32% (95% CI: 0.00-1.58%), SVT recurrence was 0.75% (95% CI: 0.00-3.30%), clinically relevant non-major bleeding was 1.95% (95% CI: 0.46-4.11%), minor bleeding was 5.68% (95% CI: 3.02-9.01%). These estimates were for patients treated with rivaroxaban 10-20 mg once daily over 42 days to 37 months. No major bleeding was reported with rivaroxaban 10 mg once daily. This systematic review and meta-analysis demonstrate that OACs, especially rivaroxaban, are effective and safe for the treatment of SVT. They offer a convenient alternative to parenteral anticoagulants, potentially improving patient compliance and outcomes. However, further large-scale studies are warranted to confirm these findings.

Antithrombotic strategies after cryptogenic stroke: a systematic review, pairwise, and network meta-analysis of randomized controlled trials

Abstract Background No definite etiology is identified in 30-40% of ischemic stroke cases, which is known as cryptogenic stroke. Several antithrombotic strategies have been investigated for cryptogenic stroke management; however, the optimal strategy remains unknown. Purpose We aim to assess the efficacy and safety of oral anticoagulants (OACs) versus aspirin, and the comparative efficacy and safety of different OACs after cryptogenic stroke. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. We used the fixed-effects model to report dichotomous outcomes using a risk ratio (RR), with a 95% confidence interval (CI). Analysis was conducted using R, version 4.2.0. Results Seven RCTs with 15.240 patients were included. In pairwise analysis, there was no difference between OACs and aspirin regarding all-cause mortality (RR: 1.13, CI [0.89, 1.43], P= 0.33) and stroke recurrence (RR: 0.93, CI [0.82, 1.07], P= 0.31). However, OACs were associated with a significantly increased incidence of major bleeding (RR: 1.6, CI [1.24, 2.05], P= 0.01), with no difference regarding the incidence of intracranial hemorrhage (RR: 1.09, CI [0.3, 3.97], P= 0.9). Moreover, in network analysis, none of the OACs showed a significant efficacy in preventing all-cause mortality and stroke recurrence compared to aspirin. However, only rivaroxaban significantly increased the incidence of major bleeding (RR: 2.69, CI [1.67, 4.33]). Conclusion OACs did not protect against stroke recurrence or decrease the incidence of all-cause mortality but increased the incidence of major bleeding in patients with cryptogenic stroke.

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave > 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level > 250 pg/mL, and left atrial diameter (LAE) > 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

Prospective Monitoring of New Drugs in Older Adults with and without Frailty: Near-Real-Time Assessment of Effectiveness and Safety of Oral Anticoagulants in Medicare Data.

Prospective sequential analyses after a new drug approval allow proactive surveillance of new drugs. In the current study, we demonstrate feasibility of frailty-specific sequential analyses for dabigatran, rivaroxaban, and apixaban versus warfarin. We partitioned Medicare data from 2011 to 2020 into datasets based on calendar year following the date of drug approval. Each calendar year of data was added sequentially for analysis. We used a new-user, active comparative design by comparing the initiators of dabigatran versus warfarin, rivaroxaban versus warfarin, and apixaban versus warfarin. Patients aged ≥ 65 years with atrial fibrillation without contraindication to the anticoagulants were included. Claims-based frailty index ≥ 0.25 was used to define frailty. The initiators of each direct oral anticoagulant were propensity-score matched to the initiators of warfarin within each frailty status. The effectiveness outcome was ischemic stroke or systemic thromboembolism, and the safety outcome was major bleeding. For each calendar year, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards models using all data available up to that year. As an example of the results, in the 2020 dataset, compared with warfarin, apixaban was associated with a reduced risk of ischemic stroke or systemic thromboembolism (frail: HR 0.73, 95% CI 0.63-0.85; non-frail: HR 0.65, 95% CI 0.59-0.72) and major bleeding (frail: HR 0.63, 95% CI 0.57-0.69; non-frail: HR 0.59, 95% CI 0.56-0.63) in both frail and non-frail patients. We found evidence for apixaban's effectiveness and safety within 1-2 years after the drug approval in frail older patients. Our frailty-specific sequential analyses can be applied to future near-real-time monitoring of newly approved drugs.

Anticoagulation in Patients With Device-Detected Atrial Fibrillation With and Without a Prior Stroke or Transient Ischemic Attack: The NOAH-AFNET 6 Trial.

Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device-detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device-detected AF but with no ECG-documented AF is unclear. This prespecified analysis of the NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device-detected AF with and without a prior stroke or TIA in the randomized, double-blind, double-dummy NOAH-AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device-detected AF randomized in the NOAH-AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time-to-event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient-year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient-year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient-year]; no anticoagulation: 6 out of 131 [2.3% per patient-year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients). Anticoagulation appears to have ambiguous effects in patients with device-detected AF and a prior stroke or TIA in this hypothesis-generating analysis of the NOAH-AFNET 6 in the absence of ECG-documented AF, partially due to a low rate of stroke without anticoagulation.

Design of the Dutch multicentre study on opportunistic screening of geriatric patients for atrial fibrillation using asmartphone PPG app: the Dutch-GERAF study.

Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC). This is amulticentre study on opportunistic screening of geriatric patients for clinical AF using asmartphone photoplethysmography (PPG) application. Inclusion criteria are age ≥ 65years and the ability to perform at least three PPG recordings within 6months. Exclusion criteria are the presence of acardiac implantable device, advanced dementia or asevere tremor. The PPG application records patients' pulse at their fingertip and determines the likelihood of clinical AF. If clinical AF is suspected after apositive PPG recording, aconfirmatory electrocardiogram is performed. Patients undergo acomprehensive geriatric assessment and afrailty index is calculated. Risk scores for major bleeding (MB) are applied. Standard laboratory testing and additional laboratory analyses are performed to determine the ABC-bleeding risk score. Follow-up data will be collected at 6months, 12months and 3years on the incidence of AF, MB, hospitalisation, stroke, progression of cognitive disorders and mortality. The Dutch-GERAF study will focus on frail older patients, who are underrepresented in randomised clinical trials. It will provide insight into the effectiveness of screening for clinical AF and the efficacy and safety of OAC in this high-risk population. NCT05337202.

Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.

Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49mL/min/1.73m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49mL/min/1.73m2. Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30mL/min/1.73m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49mL/min/1.73m2.

Anticoagulation in Patients with Atrial High-rate Episodes Detected by Cardiac Implantable Electronic Devices.

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias that are identified by the use of continuous rhythm monitoring devices such as pacemakers, defibrillators, or implantable cardiac monitors. Nevertheless, the therapeutic implications of these rhythm disturbances remain uncertain. The presence of AHRE is associated with an increased risk of stroke as compared to patients who do not exhibit AHRE. The utilisation of oral anticoagulation has the ability to mitigate the likelihood of stroke occurrence in patients with AHRE. However, it is important to note that this treatment approach is also linked to a severe bleeding rate of approximately 2% per year. The stroke rate among individuals diagnosed with AHRE appears to be comparatively lower when compared to patients diagnosed with atrial fibrillation. The efficacy and safety of anticoagulation in patients with AHRE have yet to be definitively established. Further research is required to provide a comprehensive understanding of the effectiveness and safety of oral anticoagulation in individuals with AHRE.

Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study

Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with AF and non-dialysis-dependent CKD stage 4/5. Propensity score-matched cohort study. 2 nationwide US claims databases, Medicare and Optum's deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n=12,488) and rivaroxaban versus apixaban (matched cohort, n= 5,720). Warfarin, rivaroxaban, or apixaban. Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders. Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR, 1.85; 95% CI, 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Compared with apixaban, rivaroxaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) and rivaroxaban (0.94; 0.81-1.10) versus apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings. Few ischemic stroke events, potential residual confounding. In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population. Different anticoagulants have been shown to reduce the risk of stroke in patients with atrial fibrillation, such as warfarin and direct oral anticoagulants like apixaban and rivaroxaban. Unfortunately, the large-scale randomized trials that compared direct anticoagulants versus warfarin excluded patients with advanced chronic kidney disease. Therefore, the comparative safety and effectiveness of warfarin, apixaban, and rivaroxaban are uncertain in this population. In this study, we used administrative claims data from the United States to answer this question. We found that warfarin and rivaroxaban were associated with increased risks of major bleeding compared with apixaban. There were few stroke events, with no major differences among the 3 drugs in the risk of stroke. In conclusion, this study suggests that apixaban has a better safety profile than warfarin and rivaroxaban.

Oral Anticoagulation Versus Antiplatelet Treatment After Mitral Valve Repair: A Systematic Review and Meta-Analysis

Oral anticoagulation with vitamin K antagonists is currently advised for a period of 3months after surgical mitral valve repair, regardless of the rhythm status. The evidence supporting this recommendation is weak and recent studies have challenged the safety and efficacy of this recommendation. A systematic review of literature was conducted by searching PubMed, Embase, Web of Science, Emcare, and Cochrane Library databases for original publications comparing the efficacy and safety of oral anticoagulation with vitamin K antagonists to antiplatelet treatment early after mitral valve surgery in patients with no atrial fibrillation. Study end points included thromboembolic complications, bleeding complications and survival. A total of 5 studies, including 5,093 patients, met the inclusion criteria; 2,824 patients were included in the oral anticoagulation and 2,269 in the antiplatelet treatment group. Pooled analyses demonstrated no beneficial effect of oral anticoagulation on the incidence of thromboembolic complications (risk ratio 1.14, 95% confidence interval 0.76 to 1.70, p=0.53, I2=8%). Moreover, oral anticoagulation did not result in a significantly increased risk of bleeding complications (risk ratio 0.89, 95% confidence interval 0.32 to 2.44, p=0.81, I2=87%). When combining the efficacy and safety end points, no difference was observed between groups (risk ratio 1.01, 95% confidence interval 0.51 to 1.97, p=0.99 I2=85%). Likewise, mortality did not differ between groups (risk ratio 0.89, 95% confidence interval 0.15 to 5.23, p=0.90 I2=71%). Our results confirmed the safety but failed to confirm the efficacy of oral anticoagulation in patients who underwent mitral valve surgery. A randomized controlled trial would provide the evidence needed to support treatment recommendations.

Electric cardioversion in patients treated with oral anticoagulants: embolic material in the left atrial appendage.

Atrial fibrillation (AF) remains the most common arrhythmia. The sinus rhythm restoration procedure without adequate anticoagulant preparation may lead to a thromboembolic event in approximately 5-7% of patients. The initiation of oral anticoagulation significantly reduces this risk by inhibiting formation of embolic material in the heart cavities, especially in the left atrial appendage (LAA). However, there is a group of patients who develop embolic material in the LAA despite oral anticoagulation treatment. The best treatment method to dissolve thrombus in the LAA is not clear, due to the lack of studies with adequate power and endpoints that can determine the best management strategy. We present clinical trials comparing the efficacy and safety of oral anticoagulants in patients undergoing AF cardioversion. We evaluate the frequency of LAA thrombus formation in patients with AF on treatment with oral anticoagulants. Furthermore, we discuss the effectiveness of various treatment strategies on LAA thrombus resolution.

Evaluating efficacy and safety of oral anticoagulation in adult patients with atrial fibrillation and cancer: A systemic review and meta-analysis

BackgroundAtrial fibrillation (AF) is common among patients with cancer. Patients with cancer and AF require anticoagulant therapy [direct oral anticoagulants (DOAC) or vitamin K antagonist (VKA)] for stroke and systemic embolism (SE) prevention. We sought to assess the rates of stroke/SE and major bleeding in patients with cancer and AF on oral anticoagulant therapy (DOAC or VKA). MethodsA systematic search of MEDLINE and EMBASE was conducted. The primary efficacy and safety outcome were stroke/SE and major bleeding (as per the International Society on Thrombosis and Haemostasis definition), respectively. Incidence rates (IR) were pooled using random effects model (event per 100 patient-years). Incidence rate ratios (IRR) were computed using a Poisson regression model with associated 95% confidence intervals (CI) using R software (version 4.0.3). ResultsOf the total 2,153 article records that were screened, 22 observational studies from 12 different countries were included in the meta-analysis (n = 94,980 patients). The IR of stroke/SE was 1.81 (95% CI: 0.89 to 3.68) and 3.41 (95% CI: 1.38 to 8.41) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.63 (95%CI: 0.47–0.84)). The IR of major bleeding was 2.59 (95%CI: 1.54 to 4.38) and 3.60 (95% CI: 1.68 to 7.71) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.76 (95% CI: 0.55 to 1.04)). ConclusionDOACs compared to VKA seem to provide a significant reduction in the risk of stroke/SE and a good risk-benefit ratio profile for safety outcomes in this patient population.

The influence of atrial high-rate episodes on stroke and cardiovascular death: an update.

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias detected by continuous rhythm monitoring by pacemakers, defibrillators, or implantable cardiac monitors. Atrial high-rate episodes occur in 10-30% of elderly patients without atrial fibrillation. However, it remains unclear whether the presence of these arrhythmias has therapeutic consequences. The presence of AHRE increases the risk of stroke compared with patients without AHRE. Oral anticoagulation would have the potential to reduce the risk of stroke in patients with AHRE but is also associated with a rate of major bleeding of ∼2%/year. The stroke rate in patients with AHRE appears to be lower than the stroke rate in patients with atrial fibrillation. Wearables like smart-watches will increase the absolute number of patients in whom atrial arrhythmias are detected. It remains unclear whether anticoagulation is effective and, equally important, safe in patients with AHRE. Two randomized clinical trials, NOAH-AFNET6 and ARTESiA, are expected to report soon. They will provide much-needed information on the efficacy and safety of oral anticoagulation in patients with AHRE.

#6667 EFFECTIVENESS AND SAFETY OF APIXABAN, RIVAROXABAN AND WARFARIN IN PATIENTS WITH ADVANCED CKD AND ATRIAL FIBRILLATION: A NATIONWIDE US COHORT STUDY

Abstract Background and Aims Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced CKD or on dialysis are lacking. We compared the effectiveness and safety of apixaban, rivaroxaban and warfarin in patients with AF and CKD stages 3 to 5, including those on dialysis. Method We conducted a new-user, active-comparator, cohort study using data from two nationwide U.S. claims databases, Medicare and Optum Clinformatics® Data Mart Database (01/01/2013–03/31/2022). We included patients with nonvalvular AF and CKD who newly initiated warfarin vs. apixaban (N = 169,702), or rivaroxaban vs. apixaban (N = 129,396). CKD stages were determined based on a validated claims-based algorithm. The primary outcome was a composite of ischemic stroke or major bleeding to represent the net benefit of treatment. Secondary outcomes included the individual components of the primary outcome and all-cause death. We used 1:1 propensity score matching to adjust for 80 confounders. Adjusted hazard ratios (aHRs) were estimated with Cox regression analyses and absolute rate differences per 1000 person years (aRDs) with generalized linear regression in the propensity score matched sample. Results Compared with apixaban, warfarin and rivaroxaban were associated with a higher risk of the composite endpoint, regardless of CKD stage. Comparing warfarin vs. apixaban, the aHRs were 1.5 (1.3–1.6), 1.4 (1.0–1.9) and 1.3 (1.2–1.5) for CKD stages 3, 4, and 5/dialysis, respectively (p-value for heterogeneity 0.31); corresponding aRDs were 27.2 (20.4, 30.0), 32.9 (−4.3, 70.2), and 36.9 (21.7, 52.2) (p-value for heterogeneity 0.51). Comparing rivaroxaban vs. apixaban, the aHRs were 1.5 (1.4–1.7), 1.7 (1.4–2.2) and 1.3 (0.9–1.8) (p-value for heterogeneity 0.38) for CKD stages 3, 4, and 5/dialysis, respectively; corresponding aRDs were 27.1 (12.3, 41.8), 53.2 (29.8, 76.6), and 20.7 (−28.9, 70.2) (p-value for heterogeneity 0.16). The higher rate of the primary endpoint for warfarin and rivaroxaban was driven by a higher risk of bleeding, with similar rates of ischemic stroke. Conclusion In patients with AF and CKD, apixaban was associated with a net benefit compared with rivaroxaban or warfarin, which was primarily driven by lower rates of bleeding. Benefits were consistent across severity of CKD.

Experience of conducting the first Russian cardiology hackathon Cardio data hack

This article is about the experience in organizing and conducting the first Russian cardiology hackathon Cardio data hack UFA 2022 which took place in Ufa in November 2022. It describes the preparation stages and organizational conditions of the hackathon conducting, the ways of interacting between the event organizer and participants, and the methods of evaluating the tasks. The first hackathon case was the recognition of ventricular bigeminy in patients with 24-hour ECG recording; the second case was performing a meta-analysis of the studies which assessed efficacy and safety of oral anticoagulants in atrial fibrillation and chronic renal failure stages IV and V. The hackathon attracted 179 registered participants who formed 42 teams, but further only 37 of them confirmed their participation and formed 8 teams. 7 teams gave the final solution of the tasks, and 5 of them presented their results with 3 of them giving solutions for both cases. Eventually, there were obtained the prototypes of solution for bigeminy recognition during Holter monitoring and high-quality meta-analyses evaluating the efficacy and safety of oral anticoagulants.

Stroke in Atrial Fibrillation and Other Atrial Dysrhythmias.

Atrial fibrillation (AF) is a major risk factor for systemic embolism and ischaemic stroke. Furthermore, AF-related strokes are associated with higher mortality, greater disability, longer hospital stays and lower rates of hospital discharge than strokes caused by other reasons. The aim of this review to summarise the existing evidence on the association of AF with ischemic stroke and provide insights on the pathophysiological mechanisms and the clinical management of patients with AF in order to reduce the burden of ischemic stroke. Beyond Virchow's triad, several pathophysiological mechanisms associated with structural changes in the left atrium, which may precede the identification of AF, may contribute to the increased risk of arterial embolism in AF patients. Individualised thromboembolic risk stratification based on CHA2DS2-VASc score and clinically relevant biomarkers provides essential tool towards a personalised holistic approach in thromboembolism prevention. Anticoagulation remains the cornerstone of stroke prevention moving from vitamin K antagonists (VKA) to safer non-vitamin K direct oral anticoagulants in the majority of AF patients. Despite the efficacy and safety of oral anticoagulation, still the equilibrium between thrombosis and haemostasis in AF patients remains suboptimal and future directions in anticoagulation and cardiac intervention may provide novel treatment options in stroke prevention. This review summarises the pathophysiologic mechanisms of thromboembolism, aiming the current and potential future perspectives in stroke prevention in AF patients.

Comparative Effectiveness and Safety of Oral Anticoagulants by Dementia Status in Older Patients With Atrial Fibrillation

The development of an optimal stroke prevention strategy, including the use of oral anticoagulant (OAC) therapy, is particularly important for patients with atrial fibrillation (AF) who are living with dementia, a condition that increases the risk of adverse outcomes. However, data on the role of dementia in the safety and effectiveness of OACs are limited. To assess the comparative safety and effectiveness of specific OACs by dementia status among older patients with AF. This retrospective comparative effectiveness study used 1:1 propensity score matching among 1 160 462 patients 65 years or older with AF. Data were obtained from the Optum Clinformatics Data Mart (January 1, 2013, to June 30, 2021), IBM MarketScan Research Database (January 1, 2013, to December 31, 2020), and Medicare claims databases maintained by the Centers for Medicare & Medicaid Services (inpatient, outpatient, and pharmacy; January 1, 2013, to December 31, 2017). Data analysis was performed from September 1, 2021, to May 24, 2022. Apixaban, dabigatran, rivaroxaban, or warfarin. Composite end point of ischemic stroke or major bleeding events over the 6-month period after OAC initiation, pooled across databases using random-effects meta-analyses. Among 1 160 462 patients with AF, the mean (SD) age was 77.4 (7.2) years; 50.2% were male, 80.5% were White, and 7.9% had dementia. Three comparative new-user cohorts were established: warfarin vs apixaban (501 990 patients; mean [SD] age, 78.1 [7.4] years; 50.2% female), dabigatran vs apixaban (126 718 patients; mean [SD] age, 76.5 [7.1] years; 52.0% male), and rivaroxaban vs apixaban (531 754 patients; mean [SD] age, 76.9 [7.2] years; 50.2% male). Among patients with dementia, compared with apixaban users, a higher rate of the composite end point was observed in warfarin users (95.7 events per 1000 person-years [PYs] vs 64.2 events per 1000 PYs; adjusted hazard ratio [aHR], 1.5; 95% CI, 1.3-1.7), dabigatran users (84.5 events per 1000 PYs vs 54.9 events per 1000 PYs; aHR, 1.5; 95% CI, 1.2-2.0), and rivaroxaban users (87.4 events per 1000 PYs vs 68.5 events per 1000 PYs; aHR, 1.3; 95% CI, 1.1-1.5). In all 3 comparisons, the magnitude of the benefits associated with apixaban was similar regardless of dementia diagnosis on the HR scale but differed substantially on the rate difference (RD) scale. The adjusted RD of the composite outcome per 1000 PYs for warfarin vs apixaban users was 29.8 (95% CI, 18.4-41.1) events in patients with dementia vs 16.0 (95% CI, 13.6-18.4) events in patients without dementia. The corresponding adjusted RD estimates of the composite outcome were 29.6 (95% CI, 11.6-47.6) events per 1000 PYs in patients with dementia vs 5.8 (95% CI, 1.1-10.4) events per 1000 PYs in patients without dementia for dabigatran vs apixaban users and 20.5 (95% CI, 9.9-31.1) events per 1000 PYs in patients with dementia vs 15.9 (95% CI, 11.4-20.3) events per 1000 PYs in patients without dementia for rivaroxaban vs apixaban users. The pattern was more distinct for major bleeding than for ischemic stroke. In this comparative effectiveness study, apixaban was associated with lower rates of major bleeding and ischemic stroke compared with other OACs. The increased absolute risks associated with other OACs compared with apixaban were greater among patients with dementia than those without dementia, particularly for major bleeding. These findings support the use of apixaban for anticoagulation therapy in patients living with dementia who have AF.

Time Trends in Patient Characteristics of New Rivaroxaban Users with Atrial Fibrillation in Germany and the Netherlands.

Use of the direct oral anticoagulant rivaroxaban has strongly increased in Europe since its market approval for non-valvular atrial fibrillation in 2011. Patients characteristics of rivaroxaban initiators may have changed over time but this has not been investigated so far. We aimed to describe time trends of patient baseline characteristics among new rivaroxaban users with non-valvular atrial fibrillation from 2011 to 2016/17 in two European countries. We used data from Germany (German Pharmacoepidemiological Research Database) and the Netherlands (PHARMO Database Network). We included new rivaroxaban users with (i) a first dispensing between 2011 and 2016/17, (ii) ≥2 years of age, and (iii) a diagnosis of non-valvular atrial fibrillation and described their baseline medication and comorbidity prior to starting rivaroxaban stratified by year of inclusion. Overall, 130,652 new rivaroxaban users were included during the study period (Germany: N=127,743, the Netherlands: N=2909). The sex ratio and median age remained relatively stable over time. The proportion of patients without prior use of oral anticoagulants before initiation of rivaroxaban increased in both countries between 2011 and 2016/17 (Germany: from 51 to 76%, the Netherlands: from 57 to 85%). In Germany, we observed a relative decrease by 27% in the proportion of new rivaroxaban users with a history of ischemic stroke and by 18% in the proportion with a transient ischemic attack at baseline. No such a pattern was observed in the Netherlands. The proportion of patients with heart failure at baseline showed a three-fold increase in the Netherlands, while there was a relative decrease by 12% in Germany. Patient characteristics of new rivaroxaban users with non-valvular atrial fibrillation changed between 2011 and 2016/17, but changes differed between countries. These patterns have methodological implications. They have to be considered in the interpretation of observational studies comparing effectiveness and safety of oral anticoagulants, especially regarding potential bias due to unmeasured confounding.

Clinical impact of oral anticoagulation among octogenarians with atrial fibrillation and anaemia.

Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in elderly patients (> or = 80 years-old) with atrial fibrillation (AF) and concomitant anaemia. Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized as anaemic and non-anaemic. The primary outcome was the occurrence of overall bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events (a composite of ischemic stroke, transient ischemic attack and systemic embolism). The secondary safety and effectiveness outcomes were major, minor bleedings and mortality, respectively. A total of 958 patients were included in the study, 120 (12.5%) were anaemic; among them, 93 patients (76.6%) were treated with VKAs and 28 (23.3%) with DOAC. Kaplan-Meier curves for major bleedings showed significant differences between anemic- and non-anemic groups (log-rank p = 0.005). In multivariate analysis, among patients on OAC, anaemia was independently associated with major bleeding (HR 2.36; 95% IC 1.2-4.4; p = 0.006), intracranial hemorrhages (HR 3.81; 95% IC 1.35-10.7; p = 0.01) and minor bleedings (HR 2.40; 95%IC 1.1-5.2; p = 0.02); these associations were not confirmed in the DOACs subgroup. No difference in survival was shown between anaemic- and non-anaemic groups and among anaemic patients, between DOAC and VKAs subgroups. Anaemic octogenarians with AF on OAC therapy showed a significantly increased risk of major bleedings, in particular ICH, and mortality compared to non-anaemic.

Electric cardioversion in patients treated with oral anticoagulants: embolic material in the left atrial appendage.

Atrial fibrillation (AF) remains the most common arrhythmia. The sinus rhythm restoration procedure without adequate anticoagulant preparation may lead to a thromboembolic event in approximately 5-7% of patients. The initiation of oral anticoagulation significantly reduces this risk by inhibiting formation of embolic material in the heart cavities, especially in the left atrial appendage (LAA). However, there is a group of patients who develop embolic material in the LAA despite oral anticoagulation treatment. The best treatment method to dissolve thrombus in the LAA is not clear, due to the lack of studies with adequate power and endpoints that can determine the best management strategy. We present clinical trials comparing the efficacy and safety of oral anticoagulants in patients undergoing AF cardioversion. We evaluate the frequency of LAA thrombus formation in patients with AF on treatment with oral anticoagulants. Furthermore, we discuss the effectiveness of various treatment strategies on LAA thrombus resolution.