Initiation Of Oral Anticoagulant Therapy Research Articles

The Danish Atrial Fibrillation Registry: A Multidisciplinary National Pragmatic Initiative for Monitoring and Supporting Quality of Care Based on Data Retrieved from Administrative Registries.

The Danish Atrial Fibrillation (AF) Registry monitors and supports improvement of quality of care for all AF patients in Denmark. This report describes the registry's administrative and organizational structure, data sources, data flow, data analyses, annual reporting, and feedback between the registry, clinicians, and the administrative system. We also report the selection process of the quality indicators and the temporal trends in results from 2017-2021. The Danish AF Registry aims for complete registration and monitoring of care for all patients diagnosed with AF in Denmark. Administrative registries provide data on contacts to general practice, contacts to private cardiology practice, hospital contacts, medication prescriptions, updated vital status information, and biochemical test results. The Danish Stroke Registry provides information on stroke events. From 2017 to 2021, the proportion with a reported echocardiography among incident AF patients increased from 39.9% (95% CI: 39.3-40.6) to 82.6% (95% CI: 82.1-83.1). The initiation of oral anticoagulant therapy among patients with incident AF and a CHA2DS2-VASc score of ≥1 in men and ≥2 in women increased from 85.3% (95% CI: 84.6-85.9) to 90.4% (95% CI: 89.9-91.0). The 1-year and 2-year persistence increased from 85.2% (95% CI: 84.5-85.9) to 88.7% (95% CI: 88.0-89.3), and from 85.4% (95% CI: 84.7-86.2) to 88.2% (95% CI: 87.5-88.8), respectively. The 1-year risk of ischemic stroke among prevalent patients with AF decreased from 0.88% (95% CI: 0.83-0.93) to 0.71% (95% CI: 0.66-0.75). Variation in clinical performance between the five administrative Danish regions was reduced. Continuous nationwide monitoring of quality indicators for AF originating from administrative registries is feasible and supportive of improvements of quality of care.

Oral Anticoagulant Therapy in Patients with Philadelphia-Negative Myeloproliferative Neoplasms: A Real-Life Comparison between Vitamin K Antagonists and Direct Oral Anticoagulants

BACKGROUND Chronic myeloproliferative neoplasms (MPN) are characterized by an high risk of thrombosis and bleeding. Historically, vitamin K inhibitors (VKAs) have been the preferred oral anticoagulant therapy (OAT) for these patients (pts). However, nowadays, VKAs are being used less frequently, and direct oral anticoagulants (DOACs) are becoming more popular. Despite this trend, there is still limited evidence in the literature regarding the efficacy and safety of these drugs in the context of MPN. Specifically, there is a lack of data directly comparing VKAs and DOACs in a real-world clinical setting. AIMS The study aimed to conduct a real-world analysis comparing the efficacy and safety of DOACs and VKAs in patients with MPN. Both medications were prescribed for the treatment and secondary prevention of venous thromboembolism (VTE) or for the prevention of thrombosis in pts with atrial fibrillation (AF). The secondary endpoints were to assess the influence of common demographic, clinical, and hematological variables on the incidence of thrombotic events (TE) and bleeding events (BE) METHODS We conducted an observational retrospective monocentric study that enrolled all consecutive pts with MPN, followed at the MPN Clinic of the IRCCS Foundation S. Gerardo dei Tintori - Monza between 1993 and 2022, who received OAT with VKAs or DOACs for VTE or AF. For each pts, we collected demographic, clinical, biological, therapeutic, and hematological data. TE were categorized based on their type (arterial or venous) and location. BE were classified as minor, major, or clinically relevant non-major bleeding, according to the ISTH classification. Thrombosis-free survival (TFS) and bleeding-free survival (BFS) were assessed from the initiation of OAT until the occurrence of the first TE or BE, respectively, and estimated using Kaplan-Meier analysis. The other analyses were conducted using common statistical methods. Multivariable analyses included previously established risk factors for BE and TE. RESULTS A total of 156 pts were enrolled: 89 were women (57%). The median age was 69 years (range 25-92); 61 were affected by myelofibrosis, 35 by polycythemia vera, and 48 by essential thrombocythemia. 64 pts received OAT with VKAs (41%), and 92 with DOACs (59%). For 82 pts OAT was prescribed for AF (52.6%), and for 74 for VTE (47.4%). 17 pts treated with DOACs for VTE received a reduced-dose extended treatment (45.9%). The median exposure time to OAT was 5.8 years in the VKAs group (range 0.2-20 years) and 1.77 years in the DOACs group (range 0.2-10 years). After a median follow-up of 3,2 years, 14 TE were reported: 5 (35.7%) in the DOAC-treated group, of which 4 were arterial (80%), and 9 (64.3%) in the VKA-treated group (7 arterial - 77.8%). The incidence rate of TE was 2.11 thrombosis/pts/year in the VKAs group and 2.14 thrombosis/pts/year in the DOACs group. There were no significant differences in terms of TFS between the two groups, whether considering the entire population or analyzing the therapeutic indications separately (respectively p=0.72, p=0.53, p=0.55). Overall, there were 27 BE: 13 in the DOACs group (51.9%), 14 in the VKAs group (48.1%). Among these, we report 8 major BE, 4 in both groups. The incidence rate of BE was 5.6/pts/year in the DOACs group and 3.3/pts/year in the VKAs group. We did not observe significant differences in terms of BFS analyzing the whole population and the VTE group (respectively p=0.13 and p=0.75), while we found a trend for lower BFS in pts treated with DOACs for AF (p=0.08, Fig. 1). In a multivariate model, adjusted for time of exposition to OAT, age, gender and antiplatelet treatment, the risk of BE was associated solely with DOACs administration (hazard ratio 3.7, p=0.01) We found no significant differences in the risk of TE and BE when considering the various types of DOACs used. Moreover, 45 (28.8%) patients received concomitant antiplatelet therapy, and we found no significant differences in the risk of BE or TE compared to the other group (p=0.39 and p=0.41, respectively). CONCLUSIONS To our knowledge, this is the largest study investigating the safety and efficacy of DOACs compared to VKAs for the treatment and prevention of TE in pts with MPN and VTE or AF. Our findings suggest that DOACs are as effective as VKAs, but they appear to exhibit a trend towards a higher overall risk of BE, especially in the AF group. More data from prospective multicentric studies are necessary to validate our results.

Anticoagulation therapy in patients with atrial fibrillation and active cancer

Abstract Background Atrial fibrillation (AF) is common among cancer patients. Oral anticoagulation therapy (OAT) is important to prevent stroke in AF patients, but active cancer may also predispose to bleeding. Current knowledge on the use of OAT among AF patients with active cancer is scarce. Purpose To assess the influence of active cancer on the initiation of OAT in patients with AF and to explore cancer features predicting withholding OAT. Methods The nationwide FinACAF registry linked data from several registries covering all levels of care as well as drug purchases and included all 123 618 patients diagnosed with incident AF in Finland during 2011- 2018 with an indication for OAT (≥1 non-sex CHA2DS2-VASc point). Patients were considered to have active cancer if they had received a new cancer diagnosis or treatment for cancer during the preceding year from AF diagnosis. The primary outcome was the initiation of OAT (including non-vitamin K oral anticoagulants (NOAC) and warfarin) and the secondary outcome the initiation of any anticoagulation therapy (AAT; including OAT and low molecular-weight heparin) during the first year from AF diagnosis. Results The mean age of the patients was 73.9 (standard deviation 11.5) years and 62 955 (50.9%) of them were women. Altogether, 7015 (5.7%) patients had active cancer at AF diagnosis. The median CHA2DS2-VASc (3 [interquartile range 2-4] for both groups) and HAS-BLED (2 [interquartile range 2-3] for both groups) scores were similar in patients with active cancer and those without cancer history. Patients with active cancer, compared to those without cancer history, less often initiated OAT (47.7% vs. 70.5 %) or AAT (61.8% vs. 71.8%) (Figure). In Fine-Gray regression analyses with all-cause mortality as a competing risk, after adjusting for confounding factors, active cancer remained associated with lower likelihood of OAT (adjusted subdistribution hazard ratio (aSHR 0.501) (95% confidence interval (CI): 0.485-0.518), p<0.001) as well as AAT (aSHR 0.745 (95%-CI 0.723-0.769, p<0.001) initiation. Among cancer patients, metastases, gastrointestinal cancer and radiotherapy were associated with lower likelihood of OAT initiation, while only metastases predicted lower likelihood of AAT initiation (Table). Among patients initiating OAT, active cancer was associated with lesser likelihood of choosing a NOAC over warfarin compared to those without cancer (36.0% vs. 39.2%; adjusted hazard ratio 0.712 (95%-CI: 0.640-0.792), p<0.001). Conclusion AF patients with active cancer are less likely to initiate anticoagulation therapy, and those starting OAT are less likely to initiate with NOACs, compared to patients without cancer history. Metastases are the most important predictor of withholding anticoagulation therapy among AF patients with cancer.

Atrial fibrillation burden and timing of anticoagulation therapy in patients with screen-detected and clinically-diagnosed AF

Abstract Purpose We evaluated the impact of atrial fibrillation (AF) burden and timing of oral anticoagulation (OAC) therapy initiation on stroke risk in patients with screen-detected and clinically-diagnosed AF. Methods Consecutive patients aged ≥65 years attending medical outpatient clinics with or without known AF were prospectively enrolled for AF-screening using handheld single-lead ECG (AliveCor) from 12/2014 to 12/2017 (NCT02409654). Repeated screening was performed in patients with >1 visit during this period. Patients who participated in repeat screening were included in final analysis. Patients with previously known AF who were in AF in the initial screening and those with repeat screen-positivity were considered probably persistent AF, otherwise paroxysmal AF (single screen-positivity) or no AF (never screen-positive). Time from AF detection to initiation of OAC (Dx-to-Rx) was divided into two exposure levels, Dx-to-Rx ≤ 1 and >1 month. Ischemic stroke risk was estimated using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC score and chronic renal disease, with no AF as reference and stratified according to AF burden and Dx-to-Rx. Results Of 11,972 patients enrolled, 3,853(32.2%) received repeated screening (mean age 76.7±7.3, female 47.5%), of which 3.7% (n=144) had screened-detected AF, 25.2% (n=972) previously known AF, 5.9% (n=226) clinically-diagnosed AF during follow-up, and 65.2% (n=2,511) no AF. Persistent AF was identified in 16.7% (n=644/3,853). Of patients with all AF categories, 55.1% (n=739/1,342) initiated OAC within 1 month after AF diagnosis. During a median follow-up period of 7.2(IQR: 6.1-7.5) years, compared to no AF, patients with paroxysmal AF and Dx-to-Rx ≤ 1m (aSHR=1.40, 95%CI:0.80-2.47) had similar low risk of ischemic stroke, while aSHR was highest for persistent AF and Dx-to-Rx >1m (aSHR=2.42, 95%CI:1.38-4.26), followed by persistent AF with Dx-to-Rx≤ 1m (aSHR=2.19,95%:1.47-3.28), and paroxysmal AF with Dx-to-Rx >1m (aSHR=2.00,95%CI:1.32-3.02) (Figure). Subgroup analysis revealed the effect of early initiation of OAC (P for interaction=0.936) and higher AF burden (P for interaction=0. 863) were consistent across screen-detected and clinically-diagnosed AF. Conclusion Among patients with screen-detected AF or clinically-diagnosed AF, lower AF burden and immediate initiation of OAC therapy were associated with reduction in risk of ischemic stroke. Early detection of AF by screening facilitating early OAC prophylaxis might improve clinical outcomes.Cumulative risk of ischemic stroke

Temporal trends of gender disparities in oral anticoagulant use in patients with atrial fibrillation.

To investigate sex-specific temporal trends in the initiation of oral anticoagulant (OAC) therapy among patients diagnosed with atrial fibrillation (AF) in Finland between 2007 and 2018. The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) Study included all patients with incident AF in Finland from 2007 to 2018. The primary outcome was the initiation of any OAC therapy. We identified 229,565 patients with new-onset AF (50.0% women; mean age 72.7 years). The initiation of OAC therapy increased continuously during the observation period. While women were more likely to receive OAC therapy overall, after adjusting for age, stroke risk factors and other confounding factors, female sex was associated with a marginally lower initiation of OACs (unadjusted and adjusted hazard ratios comparing women to men: 1.08 (1.07-1.10) and 0.97 (0.96-0.98), respectively). Importantly, the gender disparities in OAC use attenuated and reached parity by the end of the observation period. Furthermore, when only patients eligible for OAC therapy according to the contemporary guidelines were included in the analyses, the gender inequalities in OAC initiation appeared minimal. Implementation of direct OACs for stroke prevention was slightly slower among women. This nationwide retrospective cohort study covering all patients with incident AF in Finland from 2007 to 2018 observed that although female sex was initially associated with a lower initiation of OAC therapy, the sex-related disparities resolved over the course of the study period.

P462 ATRIAL FIBRILLATION CIED DETECTED; WHEN TO SCOAGULATE? OUR EXPERIENCE ON A STILL VERY CONTROVERSIAL TOPIC

Abstract Introduction Atrial fibrillation (AF), which is constantly increasing in the population, is associated with an important care burden linked, in particular, to its consequences (stroke, heart failure, etc.). In patients with an implantable cardiac device (CIED) it is frequent the detection of high atrial frequency episodes (AHRE), often asymptomatic, for which an increased thromboembolic risk has been described (about 2.5 times) but lower than the clinical AF for which there is still no unanimous consensus regarding the initiation of oral anticoagulant therapy (OAT). We report below our experience in patients undergoing CIED implantation in whom AHRE was detected and OAT started, evaluating the characteristics of thromboembolic risk and the follow–up of complications. Methods From 01 January 2020 to 31 December 2021, 242 patients (mean age 74.8 years) underwent CIED implant. Among these, 41 patients (16.9% mean age 78.6 years – 30 males and 11 females) presented episodes of AHRE, detected by remote monitoring, lasting between a few seconds and more than 24 hours. The mean CHADsVasc score of these patients was 3.8. Seven patients were not anticoagulated due to arrhythmic episodes lasting a few minutes and CHADsVasc score equal to 1–2, while the other 34 started OAT with DOAC. Results No thromboembolic events or major bleeding events have been recorded to date; only minor bleedings (11 epistaxis, 4 haematuria and 5 SOF positivity) were easily treated. Conclusions The current guidelines indicate to prolong monitoring until the detection of clinical AF or an arrhythmic burden > 24 hours before considering OAT; however, there are studies that recommend carefully correlating the duration of arrhythmic events with the determination of the thromboembolic risk. In our experience, the high thromboembolic risk of patients, sometimes not adequately represented by the CHADsVasc score, led us to start OAT even when the duration of the episodes was not particularly long and at the moment no major complications have been observed. The two ongoing trials (ARTESia and NOAH) dedicated to the evaluation of these situations will provide valuable indications on the treatment of these patients in whom the thromboembolic risk is certainly lower than that of patients with clinical AF but still not negligible.

Rural-urban differences in the initiation of oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

Little is known about rural-urban differences in the treatment and outcomes in patients with atrial fibrillation (AF). We aimed to assess whether the initiation of oral anticoagulant (OAC) therapy in patients with AF differs between those with rural and urban residence. The registry-based FinACAF cohort covers all patients with AF from all levels of care in Finland. Patients were divided into rural and urban categories and into urbanization degree tertiles based on their municipality of residence at the time of AF diagnosis. The outcome was the first redeemed OAC prescription. We identified 222 419 patients (50.1% female; mean age 72.8 (SD 13.2) years) with incident AF during 2007-2018. Urban residence was associated with a lower rate of OAC therapy initiation (adjusted subdistribution hazard ratio (SHR) (95% CI) 0.96 (0.95-0.97)). Correspondingly, an inverse graded dose-response relationship was observed between higher urbanization degree tertile and OAC initiation rate (highest tertile compared to lowest: adjusted SHR (95% CI) 0.94 (0.93-0.95)). The adoption of direct oral anticoagulants for stroke prevention was faster among patients with urban residence. This nationwide cohort study documented that urban residence is associated with a slightly lower rate of OAC therapy initiation in patients with incident AF, but faster adoption of direct oral anticoagulant use.

Safety of Nonvitamin K Antagonists Compared with Warfarin in Patients with Atrial Fibrillation and End-Stage Kidney Disease.

This study evaluated the occurrence of major bleeding following the initiation of oral anticoagulation therapy in patients with end-stage kidney disease (ESKD) in a community teaching hospital. This was a single-center retrospective study that enrolled patients admitted to the study hospital with ESKD and who received oral anticoagulation (warfarin or nonvitamin K oral antagonists [NOACs]). The primary endpoint was the occurrence of major bleeding at any time while taking oral anticoagulation. Key secondary endpoints included occurrence of minor bleeding, thrombotic events, and hospitalizations because of bleeding or thrombosis. There were 36 patients who received warfarin and 32 patients who received a NOAC. A major bleeding event occurred in 15 of 36 patients (42%) in the warfarin group and in 5 of 32 patients (16%) in the NOAC group (P = 0.032). Hospitalizations as a result of either a bleeding event or a thrombosis occurred in 19 of 36 patients (53%) in the warfarin group and in 8 of 32 patients (25%) in the NOAC group (P = 0.026). The majority of patients in the NOAC group (69%) received a reduced dose for the indication. Warfarin increased the risk of major bleeding in patients with ESKD compared with NOACs and did not reduce the risk of thrombotic events.

Association of income and educational levels on initiation of oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

Socioeconomic disparities have been reported in the outcomes of patients with atrial fibrillation (AF). We assessed the hypothesis that AF patients with higher income or educational level are more frequently initiated with oral anticoagulant (OAC) therapy for stroke prevention. The nationwide registry-based Finnish AntiCoagulation in Atrial Fibrillationcohort covers all patients with AF from all levels of care in Finland. Patients were divided into income quartiles according to their highest annual income during 2004-2018 and into three categories based on educational attainment. The outcome was the first redeemed OAC prescription. We identified 239 222 patients (mean age 72.7 ± 13.2 years, 49.8% female) with incident AF during 2007-2018. Higher income was associated with higher OAC initiation rate: compared to the lowest income quartile the adjusted SHRs (95% CI) for OAC initiation were 1.09 (1.07-1.10), 1.13 (1.11-1.14) and 1.13 (1.12-1.15) in the second, third and fourth income quartiles, respectively. Patients in the highest educational category had a slightly lower OAC initiation rate than patients in the lowest educational category (adjusted SHR 0.92 [95% CI 0.90-0.93]). Income-related disparities were larger and education-related disparities only marginal among patients at high risk of ischemic stroke. The socioeconomic disparities in OAC initiation within 1-year follow-up decreased from 2007 to 2018. The adoption of direct OACs as the initial anticoagulant was faster among patients with higher income or educational levels. These findings highlight potential missed opportunities in stroke prevention, especially among AF patients with low income, whereas the education-related disparities in OAC initiation appear controversial.

Geographic and temporal variation in the treatment and outcomes of atrial fibrillation: a population-based analysis of national quality indicators.

Background:Assessment of potential geographic variation in quality indicators of atrial fibrillation care may identify opportunities for improvement in the quality of atrial fibrillation care. The objective of this study was to assess for potential geographic variation in the quality of atrial fibrillation care in Alberta, Canada.Methods:In a population-based cohort of adults (age ≥ 18 yr) with incident nonvalvular atrial fibrillation (NVAF) diagnosed between Apr. 1, 2008, and Mar. 31, 2016, in Alberta, we investigated the variation in national quality indicators of atrial fibrillation care developed by the Canadian Cardiovascular Society. Specifically, we assessed the geographic and temporal variation in the proportion of patients with initiation of oral anticoagulant therapy, persistence with therapy, ischemic stroke and major bleeding outcomes 1 year after atrial fibrillation diagnosis using linked administrative data sets. We defined stroke risk using the CHADS2 score. We assessed geographic variation using small-area variation statistics and geospatial data analysis.Results:Of the 64 093 patients in the study cohort (35 019 men [54.6%] and 29 074 women [45.4%] with a mean age of 69 [standard deviation 15.9] yr), 36 199 were at high risk for stroke and 14 411 were at moderate risk. Within 1 year of NVAF diagnosis, 20 180 patients (55.7%) in the high-risk group and 6448 patients (44.7%) in the moderate-risk group were prescribed anticoagulation. A total of 2187 patients (3.4%) had an ischemic stroke, and 2996 patients (4.7%) experienced a major bleed. There was substantial regional variation observed in initiation of oral anticoagulant therapy but not in the proportion of patients with ischemic stroke or major bleeding. Among the 64 Health Status Areas in Alberta, therapy initiation rates ranged from 22.6% to 71.2% among patients at high stroke risk and from 22.7% to 55.8% among those at moderate stroke risk, with clustering of lower therapy initiation rates in rural northern regions.Interpretation:The rate of initiation of oral anticoagulant therapy among adults with incident atrial fibrillation was less than 60% in patients in whom oral anticoagulant therapy would be considered guideline-appropriate care. The large geographic variation in oral anticoagulant prescribing warrants additional study into patient, provider and health care system factors that contribute to variation and drive disparities in high-quality, equitable atrial fibrillation care.

Left atrial appendage thrombus in patients with atrial fibrillation who underwent oral anticoagulation.

Electric cardioversion of atrial fibrillation (AF) is associated with an increased risk of embolism, with embolic material existing in the heart cavities. The initiation of oral anticoagulation therapy reduces the risk of thromboembolic events. The aims of this study were to evaluate the prevalence of left atrial appendage (LAA) thrombi in non-valvular AF, to compare vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) with respect to thrombus prevalence, and to evaluate the rate of LAA thrombus persistence on repeat transesophageal echocardiography (TEE) after treatment change. We enrolled 160 consecutive AF patients who presented with an AF duration > 48 h and had undergone TEE before cardioversion. Left atrial appendage thrombus was observed in 12 (7.5%) patients, and spontaneous echo contrast 4 was observed in 19 (11.8%) patients; the incidence was similar between the NOAC and VKA groups (8.9% vs. 3.6% and 12.4% vs. 18.5 %, respectively). Among patients on NOAC, thrombus prevalence was detected in 8.4% of users of rivaroxaban, 8% of users of dabigatran, and 12.5% of users of apixaban. The LAA thrombus developed in 7.5% of patients despite anticoagulation therapy, demonstrating similar prevalence rates among patients either on NOAC or VKA. Lower mean LAA flow velocity and a history of vascular disease were independent predictors of embolic material in the LAA. It seems that in the case of embolic materials in LAA under NOAC treatment, switching to VKA provides additional clinical benefit to the patients.

Disparities in oral anticoagulation initiation in patients with schizophrenia and atrial fibrillation: A nationwide cohort study

AimsSchizophrenia is associated with poor anticoagulation control and clinical prognosis in patients with atrial fibrillation (AF). Little is known about initiation of oral anticoagulation therapy (OAC) in this patient population.MethodsIn the nationwide Danish health registries, we identified all patients with incident AF and schizophrenia with indication for OAC treatment. Patients with schizophrenia (n = 673) were matched 1:5 on sex, age, stroke risk score, and calendar‐period to incident AF patients without schizophrenia. We calculated absolute risk and risk difference (RD) of OAC initiation, adjusting for stroke and bleeding risk factors. Analyses were stratified by calendar period (2000–2011 and 2012–2018) to account for changes after the introduction of non‐vitamin K OACs (NOAC).ResultsAmong patients with schizophrenia (mean age 69.5 years, 50.3% females), 33.7% initiated OAC within the first year after AF diagnosis, compared with 54.4% of patients without schizophrenia, corresponding to an adjusted RD of −20.7 (95% confidence interval [CI]: −24.7 to −16.7). OAC initiation increased over time regardless of schizophrenia status. During 2000–2011, 18.3% of patients with schizophrenia and 42.9% without schizophrenia initiated OAC (adjusted RD −23.6%, 95% CI −28.8 to −18.6). During 2012–2018, this was 48.5% and 65.7%, respectively (adjusted RD −14.4%, 95% CI −20.4 to −8.4).ConclusionInitiation of OAC was substantially lower among patients with AF and schizophrenia compared with matched AF peers. These findings accentuate the importance of close attention to disparities in initiation of OAC treatment, and potential missed opportunities for prevention of disabling strokes in AF patients with schizophrenia.

Extent of white matter lesion is associated with early hemorrhagic transformation in acute ischemic stroke related to atrial fibrillation.

BackgroundHemorrhagic transformation (HT) after stroke, related to atrial fibrillation (AF), is a frequent complication, and it can be associated with a delay in the (re‐)initiation of oral anticoagulation therapy. We investigated the effect of the presence and severity of white matter disease (WMD) on early HT after stroke related to AF.MethodsA consecutive series of patients with recent (<4 weeks) ischemic stroke and AF, treated at the Hyper Acute Stroke Unit of the Imperial College London between 2010 and 2017, were enrolled. Patients with brain MRI performed 24–72 h from stroke onset and not yet started on anticoagulant treatment were included. WMD was graded using the Fazekas score.ResultsAmong the 441 patients eligible for the analysis, 91 (20.6%) had any HT. Patients with and without HT showed similar clinical characteristics. Patients with HT had a larger diffusion‐weighted imaging (DWI) infarct volume compared to patients without HT (p < .001) and significant difference in the distribution of the Fazekas score (p = .001). On multivariable analysis, HT was independently associated with increasing DWI infarct volume (odd ratio (OR), 1.03; 95% confidence interval (CI), 1.01–1.05; p < .001), higher Fazekas scores (OR, 1.94; 95% CI, 1.47–2.57; p < .001) and history of previous intracranial hemorrhage (OR, 4.80; 95% CI, 1.11–20.80; p = .036).ConclusionsPresence and severity of WMD is associated with increased risk of development of early HT in patients with stroke and AF. Further evidence is needed to provide reliable radiological predictors of the risk of HT in cardioembolic stroke.

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

New-Onset Atrial Fibrillation Among Patients With Infection in the Emergency Department: A Multicenter Cohort Study of 1-Year Stroke Risk

BackgroundPatients with new-onset atrial fibrillation in relation to infection are frequent in emergency departments (EDs) and may require antithrombotic therapy because of the increased risk of stroke. Our objective was to describe the 1-year risk of stroke in patients in the ED with infection, new-onset atrial fibrillation, and no antithrombotic therapy. MethodsThis was a population-based cohort study at 4 EDs in Denmark and Sweden. Atrial fibrillation was identified by electrocardiogram (ECG) upon arrival at the ED, and infection was identified by discharge diagnosis. Patient history was followed for 12 months or until initiation of oral anticoagulant therapy, ischemic stroke, or death. Primary outcome was stroke within 12 months compared to patients with infection and no atrial fibrillation. ResultsIn the analysis, 15,505 patients were included; 48.7% were male and the median age was 71 (IQR, 56-83). Among the included patients, 2107 (13.6%) had atrial fibrillation of any kind and 822 (39.0%) of these had new-onset atrial fibrillation with a median CHA2DS2-VASc score of 3 (IQR 2-4).New-onset atrial fibrillation during infection showed an absolute postdischarge 1-year risk of stroke of 2.7% (95% CI 1.6-4.2), corresponding to a crude hazard ratio (HR) of 1.4 (95% CI 0.9-2.3), a sex and age adjusted HR of 1.0 (95% CI 0.6-1.6), and a CHA2DS2-VASc adjusted HR of 1.1 (95% CI, 0.7-1.8) compared to patients with infection but no atrial fibrillation. ConclusionsPatients in the ED with infection and new-onset atrial fibrillation without current oral anticoagulant therapy had a 2.7% absolute 1-year risk of stroke. Stroke events were mainly related to sex and age and risk factors identified by the CHA2DS2-VASc score.

Continuous 4-week ECG monitoring with adhesive electrodes reveals AF in patients with recent embolic stroke of undetermined source.

BackgroundAtrial fibrillation (AF) frequently escapes routine stroke workup due to its unpredictable and often asymptomatic nature, leaving a significant portion of patients at high risk of recurrent stroke. Recent trials emphasized continuous electrocardiogram (ECG) monitoring in the detection of occult AF. We screened AF in patients meeting the embolic stroke of unknown source (ESUS) criteria using an external miniaturized recorder with an adhesive electrode.MethodsPatients aged ≥50 with recent ESUS were prospectively screened and assigned to wear a 1‐lead ECG device capable to record continuous ECG for up to 4 weeks. Electrodes were replaced every 3–4 days. Primary outcome was proportion of patients completing at least 80% of monitoring. Secondary outcome measures included incidence of AF and initiation of oral anticoagulation therapy after AF detection.ResultsFifty‐seven patients were monitored (mean age 64.5 ± 8.2 years, median delay from stroke to the start of monitoring 8 days, IQR 4–44). Of these, 51 patients (89.5%) completed at least 80% of the desired monitoring period. We detected AF ≥30 s in seven patients (12.3%), all of whom initiated anticoagulation therapy. Atrial fibrillation was revealed in six patients (85.7%) within the first week of monitoring. Compared to patients without AF, patients with AF were older (70.6 ± 5.1 vs. 63.6 ± 8.3 years, p < 0.011) and more obese (body mass index 30.0 ± 3.4 vs. 26.6 ± 4.6, p < 0.039).ConclusionsProlonged ECG monitoring with an external device using adhesive electrodes is feasible in ESUS patients, since nine out of ten patients used the device appropriately and AF was detected in one out of eight patients.

Impact of Antithrombotic Regimen and Platelet Inhibition Extent on Leaflet Thrombosis Detected by Cardiac MDCT after Transcatheter Aortic Valve Replacement.

The impact of antithrombotic regimen and platelet inhibition extent on subclinical leaflet thrombosis (SLT) detected by cardiac multidetector computed tomography (MDCT) after transcatheter aortic valve replacement (TAVR) is not well established. Hypoattenuation affecting motion (HAM) has been proposed as a surrogate marker of SLT, and is characterized by hypoattenuated leaflet thickening (HALT) and concomitant reduction in leaflet motion (RELM). We sought to investigate (i) the prevalence of HAM and HALT after TAVR detected by MDCT, (ii) the predictors of SLT, (iii) the impact of oral anticoagulant (OAC) and platelet inhibition extent assessed by platelet reactivity index vasodilator stimulated phosphoprotein (PRI-VASP) and closure time adenosine diphosphate (CT-ADP) on SLT. Of 187 consecutive patients who underwent TAVR from 1 August 2017 to 31 March 2018, 90 of them had cardiac CT at relevant follow-up. Clinical, biological, echocardiographic, procedural characteristics and treatments were collected before, at discharge, and 1 year after TAVR. P2Y12 platelet inhibition extent and primary haemostasis disorders were investigated using platelet PRI-VASP and CT-ADP point-of-care assays. Eighty-five post-TAVR CTs out of 90 were ranked for clarity and assessed with sufficient diagnostic quality. HAM was evidenced in 13 patients (15.3%) and HALT in 30 patients (35%). Procedural characteristics, including aortic valve calcium score, annulus size, or procedural heparin regimens, were equivalent between groups. Likewise, no impact of P2Y12 inhibition (PRI-VASP) nor primary haemostasis disorders (CT-ADP) on SLT could be evidenced. No impact of SLT on valve deterioration evaluated by transthoracic echocardiography (TTE) and clinical events could be established at 12 months follow-up. By multivariate analysis, lack of oral anticoagulant therapy at discharge (HR 12.130 CI 95% (1.394–150.582); p = 0.028) and higher haemoglobin levels were evidenced as the sole independent predictors of SLT. In four patients with HAM, MDCT follow-up was obtained after initiation of OAC therapy and showed a complete regression of HAM. SLT was evidenced in a sizeable proportion of patients treated by TAVR and was mainly determined by the lack of oral anticoagulant therapy. Conversely, no impact of platelet inhibition extent on SLT could be evidenced.

Hemorrhagic Transformation in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Time to Initiation of Oral Anticoagulant Therapy and Outcomes.

BackgroundIn patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days.Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35).ConclusionsIn patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

Guideline-concordant initiation of oral anticoagulant therapy for stroke prevention in older veterans with atrial fibrillation eligible for Medicare Part D.

To characterize the rate of guideline-concordant initiation of oral anticoagulation (OAC) among elderly Veterans with atrial fibrillation (AF) and high stroke risk. Veterans Health Administration (VHA) Corporate Data Warehouse (CDW) linked with Medicare claims 2011-2015. We identified 6619 elderly, high stroke-risk patients with a new episode of AF initially diagnosed in the VHA during fiscal years 2012-2015. We used logistic regression to estimate marginal effects of associations between patient characteristics and OAC initiation within 90days of the first AF episode. We identified OACs using generic drug names. We calculated comorbidities and risk scores using diagnosis codes from 1year of baseline data. Overall, 66.5% of Medicare-eligible Veterans with AF at high risk of stroke initiated an OAC within 90days. We found lower initiation rates for patients enrolled in Medicare Part D and those ineligible for drug co-payment subsidies. OAC initiation rates increased during the study among VHA-reliant patients but not among dual VHA-Part D enrollees. One-third of elderly Veterans at risk of stroke are not receiving recommended therapy. Increased coordination between Medicare and VHA providers may lead to improvements in anticoagulation quality and stroke prevention.

Atrial fibrillation ablation

Transcatheter ablation can be used in case of atrial fibrillation (AF) not controlled by medical therapy due to lack of efficacy or poor tolerability.The procedure is however associated with the risk of periprocedural events and therefore requires particular attention to systemic anticoagulant therapy. In this clinical setting dabigatran may represent a valid therapeutic option to ensure adequate patient protection during the ablation procedure, as demonstrated by the results of the RE-CIRCUIT study. Here we describe an elderly patient, treated for hypertension, with a slightly impaired renal function, a long history of highly symptomatic paroxysmal AF resistant to antiarrhythmic drugs. It describes the common clinical practice prior to the publication of the RE-CIRCUIT study results, which support performing the AF ablation procedure without interrupting the anticoagulant therapy in place with dabigatran. It also highlights the potential efficacy of dabigatran in the treatment of endoauricular thrombus in patients with FA, for whom the currently recommended treatment is bridging with LMWH and the initiation of oral anticoagulant therapy with VKA, which however may be ineffective, as in this case (Diabetology).