key: cord-0709232-pisnhvhm
authors: Chao, Tze‐Fan; Joung, Boyoung; Takahashi, Yoshihide; Lim, Toon Wei; Choi, Eue‐Keun; Chan, Yi‐Hsin; Guo, Yutao; Sriratanasathavorn, Charn; Oh, Seil; Okumura, Ken; Lip, Gregory Y. H.
title: 2021 Focused update of the 2017 consensus guidelines of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation
date: 2021-11-13
journal: J Arrhythm
DOI: 10.1002/joa3.12652
sha: d829af38efc01b100c575ef00b767e585e7ccf89
doc_id: 709232
cord_uid: pisnhvhm

The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical guidance for cardiologists, neurologists, geriatricians, and general practitioners in Asia‐Pacific region. In these years, many important new data regarding stroke prevention in AF were reported. The Practice Guidelines subcommittee members comprehensively reviewed updated information on stroke prevention in AF, and summarized them in this 2021 focused update of the 2017 consensus guidelines of the APHRS on stroke prevention in AF. We highlighted and focused on several issues, including the importance of AF Better Care (ABC) pathway, the advantages of non–vitamin K antagonist oral anticoagulants (NOACs) for Asians, the considerations of use of NOACs for Asian patients with AF with single 1 stroke risk factor beyond gender, the role of lifestyle factors on stroke risk, the use of oral anticoagulants during the “coronavirus disease 2019” (COVID‐19) pandemic, etc. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician's decision remains the most important factor in the management of AF.

Atrial fibrillation (AF) is a global problem, with an increasing incidence and prevalence with an ageing population. 1 Although the prevalence of AF appears to be greater in Western countries compared with Asian countries, numerically the population with AF in Asia is substantially greater than in Europe or North America.

In a recent meta-analysis of 58 articles from eight countries in Asia, the community-and hospital-based AF prevalence ranged from 0.37% to 3.56% and 2.8% to 15.8%, respectively. 2 In the year 2020, the prevalence rates of AF are around 1.5% in Taiwan and 2.1% in South Korea. 3, 4 Similar to western countries, the prevalence rates of AF will continuously increase in the following decades, which are projected to be 4.0% in Taiwan and 5.4% in South Korea in the year 2050 ( Figure 1 ). 3, 4 Notably, the stroke risk of newly diagnosed patients with AF reprented by CHA 2 DS 2 -VASc score of each year gradually in- For Asian patients with AF, the annual risk of ischemic stroke is around 3.0% (1.60%-4.95%) based on the pooled analysis of eight studies. 2 In the Taiwan nonanticoagulated AF cohort, the annual risk of ischemic stroke was 3.4% which was 3.34-fold higher compared with patients without AF. 3 Importantly, the 1-year risk of ischemic stroke after newly diagnosed AF was similar from the year 2000 (4.45%) to 2010 (3.95%), 3 and gradually decreased in the era of nonvitamin K antagonist oral anticoagulants (NOACs). 5 The observed reduction in stroke risk may be contributed to the increasing initiation rates of oral anticoagulants (OACs) in newly diagnosed patients with AF which signifcantly increased from 13.6% to 35.6%, contemporaneous with the introduction of NOACs ( Figure 2 ). 5 A similar trend was also reported in Korean AF cohort. 4, 6, 7 In the study by Lee et al., the increasing use of OACs (especially with the introduction of NOACs) had led to a reduction in ischaemic stroke-related emergency department visits with no appreciable rise in serious bleeds (Figure 3) . 7 The impact of AF on healthcare costs reflects the increased risk of mortality and morbidity of AF from stroke, heart failure and hospitalisations, which is projected to increase over the next decades in Asia. 8 Data from UK suggest that AF confers a major impact on healthcare costs, accounting for approx 0.9%-1.6% of NHS expenditure, mostly from primary admissions. 9 The total cost of AF care was equivalent to 0.78% of the Korean NHIS total expenditure in 2015. 10 The stroke and mortality risks of AF are often in association with multiple cardiovascular and noncardiovascular comorbidities, that often occur in multimorbidity clusters, that would impact on prognosis. 11 The increasing use of OACs (particularly the NOACs) would result in a major reduction in stroke and cardiovascular events, but a more integrated approach to AF management is needed to address the healthcare burden and risks associated with AF. • "A" Avoid stroke with anticoagulation, that is, well-managed warfarin (time in therapeutical range [TTR] > 65%-70%) or NOAC;

• "B" Better symptom management with patient-centred, symptomdirected decisions for rate or rhythm control; and

• "C" Cardiovascular risk and comorbidity management (BP control, heart failure, cardiac ischemia, sleep apnea, etc.) as well as lifestyle changes (obesity reduction, regular exercise, reducing alcohol/stimulants, psychological morbidity, etc.).

With the focus on patient-centered management, explanation using the simple ABC concept can also lead to improved understanding and disease awareness amongst patients, better knowledge about their condition and the priorities of management. Different healthcare professionals managing the patient with AF can also discuss the management based on the A, B, and C pillars of the ABC pathway.

The beneficial effect on clinical outcomes of ABC pathway adherent management, against non-ABC adherent care, have been consistently shown in different settings: post hoc analyses of adjudicated outcomes from clinical trial cohorts, 13, 14 prospective population cohorts globally, [15] [16] [17] and a prospective cluster randomized trial published in 2020. 18 These studies (including some from Asia [ Figure 5 ]) 17 have been recently reviewed. 19 A systematic review and meta-analysis showed a lower risk of all-cause death (OR: 0.42, 95% CI 0.31-0.56), cardiovascular death (OR: 0.37, 95% CI 0.23-0.58), stroke (OR: 0.55, 95% CI 0.37-0.82), and major bleeding (OR: 0.69, 95% CI 0.51-0.94), with management adherent to the ABC pathway compared with noncompliance ( Figure 6 ). 20 A prospective cluster randomized trial conducted in China (mobile Health for improving screening and integrated care in AF, mAFA-II trial) 18 showed that patients allocated to ABC pathway intervention (using mHealth technology) were associated with lower rates of the composite outcome of "ischemic stroke/systemic thromboembolism, death, and rehospitalization" compared with usual care (1.9% vs. 6.0%; F I G U R E 3 Temporal trends of incidence of ED visits from AF-related complications and OAC prescription rate. The figure was redraw and modified from the paper by Lee The long-term extension cohort of mAFA-II showed that the beneficial impact of ABC pathway on clinical outcomes were maintained >1 year with high adherence (>70%) and persistence (>90%) of the intervention. 22 A healthcare costs analysis has shown major cost savings by ABC pathway adherent treatment compared with non-ABC adherence. 23 Other population-based studies show that ABC pathway adherence was associated with a reduction in dementia risk, 24 and improved outcomes in patients with AF with high frailty risk. 25 The integrated care AF pathway approach ("simple as ABC…") has been adopted and promoted in the Primary Care Clinical Pathway for AF Detection & Management; https://bit.ly/2FhrwXQ). The key feedback from multidisciplinary colleagues is the reassurance felt that a holistic approach to management can be streamlined across primary-secondary care, not being regarded as complex but is "simple as ABC…" The ABC pathway is now included within guidelines from American College of Chest Physicians, 26 the Korean national AF guidelines, 27 and the 2020 European AF guidelines, 28 and is, therefore, recommended in this guideline as part of the holistic approach to AF management.

1. An integrated care or holistic management approach, based on the ABC (AF Better Care) pathway is recommended to improve outcome in the Asian AF population:

• "A" Avoid stroke with Anticoagulation, that is, well-managed warfarin (TTR > 65%-70%) or NOAC;

• "B" Better symptom management with patient-centred, symptom-directed decisions for rate or rhythm control; and

• "C" Cardiovascular risk and comorbidity management (BP control, heart failure, cardiac ischemia, sleep apnea, etc.) as well as lifestyle changes (obesity reduction, regular exercise, reducing alcohol/stimulants, psychological morbidity, etc.).

We highly emphasize the importance and recommend the use of ABC pathway for AF patient care. In this APHRS consensus document focused update, we will particularly focus on the "A" domain and update data for stroke prevention in AF, but would highlight the importance of full compliance with the ABC pathway to improve outcomes in patients with AF.

In our 2017 consensus document, we recommended the use of the CHA 2 DS 2 -VASc score for stroke risk assessment for Asian patients with AF. 29 In this focused update, we still recommend the use of the CHA 2 DS 2 -VASc score as the stroke risk prediction scheme since it has been well validated in Asian AF population. [30] [31] [32] [33] [34] [35] We recognise that there are more complicated clinical risk scores incorporating more clinical variables (e.g., Qstroke, GARFIELD score), 36 complex methodology (e.g., machine-learning approaches), 37 or the addition of biomarkers such as proteinuria (e.g., ATRIA-stroke) or other blood-based biomarkers (e.g., ABC-stroke), but these are not recommended in this focused update, given the importance to balance simplicity and practicality for daily clinical use against marginal improvements (at least statistically) in risk prediction. 38, 39 Many biomarkers are also nonspecific, indicative of a sick patient or a sick heart, being predictive of adverse outcomes other than what they were proposed. 40, 41 We should acknowledge that all clinical risk stratification scores are simplifications to aid decision-making and to recognise the limitations of such scores. For example, there are many stroke risk factors, 42 and only the more common and validated ones have been included into risk scores, such as the CHA 2 DS 2 -VASc score.

The impact of individual stroke risk factors is not uniform, and for a single CHA 2 DS 2 -VASc risk factor in those aged <65, and assuming an ischaemic stroke risk treatment threshold of ≥1%/year with NOACs, the tipping point with heart failure as a single risk was F I G U R E 6 Impacts of adherence to the ABC pathway on clinical outcomes in patients with AF. ABC, Atrial fibrillation Better Care; CI, confidence interval; OR, odds ratio. The figure was redraw and modified from the paper by Romiti et al 20 age 35 years, whereas for patients with hypertension, diabetes mellitus, and vascular diseases the age thresholds for treatment were 50 years, 50 years, and 55 years, respectively. 43, 44 Not all CHA 2 DS 2 -VASc risk factors carry equal weight, as event rates would be dependent on population studied (e.g., hospitalised vs. community), study type (trial vs. real world), ethnicity, and study methodology. 45 In addition, female gender is a stroke risk modifier rather than a risk factor, with an age dependency to risk; however, ignoring the female gender criterion may underestimate the stroke risks in female patients with ≥1 non gender stroke risks and lead to undertreatment of female patients. 46 In addition, stroke risk is not static, given that ageing and incident comorbidities would increase risk and the dynamic nature of stroke risk in AF would result in increments of their CHA 2 DS 2 -VASc scores. 47 For example, in a study from Taiwan which enrolled 31,039 patients with AF without comorbidities of the CHA 2 DS 2 -VASc score except for age and gender at baseline, the mean CHA 2 DS 2 -VASc scores increased from 1.29 to 2.31 during a follow-up of 171,956 person-years. 48 About 16.1% of men and 16.2% of women who were initially at low risk (score 0 for males or 1 for females) would have a CHA 2 DS 2 -VASc score of at least 1 (men) or 2 (women) at 1 year after incident AF (Figure 7 ). 49 Similar observations were reported in the study by Yoon et al. using the Korean nationwide AF registry. 50 Both the follow-up CHA 2 DS 2 -VASc score and change in stroke risk ("delta-CHA 2 DS 2 -VASc" score, i.e., the difference between the baseline and follow-up scores) had betteer predictive value for ischaemic stroke compared with the baseline CHA 2 DS 2 -VASc score. 48, 51 Almost 90% of initailly low-risk patients with AF had a delta CHA 2 DS 2 -VASc score ≥1 before the occurrence of ischemic stroke. 48 For initially low-risk (CHA 2 DS 2 -VASc score 0 for males or 1 for females) nonanticogulated patients with AF, the use of OACs once their CHA 2 DS 2 -VASc scores increased was associated with a lower risk of clinical events. 52 In summary, regular re-assessment of stroke risk of patients with AF and the timely prescriptions of OACs once the stroke risk of patients increased is important, given the increase in stroke risks with age and new comorbidities.

Data regarding the reasonable timing interval at which the stroke risk of patients with AF should be reassessed are limited. In the study by Chao et al. which studied 14,606 patients with AF with a baseline CHA 2 DS 2 -VASc score of 0 (males) or 1 (females), 6188 patients acquired new risk factors with the acquisition of 1 or more new comorbidities approx 4-5 months after their initial AF diagnosis. The most common incident comorbidity was hypertension, followed by heart failure, diabetes mellitus, and vascular disease;

indeed, the onset of new comorbidities would depend on the type of comorbidity. Importantly, 596 of these original experienced ischemic stroke, and the duration from the acquirement of incident comorbidities to the occurrence of ischemic stroke was an average of 4.4 months for 90% of the patients. 52 Based on these data, 4 months may be a reasonable timing interval at which the stroke risk of patients with AF should be reassessed. However, the optimal timing interval may be different in different healthcare systems.

1. The CHA 2 DS 2 -VASc score is recommended for stroke risk assessment for Asian patients with AF.

2. The stroke risk of patients with AF is not static and should be reassessed regularly (at least annually and every 4 months if possible). F I G U R E 7 Cumulative incidences of increment of CHA 2 DS 2 -VASc score to ≥1 (males) or ≥2 (females). AF, atrial fibrillation. The figure was redraw, and data were adapted from the papers by Chang et al. and Chao et al 47, 49 3. In patients with AF initially at low risk of stroke (CHA 2 DS 2 -VASc = 0 in men or 1 in women), a reassessment of stroke risk should ideally be made at 4 months after the index evaluation and OACs should be prescribed timely once their CHA 2 DS 2 -VASc scores increase.

As with the 2017 consensus document, the HAS-BLED score is recommended for bleeding risk assessment for Asian patients with AF in this focused update. In a PCORI systematic review and evidence appraisal, the HAS-BLED score was found to be the best score for bleeding risk prediction. 53 The HAS-BLED score is also validated for the prediction of intracranial bleeding, unlike other scores. In a recent analysis of ESC-EHRA EORP-AF General Long-Term Registry, the HAS-BLED score still performed better than ORBIT score in the contemporary cohort of patients with AF treated with NOACs. 54 Like the CHA 2 DS 2 -VASc score, bleeding risks scores are simplifications, based on the more common and validated bleeding risk factors. 55 Indeed, individual components of the risk scores such as HAS-BLED do not carry equal weight, for example, uncontrolled BP is associated with a higher risk of intracranial bleeding (and other cardiovascular complications, including ischaemic stroke, mortality, and heart failure) compared with controlled BP (120-129/<80 mmHg). 56 The HAS-BLED score has been well validated in Asian cohorts, outperforming other bleeding risk scores (e.g., ATRIA, ORBIT, HEMORRH2AGES) and an approach simply focused only on modifiable bleeding risks. 57 Bleeding risk is also not static and may change among patients with AF initially having a low HAS-BLED score (≤2). 58 In a previous study from Taiwan, the accuracy of the follow-up or delta HAS-BLED score in the prediction of major bleeding was significantly higher than that of the baseline HAS-BLED score;

importantly, the bleeding risk is higher within several months after the increment of the HAS-BLED score. 58 The HAS-BLED score has also been validated in patients with AF who are taking no antithrombotic therapy (e.g., when first diagnosed), antiplatelet therapy (e.g., when AF develops in patients on aspirin for vascular disease) and on anticoagulation (whether warfarin or NOACs). Thus, the HAS-BLED score would be applicable at all steps of the patient pathway.

Appropriate use of the HAS-BLED score has been tested in the mAFA-II trial, 18 which was a prospective cluster randomised trial, which compared a mHealth integrated care approach against usual care. The intervention arm used the HAS-BLED to identify and mitigate modifiable bleeding risks, and schedule high bleeding risk patients for regular review and follow-up; this led to lower major bleeding rates at one year and an increase in OAC use. 21 In contrast, the usual care arm has higher major bleeding and a decline in OAC use ( Figure 8) . A recent study from Taiwan further demonstrated that for anticoagulated patients with AF with a baseline HAS-BLED score of 0-2 which increased to ≥3, the continuation of OACs was associated with better clinical outcomes. 59 A high HAS-BLED score is not a reason to withhold OACs even among patients with AF with one nongender risk factor (CHA 2 DS 2 -VASc score 1 for males and 2 for females) but a high bleeding risk (HAS-BLED score ≥3) as the use of OACs was still associated with a lower risk of composite adverse events of ischemic stroke, intracranial hemorrhage (ICH) or mortality (adjust hazard ratio [aHR] 0.781) in this population. 60 In summary, bleeding risk reassessment is important for anticoagulated patients with AF, and the appropriate and responsible use of bleeding risk scoress such as the HAS-BLED score is to identify and mitigate modifiable bleeding risk factors and to identify high bleeding risk patients for early review and follow-up.

1. For bleeding risk assessment, a formal structured risk-scorebased bleeding risk assessment with the HAS-BLED score is recommended to help identify nonmodifiable and address modifiable bleeding risk factors and to identify patients potentially at high bleeding risk for early and more frequent clinical review and follow-up.

2. The bleeding risk of patients with AF is not static which should be re-assessed regularly, and the identified modifiable bleeding risk factors should be corrected. 

Given the limitations of all stroke risk scores in predicting high stroke risk in patients with AF and the dynamic nature of stroke risk, the artificial categorisation into low-, moderate-, and high-risk strata is discouraged. Thus, stroke prevention (which is oral anticoagulation) should be the default strategy, unless patients are at low risk (defined as CHA 2 DS 2 VASc score 0 in males or 1 in females). Figure 10 shows our recommendations, which were consistent to other guidelines. 26 Patients with AF and significant valvular heart disease (VHD) (previously referred to as "valvular AF") defined as prosthetic mechanical heart valves or moderate-severe mitral stenosis, should be offered warfarin, when oral anticoagulation is recommended. 61 Indeed, NOACs are contraindicated in such patients.

In other patients without significant VHD (so-called "nonvalvular AF"), the first step (Step 1) is to identify low-risk patients (CHA 2 DS 2 VASc score 0 in males or 1 in females) where no antithrombotic therapy is recommended. The next step (Step 2) is to offer stroke prevention (i.e., oral anticoagulation) to patients with ≥1 nongender stroke risk factors (i.e., CHA 2 DS 2 VASc score ≥1 in males or ≥2 in females). Most of the randomised trials included patients with ≥2 nongender stroke risk factors, but some clinical trials with warfarin (ACTIVE-W), dabigatran and apixaban [RE-LY, ARISTOTLE, AVERROES] included patients with a single nongender stroke risk factor. [62] [63] [64] The simple classification of the recommendation as "class IIa" or "class IIb" may be too simplistic regarding this issue, and a more F I G U R E 9 Stroke and bleeding risk assessment in AF. AF, atrial fibrillation; BP, blood pressure; INR, international normalized ratio; NOAC, non-vitamin K antagonist oral anticoagulant; NSAIDs, nonsteroidal anti-inflammatory drugs; OACs, oral anticoagulants; TTR, time in therapeutic range. The figure was redraw and modified from the paper by Chang et al 47 delicate approach for these patients is required. 65 Because the risk of stroke of each CHA 2 DS 2 -VASc risk component was not the same and age is an important driver, patients' ages and the comorbidities, which contribute to the score 1 for males or 2 for females could be considered when making management decisions about the use of OACs or not. 43,66-69 as summarized in Figure 11 . As OAC is being started, bleeding risk assessment is recommended, using the HAS-BLED score to identify and mitigate modifiable bleeding risks, and to identify high bleeding risk patients for early review and follow-up.

Step 3 is to make the choice of OAC. We recommend the use of NOACs in preference to warfarin for stroke prevention. If NOACs are used, the recommended label dosing is important, given that the best outcomes are with label-adherent prescribing. [70] [71] [72] [73] [74] [75] Apart from guideline-directed anticoagulation prescribing, adherence, and persistence with therapy are important. [76] [77] [78] If warfarin is considered, we recommend a target INR 2.0-3.0 with an average TTR ≥65% (ideally ≥70%). We do not recommend low intensity anticoagulation or lower target INRs, given the higher risk of thromboembolism although bleeding risk is lower. 79 Of note, a "one-off" INR reading gives no indication of the quality of anticoagulation control, and many serious bleeds occur when the INR is between 2.0 and 3.0. 80 A high TTR is associated with low rates of stroke and bleeding, 81 but many factors influence the quality of anticoagulation control. The more common and validated factors associated with poor labile INRs have been used to formulate clinical risk scores such as the SAMe-TT 2 R 2 scores. A high SAMe-TT 2 R 2 score (>2) is associated with a likelihood of poor TTR, and such patients should be flagged up for more attention to ensure good quality anticoagulation (e.g., education and counselling, more frequent INR checks) or to reconsider the decision to prescribe NOACs (if suitable). 82-86

1. In patients with AF with mechanical heart valves or moderateto-severe mitral stenosis, warfarin is recommended.

2. For stroke prevention in patients with AF without significant VHD (i.e., mechanical heart valves or moderate-to-severe mitral stenosis; so-called "valvular AF") who are eligible for OAC, 4. For stroke risk assessment, a risk-factor-based approach is recommended, using the CHA 2 DS 2 -VASc stroke risk score to initially identify patients at "low stroke risk" (CHA 2 DS 2 -VASc = 0 in men or 1 in women) who should not be offered antithrombotic therapy.

In patients with AF with CHA 2 DS 2 -VASc score ≥2 in men or ≥3 in women, OAC is recommended for stroke prevention. 6 . In patients with AF with a CHA 2 DS 2 -VASc score of 1 in men or 2 in women, OAC should be considered for stroke prevention.

Different age thresholds for different comorbidities may help guide NOACs use (e.g., age 35 years for heart failure, 50 years for hypertension or diabetes mellitus and 55 for vascular diseases). 

When OAC is being considered, NOACs are the preferred option for stroke prevention in AF because the benefits of NOAC on efficacy and safety compared with the VKAs are more profound in Asian than non-Asian population. 87 In some settings, the use of VKA is still needed because of the high cost of NOACs or in patients with specific indications including moderate to severe mitral stenosis and mechanical heart valves. Maintenance of a high TTR has been shown to reduce the risk

Considerations about the use of NOACs for Asian patients with AF with a CHA 2 DS 2 -VASc score of 1 (males) or 2 (females). AF, atrial fibrillation; NOAC, non-vitamin K antagonist oral anticoagulant of ischemic and bleeding events and should be the primary goal in the treatment of these patients independent of the type management approach. Conversely, a change in the approach to these patients needs to be considered if a low TTR is consistently observed.

For the optimal management of VKA therapy, INR of 2.0-3.0 is recommended. However, there is some debate about optimal INR in Asian patients with nonvalvular AF. Japanese guidelines have stated that INR of 1.6 to 2.6 is recommended in elderly Japanese patients with AF. The recommendations on INR range for stroke prevention in different Asian guidelines is summarized in Table 1 . 27, [88] [89] [90] [91] Several observational studies suggested that low-intensity warfarin therapy can reduce hemorrhage without increasing thromboembolism for East Asian patients with NVAF receiving warfarin therapy, but the evidence is weak and no focus on quality of anticoagulation control, as reflected by TTR. 92, 93 In a systematic review and evidence appraisal, low-intensity anticoagulation, or lower target INRs is associated with a higher risk of thromboembolism although bleeding risk may be lower. 79 Of note, a "one-off" INR reading does not reflect the quality of anticoagulation control, especially since many serious bleeds actually occur when the INR is between 2.0 and 3.0. 80 Hence, we strongly recommend evidence-based management, with the strongest data currently for INR 2.0 to 3.0 and TTR ideally ≥65% (or even 70%) in Asian patients. 91 We should ensure TTR is ≥65% (optimal ≥70%), with appropriate education and counselling, or more frequent INR checks.

Efforts to improve OAC uptake, adherence, and persistence with therapy are also crucial, as are efforts to improve service provisions. 94-96

to severe mitral stenosis and mechanical heart valve.

2. For the optimal management of VKA therapy, INR of 2.0-3.0 is recommended in Asian patients with AF, with attention to ensure TTR is ≥65%.

The results of the four pivotal Phase III NOAC trials showed that all NOACs were at least noninferior to warfarin in prevention of stroke/thromboembolism, and NOACs were associated with lower rates of intracranial bleeding than was warfarin. In the metaanalysis of four NOACs, 97 NOACs also showed better effectiveness and safety than warfarin in "high-risk" real-world Asian AF populations including the very elderly, those with low body weight or liver disease. 68,100-105 In the warfarin era, a major concern in Asian patients with AF was the risk of serious bleeding by combining OAC with antiplatelets; however, temporal trends of patients with AF undergoing PCI after introduction of NOAC show increasing use of OAC and combination therapy with antiplatelets, especially in the NOAC era ( Figure 12 ). 114 Patients with CAD and AF are not only at risk of stroke but also at risk of bleeding due to associated comorbidities, and decisionmaking should balance ischemic and bleeding risks when considering the duration, type, and treatment regime especially given the potential sensitivity of Asians to bleeding risks on OAC ( Figure 13 ). 115, 116 In the warfarin era, the WOEST study demonstrated a higher Based on these trials, an NOAC-based anticoagulation strategy was safer than a warfarin-based strategy in terms of bleeding.

The role of aspirin was tested in the AUGUSTUS trial using a two-by-two factorial design. 120 In the AUGUSTUS trial, the use of apixaban reduced bleeding by 31% as compared with VKAs, and the use of aspirin resulted in an increase in bleeding by 47%, that is, dual therapy with apixaban and a P2Y12 inhibitor was associated with a lower rate of bleeding than triple therapy or dual therapy with warfarin. Furthermore, patients taking apixaban had a lower incidence of death or hospitalization than those taking VKAs, mainly driven by a reduction in the incidence of hospitalizations. The rate of the incidence of death or ischemic events did not differ significantly between aspirin and a placebo or between apixaban and VKAs, although was numerically greater in the placebo treated patients compared with aspirin. The incidence of stroke decreased by 50% in patients with apixaban as compared with VKAs.

In all four trials, randomization was performed after the PCI, and all patients were treated by triple therapy during the periprocedural period, in which stent thromboses were most likely to occur. Thus, this consensus recommends an initial period of triple therapy with OAC plus a DAPT during the PCI and following 7-28 days, depending on the balance between thrombotic and bleeding risks (Figure 14 Beyond 1 year, the evidence suggests that OAC monotherapy is the preferred option, given similar or worse MACE and more bleeding with combining NOAC and antiplatelets. 124 The AFIRE trial included patients with AF who underwent PCI or coronary artery bypass grafting (CABG) more than 1 year earlier or did not require revascularization. 125 The patients were assigned to receive monotherapy with rivaroxaban (10 mg once daily for patients with an eGFR of 15 to 49 ml/min or 15 mg once daily for patients with an eGFR ≥50 ml/min) or a combination of rivaroxaban plus a single antiplatelet drug. This trial was stopped early because of mortality in the combination therapy. 2. Triple therapy with aspirin, clopidogrel, and an OAC for longer than 1 week after an ACS should be considered when risk of stent thrombosis outweighs the bleeding risk, with the total duration (≤1 month) decided according to assessment of these risks. and ELIMINATE-AF study for edoxaban versus VKA. 133 In these Table 3 .

In a meta-analysis of these four trials comparing NOACs versus VKA, 133 Notwithstanding the small-sized study cohorts which may be underpowered for the thromboembolic outcomes, an ablation strategy with minimally interrupted periprocedural NOACs may be an option.

• We recommend a preferential use of NOACs over VKA because of their safety profile relative to VKA in addition to their ease of management before and after ablation. Figure 15 ).

a. For most patients, an uninterrupted NOAC strategy may be the preferred option.

• When VKA is used, it should be controlled within a therapeutic range and uninterrupted throughout the periprocedural period unless bleeding events preclude its continuous use.

• In general, OAC therapy is continued for 2 months following ablation in all patients. Beyond this time, a decision to continue OAC long term is determined primarily by the presence of CHA 2 DS 2 -VASc stroke risk factors rather than the rhythm status.

The general principles of managements of bleeding are summarized in Figure 16 . For severe bleeding or life-threatening bleeding, reversal agents could be considered to reverse the anticoagulant effects of NOACs.

dabigatran with an affinity that is 350 times as high as that observed with thrombin. 140 In the RE-VERSE AD study, the efficacy and safety of idarucizumab was tested in patients who had serious bleeding or required urgent procedures. In an interim analysis of the first 90 patients, idarucizumab reversed the anticoagulant effect of dabigatran within minutes in 88%-98% of patients. 141 In the whole cohort of 503 patients, median time to cessation of bleeding 2.5 h in those with uncontrolled bleeding who could be assessed. 142 

• Idarucizumab is indicated for the reversal of dabigatran in patients with serious bleeding or requiring urgent procedures.

• Andexanet alfa can be useful for reversing anticoagulation in patients treated with Factor Xa inhibitors with life-threatening or uncontrolled bleeding.

• The possibility of occult malignancies that are the cause/origin of the bleeding should be kept in mind when managing OAC-related bleeding.

The prevalence of AF is increasing in recent decades, and the prevalence in elderly population has increased more rapidly, in worldwide and also in Asians. 3 AF is important as stroke risk increased dramatically with age. 67, 68 However, oral anticoagulant (OAC) treatment has been underutilized in elderly. 152 In pivotal trials of NOAs, the proportions of elderly patients (age ≥75 years) included ranged from 31% to 43%. 63, [153] [154] [155] Metaanalyses of pivotal NOAC trials showed no interaction between different age groups and efficacy/safety of NOAC compared with warfarin. 97 Generally, the higher events rate in elderly population resulted in a larger absolute risk reduction from NOAC compared with warfarin; but the presence of interaction by different age groups varied by different clinical outcomes in each NOAC trial ( 

Although there is no absolute cutoff for defining low body weight, Asians tend to be smaller and leaner than non-Asians (e.g., 20 kg less on average in ENGAGE AF-TIMI 48) 98 ; thus, patients with low body weight are more common among Asians than among non-Asians. The effects of NOACs are closely related to plasma concentrations, which are affected by body distribution volume. 163 Extremely low body weight may influence the efficacy and safety of NOACs. Although NOACs have shown better net clinical benefits than warfarin, being underweight has been associated with an increased risk of major bleeding in patients taking NOACs. 164 Body weight ≤60 kg was a dose reduction criterion for apixaban and edoxaban. 154, 155 For apixaban, there was no interaction between different body weight groups (≤60 kg, 61-120 kg, and >120 kg) and the efficacy of apixaban compared with warfarin. 165 In terms of safety outcome such as major bleeding, a large RR reduction was observed in patients with ≤60 kg than those with 61-120 kg and >120 kg. 165 For edoxaban versus warfarin, there was no significant interaction between different body mass index (BMI) category groups and the outcomes; however, the underweight patients defined as BMI <18.5 kg/m 2 occupied small proportion of total population (0.8%, n = 177), so data were limited especially in the comparison between edoxaban and warfarin. 166 A recent subanalysis of ENGAGE AF-TIMI 48 trial, which focused on patients at extremes of body weight has demonstrated that the pharmacokinetic/pharmacodynamic profile of edoxaban was consistent across extremes of BW, resulting in similar efficacy compared with warfarin, while major or clinically relevant nonmajor bleeding and net outcomes were most favorable with edoxaban compared with warfarin in patients with LBW. 167 For rivaroxaban, limited data are available for patients with <60 or <50 kg. In recent observational data including a large population of patients with AF with ≤60 kg taking OACs (n = 21,589), NOAC was associated with lower risks of ischemic stroke and major bleeding than warfarin, and these results were largely consistent in patients with <50 kg. 101 In addition, onlabel NOAC dosing should still be applied in patients with low body weight to achieve the best net clinical benefit. 101

CKD is an independent predictor of risk of thromboembolic and bleeding events. 168 All NOACs have some degree of renal elimination, with the greatest renal dependency for excretion with dabigatran (80%) and the least with renal dependency for apixaban (27%). However, there are no head-to-head NOAC comparison trials and, therefore, insufficient evidence to recommend one agent over another. The dose adapted on the basis of CCr according to approved indications ( Figure 17 ).

There have been several meta-analyses addressing the efficacy and safety of NOACs compared with warfarin in patients with mild to moderate CKD. [169] [170] [171] The data are consistent across studies that all NOACs are associated with lower risks of thromboembolic events compared with warfarin in patients with mild to moderate CKD (CCr 30 to 79 ml/min). 169, 170 For major bleeding, NOAC showed significantly lower risk of major bleeding compared with warfarin in patients with mild CKD (defined as CCr 50 to 79 ml/min); however, there was no significant difference between NOAC and warfarin in patients with moderate CKD (defined as CCr 30 to 49 ml/min). 169, 170 Indirect comparisons suggested that apixaban and edoxaban highdose regimen might be more likely associated with a better net clinical profile in patients with AF with moderate CKD (defined as CCr from 25-30 to 50 ml/min). 171

The CHA 2 DS 2 -VASc score could also be used to predict ischemic stroke risk in patients with AF with ESRD undergoing dialysis. 172 However, the benefit of OAC treatment in patients with AF and ESRD has been controversial. In a Korean nationwide cohort study, 

Liver disease is often accompanied by a combination of complex abnormalities of the coagulation pathways 180, 181 ; thus, patients with advanced liver disease have higher risks of thromboembolism and bleeding. 182, 183 In addition, significant impairment of liver function can affect hepatic clearance and drug metabolism. 184 However, even in patients with liver cirrhosis, warfarin-based oral anticoagulation was associated with a lower risk of ischemic stroke and a positive net benefit compared with no antithrombotic therapy. 103 The use of warfarin in patients with advanced liver disease is challenging due to intrinsically prolonged prothrombin time. 185 Although NOAC could be considered as an alternative to warfarin, patients with liver function abnormalities (i.e., active or significant liver disease including vital hepatitis and cirrhosis, alanine 

AF often co-exists with various types of VHDs. Valvular AF is defined as patients with AF and VHD including moderate to severe rheumatic mitral stenosis or having mechanical prosthetic valve (EHRA type 1 VHDs). 193 Patients with valvular AF have significantly higher risks of thromboembolic events than those with nonvalvular AF. 194 Other VHDs are defined as EHRA type 2 VHDs 193 and these patients also showed higher thromboembolic and bleeding risk. 195 The efficacy of warfarin in stroke prevention in patients with valvular AF has long been established. Although the pivotal clinical trials of NOACs did not include patients with valvular AF (EHRA type 1 VHDs), patients with EHRA type 2 VHDs were allowed to participate. [196] [197] [198] [199] The efficacy and safety of NOACs do not appear to There has been only one published randomized controlled study comparing warfarin and NOAC in patients with mechanical prosthetic valve. 203 This study was prematurely terminated because of excessive thromboembolic and bleeding events with dabigatran. 203 Although there was a signal for the positive net benefit of NOACs 

Obesity is an important and potentially modifiable risk factor for AF and can affect the incidence and persistence of AF. 269, 270 Obesity is also associated with other cardiovascular disease risks, including hypertension, sleep apnea, impaired glucose tolerance, and diabetes, which are all associated with incident AF and AF-related complications.

Aggressive weight reduction and risk factor modification has been shown to reduce AF recurrences and arrhythmia burden, as well as AF symptom burden; thus, there is improved maintenance of sinus rhythm and beneficial effects on cardiac remodeling compared with conventional therapy in patients with obesity. 260, 262, 271, 272 For example, in patients diagnosed with overweight or obesity concomitant with AF, >10% weight reduction was associated with reduction in the AF burden and reversal of AF type and natural progression. 260, 273 Underweight patients are not uncommon in the Asian population, and these patients show an increased risk of AF. 274 Moreover, fluctuations in body weight were associated with an increased risk of AF, particularly among those with low body weight. 275 With regard to clinical outcomes, the risk of the composite outcome of ischemic stroke, thromboembolism, or death is higher in those with overweight and obesity, even after adjustment for CHA 2 DS 2 -VASc scores. 276 However, in a systematic review and meta-analysis, an obesity paradox was observed in patients with AF taking anticoagulation therapy, particularly with regard to all-cause and cardiovascular death in subgroup analyses of randomized trial cohorts. 277 Another study showed that the risk of ischemic stroke, major bleeding, and mortality was lower in Asian patients with AF, who showed a high BMI and received OACs compared with those with normal weight, whereas underweight patients had an increased risk of mortality and composite outcome compared with normal weight. 278 For stroke prevention, NOACs are generally associated with better outcomes than those with warfarin administration in Asians across patients of different body weights, particularly in underweight patients. 101 Given the observed obesity paradox in patients with AF, keeping a normal body weight is recommended.

Excessive alcohol consumption is a well-known risk factor and trigger for AF. 279 Excessive alcohol consumption acts synergistically with other lifestyle risk factors for AF, including hypertension, obesity, obstructive sleep apnea, and cardiomyopathy to magnify their effects. Excessive alcohol consumption is a known clinical risk factor for bleeding during anticoagulation therapy and is included in the HAS-BLED score. 280 High alcohol consumption is also associated with an increased risk of thromboembolism and death in patients with incident AF. 281 Asian data have shown that high alcohol consumption was associated with a high ischemic stroke risk. 282 One recent randomized trial has reported that alcohol abstinence reduced the risk of recurrent AF in those with heavy alcohol consumption patterns. 283 Alcohol abstinence was also associated with a low risk of incident AF in patients with newly diagnosed type 2 diabetes, 284 and alcohol abstinence after a diagnosis of AF was associated with a low risk of ischemic stroke. 282

Smoking is associated with an increased risk of incident AF, 285, 286 and smoking cessation seems to lower the risk of AF compared with current smokers. 285, 286 In Asian patients with AF with a low CHA 2 DS 2 -VASc score, smoking was identified as a risk factor for ischemic stroke. 287 Furthermore, quitting smoke after incident AF was associated with a low risk of ischemic stroke, lower stroke severity, and death from cerebrovascular events. 288 

Epidemiological studies have suggested that elevated ambient particulate matter (PM) <2.5 μm (PM 2.5 ) or <10 μm (PM 10 ) in aerodynamic diameter are consistently associated with adverse cardiac events. In the Asian general population, long-term exposure of PM2.5 is associated with the increased incidence of new-onset AF. 289,290

Moderate-intensity exercise (150 min/week) or vigorous-intensity exercise (75 min/week) recommended by the 2018 Physical Activity Guidelines Advisory Committee is known to improve cardiovascular health. Physical inactivity is associated with an increased risk of incident AF, 291 and regular exercise could reduce AF burden and improve AF-related symptoms and patients' quality of life. [292] [293] [294] [295] However, the risk of AF increased in those who participate in extreme endurance exercise that far exceeds the levels recommended by the Physical Activity Guidelines Advisory Committee report. 296 Cardiorespiratory fitness generally reduces the AF burden and symptom severity in patients with obesity and concomitant AF, which may be attributable to the beneficial effects of weight loss. 261 One recent observational study in Asian patient with incident AF reported that regular exercise was associated with low risks of heart failure, mortality, and dementia in addition to a marginal benefit on ischemic stroke. 297, 298 Regular moderate exercise (170-240 min/

week) showed maximal cardiovascular benefits in patients who initiated exercise after diagnosis of AF. Patients who initiated or continued regular exercise after diagnosis of AF were associated with a lower risk of dementia than persistent non-exercisers, with no risk reduction associated with exercise cessation. 298

• The promotion of a healthy lifestyle (smoking cessation, reduced alcohol consumption, regular exercise) is recommended to lower the risk of new-onset AF and AF-related complications ( Figure 19 ).

• Appropriate weight control is an important strategy to improve outcomes in patients with AF.

• Reduced consumption or alcohol abstinence is recommended in patients with AF with moderate-to-high levels of alcohol use to minimize AF burden and stroke risk.

• Smoking cessation is recommended in patients with AF to reduce the stroke risk, even in those categorized as low-risk patients based on the CHA 2 DS 2 -VASc score.

• Regular exercise based on the recommendations of the 2018

Physical Activity Guidelines Advisory Committee (150 min/week of moderate-intensity exercise or 75 min/week of vigorousintensity exercise) can improve cardiovascular outcomes in patients with AF.

The integration of lifestyle management in patients with AF. AF, atrial fibrillation

AF is a common clinical manifestation in hospitalized patients with COVID-19 infection and is associated with a higher risk of mortality and/or requirement for intensive care. [299] [300] [301] [302] The latter is perhaps unsurprising given the higher risk of adverse outcomes in COVID-19

with associated cardiovascular comorbidities. 302 During the COVID- 19 infection as long as antiviral agents are deemed necessary and until discharge. LMWH regimes have been tested in recent clinical trials of hospitalized COVID-19 patients but showed conflicting results. [312] [313] [314] [315] [316] For example, in noncritically ill patients with COVID-19, the ATTACC, ACTIV-4a, and REMAP-CAP investigators found that an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. 313 However, in patients hospitalized with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation in ACTION trial. 316 Besides, these studies did not specifically enroll patients with AF, and therefore, data about the optimal dosage of LMWH for hospitalized AF COVID-19 patients were very limited.

COVID-19 vaccines are usually administered by intramuscular injection and are an important part of our pandemic response. 317 An opportunity to screen for AF amongst attendees for vaccination has been promoted. 318 In patients with AF treated with NOACs, it is advisable to follow the scheme for "minor risk" interventions, and therefore, it is not necessary to withhold any NOAC dosage before and after the injection procedure. 319 However, it is recommended to use a fine-gauge needle for injection, and apply firm pressure for 5-10 min after the injection. If the scheduled NOAC dosage is close to the injection time before, the scheduled NOAC dosage may be postponed until after the injection if no progression of local hematoma noted. 3. In patients with AF taking NOACs planned to receive COVID-19

vaccine injection, it is advisable to follow the scheme for "minor risk" interventions, and therefore, it is not necessary to withhold any NOAC dosage before and after the injection procedure. 

Epidemiology of atrial fibrillation: geographic/ecological risk factors, age, sex, genetics

The global burden of atrial fibrillation and stroke: a systematic review of the clinical epidemiology of atrial fibrillation in Asia

Lifetime risks, projected numbers, and adverse outcomes in Asian patients with atrial fibrillation: a report from the Taiwan nationwide

10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population

Evolving changes of the use of oral anticoagulants and outcomes in patients with newly diagnosed atrial fibrillation in Taiwan

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Temporal trends of emergency department visits of patients with atrial fibrillation: a nationwide population-based study

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Atrial fibrillation in the United Kingdom: predicting costs of an emerging epidemic recognising and forecasting the cost drivers of atrial fibrillation-related costs

Increasing trends in hospital care burden of atrial fibrillation in Korea

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Integrated care and outcomes in patients with atrial fibrillation and comorbidities

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Regular bleeding risk assessment associated with reduction in bleeding outcomes: the mA-FA-II Randomized Trial

Mobile health technology-supported atrial fibrillation screening and integrated care: a report from the mAFA-II trial Long-term Extension Cohort

ABC (Atrial fibrillation Better Care) pathway and healthcare costs in atrial fibrillation: the ATHERO-AF study

The effect of integrated care management on dementia in atrial fibrillation

Application of the simple atrial fibrillation better care pathway for integrated care management in frail patients with atrial fibrillation: a nationwide cohort study

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Korean guideline of atrial fibrillation management

ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC

2017 consensus of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation

Using the CHA2DS2-VASc score for refining stroke risk stratification in 'low-risk' Asian patients with atrial fibrillation

The CHADS2 and CHA2DS2-VASc scores for predicting ischemic stroke among East Asian patients with atrial fibrillation: a systemic review and meta-analysis

Comparisons of CHADS2 and CHA2DS2-VASc scores for stroke risk stratification in atrial fibrillation: which scoring system should be used for Asians? Heart Rhythm

Risk of ischemic stroke in patients with non-valvular atrial fibrillation not receiving oral anticoagulants-Korean nationwide populationbased study

DS(2)-VASc score (congestive heart failure, hypertension, age ≥75 [doubled], diabetes mellitus, prior stroke or transient ischemic attack [doubled], vascular disease, age 65-74, female) for stroke in Asian patients with atrial fibrillation: a Korean nationwide sample cohort study

)DS(2)-VASc score for identifying truly low-risk atrial fibrillation for stroke: a Korean nationwide cohort study

Stroke and thromboembolism in warfarin-treated patients with atrial fibrillation: comparing the CHA2DS2-VASc and GARFIELD-AF risk scores

Improving dynamic stroke risk prediction in non-anticoagulated patients with and without atrial fibrillation: comparing common clinical risk scores and machine learning algorithms

Beyond the 2020 guidelines on atrial fibrillation of the European society of cardiology

Stroke and bleeding risk stratification in atrial fibrillation: a critical appraisal

Predicting adverse events beyond stroke and bleeding with the ABC-stroke and ABC-bleeding scores in patients with atrial fibrillation: the Murcia AF project

The use of biomarkers in clinical management guidelines: a critical appraisal

A meta-analysis of clinical risk factors for stroke in anticoagulant-naïve patients with atrial fibrillation

Age threshold for the use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation: insights into the optimal assessment of age and incident comorbidities

Age threshold for ischemic stroke risk in atrial fibrillation

Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: a nationwide cohort study

Female sex as a risk modifier for stroke risk in atrial fibrillation: using CHA2DS2-VASc versus CHA2DS2-VA for stroke risk stratification in atrial fibrillation: a note of caution

Importance of risk reassessment in patients with atrial fibrillation in guidelines: assessing risk as a dynamic process

Relationship of aging and incident comorbidities to stroke risk in patients with atrial fibrillation

Reassessment of risk for stroke during follow-up of patients with atrial fibrillation

Dynamic changes of CHA2DS2-VASc score and the risk of ischaemic stroke in Asian patients with atrial fibrillation: a nationwide cohort Study

Incident comorbidities, aging and the risk of stroke in 608,108 patients with atrial fibrillation: a nationwide analysis

Incident co-morbidities in patients with atrial fibrillation initially with a CHA2DS2-VASc score of 0 (males) or 1 (females): implications for reassessment of stroke risk in initially 'low-risk' patients

Predicting thromboembolic and bleeding event risk in patients with non-valvular atrial fibrillation: a systematic review

Comparison of HAS-BLED and ORBIT bleeding risk scores in AF patients treated with NOACs: a report from the ESC-EHRA EORP-AF general long-term registry

Bleeding risk scores in atrial fibrillation and venous thromboembolism

Ideal blood pressure in patients with atrial fibrillation

Comparing bleeding risk assessment focused on modifiable risk factors only versus validated bleeding risk scores in atrial fibrillation

Incident risk factors and major bleeding in patients with atrial fibrillation treated with oral anticoagulants: a comparison of baseline, follow-up and delta HAS-BLED scores with an approach focused on modifiable bleeding risk factors

Continuation or discontinuation of oral anticoagulants after HAS-BLED scores increase in patients with atrial fibrillation

Should oral anticoagulants still be prescribed to patients with atrial fibrillation with a single stroke risk factor but at high bleeding risk? A nationwide cohort study

Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: executive summary of a joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC working group on valvular heart disease, Cardiac Arrhythmia Society of Southern Africa (CASSA)

Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial

Dabigatran versus warfarin in patients with atrial fibrillation

Apixaban in patients with atrial fibrillation

Recommendations on stroke prevention for patients having a CHA(2)DS(2)-VASc score of 1 (males) or 2 (females) in 2019 atrial fibrillation guidelines

Should atrial fibrillation patients with 1 additional risk factor of the CHA2DS2-VASc score (beyond sex) receive oral anticoagulation?

Age threshold for increased stroke risk among patients with atrial fibrillation: a nationwide cohort study from Taiwan

Comparing the effectiveness and safety of nonvitamin K antagonist oral anticoagulants and warfarin in elderly Asian patients with atrial fibrillation: a nationwide cohort study

Stroke and bleeding risk assessment in atrial fibrillation: where are we now?

Label adherence for non-vitamin K antagonist oral anticoagulants in a prospective cohort of Asian patients with atrial fibrillation

Optimal rivaroxaban dose in Asian patients with atrial fibrillation and normal or mildly impaired renal function

Lowdose rivaroxaban and risks of adverse events in patients with atrial fibrillation

Offlabel dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in Asian patients with atrial fibrillation

Label adherence of direct oral anticoagulants dosing and clinical outcomes in patients with atrial fibrillation

Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation

The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients

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Quality indicators in the management of elderly Chinese patients with atrial fibrillation: a report from the Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry

Lower versus standard INR targets in atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials

Prediction of functional outcome and in-hospital mortality after admission with oral anticoagulant-related intracerebral hemorrhage

Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review

Relation of the SAMe-TT2R2 score to quality of anticoagulation control and thromboembolic events in atrial fibrillation patients: observations from the SPORTIF trials

Use of the SAMe-TT2R2 score to predict good anticoagulation control with warfarin in chinese patients with atrial fibrillation: relationship to ischemic stroke incidence

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SAMe-TT2R2 score, time in therapeutic range, and outcomes in anticoagulated patients with atrial fibrillation

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Should we adopt a standard international normalized ratio range of 2.0 to 3.0 for Asian patients with atrial fibrillation? An appeal for evidence-based management, not eminence-based recommendations

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NOAC adherence of patients with atrial fibrillation in the real world: dosing frequency matters?

A systematic review of economic aspects of service interventions to increase anticoagulation use in atrial fibrillation

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Direct oral anticoagulants in patients with atrial fibrillation and liver disease

Liver cirrhosis in patients with atrial fibrillation: would oral anticoagulation have a net clinical benefit for stroke prevention?

Nonvitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: a nationwide population-based study

Non-vitamin K antagonist oral anticoagulants versus warfarin in AF patients ≥85 years

Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction

When less is not more

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Optimal management of anticoagulation therapy in Asian patients with atrial fibrillation

Impacts of different renal function estimation formulas on dosing of DOACs and clinical outcomes

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Antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a north American perspective-2016 update

Temporal trends in prevalence and antithrombotic treatment among Asians with atrial fibrillation undergoing percutaneous coronary intervention: a nationwide Korean population-based study

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Antithrombotic treatment in atrial fibrillation patients undergoing percutaneous coronary interventions: focus on stent thrombosis

The east Asian paradox: an updated position statement on the challenges to the current antithrombotic strategy in patients with cardiovascular disease

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial

Prevention of bleeding in patients with atrial fibrillation undergoing PCI

Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation

Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation

Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, openlabel, phase 3b trial

Dabigatran dual therapy with ticagrelor or clopidogrel after percutaneous coronary intervention in atrial fibrillation patients with or without acute coronary syndrome: a subgroup analysis from the RE-DUAL PCI trial

European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Meta-analysis of oral anticoagulant monotherapy as an antithrombotic strategy in patients with stable coronary artery disease and nonvalvular atrial fibrillation

Antithrombotic therapy for atrial fibrillation with stable coronary disease

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HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation

Influence of substrate modification in catheter ablation of atrial fibrillation on the incidence of acute complications: analysis of 10 795 procedures in J-CARAF Study

Safety and efficacy of dabigatran etexilate during catheter ablation of atrial fibrillation: a meta-analysis of the literature

Uninterrupted rivaroxaban vs. uninterrupted vitamin K antagonists for catheter ablation in non-valvular atrial fibrillation

Uninterrupted dabigatran versus warfarin for ablation in atrial fibrillation

Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

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A meta-analysis of randomized controlled trials of uninterrupted periprocedural anticoagulation strategy in patients undergoing atrial fibrillation catheter ablation

An updated meta-analysis of novel oral anticoagulants versus vitamin K antagonists for uninterrupted anticoagulation in atrial fibrillation catheter ablation

Uninterrupted vs. interrupted periprocedural direct oral anticoagulants for catheter ablation of atrial fibrillation: a prospective randomized single-centre study on post-ablation thrombo-embolic and haemorrhagic events

When is it appropriate to stop non-vitamin K antagonist oral anticoagulants before catheter ablation of atrial fibrillation? A multicentre prospective randomized study

Safety and efficacy of minimally interrupted dabigatran vs uninterrupted warfarin therapy in adults undergoing atrial fibrillation catheter ablation: a randomized clinical trial

Efficacy and safety of uninterrupted periprocedural edoxaban in patients undergoing catheter ablation for atrial fibrillation-the prospective KYU-RABLE study

A specific antidote for dabigatran: functional and structural characterization

Idarucizumab for dabigatran reversal

Idarucizumab for dabigatran reversal-full cohort analysis

Dabigatran reversal with idarucizumab in patients with renal impairment

Global use of idarucizumab in clinical practice: outcomes of the RE-VECTO surveillance program

A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa

Andexanet alfa for the reversal of factor Xa inhibitor activity

Full study report of andexanet alfa for bleeding associated with Factor Xa inhibitors

Risks and outcomes of gastrointestinal malignancies in anticoagulated atrial fibrillation patients experiencing gastrointestinal bleeding: a nationwide cohort study

Clinical significance of hematuria in atrial fibrillation with oral anticoagulation therapy

Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study

Trends in the incidence and prevalence of atrial fibrillation and estimated thromboembolic risk using the CHA(2)DS(2)-VASc score in the entire Korean population

Nonvitamin K antagonist oral anticoagulants in elderly (≥85 years) patients with newly diagnosed atrial fibrillation: changing clinical practice and outcomes for stroke prevention in a nationwide cohort study

Rivaroxaban versus warfarin in nonvalvular atrial fibrillation

Apixaban versus warfarin in patients with atrial fibrillation

Edoxaban versus warfarin in patients with atrial fibrillation

Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial

Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial

Efficacy and safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial

Oral anticoagulants in extremely-high-risk, very elderly (>90 years) patients with atrial fibrillation

Edoxaban for the management of elderly Japanese patients with atrial fibrillation ineligible for standard oral anticoagulant therapies: rationale and design of the ELDERCARE-AF study

Low-dose edoxaban in very elderly patients with atrial fibrillation

The non-vitamin K antagonist oral anticoagulants (NOACs) and extremes of body weight-a systematic literature review

Increased risk of major bleeding in underweight patients with atrial fibrillation who were prescribed non-vitamin K antagonist oral anticoagulants

Efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation and extremes in body weight

Relationship between body mass index and outcomes in patients with atrial fibrillation treated with edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial

Edoxaban versus warfarin in patients with atrial fibrillation at the extremes of body weight: an analysis from the ENGAGE AF-TIMI 48 trial

Risk of thromboembolic events in atrial fibrillation with chronic kidney disease

Novel oral anticoagulants in patients with renal insufficiency: a meta-analysis of randomized trials

Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with chronic kidney disease: a systematic review and network meta-analysis

Incidence and prediction of ischemic stroke among atrial fibrillation patients with end-stage renal disease requiring dialysis

Warfarin use in patients with atrial fibrillation undergoing hemodialysis: a nationwide population-based study

Outcomes associated with apixaban use in patients with endstage kidney disease and atrial fibrillation in the United States

Safety and efficacy of apixaban versus warfarin in patients with endstage renal disease: meta-analysis

Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and severe kidney disease or undergoing hemodialysis

Safety and efficacy of vitamin K antagonists versus rivaroxaban in hemodialysis patients with atrial fibrillation: a multicenter randomized controlled trial

Oral anticoagulation for patients with atrial fibrillation on long-term hemodialysis

Effectiveness and safety of direct oral anticoagulants in an Asian population with atrial fibrillation undergoing dialysis: a population-based cohort study and meta-analysis

The coagulopathy of chronic liver disease

Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management

The complex role of anticoagulation in cirrhosis: an updated review of where we are and where we are going

Oral anticoagulation in patients with liver disease

The importance of patientspecific factors for hepatic drug response and toxicity

Stratifying the risks of oral anticoagulation in patients with liver disease

Non-vitamin K antagonist oral anticoagulants and risk of serious liver injury

Efficacy and safety of non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with impaired liver function: a retrospective cohort study

Edoxaban versus warfarin in patients with atrial fibrillation and history of liver disease

European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

The efficacy and safety of direct oral anticoagulants vs traditional anticoagulants in cirrhosis

Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation

Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor

Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: a joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac Arrhythmia Society of Southern Africa (CASSA)

What is 'valvular' atrial fibrillation? A reappraisal

Thromboembolism and bleeding complications in anticoagulated patients with atrial fibrillation and native aortic or mitral valvular heart disease: a descriptive nationwide cohort study

Comparison of dabigatran and warfarin in patients with atrial fibrillation and valvular heart disease: the RE-LY trial (randomized evaluation of long-term anticoagulant therapy)

Apixaban in comparison with warfarin in patients with atrial fibrillation and valvular heart disease: findings from the apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOTLE) trial

Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial

Valvular heart disease patients on edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial

Edoxaban for the prevention of thromboembolism in patients with atrial fibrillation and bioprosthetic valves

Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease

Nonvitamin K antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease

Dabigatran versus warfarin in patients with mechanical heart valves

Outcomes of direct oral anticoagulants in patients with mitral stenosis

Protocol, rationale and design of DAbigatran for Stroke PreVention In Atrial Fibrillation in MoDerate or Severe Mitral Stenosis (DAVID-MS): a randomised, open-label study

Atrial fibrillation and thromboembolism in patients with hypertrophic cardiomyopathy: systematic review

Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy

Impact of atrial fibrillation on the clinical course of apical hypertrophic cardiomyopathy

Temporal trends of the prevalence and incidence of atrial fibrillation and stroke among Asian patients with hypertrophic cardiomyopathy: a nationwide population-based study

Hypertrophic cardiomyopathy in patients with atrial fibrillation: prevalence and associated stroke risks in a nationwide cohort study

Stroke risk stratification for atrial fibrillation patients with hypertrophic cardiomyopathy

Novel oral anticoagulants for primary stroke prevention in hypertrophic cardiomyopathy patients with atrial fibrillation

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation with hypertrophic cardiomyopathy: a nationwide cohort study

Arch Intern Med Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials

Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation

Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial

Outcomes with edoxaban versus warfarin in patients with previous cerebrovascular events: findings from ENGAGE AF-TIMI 48 (effective anticoagulation with factor Xa next generation in atrial fibrillation-thrombolysis in myocardial infarction 48)

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF

Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial

Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: an updated systematic review and meta-analysis of randomized controlled trials

Effectiveness and safety of direct oral anticoagulant for secondary prevention in Asians with atrial fibrillation

Use of oral anticoagulants for stroke prevention in patients with atrial fibrillation who have a history of intracranial hemorrhage

Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: a nationwide cohort study

Outcomes associated with resuming warfarin treatment after hemorrhagic stroke or traumatic intracranial hemorrhage in patients with atrial fibrillation

Use of antithrombotic therapy and long-term clinical outcome among patients surviving intracerebral hemorrhage

Restarting anticoagulant therapy after intracranial hemorrhage: a systematic review and meta-analysis

Association of ischemic stroke, major bleeding, and other adverse events with warfarin use vs non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation with a history of intracranial hemorrhage

Oral anticoagulation in asian patients with atrial fibrillation and a history of intracranial hemorrhage

ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

Adherence to oral anticoagulant therapy in patients with atrial fibrillation. Focus on non-vitamin K antagonist oral anticoagulants

Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the veterans health administration

Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study

Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation

Adherence and outcomes to direct oral anticoagulants among patients with atrial fibrillation: findings from the veterans health administration

Adherence to anticoagulant treatment with dabigatran in a real-world setting

Telemonitoring-based feedback improves adherence to non-vitamin K antagonist oral anticoagulants intake in patients with atrial fibrillation

EHRA/EAPCI expert consensus statement on catheterbased left atrial appendage occlusion-an update

Left atrial appendage occlusion during cardiac surgery to prevent stroke

Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial

Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial

Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry

Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level metaanalysis

Interventional left atrial appendage closure vs novel anticoagulation agents in patients with atrial fibrillation indicated for long-term anticoagulation (PRAGUE-17 study)

Left atrial appendage closure versus direct oral anticoagulants in high-risk patients with atrial fibrillation

Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial

Percutaneous Left Atrial Appendage Closure with WATCHMAN™ device: peri-procedural and mid-term outcomes from the TRAPS Registry

Evaluating real-world clinical outcomes in atrial fibrillation patients receiving the WATCHMAN left atrial appendage closure technology: final 2-year outcome data of the EWOLUTION trial focusing on history of stroke and hemorrhage

Left atrial appendage closure with WATCHMAN in Asian patients: 2 year outcomes from the WASP registry

Percutaneous WATCHMAN left atrial appendage closure for Japanese patients with nonvalvular atrial fibrillation at increased risk of thromboembolism-first results from the SALUTE Trial

Percutaneous left atrial appendage occlusion for stroke prophylaxis in nonvalvular atrial fibrillation: a systematic review and analysis of observational studies

Utilization and adverse outcomes of percutaneous left atrial appendage closure for stroke prevention in atrial fibrillation in the United States: influence of hospital volume

Device-associated thrombus formation after left atrial appendage occlusion: a systematic review of events reported with the Watchman, the Amplatzer Cardiac Plug and the Amulet

Device-related thrombosis after percutaneous left atrial appendage occlusion for atrial fibrillation

Major adverse events with percutaneous left atrial appendage closure in patients with atrial fibrillation

Device-related thrombus after left atrial appendage closure: data on thrombus characteristics, treatment strategies, and clinical outcomes from the EUROC-DRT-registry

The assessment of the watchman device in patients unsuitable for oral anticoagulation (ASAP-TOO) trial

Cost-effectiveness of left atrial appendage closure for stroke reduction in atrial fibrillation: analysis of pooled, 5-year, long-term data

Time to cost-effectiveness following stroke reduction strategies in AF: warfarin versus NOACs versus LAA closure

Long-term effect of goal-directed weight management in an atrial fibrillation cohort: a long-term follow-up study (LEGACY)

Impact of CARDIOrespiratory FITness on arrhythmia recurrence in obese individuals with atrial fibrillation: the CARDIO-FIT study

Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study

Risk Factor Management for Atrial Fibrillation

Effect of alcohol consumption on the risk of adverse events in atrial fibrillation: from the COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry

Effect of hypertension duration and blood pressure level on ischaemic stroke risk in atrial fibrillation: nationwide data covering the entire Korean population

Clinical implication of an impaired fasting glucose and prehypertension related to new onset atrial fibrillation in a healthy Asian population without underlying disease: a nationwide cohort study in Korea

Association between clustering of unhealthy lifestyle factors and risk of newonset atrial fibrillation: a nationwide population-based study

Association of cardiovascular health and incident atrial fibrillation in elderly population

Obesity and the risk of new-onset atrial fibrillation

Associations of abdominal obesity and new-onset atrial fibrillation in the general population

Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial

Body mass index variability and long-term risk of new-onset atrial fibrillation in the general population: a Korean nationwide cohort study

PREVEntion and regReSsive Effect of weight-loss and risk factor modification on Atrial Fibrillation: the REVERSE-AF study

Underweight is a risk factor for atrial fibrillation: a nationwide population-based study

Bodyweight fluctuation is associated with increased risk of incident atrial fibrillation

Body mass index and adverse events in patients with incident atrial fibrillation

Is there an obesity paradox for outcomes in atrial fibrillation? A systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulant trials

Body mass index and clinical outcomes in Asian patients with atrial fibrillation receiving oral anticoagulation

Alcohol consumption and risk of atrial fibrillation: a prospective study and dose-response meta-analysis

A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey

Alcohol intake and prognosis of atrial fibrillation

Lower risk of stroke after alcohol abstinence in patients with incident atrial fibrillation: a nationwide population-based cohort study

Alcohol abstinence in drinkers with atrial fibrillation

Alcohol abstinence and the risk of atrial fibrillation in patients with newly diagnosed type 2 diabetes mellitus: a nationwide population-based study

Smoking and incidence of atrial fibrillation: results from the Atherosclerosis Risk in Communities (ARIC) study

Association of smoking with the risk of incident atrial fibrillation: a meta-analysis of prospective studies

Predictors of ischemic stroke for low-risk patients with atrial fibrillation: a matched case-control study

Smoking cessation after diagnosis of new-onset atrial fibrillation and the risk of stroke and death

Long-term exposure of fine particulate matter air pollution and incident atrial fibrillation in the general population: a nationwide cohort study

Long-term PM(2.5) exposure and the clinical application of machine learning for predicting incident atrial fibrillation

Physical activity and incidence of atrial fibrillation in older adults: the cardiovascular health study

Effects of short-term exercise training on symptoms and quality of life in patients with chronic atrial fibrillation

A randomized study of the effects of exercise training on patients with atrial fibrillation

Exercise capacity and atrial fibrillation risk in veterans: a cohort study

Physical activity and risk of atrial fibrillation: a nationwide cohort study in general population

Is the risk of atrial fibrillation higher in athletes than in the general population? A systematic review and meta-analysis

Association between exercise habits and stroke, heart failure, and mortality in Korean patients with incident atrial fibrillation: a nationwide population-based cohort study

Exercise and the risk of dementia in patients with newly diagnosed atrial fibrillation: a nationwide population-based study

The prognostic value of electrocardiogram at presentation to emergency department in patients with COVID-19

Atrial fibrillation in patients hospitalized with COVID-19: incidence, predictors, outcomes, and comparison to influenza

Incident atrial fibrillation and its risk prediction in patients developing COVID-19: a machine learning based algorithm approach

Prevalence and impact of atrial fibrillation in hospitalized patients with COVID-19: a systematic review and meta-analysis

COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review

Evaluation of bleeding rate and time in therapeutic range in patients using warfarin before and during the COVID-19 pandemic-warfarin

Anticoagulation therapy in nonvalvular atrial fibrillation in the COVID-19 era: is it time to reconsider our therapeutic strategy?

Evaluation of remote pharmacist-led outpatient service for geriatric patients on rivaroxaban for nonvalvular atrial fibrillation during the COVID-19 pandemic

Pharmacological agents targeting thromboinflammation in COVID-19: review and implications for future research

Anticoagulation, bleeding, mortality, and pathology in hospitalized patients with COVID-19

Reduction in all-cause mortality in COVID-19 patients on chronic oral anticoagulation: a population-based propensity score matched study

Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes

COVID-19 and atrial fibrillation in older patients: does oral anticoagulant therapy provide a survival benefit?-an insight from the GeroCovid registry

Recent randomized trials of antithrombotic therapy for patients with COVID-19: JACC state-of-the-art review

Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19

Intermediate-dose versus standard-dose prophylactic anticoagulation in patients with COVID-19 admitted to the intensive care unit: 90-day results from the INSPIRATION randomized trial

Effect of intermediatedose vs standard-dose prophylactic anticoagulation on thrombotic events, extracorporeal membrane oxygenation treatment, or mortality among patients with COVID-19 admitted to the intensive care unit: the INSPIRATION randomized clinical trial

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

The COVID-19 pandemic and the need for an integrated and equitable approach: an international expert consensus paper

Targeted atrial fibrillation (AF) detection in COVID-19 vaccination clinics

SARS-CoV-2 vaccine and thrombosis: an expert consensus on vaccine-induced immune thrombotic thrombocytopenia

Focused update of the 2017 consensus guidelines of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation