Anticoagulation For Stroke Prevention Research Articles

Quality of life when switching from a vitamin K antagonist to non-vitamin K antagonist oral anticoagulation in frail older patients with atrial fibrillation

Abstract Background Many older patients with atrial fibrillation (AF) are frail, putting them at high risk of adverse outcomes including mortality, hospitalization, functional decline, and dependency on others. In this special population, management strategies – such as anticoagulation for stroke prevention – need special consideration. To what extent the type of anticoagulation influences the quality of life (QoL) in frail patients with AF is unclear. Purpose To assess QoL in frail older patients with AF switching from a vitamin K antagonist (VKA) to a non-VKA oral anticoagulant (NOAC), as compared to patients continuing a VKA. Methods We used data from the FRAIL-AF trial that randomized frail older AF patients between continuing VKA treatment or switching to any NOAC. At baseline, after six months and twelve months of follow-up, QoL was assessed using the EQ-5D-5L questionnaire. For every timepoint, the mean EQ-5D-5L score was calculated with corresponding 95% confidence intervals (CI), missing data were imputed using ten-fold multiple imputation. Absolute differences in EQ-5D-5L score were calculated between patients switching to a NOAC and patients continuing with a VKA, with corresponding 95% CI. The distribution of the scores on each domain of the EQ-5D-5L was compared using a chi-square test. Results In total 661 patients continued VKA treatment, and 663 switched to a NOAC. The median age was 82.2 years (interquartile range (IQR) 78.7 – 86.5), 61.3% were male. Major bleeding or clinically relevant non-major bleeding occurred in 101 patients (17.8 per 100 person-years) switching to NOAC therapy, and 62 patients (10.5 events per 100 person-years) continuing with a VKA (hazard ratio 1.69, 95% confidence interval 1.23 – 2.32). Mortality occurred in 44 and 46 patients, respectively. In 25 patients data was missing. Table 1 shows the mean EQ-5D-5L scores at baseline, at 6 months follow-up and at 12 months follow-up. Scores were similar between patients switching to NOAC treatment or continuing with a VKA and did not change significantly during 12 months follow-up. Table 2 shows the distribution of the scores on all domains of the EQ-5D-5L, with no significant differences between groups. Conclusion Switching from a VKA to a NOAC in frail older patients with AF was associated with an increased risk of bleeding, yet without any effect on overall and different domains of QoL.

The grey areas in anticoagulation for stroke prevention and a focus on chronic stress in carotid atherosclerosis.

The grey areas in anticoagulation for stroke prevention and a focus on chronic stress in carotid atherosclerosis.

Cardiovascular Management in Asymptomatic (Silent) Cerebral Microbleeds and Suspected Cerebral Amyloid Angiopathy.

Cerebral microbleeds (CMBs) detected on blood-sensitive magnetic resonance imaging sequences are usually a sign of an underlying cerebral small vessel disease such as sporadic cerebral amyloid angiopathy or sporadic nonamyloid small vessel pathology (eg, arteriolosclerosis). Much of the enduring interest in CMBs relates to their high prevalence (partly due to the widespread use of magnetic resonance imaging) in the context of stroke, cognitive impairment and in healthy individuals, and the clinical uncertainties created about the safety of antithrombotic medications due to their association with both future hemorrhagic and ischemic stroke. Historically, the research literature overwhelmingly emphasized the future hemorrhagic risk associated with CMBs, potentially leading to unnecessary withholding of treatments proven effective at preventing thrombosis, such as anticoagulants in patients with atrial fibrillation who happened to have some microbleeds. The lack of strong guidelines in this area contributes to wide variation in clinical practice. In this article, we critically review and discuss the implications of silent CMBs and cortical superficial siderosis (ie, without symptomatic intracerebral hemorrhage) in different clinical settings: the general population, patients with ischemic stroke, and the memory clinic. Emerging evidence, albeit not from randomized controlled trials, suggests that in most patients, CMBs alone should not prevent the use of antithrombotics or anticoagulants for stroke prevention, when they are otherwise indicated. Where possible, we provide specific suggestions for clinical care grounded in both the limited available literature and our personal clinical practice.

The AZALEA-TIMI 71 Study and the Future of Factor XI Inhibition: Reflections from the American Heart Association Scientific Congress 2023

Since its earliest days, the effective use of anticoagulation for prevention of stroke and other thromboembolic events has been limited by the risk and fear of bleeding, which was long believed to be inevitable. However, new understanding of the coagulation cascade suggests that, by targeting factor XI, it may be possible to protect patients from pathological thrombosis without significantly affecting physiological haemostasis, and thus greatly reduce the risk of bleeding. The AZALEA-TIMI 71 trial is the first study to provide definitive evidence that factor XI inhibition substantially reduces bleeding compared to a standard-of-care direct oral anticoagulant (DOAC). Based on an interview with Principal Investigator Christian T. Ruff, Thrombolysis in Myocardial Infarction (TIMI) Study Group, Boston, Massachusetts, USA, this article explains the significance of the AZALEA-TIMI 71 trial results, which showed an unprecedented reduction in the rate of bleeding with abelacimab, an investigational dual-acting factor XI/XIa inhibitor, compared with the DOAC rivaroxaban in patients with atrial fibrillation (AF) at moderate-to-high risk of stroke.

Safety and efficacy of direct oral anticoagulants in stroke prevention in patients with atrial fibrillation complicated with anemia and/or thrombocytopenia: a retrospective cohort study

BackgroundThere are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia.MethodsThis is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis.ResultsHigher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12–2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19–2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14–4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66–5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46–6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23—13.54, P = 0.577).ConclusionsHigher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia.

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24 h.

Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Electronic alerts for ambulatory patients with atrial fibrillation not prescribed anticoagulation: A randomized, controlled trial (AF-ALERT2)

BackgroundDespite widely available risk stratification tools, safe and effective anticoagulants, and guideline recommendations, anticoagulation for stroke prevention in atrial fibrillation (AF) is under-prescribed in ambulatory patients. To assess the impact of alert-based computerized decision support (CDS) on anticoagulation prescription in ambulatory patients with AF and high-risk for stroke, we conducted this randomized controlled trial. MethodsPatients with AF and CHA2DS2−VASc score ≥ 2 who were not prescribed anticoagulation and had a clinic visit at Brigham and Women's Hospital were enrolled. Patients were randomly allocated, according to Attending Physician of record, to intervention (alert-based CDS) versus control (no notification). The primary efficacy outcome was the frequency of anticoagulant prescription. ResultsThe CDS tool assigned 395 and 403 patients to the alert and control groups, respectively. Alert patients were more likely to be prescribed anticoagulation within 48 h of the clinic visit (15.4 % vs. 7.7 %, p < 0.001) and at 90 days (17.2 % vs. 9.9 %, p < 0.01). Direct oral anticoagulants were the predominantly prescribed form of anticoagulation. No significant differences were observed in stroke, TIA, or systemic embolic events (0 % vs. 0.8 %, p = 0.09), symptomatic VTE (0.5 % vs. 1 %, p = 0.43), all-cause mortality (2 % vs. 0.7 %, p = 0.12), or major adverse cardiovascular events (2.8 % vs. 2.5 %, p = 0.79) at 90 days. ConclusionsAn alert-based CDS strategy increased a primary efficacy outcome of anticoagulation in clinic patients with AF and high-risk for stroke who were not receiving anticoagulation at the time of the office visit. The study was likely underpowered to assess an impact on clinical outcomes. Trial registrationClinicalTrials.gov Identifier- NCT02958943.

"Pill-in-Pocket" anticoagulation for stroke prevention in atrial fibrillation.

Uninterrupted anticoagulation for atrial fibrillation (AF), regardless of AF burden, is deeply rooted in practice since the early anticoagulation trials. However, uninterrupted anticoagulation is not without risks, and may not be beneficial for allcomers with a history of AF. Indeed, contemporary data that support a critical duration threshold of AF that benefits from anticoagulation, and a temporal association between stroke and multihour AF episodes, compel the study of a more targeted approach to AF anticoagulation. In this review, we discuss data that support further investigation of "pillinthepocket" anticoagulation for AF, and introduce the pivotal Rhythm Evaluation for Anticoagulation Therapy for Atrial Fibrillation(REACT-AF) trial that will robustly evaluate this strategy.

Development of Complementary Encounter and Patient Decision Aids for Shared Decision Making about Stroke Prevention in Atrial Fibrillation.

Decision aids (DAs) are helpful instruments used to support shared decision making (SDM). Patients with atrial fibrillation (AF) face complex decisions regarding stroke prevention strategies. While a few DAs have been made for AF stroke prevention, an encounter DA (EDA) and patient DA (PDA) have not been created to be used in conjunction with each other before. Using iterative user-centered design, we developed 2 DAs for anticoagulation choice and stroke prevention in AF. Prototypes were created, and we elicited feedback from patients and experts via observations of encounters, usability testing, and semistructured interviews. User testing was done with 33 experts (in AF and SDM) and 51 patients from 6 institutions. The EDA and PDA underwent 1 and 4 major iterations, respectively. Major differences between the DAs included AF pathophysiology and a preparation to meet with the clinician in the PDA as well as different language throughout. Content areas included personalized stroke risk, differences between anticoagulants, and risks of bleeding. Based on user feedback, developers 1) addressed feelings of isolation with AF, 2) improved navigation options, 3) modified content and flow for users new to AF and those experienced with AF, 4) updated stroke risk pictographs, and 5) added structure to the preparation for decision making in the PDA. These DAs focus only on anticoagulation for stroke prevention and are online, which may limit participation for those less comfortable with technology. Designing complementary DAs for use in tandem or separately is a new method to support SDM between patients and clinicians. Extensive user testing is essential to creating high-quality tools that best meet the needs of those using them. First-time complementary encounter and patient decision aids have been designed to work together or separately.User feedback led to greater structure and different experiences for patients naïve or experienced with anticoagulants in patient decision aids.Online tools allow for easier dissemination, use in telehealth visits, and updating as new evidence comes out.

Racial, ethnic, and sex disparities in atrial fibrillation management: rate and rhythm control.

Atrial fibrillation (AF) affects around 6 million Americans. AF management involves pharmacologic therapy and/or interventional procedures to control rate and rhythm, as well as anticoagulation for stroke prevention. Different populations may respond differently to distinct management strategies. This review will describe disparities in rate and rhythm control and their impact on outcomes among women and historically underrepresented racial and/or ethnic groups. This is a narrative review exploring the topic of sex and racial and/or ethnic disparities in rate and rhythm management of AF. We describe basic terminology, summarize AF epidemiology, discuss diversity in clinical research, and review landmark clinical trials. Despite having higher rates of traditional AF risk factors, Black and Hispanic adults have lower risk of AF than non-Hispanic White (NHW) patients, although those with AF experience more severe symptoms and report lower quality-of-life scores than NHW patients with AF. NHW patients receive antiarrhythmic drugs, cardioversions, and invasive therapies more frequently than Black and Hispanic patients. Women have lower rates of AF than men, but experience more severe symptoms, heart failure, stroke, and death after AF diagnosis. Women and people from diverse racial and ethnic backgrounds are inadequately represented in AF trials; prevalence findings may be a result of underdetection. Race, ethnicity, and gender are social determinants of health that may impact the prevalence, evolution, and management of AF. This impact reflects differences in biology as well as disparities in treatment and representation in clinical trials.

Oral anticoagulant treatment in rheumatoid arthritis patients with atrial fibrillation results of an international audit.

To describe the prevalence of atrial fibrillation (AF) in patients with rheumatoid arthritis (RA), and to evaluate the proportion of patients with AF receiving guideline-recommended anticoagulation for prevention of stroke, based on data from a large international audit. The cohort was derived from the international audit SUrvey of cardiovascular disease Risk Factors in patients with Rheumatoid Arthritis (SURF-RA) which collected data from 17 countries during 2014-2019. We evaluated the prevalence of AF across world regions and explored factors associated with the presence of AF with multivariable logistic regression models. The proportion of AF patients at high risk of stroke (CHA2DS2-VASc≥2 in males and≥3 in females) receiving anticoagulation was examined. Of the total SURF-RA cohort (n=14,503), we included RA cases with data on whether the diagnosis of AF was present or not (n=7,665, 75.1% women, mean (SD) age 58.7 (14.1) years). A total of 288 (3.8%) patients had a history of AF (4.4% in North America, 3.4% in Western Europe, 2.8% in Central and Eastern Europe and 1.5% in Asia). Factors associated with the presence of AF were older age, male sex, atherosclerotic cardiovascular disease, heart failure and hypertension. Two-hundred and fifty-five (88.5%) RA patients had a CHA2DS2-VASc score indicating recommendation for oral anticoagulant treatment, and of them, 164 (64.3%) were anticoagulated. Guideline-recommended anticoagulant therapy for prevention of stroke due to AF may not be optimally implemented among RA patients, and requires special attention.

Expert Opinion on the Use of Novel Oral Anticoagulants for Stroke Prevention in Non-valvular Atrial Fibrillation for the Primary Care Setting in India: A Literature Review.

Atrial fibrillation (AF), the most prevalent cardiac arrhythmia encountered in clinical practice, is linked with substantial morbidity and mortality due to accompanying risk of stroke and thromboembolism. Patients with AF are at a five-fold higher risk of suffering from a stroke. Anticoagulation therapy, with either vitamin K antagonists or novel oral anticoagulants (NOACs), is a standard approach to reduce the risk. Consultant physicians (CPs) in India are the primary point of contact for the majority of patients before they approach a specialist. The CPs may face challenges in screening and diagnosing AF patients. The apprehensions associated with managing AF patients with anticoagulants, further add to the challenges of a CP. This review aimed to identify the key decision points for the CPs to diagnose AF and initiate anticoagulation in patients with non-valvular AF (NVAF) and bring to the table a simplified recommendation supported by expert opinion and guidelines for stroke prevention in NVAF patients.

Identifying gaps in the management of atrial fibrillation with anticoagulation for stroke prevention (GIANTS): a quality improvement initiative

Direct oral anticoagulants (DOACs) are indicated for preventing ischemic stroke in 95% of patients with atrial fibrillation (AF). However, DOACs are largely underutilized or inappropriately dosed. This study aimed to explore the rates of appropriate DOAC use between repatriated and non-repatriated patients with AF who presented with an acute ischemic stroke not deemed candidates for revascularization therapies. Data were collected via electronic medical records and patients were contacted via telephone to obtain medication information and other missing clinical information. Multivariate logistic regression analyses were conducted to determine associations between appropriate use of a DOAC and repatriation status adjusting for age, sex, and comorbidities. A total of 49 patients were included in the study with a mean follow-up of 31.5 (± 11.9) months. Eleven patients (22.4%) died, and 4 (8.2%) patients were lost to follow-up. Overall, 9 (26.5%) patients (3 non-repatriated and 6 repatriated) were found to be on suboptimal or inappropriate anticoagulation. Repatriation was associated with over six fold (OR 6.53; 95% CI 1.20-35.7) likelihood of suboptimal or inappropriate anticoagulation. Awareness of this finding is critical to overcome therapeutic inertia in the use of DOACs for ischemic stroke patients with AF. With stroke care becoming increasingly nuanced, peripheral centers may lack the ability to guide anticoagulation in a timely and effective manner. Creation of tertiary short-term follow-up stroke clinics with cardiology follow-up may be an effective strategy to ensure standard of care. Research into systems contributors affecting the appropriate use of DOACs should be elucidated.

Temporal changes in anticoagulant prescribing and atrial fibrillation: results of interrupted time-series analysis of openly available routine data in England

Abstract Introduction The use of anticoagulants for stroke prevention in patients with atrial fibrillation (AF) has been increasing in England in the recent years (1, 2). The changes in practice coincided with several developments in the area of anticoagulants and AF, including: the emergence of evidence supporting anticoagulant use for stroke prevention in AF, changes in guideline recommendations, and the licensing of direct oral anticoagulants (DOACs) as an alternative to warfarin, which was the mainstay of stroke prevention in AF. Currently, there are four DOACs available for use: dabigatran, rivaroxaban, apixaban, and edoxaban. Recent analyses of time trends of anticoagulant prescribing in England showed an increase in DOACs prescribing and a decrease in warfarin prescribing (1, 2). However, more recent exploration of recent anticoagulant prescribing trends is needed. Aim To explore the changes in anticoagulant prescribing for AF in England. Methods Interrupted time-series analysis (ITSA) of openly available data on anticoagulant prescribing and AF. Separate analyses were conducted for data from Sentinel Stroke National Audit Programme (SSNAP) and Quality and Outcomes Framework (QOF). The timeframe of the analysis and the length of time intervals depended on the characteristics of each dataset. Results Analysis of data from SSNAP showed that the proportion of stroke patients who have a diagnosis of AF who were taking an anticoagulant alone prior to admission increased from 32.51% in the third quarter of 2013 to 62.63% in the third quarter of 2020; this coincided with a decreased proportion of stroke patients who have a diagnosis of AF taking antiplatelets alone from 37.10% to 8.31% during the same period. Analysed QOF data on anticoagulants and AF included information about AF prevalence in QOF datasets, the eligibility of patients with AF for anticoagulant based on stroke risk assessment, and the use of anticoagulants among eligible patients. Prevalence of AF in England in QOF datasets increased from 1.52% in 2012/2013 to 2.05% in 2019/2020 (ITSA gradient=0.08, p-value&amp;lt;.001, 95% confidence interval: 0.07- 0.09). The proportion of patients with AF who are considered eligible for anticoagulation per all patients with AF in QOF datasets increased from 44.95% in 2012/2013 to 80.87% in 2019/2020; there was an increase by 25.24% between 2014/2015 and 2015/2016 which corresponds to modifying risk assessment scores to include additional criteria. The proportion of eligible patients with AF being prescribed anticoagulants also increased in the period between 2012/2013 and 2019/2020 (ITSA gradient = 1.98, p-value&amp;lt;.001, 95% confidence interval: 1.52- 2.44). Conclusion The analysis of data from different sources identified an increase in anticoagulant prescribing for patients with AF in England, which is likely to translate into health gains. However, the use of aggregate data in the analysis did not allow for detailed inspection of patient characteristics, and individual anticoagulants were not specified in the datasets. Therefore, quantitative analyses of primary care data of individual anticoagulant prescribing for different patient groups with AF are needed to further understand whether additional improvements are possible in the prevention of complications from atrial fibrillation. References (1) Adderley NJ, Ryan R, Nirantharakumar K, Marshall T. Prevalence and treatment of atrial fibrillation in UK general practice from 2000 to 2016. Heart. 2019;105(1):27-33. (2) Loo SY, Dell’Aniello S, Huiart L, Renoux C. Trends in the prescription of novel oral anticoagulants in UK primary care. British Journal of Clinical Pharmacology. 2017;83(9):2096-106.

Determining patient knowledge of direct oral anticoagulants: a questionnaire study

Abstract Introduction There has been a significant increase in the number of patients prescribed Direct Oral Anticoagulants (DOACs) (1). One of the advantages of DOACs is reduced need for monitoring compared to warfarin, however less frequent contact with healthcare professionals (HCPs) may contribute to poor patient knowledge leading to negative health consequences. Aim To determine patients’ knowledge on DOACs in the hospital and community pharmacy setting. Methods Participants were recruited from a university hospital and from a convenience sample of community pharmacies. Potential participants were identified by the pharmacist in that setting using the following criteria: age ≥18 years, adequate cognition, DOAC use ≥3 months. Following consent, the participant completed a questionnaire which consisted of participant demographics and questions from the KODOA (The Knowledge of Direct Oral Anticoagulants) questionnaire. Depending on participant preference, they either self-completed the questionnaire or provided oral answers which the researcher documented. Based on previous research (2), a target sample of 40 participants was set. Descriptive statistics were performed. Results 40 participants were recruited; the mean (SD) age was 70.2 years (10.1), with 70% of participants reporting male gender. 62.5% of participants had an indication of atrial fibrillation. Mean (SD) duration of DOAC use was 5.6 years (3.6). Most patients rated their knowledge of their DOAC as moderate (50%) or good (27.5%). The results of the KODOA are presented in the table. The average score achieved by participant was 11.55/15 (± 1.88 SD). Participants scored high in areas such as DOAC indication, frequency of dosing, side-effects, drug interactions and when to seek further help. Areas of knowledge deficits included what to do when patients have forgotten a dose or have taken too much DOAC. Conclusion One limitation of the questionnaire is that the questions are presented in a multiple-choice format and it is possible that participants may have selected the correct answer due to chance. However, overall, participants demonstrated good levels of knowledge of their DOAC therapy. This study has identified areas of knowledge deficits which could be included in patient education when HCPs are counselling patients, when starting their DOAC and continually throughout treatment. References (1) Barry, Michael. Medicines Management Programme: Oral anticoagulants for stroke prevention in non-valvular atrial fibrillation [Internet]. 2019 [cited 2021 Jul 24]. Available from: https://www.hse.ie/eng/about/who/cspd/ncps/medicines-management/oral-anticoagulants/oral-anticoagulants-for-stroke-prevention-in-non-valvular-atrial-fibrillation-march-2019.pdf (2) Metaxas C, Albert V, Stahl M, Hersberger KE, Arnet I. Development and validation of a questionnaire to self-assess patient knowledge of direct oral anticoagulants (KODOA-test). Drug Healthc Patient Saf. 2018 Jul 20;10:69–77.

Abstract 10688: The Association of Atrial Cardiomyopathy with Ischemic Stroke is Minimally Explained by Atrial Fibrillation: The Atherosclerosis Risk in Communities (aric) Study

Introduction: Atrial cardiomyopathy, characterized by abnormalities in left atrial (LA) size and function, is a risk factor for atrial fibrillation (AF) and ischemic stroke. We aimed to determine if 2D-echocardiographic (2DE) LA strain and volumetric parameters are independently associated with ischemic stroke and the extent to which AF mediates this risk in the ARIC study, a community-based cohort study. Methods: We included 4817 ARIC participants (mean age 75; 59% women; 22% Black) and who had 2DE in 2011-13. We evaluated LA volume index (maximum, minimum), LA emptying fraction (total, passive, active), LA strain (reservoir, conduit, contractile). Incident ischemic strokes (2013-2019) were physician adjudicated after review of medical records. AF was ascertained from hospitalization discharge codes and 2-week ambulatory rhythm monitoring in 2016-17. We used multivariable Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals (CI) of LA parameters for stroke and performed mediation analyses to quantify the indirect effect of AF in these associations. Results: After a median follow-up of 5.9 years, each SD increment in LA reservoir stain, LA conduit strain, LA contractile strain, total LA emptying fraction, and active LA emptying fraction was associated with a percent (95% CI) decrease in stroke risk of 27 (14-38), 19 (4-32), 17 (4-29), 19 (6-31), and 14 (1-26), respectively. Greater left atrial minimum, but not maximum volume index was associated with higher stroke risk. The proportion of these associations which was mediated by AF ranged from 3-36%. Our findings remained unchanged in sensitivity analysis excluding participants with AF and on anticoagulants. Conclusions: The associations of LA strain and volumetric parameters with stroke are minimally mediated by AF. Future research should determine whether LA strain and volumetric analysis can guide anticoagulation for stroke prevention in people independent of AF status.

Anticoagulation for Stroke Prevention after Restoration of Haemostasis with Emicizumab in Acquired Haemophilia A

Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by the development of autoantibodies inhibiting factor VIII function. It predominantly affects the elderly, who are often burdened with a considerable number of comorbidities, and can result in life-threatening bleeding. The management of AHA consists of two aspects: inhibitor eradication with an immunomodulator and bleed control with a bypassing agent. Here we present a case of AHA with a high titre inhibitor in a patient with extensive comorbidities and atrial fibrillation in whom inhibitor eradication could not be achieved within a few weeks using corticosteroids alone. Due to coronavirus disease (COVID)-19 restrictions and complications of care, emicizumab offered an effective and convenient therapy, not only sparing the need for continued and intensified inhibitor eradication, but also allowing anticoagulation for stroke prophylaxis.

Anticoagulation for Stroke Prevention after Restoration of Haemostasis with Emicizumab in Acquired Haemophilia A.

Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by the development of autoantibodies inhibiting factor VIII function. It predominantly affects the elderly, who are often burdened with a considerable number of comorbidities, and can result in life-threatening bleeding. The management of AHA consists of two aspects: inhibitor eradication with an immunomodulator and bleed control with a bypassing agent.Here we present a case of AHA with a high titre inhibitor in a patient with extensive comorbidities and atrial fibrillation in whom inhibitor eradication could not be achieved within a few weeks using corticosteroids alone. Due to coronavirus disease (COVID)-19 restrictions and complications of care, emicizumab offered an effective and convenient therapy, not only sparing the need for continued and intensified inhibitor eradication, but also allowing anticoagulation for stroke prophylaxis.LEARNING POINTSEmicizumab may offer a suitable option for bleeding prophylaxis when inhibitor eradication is not achievable with immunotolerance treatment, especially in the age of the COVID-19 pandemic when the consequences of immunosuppression can be detrimental.Bleeding prophylaxis with emicizumab may enable long-term anticoagulation in patients with acquired haemophilia A during inhibitor eradication.The prothrombotic risks of emicizumab are not yet sufficiently characterized.

Anticoagulation for stroke prevention after embolic stroke of undetermined source of presumably cardiac source: The sail to Ithaca

During the last decade, the term embolic stroke of undetermined source (ESUS) was introduced in a pursue to standardized diagnostic workup in a more targeted sub-population of cryptogenic stroke patients [1]. ESUS is comprised of several vascular and cardiac sources of emboli including atrial cardiopathy, valvular disease, patent foramen ovale (PFO) and left ventricular disease which represent the majority of the potential causes of ESUS [2,3-6].

Low and full dose apixaban in patients with atrial fibrillation and renal dysfunction: findings from a national registry

Abstract Background The use of direct oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation is robust. However, the efficacy and safety of different dosage in patients with renal dysfunction is still a clinical challenge. We aimed to evaluate the clinical characteristics and outcomes of patients treated with apixaban in its different doses. Methods A multicenter prospective cohort study, where consecutive eligible apixaban or warfarin treated patients with non-valvular atrial fibrillation and renal impairment (eGFR MDRD &amp;lt;60 ml/min/BSA) were registered. All patients were prospectively followed-up for clinical events and dosing adjustments over a mean period of 1 year. Analyses were performed according to the dose of apixaban given, with consideration to the standard indications for dose reduction. The primary outcomes were 1 year: mortality, stroke or systemic embolism, major bleeding and myocardial infarction as well as their composite occurrence. Results Among the study population (n=2140), the risk for composite outcome and for mortality were both significantly lower in the high dose apixaban group (n=491) than that of the warfarin group (n=976) and the low dose apixaban group (n=673, figure 1); Dosing analysis revealed Dosing analysis revealed that only 65% of the apixaban treated patients were appropriately dosed (figure 2), and 53% of the patients who were treated by low dose apixaban were under-dosed. Treatment with inappropriately under-dose apixaban was associated with improved survival rate and composite endpoint than treatment with appropriately low dose apixaban. Appropriately high dose apixaban compared to inappropriately over-dosed patients resulted in no significant difference. Overall, appropriately dosed apixaban treated patients (any dose) had better prognosis than matched warfarin treated patients. Conclusion Apixaban at any dose is a reasonable alternative to warfarin in patients with renal impairment, possibly associated with improved outcomes. Apixaban is still largely under-dosed in patients with renal dysfunction. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Educational grant from Pfizer Figure 1Figure 2