Stroke Prevention In Atrial Fibrillation Research Articles

Will Factor XI Inhibitors Replace Current Anticoagulants for Stroke Prevention in Atrial Fibrillation?

This review provides an overview of the factor XI (FXI) inhibitor hypothesis for the development of novel anticoagulants which may be safer to those currently used in clinical practice and describes preliminary clinical data from phase 2 dose-ranging studies of patients with atrial fibrillation. Recent data from phase 2 dose ranging studies demonstrate substantial reductions in bleeding with FXI pathway inhibition compared with currently approved anticoagulants. However, larger studies are necessary to demonstrate efficacy of FXI inhibition for stroke prevention in atrial fibrillation. FXI pathway inhibition holds great promise for revolutionizing the landscape of anticoagulation for atrial fibrillation, primarily by reducing bleeding risk; however, further data are necessary to demonstrate efficacy.

Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives.

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC.

Exploring the therapeutic utility of the factor XIa inhibitor asundexian.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Factor XIa inhibitors are a promising novel class of anticoagulants that attenuate pathological thrombosis with minimal interference with hemostasis. These effects contrast with those of conventional anticoagulants, which may exhibit adverse events of untoward bleeding precluding treatment in some patients. A variety of investigational pharmacological modalities have been developed and studied to target factor XIa. Asundexian is a small molecule inhibitor of factor XIa that has been evaluated in several clinical studies. It has been studied as an oral, once-daily medication and found to inhibit approximately 90% of factor XIa activity at doses of 20 to 50mg. Phase 2 trials have demonstrated the potential for improved safety compared to standard of care in certain treatment settings, such as in atrial fibrillation. For other indications, such as noncardioembolic stroke and acute myocardial infarction, asundexian has been used in addition to background antiplatelet therapy. In these instances, asundexian did not show a difference in the incidence of bleeding events compared to placebo. Phase 3 trials have recently been launched; however, the OCEANIC-AF trial was prematurely discontinued due to inefficacy of asundexian vs apixaban for stroke prevention in atrial fibrillation. Another phase 3 trial, OCEANIC-AFINA, is planned to compare asundexian to placebo in patients with atrial fibrillation at high risk for stroke who are deemed ineligible for anticoagulation.

Uncovering the Role of Direct Oral Anticoagulants in Stroke Prevention for Atrial Fibrillation: A Review of the Literature

Uncovering the Role of Direct Oral Anticoagulants in Stroke Prevention for Atrial Fibrillation: A Review of the Literature

Direct oral anticoagulants versus vitamin K antagonists as stroke prevention in atrial fibrillation after cardiac surgery: a systematic review and meta-analysis

Abstract Background Cardiothoracic surgery guidelines advocate the use of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) in the first days to months after major cardiac surgery. No recommendations on choice of anticoagulant in the first months after cardiac surgery have been issued since 2008, before the use of direct oral anticoagulants (DOACs). The basis for this is a lack of data on the safety and efficacy of DOACs after cardiac surgery. Purpose To systematically assess and meta-analyze the existing evidence on the effect of DOACs compared with VKAs on efficacy and safety after cardic surgery. We hypothesized that DOACs are non-inferior to VKAs in the setting of AF after cardiac surgery. Methods We searched Ovid MEDLINE, Ovid EMBASE, the Cochrane Central Register of Controlled trials and Clinicaltrials.gov from inception till 20 June 2023 and screened references in relevant reviews as grey literature search. Observational studies and randomized controlled trials comparing DOACs with VKAs for stroke prevention in patients with (postoperative) atrial fibrillation after cardiac surgery were included, focusing on procedures through thoracoscopy or thoracotomy. Outcomes of interest included thromboembolic events, all-cause stroke, major bleeding and mortality up to 6 months after cardiac surgery and admission duration. A random effects model was used to determine pooled treatment effects. The level of evidence was rated following the GRADE recommendations. Results We identified 4,146 records of which ten were included, together reporting on > 30,000 patients. There were no significant differences in thromboembolic events (OR 0.98; 95% CI 0.61-1.58; I^2 0%; GRADE: very low), all-cause stroke (OR 1.14; 95% CI 0.51-2.54; I^2 0%; GRADE: very low), major bleeding (OR 0.91; 95% CI 0.51-1.62; I^2 53%; GRADE: very low), all-cause mortality (OR 1.00; 95% CI 0.73-1.37; I^2 0%; GRADE: low), admission duration (MD -0.33; 95% CI -1.16 – 0.49; I^2 0%; GRADE: very low) between DOACs and VKAs in the first 6 months after cardiac surgery. Conclusion Efficacy and safety of DOACs as stroke prevention in AF following cardiac surgery were similar to that of VKAs in ten studies comprising more than 30,000 patients. Based on the existing literature, there is insufficient evidence to recommend one class of oral anticoagulants over another in the first months after cardiac surgery.Forest plot of primary outcomes

Acute haemodynamic changes during left atrial appendage closure

Abstract Purpose Left atrial appendage closure (LAAC) presents an alternative treatment for stroke prevention in atrial fibrillation (AF) in patients with contraindication for long-term anticoagulation. However, even in patients in AF, left atrial appendage plays an important role in reservoir function of left atrium. The purpose of this study was to assess acute hemodynamic effects during LAAC. Methods Consecutive patients indicated for LAAC from January 2022 to October 2023 were enrolled. The invasive hemodynamic measurements were done at the beginning of the procedure after transseptal puncture, and at the end from the procedure after device deployment. Following parameters were measured: systolic, and diastolic blood pressure, and pressure in left atrium (LA), all measurements were done at rest and after 3 minute isometric exercise (handgrip). Results Thirty-two patients were included (age 76,2+7,1 yrs, 22 (69%) males, 23 (72%) permanent AF, left ventricular ejection fraction 52+11,8%). No patients experienced moderate/severe mitral insufficiency, the saline intake during procedure was 738 ml. Isometric exercise significantly increased the LA pressure: the LA pressures (rest/exercise) were 13.7+6.7 mmHg/16.7+8.8 mmHg (p=0.003) at the beginning of the procedure, and 17.0+7.3mmHg/20.0+7.3 mmHg (p=0.005) after device deployment. The LA pressure obtained after device deployment (both rest/exercise) were significantly higher compared to values obtained at the beginning of the procedure. (p=0.003). Conclusions LAAC is associated acute increase of both rest and exercise LA pressure. Whether its acute negative effect remains over time needs further investigation.

One-year effectiveness and safety outcomes of edoxaban treatment in Chinese patients with atrial fibrillation: First snapshot of more than 4,800 patients from the ETNA-AF-China study

Abstract Background Direct oral anticoagulants (DOACs) have become the first-line therapy for ischaemic stroke prevention in atrial fibrillation (AF) patients. Data on the effectiveness and safety of single DOAC in large Chinese populations are scarce. Purpose We firstly present the one-year outcome data of edoxaban treatment in 5001 Chinese AF patients. Methods This is a multi-centre, prospective, observational study, ETNA-AF-China, conducted in 89 centres from four economic regions in Mainland of China with a follow-up of two years. Primary endpoint of safety [bleeding events including intracranial hemorrhage (ICH), all-cause and cardiovascular (CV) mortality] and efficacy endpoints [stroke, systemic embolic events (SEE), transient ischemic attack (TIA)] were adjudicated. Annualised event rates and Kaplan­Meier (KM) survival curves are given. Results A total of 4822 patients (57.1% male) using edoxaban (60 mg OD: n=2614, 30 mg OD: n=2208) who completed one-year follow-up were included in the full analysis set. The mean (SD) age of the overall patient population was 70.3 (9.5) years, CHA2DS2-VASc and HAS-BLED scores were 2.9 (1.4), 1.7 (1.0), with creatinine clearance (CrCl) of 71.2 (27.7) mL/min. Patients receiving 30 mg OD edoxaban at baseline were older (73.4 vs 67.7 years), with higher CHA2DS2-VASc score (3.3 vs 2.6), larger percentage of frail (9.9% vs 3.4%), and higher renal impairment (defined as CrCl ≤80 mL/min, 70.3% vs 42.9%). Annualised rates for all-cause and cardiovascular death in the overall population were very low with 2.22%/year and 0.41%/year, respectively. (Figure 1) The death rates were nearly three times lower in those receiving standard dose (60 mg) than reduction dose (30 mg) of edoxaban. Annualised event rates for all stroke/SEE (1.03%/year) and ischemic stroke (0.60%/year) were similar between two dose groups. Overall, annualised rates for major bleeding (1.03%/year), ICH (0.18%/year), major gastrointestinal (GI) bleeding (0.48%/year) events were relatively low, and those on 60 mg dose experienced less above bleeding events. Cumulative survival analysis demonstrated a slow increase in time-to-first event curve of all-cause death; and from baseline to 1-year follow-up, significant lower events of all-cause death (log-rank p<0.001), major bleeding (p=0.002) in 60 mg vs 30 mg edoxaban groups. (Figure 2). Conclusion Low incidences of major bleeding, notably ICH, major GI bleeding, and CV death were observed in unselected 4822 patients with AF during 1-year of edoxaban treatment. These findings confirm the effectiveness and safety of routine edoxaban use in China, consistent with other countries, and reinforce the results of the ENGAGE AF-TIMI 48 trial.Figure 1Figure 2

Assessment of Days Alive Out of Hospital as a Possible End Point in Trials of Stroke Prevention for Atrial Fibrillation: A ROCKET AF Analysis.

Days alive out of hospital (DAOH) is an objective and patient-centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double-blind, double-dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator-reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (P=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P=0.88). DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.

Stroke prevention in atrial fibrillation : The ARTESIA study in the light of current knowledge

Stroke prevention in atrial fibrillation : The ARTESIA study in the light of current knowledge

Safety of DOACs in patients with Child-Pugh Class C cirrhosis and trial fibrillation.

Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child-Pugh class C cirrhosis (CPC). We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM). Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3-year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs. Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.

Safety and efficacy of apixaban dosage for stroke prevention in atrial fibrillation with acute kidney injury populations in a tertiary care hospital

Safety and efficacy of apixaban dosage for stroke prevention in atrial fibrillation with acute kidney injury populations in a tertiary care hospital

Acute severe renal failure in a patient receiving apixaban: a case report

Because there is little clinical experience with apixaban in patients with severe renal impairment and non-valvular atrial fibrillation, the European Medicines Agency does not advise using it to prevent strokes in these patients. However, only a small number of pharmacokinetic and pharmacodynamic investigations showed how crucially different elimination pathways contribute to the clearance of apixaban. A 74-year-old male patient who was receiving apixaban treatment for stroke prevention in atrial fibrillation was referred to our hospital because of acute severe renal failure brought on by dehydration and abnormally elevated apixaban plasma levels. The patient was treated only with intravenous fluid therapy; serum creatinine recovered slowly over the course of six days, but plasma apixaban levels recovered quickly. No bleeding events have been recorded. Our experience demonstrates the safety profile of apixaban in cases of severe renal failure, but it also emphasizes the need for more research to confirm this evidence.

Antithrombotic therapy in acute coronary syndrome

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. In patients with acute coronary syndromes, balancing the reduction in cardiovascular events and increase in major bleeding during treatment with more potent P2Y12 inhibitors such as prasugrel and ticagrelor is still an issue. A special focus is on patients already treated with oral anticoagulants for stroke prevention in atrial fibrillation who require additional platelet inhibition following coronary stenting. This article summarizes the major recommendations given in the most recent Guideline for "Acute Coronary Syndromes" published by the European Society of Cardiology (ESC). The recommendations finally address strategies to reduce an increased bleeding risk based on clinical predictors.

Drug-Drug Interactions of FXI Inhibitors: Clinical Relevance.

Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus, they have very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo drug-drug interactions (DDIs) with other concomitant therapies. Although only little clinical evidence is available, it is possible to predict clinically relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters, and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDIs of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa.

Comparative Safety and Effectiveness of Reduced Doses of Direct Acting Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation

This Nordic observational cohort study aims to assess the effectiveness and safety of reduced-dose direct-acting oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared to standard warfarin for stroke prevention in nonvalvular atrial fibrillation. The study, utilizing nationwide administrative databases from Denmark, Sweden, Norway, and Finland, spanned from January 1, 2011 to December 31, 2018 (2017 for Sweden). The cohort included 26,883 patients initiating reduced-dose DOACs and 108,014 comparable warfarin patients. Effectiveness was measured by the composite endpoint of ischemic stroke and systemic embolism, while safety was assessed through intracranial hemorrhage. The meta-analysis across countries revealed similar or lower incidences of ischemic stroke and systemic embolism in patients on reduced-dose DOACs compared to standard warfarin (rivaroxaban: HR 0.93, dabigatran: HR 0.88, apixaban: HR 0.79). Incidences within warfarin groups ranged from 2.16 to 3.71 per 100 person-years, comparable to DOAC recipients. Intracranial hemorrhage rates were generally low, ranging from 0.16 to 1.85 per 100 person-years. In comparison with warfarin patients, meta-analyses yielded HRs for rivaroxaban (1.41), dabigatran (0.35), and apixaban (0.72). In this study, atrial fibrillation patients initiating reduced-dose rivaroxaban and dabigatran exhibited incidences of ischemic stroke and systemic embolism similar to warfarin, and for apixaban, even lower. Rates of intracranial hemorrhage were comparable to or lower for patients on DOACs compared to warfarin.

FactorXI Inhibitors: A New Horizon in Anticoagulation Therapy.

Anticoagulation therapy has undergone significant evolution, marked by the emergence of direct oral anticoagulants with distinct advantages. Despite these advancements, challenges persist in managing residual thrombotic and bleeding risks, particularly among vulnerable populations. The pursuit of alternative drugs has honed in on factorXI/XIa inhibitors. This comprehensive review delves into several key aspects regarding this new target: (i) the role of factorXI in the coagulation cascade; (ii) the genetic evidence and pathophysiologic rationale supporting factorXI inhibition as a therapeutic target; (iii) an exploration of the various types of factorXI/XIa inhibitors currently under investigation; (iv) potential applications of these medications, spanning thromboprophylaxis after orthopedic surgery, stroke prevention in atrial fibrillation, secondary prevention after acute coronary syndrome, non-cardioembolic stroke, thromboprophylaxis after foreign material implantation, end-stage renal disease, and patients with cancer; and (v) an overview of ongoing studies, recent findings, and the future trajectory of research into these drugs.

Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Stroke prevention in atrial fibrillation with chronic kidney disease: a delicate balance of efficacy and safety considerations

Stroke prevention in atrial fibrillation with chronic kidney disease: a delicate balance of efficacy and safety considerations

Abstract 66: Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation: Primary Results of the START Trial

Introduction: Clinical practice guidelines recommend initiation of anticoagulation within 2 weeks after stroke due to atrial fibrillation (AF). It is unknown whether there is an optimal day within that 14-day period that balances the risks of recurrent embolic vs serious hemorrhagic events. Methodology: The Lone Start Stroke START trial is a pragmatic, prospective, multi-center, response-adaptive randomized Phase 2 study of 200 patients prescribed a direct oral anticoagulant (DOAC) for secondary prevention of stroke due to AF. Patients were randomized into one of 4 Arms: Day 3-4 from stroke onset, Day 6, Day 10, or Day 14. The primary outcome was an ischemic (stroke or systemic embolus) or hemorrhagic (ICH or major systemic hemorrhage) event observed within 30 days from the index stroke time of onset. Posterior probabilities that each arm was the best were calculated at predefined intervals and randomization allocations were adjusted to favor the Arms with higher probabilities. Results: The median age was 75 (IQR 65-81), median NIHSS at presentation was 7 (IQR 4-14), median lesion diameter was 3.1 cm (IQR 2.0-4.4) at the time of randomization. The sample was 50% female, 17.5% non-white, and 16.5% Hispanic. Apixaban was the prescribed DOAC in 89% of the patients. No ischemic events were observed for Arm 1, and no hemorrhage events were observed for Arm 4. Arm 1 (3-4 days) had a posterior 41.1% probability of being the best among the four, with probabilities of 26.4%, 17.1%, and 15.4 % respectively, for the other arms. Response adapted randomization was feasible and favored the earlier two arms. Expected event rates for each arm are presented in the Table. The timing and severity of the outcome events will be presented at the conference. Conclusion: Although the START trial did not identify a clearly superior day to initiate DOAC for secondary stroke prevention in AF, the evidence suggests that initiating DOAC early is better than at later times within the first 2 weeks after stroke onset.

Consensus on Stroke Prevention in Atrial Fibrillation and Utilization of NOACs in the Real-World Setting in India

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. Prevention of stroke and systemic thromboembolism remainsthe cornerstone of the management of AF. Even today, there are unresolved knowledge gaps in AF pathophysiology, screeningand therapeutic strategies and stroke prevention. The modified DELPHI method was used to develop the best practicerecommendations for the management of AF in a real-world setting with the participation of 500 cardiologists across India.The experts concurred that the decision to initiate antithrombotic treatment in patients with transient AF could be based onthe duration of transient AF, the co-existence of the risk factor for stroke and echocardiographic abnormalities impact thedecision. The decision to initiate anticoagulant therapy in device-detected atrial high-rate episodes (AHRE) can be decidedbased on the duration of AHRE, the burden of AHRE and the individual’s risk of stroke and thromboembolism. The benefitof early anticoagulation should be balanced with the risk of intracerebral hemorrhage (ICH), especially in elderly patientsand in severe strokes. Apixaban is the preferred drug in patients with concomitant ischemic heart disease (IHD), patientswith a history of gastrointestinal (GI) bleeding, patients with underlying malignancy, elderly patients with AF, patients withcomorbid diseases and patients with hepatic disease or renal disease. Apixaban was considered to be an affordable noveloral anticoagulant (NOAC) for Indian patients for primary and secondary stroke prophylaxis in AF patients