Anticoagulation In Nonvalvular Atrial Fibrillation Research Articles

Comparative effectiveness of factor Xa non-vitamin K antagonist oral anticoagulants versus phenprocoumon in patients with non-valvular atrial fibrillation

BackgroundNon-vitamin K antagonist oral anticoagulants (NOACs) have largely supplanted vitamin K antagonists (VKAs) for oral anticoagulation in non-valvular atrial fibrillation (NVAF). However, data on the real-world effectiveness of NOACs vs. phenprocoumon, a VKA widely used in Germany, are limited. The RELOADED study aimed to compare effectiveness of factor Xa NOACs and phenprocoumon in NVAF in clinical practice. MethodsPatients who started on a factor Xa NOAC or phenprocoumon for NVAF during the study period were enrolled from the Institute for Applied Healthcare Research Berlin. Patients were followed from first prescription until the end of exposure or available data. Primary outcomes were analyzed by Cox proportional hazard regression models and included ischemic stroke and systemic embolism for effectiveness, and intracranial hemorrhage (ICH) for safety. Subgroups of interest were patients with diabetes and patients with renal impairment. ResultsThe total study population was 64,920; 36.3% of patients initiated phenprocoumon, 34.4% initiated rivaroxaban, 25.0% apixaban, and 4.4% edoxaban. Treatment with phenprocoumon is associated with a similar risk of ischemic stroke/systemic embolism as treatment with rivaroxaban or apixaban; while rivaroxaban (adjusted hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.43–0.75) and apixaban (adjusted HR 0.43, 95% CI 0.31–0.6) were associated with a lower risk of ICH compared to phenprocoumon in NVAF patients. The use of rivaroxaban and apixaban was associated with a lower risk of developing kidney failure in patients with diabetes or renal impairment in comparison to those treated with phenprocoumon. ConclusionThe factor Xa NOACs rivaroxaban and apixaban demonstrated similar effectiveness and lower rates of ICH compared with phenprocoumon in this study.

非瓣膜性心房颤动口服抗凝药物临床应用研究进展

非瓣膜性心房颤动口服抗凝药物临床应用研究进展

Clinical value of a tool for managing oral anticoagulation in nonvalvular atrial fibrillation in primary health care. Randomized clinical trial

Introduction and objectivesThe management of atrial fibrillation is complex and requires improvement at strategic points, such as in the control of patients treated with vitamin K antagonists. The aim of this study was to evaluate the impact on health outcomes of a nonvalvular atrial fibrillation decision support tool based on visualization of the time in therapeutic range in primary care. MethodsThe present randomized clinical trial was conducted in 2018 with a 1-year follow-up in 325 primary care centers in Catalonia. In the intervention centers, the decision support tool was installed to control the time in therapeutic range of patients treated with vitamin K antagonists. The tool was not visualized in the control group. This clinical trial was registered with ClinicalTrials.gov (NCT03367325). ResultsIn total, 44 556 patients were studied. The intervention protected against admission for stroke (adjusted odds ratio [OR], 0.70; 95% confidence interval [95%CI], 0.55-0.88). The number needed to treat was 3502 (95%CI, 3305-3725) while the number of admissions for stroke avoided was 12.63 (95%CI, 11.88-13.38). The intervention also protected against mortality (adjusted OR, 0.78; 95%CI, 0.67-0.90), with a number needed to treat of 13 687 (95%CI, 10 789-18 714) and number of deaths avoided of 3.23 (95%CI, 2.36-4.10). ConclusionsThe decision support tool was associated with slight reductions in the numbers of admissions for ischemic stroke and mortality. Although the follow-up time was short and the effect of the intervention was small, the results are valuable and could improve implementation of the tool.

Effectiveness and safety of oral anticoagulants for non-valvular atrial fibrillation: a population-based cohort study in primary healthcare in Catalonia.

Objectives: Our objective was to analyse effectiveness and safety of oral anticoagulants (OAC) for stroke prevention in non-valvular atrial fibrillation. Material and methods: Population-based cohort study including adults initiating oral anticoagulants, either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA), during 2011-2020. Data source: SIDIAP, capturing information from the electronic health records of Primary Health Care in Catalonia, Spain. Study outcomes: stroke, cerebral and gastrointestinal (GI) haemorrhage, assessed by patients' subgroups according to different clinical characteristics. Results: We included 90,773 patients. Male sex, older than 75, previous event, peripheral artery disease, deep vein thrombosis, or receiving antiplatelets, antidiabetics or proton pump inhibitors (PPI) was associated with higher stroke risk. For DOAC-treated, treatment switch increased stroke risk, while being adherent had a protective effect. Men, antidiabetic treatment or a previous event increased the risk of cerebral bleeding. Receiving direct oral anticoagulants had a protective effect in comparison to vitamin K antagonists. For DOAC-treated, treatment switch increased, and adherence decreased the bleeding risk. Men, people with chronic kidney disease or a previous event posed an increased risk of gastrointestinal bleeding, whereas receiving PPI had a protective effect. For DOAC-treated, switch was associated with a higher bleeding risk. Conclusion: Being men, a previous event and DOAC-switch posed a higher risk for all study outcomes. direct oral anticoagulants had a protective effect against cerebral bleeding in comparison to vitamin K antagonists. Adherence to direct oral anticoagulants resulted in lower risk of stroke and cerebral bleeding. We found no differences in the risk of stroke and gastrointestinal bleeding when we compared direct oral anticoagulants vs. vitamin K antagonists.

Effect of edaravone on symptomatic intracranial hemorrhage in patients with acute large vessel occlusion on apixaban for non-valvular atrial fibrillation

BackgroundEdaravone administration was associated with lower incidence of symptomatic intracranial hemorrhage (sICH) in patients with acute large vessel occlusion (LVO). However, its protective effect on sICH in patients with LVO who receive direct oral anticoagulants for non-valvular atrial fibrillation (NVAF) is uncertain. ObjectivesTo explore the effect of edaravone administration on the incidence of sICH in patients with acute LVO receiving apixaban for NVAF. MethodsA Japanese multicenter registry of apixaban on clinical outcome of the patients with LVO or stenosis (ALVO study) included patients who were admitted within 24 h after stroke onset and were received apixaban within 14 days of stroke onset. Patients were divided into two groups according to edaravone administration (Edaravone and No-Edaravone groups). The incidence of sICH within one year and infarct growth before apixaban administration were compared between these groups. ResultsOf the 686 enrolled patients, 622 were included and edaravone was administered to 407 (65.4%). The incidences of sICH in Edaravone and No-Edaravone groups were 1.3% and 5.0%, respectively (p = 0.01). The inverse probability of treatment-weighting (IPTW) hazard ratio (HR) (95% confidence interval [CI]) of Edaravone group for sICH within one year was 0.36 (0.15–0.80) compared to No-Edaravone group. The incidences of infarct growth in Edaravone and No-Edaravone groups were 35.3% and 42.0%, respectively (p = 0.13). IPTW HR (95% CIs) for infarct growth was 0.76 (0.60–0.97). ConclusionsEdaravone administration was associated with a lower incidence of sICH in patients with LVO and NVAF who administrated apixaban.

Appropriateness of rivaroxaban and apixaban dosing in hospitalized patients with a newly diagnosed nonvalvular atrial fibrillation at a single tertiary hospital.

Possible challenges in dosing non-vitamin K antagonist oral anticoagulants in nonvalvular atrial fibrillation (NVAF) and limited evidence in Saudi Arabia make it difficult to assess their appropriateness. This study aimed to assess the appropriateness of prescribing rivaroxaban and apixaban in hospitalized patients with newly diagnosed NVAF. This single-center, descriptive, retrospective study was conducted at a tertiary hospital in Saudi Arabia between December 2018 and December 2019. The included patients were aged 18 years and older with newly diagnosed NVAF who received either rivaroxaban or apixaban during hospitalization. The primary outcome was the dosing appropriateness of rivaroxaban and apixaban in NVAF based on recent food and drug administration prescribing guidelines. Descriptive statistics including frequencies and percentages as well as mean ± standard deviation was used to summarize the data. Pearson Chi-square was used to test for significant difference in proportions of appropriate and inappropriate dosing. Pearson Correlation was used to test for associations between underdosing and overdosing with other patients characteristics. A priori P value < .05 was considered significant throughout. A total of 203 patients were included in our analysis. Majority of the patients {125 (61.6%), P = .001} received rivaroxaban. Overall, the dosing appropriateness observed in 143 (70.5%) of the patients who received the rivaroxaban and apixaban was significantly higher than the dosing inappropriateness observed in 60 (29.5%) of the patients who received the same drugs, P < .001. Apixaban had the highest proportion of patients, 45 (57.7%) with dosing inappropriateness. Overall, underdosing was the most common dosing inappropriateness observed in 53 (26.1%) of the patients. There was a significant negative correlation between the drugs underdosing and creatinine clearance, r = -0.223, P = .001. The findings in our present study showed that majority of the patients received appropriate dosing of rivaroxaban and apixaban in hospitalized patients with NVAF. Healthcare providers should update themselves with the recent dosing recommendations for the non-vitamin K-antagonist oral anticoagulants in NVAF to further improve the dosing appropriateness in hospitalized patients with NVAF.

5-year stroke rates in nonvalvular atrial fibrillation after watchman compared to direct oral anticoagulants

BackgroundThe WATCHMAN device (Boston Scientific; Marlborough, MA, USA) is noninferior to warfarin in preventing ischemic strokes while reducing bleeding risks associated with long term anticoagulation in nonvalvular atrial fibrillation (AFib). The device's performance compared to direct oral anticoagulants (DOAC) is less well known. ObjectiveTo compare 5-year major bleeding and ischemic stroke rates in patients with nonvalvular AFib who received a WATCHMAN device or DOAC therapy after a major bleeding event. MethodsThis retrospective, multicenter, 1:1 matched cohort study was derived from the PearlDiver Mariner database from 2010 to 2020. Patients with nonvalvular AFib on oral anticoagulation who had a major bleeding event were identified. Those who received either WATCHMAN or DOAC after resolution of the bleeding event were selected. The two groups were exactly matched 1:1 based on various comorbidities. Rates of ischemic stroke, transient ischemic attack (TIA), major bleeding, and hemorrhagic stroke were compared over 5 years. ResultsEach cohort consisted of 2248 patients after 1:1 matching. The mean CHADS2-VASC score was 4.81 ± 1.25. At 5 years, the WATCHMAN cohort had significantly lower rates of major bleeding events [OR 0.24 (0.21, 0.27)], TIAs [OR 0.75 (0.58, 0.95)], and ischemic strokes [OR 0.72 (0.61, 0.86)]. There was no significant difference in hemorrhagic strokes [OR 1.14 (0.83, 1.58)]. ConclusionEven in a high-risk population, the WATCHMAN is comparable to DOAC therapy in the primary prevention of hemorrhagic strokes and may provide benefit in the rates of bleeding events, TIAs, and ischemic strokes.

Impact of anemia on major bleeding in patients taking oral anticoagulants for nonvalvular atrial fibrillation.

Anemia is encountered in patients with nonvalvular atrial fibrillation (NVAF) on oral anticoagulants (OACs) but the prognostic impact was not well scrutinized in real-world settings. We conducted a historical multicenter registry of patients with NVAF taking OACs at 71 centers in Japan. Those with mechanical heart valves or a history of pulmonary thrombosis or deep venous thrombosis were excluded. Anemic patients were divided into three groups of hemoglobin (Hb) level: moderate/severe (Hb < 11.0 g/dL), mild (men: Hb of 11.0-12.9 g/dL; women: Hb of 11.0-11.9 g/dL), and no anemia. The endpoints included major bleeding, hemorrhagic stroke, ischemic events, ischemic stroke, and all-cause mortality. Among 7558 consecutive patients (mean age, 73 years; men 67%) registered in February 2013 and followed until February 2017, 2100 (28%) patients had anemia. The anemic patients were older (moderate/severe: 79 years; mild: 77 years; no anemia: 71 years, p < .001), and HAS-BLED score was significantly higher in the anemic patients (p < .001). The cumulative incidences at 4 years of major bleeding in moderate/severe, mild, and no anemia group, were 14.9%, 10.7%, and 6.4%, respectively. The adjusted hazard ratios (HRs) (95% confidential intervals (CIs)) of major bleeding of moderate/severe and mild anemia group were 1.96 (1.49-2.58) and 1.48 (1.17-1.87) compared to no anemia group. The adjusted HRs (95% CIs) for ischemic events were 0.63 (0.39-0.99) and 1.03 (0.76-1.39). The severity of anemia in the patients with NVAF on OACs was associated with major bleeding.

Patterns and outcomes of switching direct oral anticoagulants in non-valvular atrial fibrillation: A real-world experience from Spain

AimsThe aim is to evaluate a management program for direct oral anticoagulants (DOACs) in non-valvular atrial fibrillation (NVAF) patients according to their profiles, appropriateness of dosing, patterns of crossover, effectiveness and safety. This is an observational and longitudinal prospective study in a cohort of patients attended in daily clinical practice in a regional hospital in Spain with 3-year a follow-up plan for patients initiating dabigatran, rivaroxaban or apixaban between JAN/2012-DEC/2016. MethodsWe analyzed 490 episodes of treatment (apixaban 2.5 9.4%, apixaban 5 21.4%, dabigatran 75 0.6%, dabigatran 110 12,4%, dabigatran 150 19.8%, rivaroxaban 15 17.8% and rivaroxaban 20 18.6%) in 445 patients. 13.6% of patients on dabigatran, 9.7% on rivaroxaban, and 3.9% on apixaban switched to other DOACs or changed dosing. ResultsApixaban was the most frequent DOAC switched to. The most frequent reasons for switching were toxicity (23.8%), bleeding (21.4%) and renal deterioration (16.7%). Inappropriateness of dose was found in 23.8% of episodes. Rates of stroke/transient ischemic attack (TIA) were 1.64/0.54 events/100 patients-years, while rates of major, clinically relevant non-major (CRNM) bleeding and intracranial bleeding were 2.4, 5, and 0.5 events/100 patients-years. Gastrointestinal and genitourinary bleeding were the most common type of bleeding events (BE). On multivariable analysis, prior stroke and age were independent predictors of stroke/TIA. Concurrent platelet inhibitors, male gender and age were independent predictors of BE. ConclusionThis study complements the scant data available on the use of DOACs in NVAF patients in Spain, confirming a good safety and effectiveness profile.

SAIL study of stroke, systemic embolism and bleeding outcomes with warfarin anticoagulation in non-valvular atrial fibrillation (S4-BOW-AF).

In patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin, the association between guideline defined international normalised ratio (INR) control and adverse outcomes in unknown. We aimed to (i) determine stroke and systemic embolism (SSE) and bleeding events in NVAF patients prescribed warfarin; and (ii) estimate the increased risk of these adverse events associated with poor INR control in this population. Individual-level population-scale linked patient data were used to investigate the association between INR control and both SSE and bleeding events using (i) the National Institute for Health and Care Excellence (NICE) criteria of poor INR control [time in therapeutic range (TTR) <65%, two INRs <1.5 or two INRs >5 in a 6-month period or any INR >8]. A total of 35 891 patients were included for SSE and 35 035 for bleeding outcome analyses. Mean CHA2DS2-VASc score was 3.5 (SD = 1.7), and the mean follow up was 4.3 years for both analyses. Mean TTR was 71.9%, with 34% of time spent in poor INR control according to NICE criteria.SSE and bleeding event rates (per 100 patient years) were 1.01 (95%CI 0.95-1.08) and 3.4 (95%CI 3.3-3.5), respectively, during adequate INR control, rising to 1.82 (95%CI 1.70-1.94) and 4.8 (95% CI 4.6-5.0) during poor INR control.Poor INR control was independently associated with increased risk of both SSE [HR = 1.69 (95%CI = 1.54-1.86), P < 0.001] and bleeding [HR = 1.40 (95%CI 1.33-1.48), P < 0.001] in Cox-multivariable models. Guideline-defined poor INR control is associated with significantly higher SSE and bleeding event rates, independent of recognised risk factors for stroke or bleeding.

Impact of left atrial appendage closure in patients on anticoagulation for atrial fibrillation and recurrent or chronic gastrointestinal bleeding

BackgroundOral anticoagulation in non-valvular atrial fibrillation is associated with an increased risk of bleeding, particularly gastrointestinal bleeding, leading to treatment withdrawal in up to 50% of patients and putting them at risk of embolic events. Left atrial appendage closure (LAAC) can be an alternative to chronic anticoagulation. We aim to describe the impact of LAAC in patients with gastrointestinal bleeding (GIB) or chronic iron deficiency anaemia (CIDA) on healthcare resources consumption. MethodsObservational retrospective study of patients who underwent LAAC for GIB or CIDA at a single centre. ResultsNineteen patients with a median age of 74 years and a median Charlson score of six points were included in the study. Angiodysplasias were the most frequent cause of GIB or CIDA. The procedural success rate of LAAC was 100% with a median anticoagulant and antiplatelet treatment duration of 92 days. One year after the LAAC, we found a significant improvement in the lowest haemoglobin concentration and a reduction in the number of red blood cells transfusion, hospital admissions due to GIB and CIDA and the number of endoscopic examinations. One patient died due to a pulmonary thromboembolism. No deaths related to GIB were observed. ConclusionsLAAC seems to be a safe and effective alternative to anticoagulation in patients with GIB or CIDA.

Sex and gender differences in the use of oral anticoagulants for non-valvular atrial fibrillation: A population-based cohort study in primary health care in catalonia.

Objectives: To describe the sex and gender differences in the treatment initiation and in the socio-demographic and clinical characteristics of all patients initiating an oral anticoagulant (OAC), and the sex and gender differences in prescribed doses and adherence and persistence to the treatment of those receiving direct oral anticoagulants (DOAC). Material and methods: Cohort study including patients with non-valvular atrial fibrillation (NVAF) who initiated OAC in 2011-2020. Data proceed from SIDIAP, Information System for Research in Primary Care, in Catalonia, Spain. Results: 123,250 people initiated OAC, 46.9% women and 53.1% men. Women were older and the clinical characteristics differed between genders. Women had higher risk of stroke than men at baseline, were more frequently underdosed with DOAC and discontinued the DOAC less frequently than men. Conclusion: We described the dose adequacy of patients receiving DOAC, finding a high frequency of underdosing, and significantly higher in women in comparison with men. Adherence was generally high, only with higher levels in women for rivaroxaban. Persistence during the first year of treatment was also high in general, being significantly more persistent women than men in the case of dabigatran and edoxaban. Dose inadequacy, lack of adherence and of persistence can result in less effective and safe treatments. It is necessary to conduct studies analysing sex and gender differences in health and disease.

Safety and efficacy of direct oral anticoagulants in geriatric patients with non-valvular atrial fibrillation: A single-center retrospective study

IntroductionDirect oral anticoagulants (DOACs) are widely employed for antithrombotic prophylaxis in patients with atrial fibrillation (AF). However, there is still uncertainty about their risk-benefit profile in older patients. Here, we evaluated the efficacy, safety, and dose appropriateness of DOACs in a real-world population of outpatients with non-valvular AF, with a specific focus on subjects aged over 80 years and/or with reduced renal function. Materials and methodsSingle-center retrospective study including patients who had been prescribed a DOAC between May 2014 and May 2021 for long-term anticoagulation in non-valvular AF. Patients anticoagulated for <4 weeks were excluded. The primary efficacy outcome was a composite of cardiovascular (CV) death, stroke, or systemic embolism. The primary safety outcome was major bleeding. ResultsA total of 1154 patients (median age 84 yrs., range 57–100 yrs.), among which 862 were 80 years and older, were included. In the subgroup of subjects ≥80 yrs., a subtherapeutic dose of DOAC was associated with an increased incidence of CV mortality, stroke, or systemic embolism (multivariable Cox regression, HR = 2.09, 95 % CI: 1.09–4.02), with no benefit in terms of prevalence of bleeding events (21.5 % vs. 18.6 %, p = 0.428), and the incidence of adverse safety and efficacy outcomes was not increased in patients with a reduced renal function (eGFR ≤30 mL/min). Plasma concentration of DOACs, assessed in a subset of 367 patients, did not increase with advanced age (≥ 80 yrs., two-way ANOVA, p = 0.656) nor with declining eGFR (≤30 mL/min, two-way ANOVA, p = 0.643) and was not associated with adverse safety and efficacy outcomes. ConclusionsData from our study support the use of DOACs in populations of older adults and remark on the risks associated with inappropriate prescriptions in terms of CV mortality and adverse events.

Major Hemorrhage Risk Associated with Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis

Background: Real-world, observational studies have investigated the safety profile of Direct Oral Anticoagulants (DOACs) on Major Hemorrhage (MH) used for stroke prevention in Non-Valvular Atrial Fibrillation (NVAF). We performed a systematic review and meta-analysis to investigate the comparative safety of DOACs versus other DOACs and versus Vitamin K Antagonists (VKAs) adhering to PRISMA guidelines. We defined MH according to the International Society on Thrombosis and Haemostasis statement or as the composite outcome of intracranial, gastrointestinal, genitourinary, respiratory, cavitary and musculoskeletal bleeding in case of studies using International Statistical Classification of Diseases codes for patient selection. Methods: We systematically investigated two databases (Medline, Embase) until April of 2021, gathered observational studies and extracted hazard ratios (HRs) with 95% confidence intervals (CI) on our outcome of interest. Additional subgroup analyses according to DOAC dosing, prior diagnosis of chronic kidney disease, prior diagnosis of stroke, history of previous use of VKA, the users’ age, the users’ gender and study population geographic region were conducted. All analyses were performed with a random-effects model. Results: From this search, 55 studies were included and 76 comparisons were performed. The MH risk associated with Rivaroxaban use was higher than the risk with Dabigatran use (HR: 1.32, 95% CI: 1.21–1.45, I2: 12.39%) but similar to VKA use (HR: 0.94, 95% CI: 0.87–1.02, I2: 76.57%). The MH risk associated with Dabigatran use was lower than the risk with VKA use (HR: 0.75, 95% CI: 0.64–0.90, I2: 87.57%). The MH risk associated with Apixaban use was lower than the risk with Dabigatran use (HR: 0.75, 95% CI: 0.64–0.88, I2: 58.66%), with Rivaroxaban use (HR: 0.58, 95% CI: 0.50–0.68, I2: 74.16%) and with VKA use (HR: 0.60, 95% CI: 0.55–0.65, I2: 58.83%). Our aforementioned subgroup analyses revealed similar results. Conclusions: All in all, Apixaban was associated with a reduced MH risk compared to Dabigatran, Rivaroxaban and VKA. Dabigatran was associated with a reduced MH risk compared to both Rivaroxaban and VKA.

Effect of tramadol and DOACs with special attention to dabigatran on concomitant use, on the risk of mayor bleeding using BIFAP database in Spain.

Tramadol, a weak opioid, inhibits the reuptake of serotonin, a key feature on vascular homeostasis. A suspected interaction exists between dabigatran and tramadol, which might trigger an excess on risk of bleeding however, there is a gap in knowledge on this topic. To estimate the effects of tramadol, dabigatran and concomitant use on the risk of hospitalized major bleeds (Gastrointestinal bleeding and intra-extracranial bleeds). Among a validated established cohort of new users of oral anticoagulants for non-valvular atrial fibrillation (NVAF) aged 18 years or older, we identified all hospitalized bleed episodes (GIB and extra/intracranial bleeds) within 2008-2015. A nested case-control analysis was conducted using conditional logistic regression. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for dabigatran, tramadol, and concomitant use. Several sensitivity analyses were carried out. aORs (95%CIs) for current use of only dabigatran, only tramadol and concomitant users were 1.73 (1.37-2.18) and 1.38 (1.13-1.67) and 2.04 (0.74-5.67) compared with non-users of both drugs (>365 days). aORs for current continuers and non-continuer users of dabigatran were 1.36 (1.00-1.86) and 2.19 (1.61-2.98), respectively. For the latter, non-continuer users with a short duration of dabigatran cumulated the highest risk (3.36 [1.88-5.99]). There also was an increased risk with concomitant use of tramadol and rivaroxaban (2.24 [1.19-4.21]), or antagonist of vitamin K (1.30 [1.00-1.69]). There was a trend towards and increased risk of excess bleeds when using concomitantly with dabigatran. The effect decreases with a narrower definition of current use.

Long-Term Outcomes of Randomized Controlled Trials Comparing Percutaneous Left Atrial Appendage Closure to Oral Anticoagulation for Nonvalvular Atrial Fibrillation: A Meta-Analysis

BackgroundOral anticoagulation (OAC) has been considered the standard of care for stroke prophylaxis for patients with nonvalvular atrial fibrillation; however, many individuals are unable or unwilling to take long-term OAC. The safety and efficacy of percutaneous left atrial appendage closure (LAAC) have been controversial, and new trial data have recently emerged. We therefore sought to perform an updated meta-analysis of randomized clinical trials (RCTs) comparing OAC to percutaneous LAAC, focusing on individual clinical endpoints. MethodsWe performed a systematic search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 2000 through December 2021 for all RCTs comparing percutaneous LAAC to OAC in patients with nonvalvular atrial fibrillation. Fixed and random effects meta-analyses of hazard ratios (HRs) were performed using the longest follow-up duration available by intention-to-treat. The prespecified primary endpoint was all-cause mortality. ResultsThree RCTs enrolling 1516 patients were identified. The weighted mean follow-up was 54.7 months. LAAC was associated with a reduced risk of all-cause mortality (HR 0.76; 95% confidence interval [CI], 0.59-0.96; p = 0.023), hemorrhagic stroke (HR 0.24; 95% CI, 0.09-0.61; p = 0.003), and major nonprocedural bleeding (HR 0.52; 95% CI, 0.37-0.74; p < 0.001). There was no significant difference between LAAC and OAC for any other endpoints. ConclusionsThe available evidence from RCTs suggests LAAC therapy is associated with reduced long-term risk of death compared with OAC. This may be driven by reductions in hemorrhagic stroke and major nonprocedural bleeding. There were no significant differences in the risk of all stroke. Further large-scale clinical trials are needed to validate these findings.

Decision of Anticoagulation in Nonvalvular Atrial Fibrillation in the Real World in the Non-Antivitamin K Anticoagulants Era.

Background. Patients with nonvalvular atrial fibrillation (NVAF) have five times higher risk of stroke than the general population. Anticoagulation (ACO) in NVAF is a class I indication after assessing the CHA2DS2-VASc and HAS-BLED scores. However, in the real world, NVAF patients receive less ACO than needed due to patients’ comorbidities that can be assessed by the Charlson comorbidity index (CCI). The use of non-antivitamin K anticoagulants (NOAC) has improved the decision to anticoagulate. Objective. We analyzed the factors influencing the ACO prescribing decision in NVAF patients in the real world and the changes induced by the introduction of NOAC. Method. We carried out an observational retrospective cross-sectional study that included consecutive patients with permanent NVAF and CHA2DS2-VASc ≥ 2, admitted to a community hospital between 2010–2011 (group 1, 286 patients), when only vitamin K antagonists (VKA) were used, and 2018–2019 (group 2, 433 patients), respectively. We calculated CHA2DS2-VASc, HAS-BLED, and CCI and recorded the ACO decision and the use of VKA or NOAC in group 2. We compared the calculated scores between ACO and non-anticoagulated (nonACO) patients in both groups and between groups. Results. A 31.5% share of patients in group 1 and 12.9% in group 2 did not receive ACO despite a CHA2DS2-VASc score ≥ 2. In group 1, nonACO patients had higher HAS-BLED and CCI scores than the ACO patients, but their CHA2DS2-VASc scores were not significantly different. Old age, dementia, severe chronic kidney disease, neoplasia, and anemia were the most frequent reasons not to prescribe anticoagulants. In group 2, more nonACO patients had dementia, diabetes mellitus, and higher HAS-BLED than ACO patients. Moderate-severe CKD, neoplasia with metastasis, liver disease, anemia, and diabetes mellitus were statistically significantly more frequent in nonACO patients from group 1 than those from group 2. In group 2, 55.7% of ACO patients received NOAC. Conclusions. In real-world clinical practice, the decision for anticoagulation in NVAF is influenced by patient age, comorbidities, and risk of bleeding, and many patients do not receive anticoagulants despite a high CHA2DS2-VASc score. The use of NOAC in the past few years has improved treatment decisions. At the same time, the correct diagnosis, treatment, and surveillance of comorbidities have cut down the risk of bleeding and allowed anticoagulant use according to guidelines.

Changes in Prescription Patterns of Oral Anticoagulants in Family Practices after Marketing Approval of Direct Oral Anticoagulants

Since 2011, non-vitamin-K-dependent oral anticoagulants (NOAC) have extended the spectrum of anticoagulation therapy. Initially, the approval of NOAC was limited to the prophylaxis of postoperative thrombosis, but in the course of time the spectrum was extended to the therapy of thrombosis and embolism as well as anticoagulation in non-valvular atrial fibrillation. The study was designed to examine how the approval of NOAC had affected the prescribing behaviour of general practitioners in the first years of their approval. In a retrospective longitudinal study, the prescriptions of anticoagulants between 2012 and 2017 were analysed in 3 general practitioners' practices in the Bonn area. The study included all patients for whom at least one prescription from a NOAC or a vitamin K antagonist (VKA) was documented in the administrative system of the practices during this period. A total of n=579 patient files were evaluated (47% female; median age 75 years). Of these, 47% received a VKA, and 40% a NOAC (59% rivaroxaban, 29% apixaban, 9% dabigatran and 3% edoxaban). During the period under examination, the share of VKA prescriptions decreased from 45% to 14% and the share of NOAC increased from 28% to 87%. Anti-coagulation was changed in 12%. The most frequent change was from a VKA to a NOAC (70%). After marketing approval, the use of NOAC in the initial prescriptions increased steadily. This trend can also be seen in other European studies. VKA are mainly prescribed to patients with stable oral anticoagulation. As recommended in the guidelines, anticoagulation is changed mainly when problems occur during therapy. If the trend in the prescription of anticoagulants continues, in the medium term, VKA will only be prescribed for patients who have been stable for many years and for patients with artificial heart valves.

Real-world Evidence Comparing Oral Anticoagulants in non-valvular Atrial Fibrillation: A Systematic Review and Network meta-analysis

Aim: To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulantsand vitamin K antagonistsamong patients with non-valvular atrial fibrillation. Materials & methods: A systematic review of electronic databases yielded 7661 citations published from January2013 to January 2020. Fifty-five studies were included in Bayesian network meta-analyses of hazard ratios. Results & conclusion: In comparison with vitamin K antagonists, apixaban, dabigatranand rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhageand all-cause mortality. Apixaban, dabigatranand edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulantsfor the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.

Oral anticoagulants in fragile patients with percutaneous endoscopic gastrostomy and atrial fibrillation: the ORIGAMI pilot investigation.

Extensive data support the superior safety without any trade-off in efficacy of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation, deep venous thrombosis or pulmonary embolism. Whether DOACs may be successfully used to treat complex and fragile patients with percutaneous endoscopic gastrostomy (PEG) remains to be proven. The purpose of this pilot study was to evaluate the feasibility, anticoagulant effect, and preliminary safety/efficacy profile of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation. In this prospective, single-arm, pilot study, 12 patients with PEG and guideline-recommended indication for anticoagulation for nonvalvular atrial fibrillation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. Quantitative measures of edoxaban's antifactor Xa activity were performed at steady state. Thromboembolic and bleeding events were assessed at one-month follow-up. Steady state edoxaban plasma levels were at therapeutic range in all patients; mean plasma concentration was 208.5 (±78.6) ng/mL. At one month follow-up, none had suffered a thromboembolic event; one developed minor bleeding, and one died from non-cardiovascular death, owing to sudden worsening of a pre-existing underlying severe condition. In this pilot investigation, we report for the first time that crushed edoxaban, administered at approved doses through PEG in fragile and complex patients, is feasible, results in therapeutic edoxaban concentrations, and is apparently effective and safe.