Search

Aims: The effectiveness of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase‐4 inhibitors (DPP4i). Materials and Methods: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. Results: After up to 5 years of follow‐up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51–0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24–0.82). SGLT2i was related to reduced risks of AF‐related hospitalisation (HR: 0.72, 95% CI: 0.56–0.93), stroke (HR: 0.75, 95% CI: 0.60–0.94), and all‐cause death (HR: 0.33, 95% CI: 0.24–0.44). The protective effects were consistent irrespective of the concurrent use of non‐vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. Conclusions: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF‐related hospitalisation, stroke, and all‐cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i. [ABSTRACT FROM AUTHOR]

Background: Although direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) are considered to be safe, over or under anticoagulation and increased bleeding or thromboembolic risk are still considered individually. We aimed to investigate whether there is an association between prothrombin time and international normalized ratio (PT-INR) or activated partial thromboplastin time (aPTT) ratio, and the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding among AF patients taking rivaroxaban or dabigatran. Methods: This multi-center cohort study in Taiwan included 3192 AF patients taking rivaroxaban and 958 patients taking dabigatran for stroke prevention where data about PT-INR and aPTT were available. Results: For patients treated with rivaroxaban, a higher INR level was not associated with a higher risk of major bleeding compared to an INR level < 1.1. The risk of IS/SE was lower for patients having an INR ≥ 1.5 compared to those with an INR < 1.1 (aHR:0.57; [95%CI: 0.37–0.87]; p = 0.01). On-label dosing of rivaroxaban and use of digoxin were independent factors associated with an INR ≥ 1.5 after taking rivaroxaban. For patients taking dabigatran, a higher aPTT ratio was not associated with a higher risk of major bleeding. The risk of IS/SE was lower for patients having an aPTT ratio of 1.1–1.2 and 1.3–1.4 than those with an aPTT ratio < 1.1. Conclusions: In AF patients, rivaroxaban with an INR ≥ 1.5 was associated with a lower risk of IS/SE. PT-INR or aPTT ratios were not associated with bleeding events for rivaroxaban or dabigatran. INR may help predict the outcome of AF patients who take rivaroxaban. [ABSTRACT FROM AUTHOR]

Objective: This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods: Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results: Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion: Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality. [ABSTRACT FROM AUTHOR]

Context: The coexistence of diabetes mellitus and atrial fibrillation (AF) is associated with substantial risks of adverse cardiovascular events., Objective: The relevant outcomes associated with the use of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) vs glucagon-like peptide-1 receptor agonists (GLP-1RAs) among patients with type 2 diabetes (T2D) with/without concomitant AF remain unknown., Methods: In this nationwide retrospective cohort study from the Taiwan National Health Insurance Research Database, there were 344 392 and 31 351 patients with T2D without AF, and 11 462 and 816 T2D patients with AF treated with SGLT2is and GLP-1RAs, respectively, from May 1, 2016, to December 31, 2019. Patients were followed from the drug index date until the occurrence of study events, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. We used propensity score-stabilized weight to balance covariates across the 2 medication groups., Results: The incidence rate of all study outcomes in patients with concomitant AF was much higher than in those without concomitant AF. For the AF cohort, SGLT2i vs GLP-1RA was associated with a lower risk of hospitalization for heart failure (HF) (2.32 vs 4.74 events per 100 person-years; hazard ratio [HR] 0.48, 95% CI 0.36-0.66), with no benefit seen for the non-AF cohort (P for homogeneity < .01). SGLT2i vs GLP-1RA was associated with a lower risk of composite kidney outcomes both in the AF (0.38 vs 0.79 events per 100 person-years; HR 0.47; 95% CI 0.23-0.96) and the non-AF cohorts (0.09 vs 0.18 events per 100 person-years; HR 0.53; 95% CI 0.43-0.64). There were no significant differences in the risk of major adverse cardiovascular events and all-cause mortality in those who received SGLT2i compared with GLP-1RA for the AF or non-AF cohorts., Conclusion: Considering the high risk of developing HF and/or high prevalence of concomitant HF in patients with concomitant diabetes and AF, whether SGLT2is should be the preferred treatment to GLP-1RAs for such a high-risk population requires further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: There are emerging concerns from case reports and pharmacovigilance analyses of a possible risk of interstitial lung disease (ILD) associated with the use of factor Xa (FXa) inhibitors., Objective: To evaluate the risk of incident ILD associated with the use of oral anticoagulants (OACs) in patients with nonvalvular atrial fibrillation (NVAF)., Design, Setting, and Participants: This nationwide retrospective cohort study used data from the Taiwan National Health Insurance Research Database. Patients with NVAF without preexisting lung disease who received OACs from June 1, 2012, to December 31, 2017, were included. Propensity score stabilized weighting (PSSW) was used to balance covariates across the medication groups (FXa inhibitors, dabigatran, and warfarin, with warfarin as the reference). Patients were followed up from the drug index date until the onset of ILD, death, or end of the study (December 31, 2019), whichever occurred first. Data were analyzed from September 11, 2021, to August 3, 2022., Exposures: Patients with NVAF were treated with FXa inhibitors, dabigatran, or warfarin., Main Outcomes and Measures: New-onset idiopathic ILD., Results: Among the 106 044 patients (mean [SD] age, 73.4 [11.9] years; 59 995 men [56.6%]) included in the study, 64 555 (60.9%) received FXa inhibitors (apixban [n = 15 386], edoxaban [n = 12 413], and rivaroxaban [n = 36 756]), 22 501 (21.2%) received dabigatran, and 18 988 (17.9%) received warfarin at baseline. The FXa inhibitors were associated with a higher risk of incident ILD (0.29 vs 0.17 per 100 patient-years; hazard ratio, 1.54 [95% CI, 1.22-1.94]; P < .001), whereas dabigatran was associated with a nonsignificant difference in risk of incident ILD compared with warfarin (reference) after PSSW. The higher risk of incident ILD for FXa inhibitors vs warfarin was consistent with several high-risk subgroups., Conclusions and Relevance: Results of this study suggest that FXa inhibitors were associated with lung injury among patients with NVAF who were treated with OACs. Physicians should be vigilant in monitoring for any potential adverse lung outcomes associated with the use of these drugs.

Background: The bleeding risk profile of patients with atrial fibrillation (AF) may change over time, and the increment of HAS-BLED score is perceived to result in discontinuations of oral anticoagulants (OACs)., Objectives: To investigate the changes of HAS-BLED scores of AF patients initially with a low bleeding risk. The associations between continuation or discontinuation of OACs and clinical outcomes after patients' bleeding risk profile worsened (ie HAS-BLED increased) were studied., Methods: The present study used Taiwan nationwide health insurance research database. From year 2000 to 2015, a total of 24,990 AF patients aged ≥ 20 years with a CHA 2 DS 2 -VASc score  ≥ 1 (males) or  ≥ 2 (females) having an HAS-BLED score of 0-2 who were treated with OACs were identified and followed up for changes of the HAS-BLED scores. Patients who did not refill OACs within 90 days after their HAS-BLED scores increased to  ≥ 3 were defined as discontinuations of OACs. The risks of clinical outcomes were compared between patients who continued or stopped OACs once their HAS-BLED scores increased to  ≥ 3., Results: Mean HAS-BLED score of study population increased from 1.54 to 3.33. At end of 1 year, 5,229 (20.9%) patients had an increment of their HAS-BLED scores to  ≥ 3, mainly due to newly diagnosed hypertension, stroke, bleeding, and concomitant drug therapies. Among 4777 patients who consistently had an HAS-BLED score  ≥ 3, 1,062 (22.2%) stopped their use of OACs. Patients who kept on OACs (n = 3715; 77.8%) even after their HAS-BLED scores increased to ≥ 3 were associated with a lower risk of ischemic stroke (aHR 0.60, 95%CI 0.53-0.69), major bleeding (aHR 0.78, 95%CI 0.67-0.91), all-cause mortality (aHR 0.88, 95%CI 0.79-0.97), and any adverse events (aHR 0.75, 95%CI 0.68-0.82) adjusted for age, sex, heart failure, and HAS-BLED score. These results were consistent among the cohorts after propensity matching., Conclusions: For patients whose HAS-BLED scores increased to ≥ 3, the continuation of OACs was associated with better clinical outcomes. An increased HAS-BLED score in anticoagulated AF patients may not be the only reason to withhold OACs, but reminds physicians to correct modifiable bleeding risk factors and follow up patients more closely. Associations between Continuation or Discontinuation of Oral Anticoagulants and Risks of Clinical Outcomes after HAS-BLED Scores Increased AF atrial fibrillation; aHR adjusted hazard ratio; ICH intra-cranial hemorrhage; OACs oral anticoagulants., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: Whether direct oral anticoagulants (DOACs) are more effective and safer than warfarin among Asian patients with non-valvular atrial fibrillation (NVAF) undergoing dialysis remains unclear., Methods: We first compared the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding associated with DOACs compared with warfarin, in NVAF Asians undergoing dialysis using the Taiwan National Health Insurance Research Database (NHIRD) (Aim 1). Next, we searched PubMed and Medline from January 1, 2010 until January 31, 2020, to perform a systematic review and meta-analysis of all observational real-world studies comparing DOACs with warfarin specifically focused on NVAF patients with stage 4 or 5 chronic kidney disease undergoing dialysis (Aim 2). Finally, we tested the hypothesis whether AF patients undergoing dialysis treated with OACs (warfarin and DOACs) would be associated with lower risk of adverse clinical outcomes as compared to those without OACs using the Taiwan NHIRD (Aim 3)., Results: From June 1, 2012, to December 31, 2017, a total of 3237 and 9263 NVAF patients comorbid with ESRD receiving oral anticoagulant (OACs) (490 on DOAC, 2747 on warfarin) or no OACs, respectively, were enrolled. Propensity score matching was used to balance covariates across the study groups. For the comparison of DOAC vs. warfarin (Aim 1), DOACs had comparable risks of IS/SE and major bleeding to warfarin in our present cohort. From the original 85 results retrieved, nine studies (including our study) with a total of 6490 and 22,494 patients treated with DOACs and warfarin were included in the meta-analysis, respectively. There were 5343 (82%) and 20,337 (90%) patients treated with DOACs and warfarin undergoing dialysis, respectively. The pooled meta-analysis also indicated no difference of the effectiveness (HR:0.90; [95%CI:0.74-1.10]; P = 0.32) and safety outcomes (HR:0.75; [95%CI:0.54-1.05]; P = 0.09) between DOACs and warfarin (Aim 2). For the comparison of OAC (+) vs. OAC (-) (Aim 3), OAC-treatment was associated with a higher risk of IS/SE (hazard ratio (HR):1.54; [95% confidential interval (CI):1.29-1.84];P < 0.0001) and comparable risk of major bleeding compared to those without OAC treatment., Conclusions: DOACs did not provide benefit over warfarin regarding effectiveness and safety in AF patients undergoing dialysis. The use of OAC was not associated with a lower risk of IS/SE in ESRD AF patients when compared to those without OAC use., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer., Methods: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups., Results: There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.50–0.80]; P=0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.24–0.70]; P=0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.23–0.61]; P<0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.56–0.94]; P=0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer (P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years (P interaction <0.05)., Conclusions: Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.

Background: The prevalence and incidence of atrial fibrillation (AF) increase with age. However, older patients often are denied oral anticoagulation (OAC), especially if they are "very elderly" (age ≥90 years) and perceived to be high risk for bleeding, for example, those with a history of intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), or chronic kidney disease., Objective: The purpose of this study was to investigate the effectiveness and safety of OAC in this high-risk, very elderly group., Methods: We used the Taiwan National Health Insurance Research Database to identify high-risk, very elderly subjects taking OAC, either warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), and compared them to non-OAC users for the composite net clinical endpoint of ischemic stroke, ICH, major bleeding, or mortality., Results: We studied 7362 subjects (mean age 92.5 years), of whom 1737 were taking NOACs, 670 warfarin, and 4955 non-OACs. Compared to non-OACs, warfarin was associated with a higher risk of the composite endpoint (adjusted hazard ratio [aHR] 1.163; 95% confidence interval [CI] 1.052-1.287), whereas NOACs were associated with a lower risk (aHR 0.763; 95% CI 0.702-0.830). After propensity matching, NOACs were associated with a lower risk of events compared to non-OACs or warfarin, whereas warfarin had a similar risk compared to non-OACs., Conclusion: Warfarin was associated with a similar or even higher risk of composite clinical outcomes compared to non-OACs. NOACs were associated with a lower risk of composite endpoint compared to warfarin or non-OACs, and their use still should be considered in these high-risk, very elderly AF patients., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Evidence of clinical outcomes for oral anticoagulants and antiplatelet treatment (APT) in patients with atrial fibrillation (AF) and critical limb ischemia (CLI) is very limited., Methods: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, 1223 patients with AF and CLI taking direct-acting oral coagulants (DOACs), warfarin, or APT were identified from June 1, 2012, to December 31, 2017. We used propensity score stabilized weighting (PSSW) to balance covariates across study groups., Results: After PSSW, DOAC (n = 446) was associated with lower risks of ischemic stroke/systemic embolism (IS/SE), all major adverse limb events, and all major bleeding events compared with warfarin (n = 237). DOAC was associated with lower risks of IS/SE, acute myocardial infarction (AMI), and all major adverse limb events and a comparable risk of major bleeding events compared with APT (n = 540). DOAC has a lower risk of composite net-clinical-benefit outcome (IS/SE, AMI, all major adverse limb events, plus all major bleeding events) compared with warfarin (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.35-0.65; P < 0.0001) or APT (HR: 0.44; 95% CI: 0.34-0.56; P < 0.0001). The composite net-clinical-benefit outcome was comparable for warfarin vs APT. The reduced risk of net-clinical-benefit outcome for DOAC vs warfarin or APT persisted in high subgroups including age > 75 years, presence of diabetes mellitus, or chronic kidney disease., Conclusions: DOAC was associated with a significantly lower risk of composite net-clinical-benefit outcome than either warfarin or APT in patients with AF and concomitant CLI. Further prospective study is necessary to validate the findings in the future., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the influences of non-vitamin K antagonist oral anticoagulants (NOACs) on rates of initiations of oral anticoagulants (OACs) and outcomes among elderly patients with atrial fibrillation (AF)., Methods: From January 1, 2009, to December 31, 2015, 33,539 newly-diagnosed AF patients older than 85 years old who survived more than 180 days after AF diagnosis were studied. Temporal trends regarding OAC initiation rates after incident AF were analyzed. The 1-year risks of ischemic stroke, intracranial hemorrhage, and mortality of incident AF patients diagnosed each year were compared with that of the year 2009., Results: Initiation rates of OACs after AF was newly diagnosed in the elderly significantly increased from 9.5% to 34.3%, mainly due to the introduction of NOACs (from 0% to 26.2%). Several clinical factors were associated with OACs underuse, including chronic obstructive pulmonary disease, abnormal renal function, anemia, and history of bleeding. Compared with year 2009 (incidence rate, 5.55%/year), the 1-year risk of ischemic stroke after AF diagnosis decreased in the era of NOACs (incidence rate, 4.20%/year; adjusted hazard ratio [aHR], 0.748 in year 2012; 4.39%/year, aHR, 0.789 in 2014; 2.75%/year; aHR, 0.513 in year 2015; all P<.01, except for year 2013, 4.80%/year [P=.07]). Also, the risks of mortality were lower in years 2012 to 2015, while the risk of ICH remained unchanged., Conclusion: Initiation rates of OACs after AF was newly diagnosed in the elderly significantly increased following the introduction of NOACs. A lower risk of ischemic stroke, mortality, and composite adverse events was observed, which was temporally associated with the increasing prescription rates of OACs., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed for Asian patients with atrial fibrillation (AF)., Objective: The purpose of this study was to investigate the associations between inappropriate dosing of NOACs and clinical outcomes., Methods: We used medical data from a multicenter health care system in Taiwan, which included 2068, 5135, 2589, 1483, and 2342 AF patients taking dabigatran, rivaroxaban, apixaban, edoxaban, and warfarin, respectively. The risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding in patients treated with underdosing or overdosing NOACs were compared to those of on-label dosing NOACs and warfarin., Results: About 27% and 5% of AF patients were treated with underdosing and overdosing NOACs, respectively. Compared to on-label dosing, underdosing NOACs were associated with a significantly higher risk of IS/SE (adjusted hazard ratio [aHR] 1.59; 95% confidence interval [CI] 1.25-2.02; P <.001), whereas overdosing NOACs were associated with a significantly higher risk of major bleeding (aHR 2.01; 95% CI 1.13-3.56; P = .017). Compared to warfarin, the 4 on-label dosing NOACs were associated with a comparable risk of IS/SE and a significantly lower risk of major bleeding, whereas underdosing NOACs were associated with a higher risk of IS/SE (aHR 1.46; P = .012)., Conclusion: About 3 in 10 Asian AF patients were treated with off-label dosing NOACs in daily practice. Compared to on-label dosing, underdosing was associated with a higher risk of IS/SE, whereas overdosing was associated with a higher risk of major bleeding. Thus, even for Asian AF patients at higher risk for bleeding, NOACs still should be prescribed at the dosing based on clinical trial criteria and guideline recommendations., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Oral anticoagulants (OACs) may serve as a "screening test" for gastrointestinal (GI) tract malignancies through the clinical presentation of bleeding., Objective: The purpose of this study was to investigate the 1-year incidence and predictors of GI cancer after GI bleeding among atrial fibrillation (AF) patients treated with warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). The risks of mortality after GI cancers between patients receiving warfarin and those receiving NOACs were compared., Methods: A total of 10,845 anticoagulated AF patients hospitalized due to GI bleeding without a previous history of GI cancer were identified from the Taiwan National Health Insurance Research Database. Patients were followed-up for incident GI cancers for up to 1 year., Results: Within 1 year after GI bleeding, 290 patients (2.67%) were diagnosed with GI tract cancer. More patients treated with NOACs were diagnosed with GI cancer than those treated with warfarin (3.87% vs 2.44%; P <.001; odds ratio [OR] 1.606; P <.001). Age (OR 1.025 per 1-year increment) and male sex (OR 1.356) were associated with the diagnosis of GI cancer. Among patients diagnosed with GI cancer, 45.2% died within 1 year. The risk of mortality was lower in patients treated with NOACs than in those treated with warfarin (23.5% vs 51.8%; adjusted hazard ratio 0.441; P <.001)., Conclusion: Incident GI cancers were diagnosed in 1 of 37 AF patients at 1 year after OAC-related GI bleeding and were more common among patients treated with NOACs (1/26) compared to warfarin (1/41). Detailed examinations for occult GI cancers are necessary, especially among elderly males., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: Patients with hyperthyroidism were excluded from the randomized clinical trials of direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF)., Methods: We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3213 and 1181 NVAF patients with hyperthyroidism who were taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53 591 and 16 564 NVAF patients without hyperthyroidism, taking DOACs and warfarin, respectively. We used propensity score stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n = 3213) and without hyperthyroidism (n = 12 852); and both taking warfarin, with (n = 1181) and without hyperthyroidism (n = 4724)., Results: After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio [HR] 0.65; 95% confidential interval [CI], 0.44-0.96; P = 0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, among patients taking warfarin, those with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR 0.61; 95% CI, 0.43-0.86; P = 0.0050)., Conclusion: Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Current guidelines recommend the use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). Data regarding warfarin sodium use compared with NOAC use in patients with AF with a history of intracranial hemorrhage (ICH) are limited., Objective: To compare the clinical outcomes of warfarin use and NOAC use in patients with AF with a history of ICH using a nationwide cohort with AF., Design, Setting, and Participants: A nationwide cohort study from January 1, 2012, to December 31, 2016, was performed using data from the Taiwan National Health Insurance Research Database. The dates of analysis were July 1 to September 1, 2019. The study population comprised patients with AF with a history of ICH and a CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, prior stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease], age 65-74 years, sex category [female]) of at least 1 for men or at least 2 for women who had received warfarin or NOACs. The clinical outcomes were examined using Cox proportional hazards regression analyses among the study population before and after propensity score matching., Exposures: Oral anticoagulation with warfarin or NOACs., Main Outcomes and Measures: The clinical outcomes measured were all-cause mortality, ischemic stroke, ICH, major bleeding, and adverse events., Results: The study cohort included 4540 patients (mean [SD] age, 76.0 [10.5] years; 2653 men [58.4%]), with 1047 patients receiving warfarin (mean [SD] age, 75.1 [11.4] years; 571 men [54.5%]) and 3493 patients receiving NOACs (mean [SD] age, 76.3 [10.2] years; 2082 men [59.6%]). Compared with warfarin use, NOAC use was associated with statistically significantly lower risk of all-cause mortality (adjusted hazard ratio [aHR], 0.517; 95% CI, 0.457-0.585), ICH (aHR, 0.556; 95% CI, 0.389-0.796), and major bleeding (aHR, 0.645; 95% CI, 0.525-0.793), whereas the rate of ischemic stroke was similar in the 2 groups (aHR, 0.879; 95% CI, 0.678-1.141). These results were generally consistent after propensity score matching among 973 patients in each group., Conclusions and Relevance: Among patients with AF with prior ICH, NOAC use was associated with lower rates of ICH and major bleeding compared with warfarin use, whereas the rate of ischemic stroke was similar in the 2 groups. Among patients with AF with prior ICH, NOACs could be the preferred choice for stroke prevention.

Background: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients., Methods: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups., Results: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI) 0.78-0.99]; P = 0.0283), major adverse limb events (MALE) (aHR:0.72;[95% CI 0.57-0.92]; P = 0.0083), and major bleeding (aHR:0.67;[95% CI 0.59-0.76]; P < 0.0001) compared to warfarin. NOACs decreased MACE in patients of ≥ 75 but not in those aged < 75 years (P interaction = 0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction < 0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age ≥ 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs., Conclusion: Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.

Background: Stroke prevention in elderly patients with atrial fibrillation (AF) can be challenging, requiring a balance between thromboembolism prevention and serious bleeding. Comparisons of nonvitamin K antagonist oral anticoagulants (NOACs) and warfarin in older adults at different age strata (65-74, 75-89, and ≥ 90 years of age) in the daily practice have not been well described, particularly in Asians. We aimed to assess the clinical outcomes of NOACs compared with warfarin for stroke prevention in elderly patients with AF., Methods: From 2012 to 2015, 64,169 patients ≥ 65 years of age with AF who received at least one NOAC (dabigatran, rivaroxaban, or apixaban) or warfarin prescription were identified from the Taiwan National Health Insurance Research Database. The risks of ischemic stroke, intracranial hemorrhage (ICH), major bleeding, mortality, and composite adverse events were compared between NOACs and warfarin in all patients ≥ 65 years of age and, specifically, with different age strata (ie, 65-74, 75-89, ≥ 90 years)., Results: Overall, NOACs were associated with a significantly lower risk of ischemic stroke (adjusted hazard ratio [aHR], 0.869; 95% CI, 0.812-0.931), ICH (aHR, 0.524; 95% CI, 0.456-0.601), major bleeding (aHR, 0.824; 95% CI, 0.776-0.875), mortality (aHR, 0.511; 95% CI, 0.491-0.532), and composite adverse events (aHR, 0.646; 95% CI, 0.625-0.667) than warfarin. There was heterogeneity in treatment effect for NOACs vs warfarin in different age strata, but the results still favored NOACs even among very older adults (≥ 90 years). The results were generally consistent with propensity matching analysis. The absolute risk difference and reductions in ICH and composite adverse events with NOAC use were even greater among older adults than warfarin., Conclusions: Compared with warfarin, NOACs were associated with a significantly lower risk of adverse events, with heterogeneity in treatment effects among different age strata. Overall, the clear safety signal in favor of NOACs over warfarin was evident irrespective of age strata, being most marked in very older adults., (Copyright © 2020. Published by Elsevier Inc.)

Background: Whether four direct oral anticoagulants (DOACs) are superior to warfarin in Asian patients with nonvalvular atrial fibrillation (NVAF) remains unclear., Methods: This nationwide retrospective cohort study was based on data from Taiwan's National Health Insurance Research Database from June 1, 2012, to December 31, 2017, covering patients with NVAF taking edoxaban (n = 4,577), apixaban (n = 9,952), rivaroxaban (n = 33,022), dabigatran (n = 22,371), and warfarin (n = 19,761). Propensity score weighting was used to balance covariates across study groups. Patients were followed up until occurrence of study outcomes or end date of study., Results: Edoxaban, apixaban, and rivaroxaban were associated with a lower risk of ischemic stroke/systemic embolism than warfarin. All DOACs had a lower risk of major bleeding than warfarin. Apixaban was associated with a lower risk of major bleeding than rivaroxaban and dabigatran, whereas the risk of major bleeding was comparable between edoxaban and apixaban. The reduced risks of thromboembolism/major bleeding for the four DOACs persisted in high-risk subgroups, including those with chronic kidney disease, elderly patients (age ≥ 75 years), secondary stroke prevention, or CHA 2 DS 2 -VASc score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65-74 years, and female sex) ≥ 4. A total of 2,924 (64%), 6,359 (64%), 31,108 (94%), and 19,821 (89%) patients received low-dose edoxaban (15-30 mg/d), apixaban (2.5 mg bid), rivaroxaban (10-15 mg/d), and dabigatran (110 mg bid), respectively. The effectiveness/safety outcomes with the four low-dose DOACs compared with warfarin were consistent with the main analysis., Conclusions: In the largest real-world practice study among Asian patients with NVAF, four DOACs were associated with a comparable or lower risk of thromboembolism, and a lower risk of bleeding than warfarin. There was consistency even among high-risk subgroups and whether standard-or low-dose regimens were compared., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background:  Oral anticoagulants (OACs) are not recommended for 'low-risk' patients with atrial fibrillation (AF). We investigated the incidences of new risk factors developing, and the temporal trends in the CHA 2 DS 2 -VASc score in initially 'low-risk' AF patients. Second, we propose a reasonable timing interval at which stroke risk should be reassessed for such AF patients., Methods:  We studied 14,606 AF patients who did not receive anti-platelet agents or OACs with a baseline CHA 2 DS 2 -VASc score of 0 (males) or 1 (females). The CHA 2 DS 2 -VASc scores of patients were followed up and updated until the occurrence of ischaemic stroke or mortality or 31 December 2011. The associations between the prescription of warfarin and risk of adverse events once patients' scores changed were analysed. Decile values of durations to incident co-morbidities and from the acquirement of new co-morbidities to ischaemic stroke were studied., Results:  During a mean follow-up of 4 years, 7,079 (48.5%) patients acquired at least one new stroke risk factor component(s) with annual risks of 6.35% for hypertension, 3.68% for age ≥ 65 years, 2.77% for heart failure, 1.99% for diabetes mellitus and 0.33% for vascular diseases. The incidence for CHA 2 DS 2 -VASc score increments was 12.1%/year. Initiation of warfarin was associated with a lower risk of adverse events (adjusted hazard ratio, 0.530; 95% confidence interval, 0.371-0.755). Among 6,188 patients who acquired new risk factors, 80% would acquire these co-morbidities after 4.2 months of AF diagnosis. The duration from the acquirement of incident co-morbidities to the occurrence of ischaemic stroke was longer than 4.4 months for 90% of the patients., Conclusion:  The CHA 2 DS 2 -VASc score increases in approximately 12% of initially 'low-risk' AF patients each year, and the initiation of warfarin once the score changed was associated with a better prognosis. Three to four months may be a reasonable timing interval at which stroke risk should be reassessed so that OACs could be prescribed in a timely manner for stroke prevention., Competing Interests: Dr. Lip reports consultancy and speaker fees from Bayer, Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo outside the submitted work. No fees were received personally. Other authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Sudden cardiac death (SCD), the most devastating manifestation of ventricular arrhythmias (VAs), is the leading cause of mortality in patients with atrial fibrillation (AF). We hypothesized that the CHA 2 DS 2 -VASc score, consisting of age and several clinical risk factors, could be used to estimate the individual risk of SCD/VAs for AF patients. From year 2000 to 2011, 288,181 newly-diagnosed AF patients without antecedent SCD/VAs were identified from "Taiwan National Health Insurance Research Database." During the follow-up of 1,065,751 person-years, 11,166 patients experienced SCD/VAs with an annual risk of 1.05% which increased from 0.34% for patients with a CHA 2 DS 2 -VASc score of 0% to 2.63% for those with a score of 9. The CHA 2 DS 2 -VASc score was a significant predictor of SCD/VAs with an adjusted hazard ratio of 1.21 (95% confidence interval 1.20 to 1.22) per 1 point increment of the score. As the CHA 2 DS 2 -VASc score increased from 1 to 9, the hazard ratio of SCD/VAs continuously increased from 1.28 to 4.17 compared with patients with a CHA 2 DS 2 -VASc score of 0. In conclusion, CHA 2 DS 2 -VASc score was a convenient scoring system which could be used to predict the risk of SCD/VAs in AF patients in addition to its ability for stroke risk stratification., (Copyright © 2018. Published by Elsevier Inc.)

Background: Several cardiovascular diseases exhibit seasonal variations, but data about cold temperature and risk of ischemic stroke in patients with atrial fibrillation (AF) are limited., Objective: The purpose of this study was to investigate the risk of ischemic stroke in different seasons, testing the hypothesis that the cold weather season would increase the risk of stroke in AF., Methods: This study used the National Health Insurance Research Database in Taiwan. From 2000 to 2012, a total of 289,559 AF patients were enrolled, and 34,991 experienced ischemic stroke after mean follow-up of 3 years. The relationship between risk of ischemic stroke and temperatures was analyzed., Results: The highest incidence of ischemic stroke was observed in winter, which was the coldest season, with an incidence rate of 0.33 per 100 person-months. Compared with the summer period, the risk of ischemic stroke increased by 10% in spring (incidence rate ratio [IRR] 1.10; 95% confidence interval [CI] 1.07-1.13) and by 19% in winter (IRR 1.19; 95% CI 1.15-1.22) but did not differ significantly between summer and autumn (IRR 1.00; 95% CI 0.97-1.03). Compared with the days with an average temperature of 30°C, the risk of ischemic stroke for days with an average temperature <20°C significantly increased. Lower 7-, 10-, or 14-day average temperatures were significantly associated with an increased risk of ischemic stroke in the case-crossover analysis., Conclusion: In this nationwide study, a seasonal variation of incidence of ischemic stroke in AF patients was observed, with an increased risk of stroke on days with an average temperature <20°C. AF-related stroke may be influenced by environmental interactions., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Stroke prevention with oral anticoagulants (OACs) is the cornerstone for the management of atrial fibrillation (AF). However, data about the use of OACs among patients ≥90 years of age are limited. We aimed to investigate the risk of ischemic stroke and intracranial hemorrhage (ICH) and the net clinical benefit of OAC treatment for very elderly patients with AF (≥90 years of age)., Methods: This study used the National Health Insurance Research Database in Taiwan. Risks of ischemic stroke and ICH were compared between 11 064 and 14 658 patients with and without AF ≥90 years of age without antithrombotic therapy from 1996 to 2011. Patients with AF (n=15 756) were divided into 3 groups (no treatment, antiplatelet agents, and warfarin), and the risks of stroke and ICH were analyzed. The risks of ischemic stroke and ICH were further compared between patients treated with warfarin and nonvitamin K antagonist OACs (NOACs) from 2012 to 2015 when NOACs were available in Taiwan., Results: Compared with patients without AF, patients with AF had an increased risk of ischemic stroke (event number/patient number, incidence = 742/11 064, 5.75%/y versus 1399/14 658, 3.00%/y; hazard ratio, 1.93; 95% confidence interval, 1.74-2.14) and similar risk of ICH (131/11 064, 0.97%/y versus 206/14 658, 0.54%/y; hazard ratio, 0.85; 95% confidence interval, 0.66-1.09) in competing risk analysis for mortality. Among patients with AF, warfarin use was associated with a lower stroke risk (39/617, 3.83%/y versus 742/11 064, 5.75%/y; hazard ratio, 0.69; 95% confidence interval, 0.49-0.96 in a competing risk model), with no difference in ICH risk compared with nontreatment. When compared with no antithrombotic therapy or antiplatelet drugs, warfarin was associated with a positive net clinical benefit. These findings persisted in propensity-matched analyses. Compared with warfarin, NOACs were associated with a lower risk of ICH (4/978, 0.42%/y versus 19/768, 1.63%/y; hazard ratio, 0.32; 95% confidence interval, 0.10-0.97 in a competing risk model), with no difference in risk of ischemic stroke., Conclusions: Among patients with AF ≥90 years of age, warfarin was associated with a lower risk of ischemic stroke and positive net clinical benefit. Compared with warfarin, NOACs were associated with a lower risk of ICH. Thus, OACs may still be considered as thromboprophylaxis for elderly patients, with NOACs being the more favorable choice., (© 2018 American Heart Association, Inc.)

Aim: When assessing bleeding risk in patients with atrial fibrillation (AF), risk stratification is often based on the baseline risks. We aimed to investigate changes in bleeding risk factors and alterations in the HAS-BLED score in AF patients. We hypothesized that a follow-up HAS-BLED score and the 'delta HAS-BLED score' (reflecting the change in score between baseline and follow-up) would be more predictive of major bleeding, when compared with baseline HAS-BLED score., Methods and Results: A total of 19,566 AF patients receiving warfarin and baseline HAS-BLED score ≤2 were studied. After a follow-up of 93,783 person-years, 3,032 major bleeds were observed. The accuracies of baseline, follow-up, and delta HAS-BLED scores as well as cumulative numbers of baseline modifiable bleeding risk factors, in predicting subsequent major bleeding, were analysed and compared. The mean baseline HAS-BLED score was 1.43 which increased to 2.45 with a mean 'delta HAS-BLED score' of 1.03. The HAS-BLED score remained unchanged in 38.2% of patients. Of those patients experiencing major bleeding, 76.6% had a 'delta HAS-BLED' score ≥1, compared with only 59.0% in patients without major bleeding ( p  < 0.001). For prediction of major bleeding, AUC was significantly higher for the follow-up HAS-BLED (0.63) or delta HAS-BLED (0.62) scores, compared with baseline HAS-BLED score (0.54). The number of baseline modifiable risk factors was non-significantly predictive of major bleeding (AUC = 0.49)., Conclusion: In this 'real-world' nationwide AF cohort, follow-up HAS-BLED or 'delta HAS-BLED score' was more predictive of major bleeding compared with baseline HAS-BLED or the simple determination of 'modifiable bleeding risk factors'. Bleeding risk in AF is a dynamic process and use of the HAS-BLED score should be to 'flag up' patients potentially at risk for more regular review and follow-up, and to address the modifiable bleeding risk factors during follow-up visits., Competing Interests: None., (Schattauer GmbH Stuttgart.)

Background: Most data on the clinical epidemiology of atrial fibrillation (AF) come from Western populations, and data for Asians are limited. We investigated the lifetime risk and projected number of AF among Asians. The annual risks of adverse events among patients with AF, time trends, and the risks compared with patients without AF were analyzed., Methods: Between 2000 and 2011, 289,559 patients aged ≥ 20 years experienced new-onset AF in Taiwan. The incidence, prevalence, and lifetime risk of AF were calculated. The risk of adverse events among patients with AF were analyzed and compared with that of age- and sex-matched patients without AF., Results: The incidence of AF in year 2011 was 1.51 per 1,000 person-years, with a lifetime risk of AF being appropriately 1 in 7 for subjects aged > 20 years. The prevalence of AF is estimated to be 4.01% in 2050. Compared with patients without AF, AF was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 2.61), heart failure (aHR, 3.31), ischemic stroke (aHR, 3.34), dementia (aHR, 1.56), sudden cardiac death (aHR, 1.83), and myocardial infarction (aHR, 1.62); all P < .01. The risks of ischemic stroke, heart failure, and mortality were especially higher compared with patients without AF in the initial period (approximately 6 months) after AF was first diagnosed., Conclusions: The burden of AF among Asian patients is increasing, with a lifetime risk of AF being 1 in 7. Optimized management of any associated comorbidities should be part of the holistic management approach for AF., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: When assessing ischemic stroke risk in patients with atrial fibrillation (AF), the CHA 2 DS 2 -VASc score is calculated based on the baseline risk factors, and the outcomes are determined after a follow-up period. However, the stroke risk in patients with AF does not remain static, and with time, patients get older and accumulate more comorbidities., Objectives: This study hypothesized that the "Delta CHA 2 DS 2 -VASc score," which reflects the change in score between baseline and follow-up, would be more predictive of ischemic stroke compared with the baseline CHA 2 DS 2 -VASc score., Methods: A total of 31,039 patients with AF who did not receive antiplatelet agents or oral anticoagulants, and who did not have comorbidities of the CHA 2 DS 2 -VASc score except for age and sex, were studied. The Delta CHA 2 DS 2 -VASc scores were defined as the differences between the baseline and follow-up CHA 2 DS 2 -VASc scores. During 171,956 person-years, 4,103 patients experienced ischemic stroke. The accuracies of baseline, follow-up, and Delta CHA 2 DS 2 -VASc scores in predicting ischemic stroke were analyzed and compared., Results: The mean baseline CHA 2 DS 2 -VASc score was 1.29, which increased to 2.31 during the follow-up, with a mean Delta CHA 2 DS 2 -VASc score of 1.02. The CHA 2 DS 2 -VASc score remained unchanged in only 40.8% of patients. Among 4,103 patients who experienced ischemic stroke, 89.4% had a Delta CHA 2 DS 2 -VASc score ≥1 compared with only 54.6% in patients without ischemic stroke, and 2,643 (64.4%) patients had ≥1 new-onset comorbidity, the most common being hypertension. The Delta CHA 2 DS 2 -VASc score was a significant predictor of ischemic stroke that performed better than baseline or follow-up CHA 2 DS 2 -VASc scores, as assessed by the C-index and the net reclassification index., Conclusions: In this AF cohort, the authors demonstrated that the CHA 2 DS 2 -VASc score was not static, and that most patients with AF developed ≥1 new stroke risk factor before presentation with ischemic stroke. The Delta CHA 2 DS 2 -VASc score, reflecting the change in score between baseline and follow-up, was strongly predictive of ischemic stroke, reflecting how stroke risk in AF is a dynamic process due to increasing age and incident comorbidities., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Sudden cardiac death (SCD) is the most devastating manifestation of ventricular arrhythmias (VAs), and is the leading cause of mortality among atrial fibrillation (AF) patients. The goal of the present study was to investigate the incidence of SCD/VAs amongst patients with and without AF. We also aimed to identify important risk factors of SCD/VAs among AF patients. Using the "National Health Insurance Research Database" in Taiwan, a total of 352,656 AF and 352,656 non-AF patients without antecedent SCD/VAs were identified. The annual risk of SCD/VAs was higher in AF than non-AF groups (0.97% versus 0.47%) with an adjusted hazard ratio (HR) of 1.64. The increased risk of SCD/VAs in AF patients was consistently observed in different age strata, various comorbidities and patients without use of class I/III anti-arrhythmic drugs or digoxin. Among AF patients, age ≥75 years, congestive heart failure, hypertension, diabetes mellitus, previous stroke/transient ischemic attack, vascular diseases, chronic kidney disease and chronic obstructive pulmonary disease were important risk factors for SCD/VAs. In conclusion, the risk of SCD/VAs amongst AF patients was 1.64-fold higher compared to non-AF patients, which was associated with the number of clinical risk factors associated with the particular AF patient.

Background and Purpose: The age threshold for an increased stroke risk for patients with atrial fibrillation may be different for Asians and non-Asians. We hypothesized that a modified CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female) scheme, mCHA2DS2-VASc, which assigned one point for patients aged 50 to 74 years, may perform better than CHA2DS2-VASc score for stroke risk stratification in Asians., Methods: This study used the Taiwan National Health Insurance Research Database, which included 224 866 newly diagnosed atrial fibrillation patients. The predictive accuracies of ischemic stroke of CHA2DS2-VASc and mCHA2DS2-VASc scores were compared among 124 271 patients without antithrombotic therapies. From the whole cohort, 15 948 patients had a CHA2DS2-VASc score 0 (males) or 1 (females), and 8654 patients had an mCHA2DS2-VASc score 1 (males) or 2 (females). The latter were categorized into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin, and the risks of ischemic stroke and intracranial hemorrhage (ICH) were compared., Results: During a follow-up of 538 653 person-years, 21 008 patients experienced ischemic stroke. The mCHA2DS2-VASc performed better than CHA2DS2-VASc score in predicting ischemic stroke assessed by C indexes and net reclassification index. For 8654 patients having an mCHA2DS2-VASc score of 1 (males) or 2 (females) because of the resetting of the age threshold, use of warfarin was associated with a 30% lower risk of ischemic stroke and a similar risk of ICH compared with nontreatment. Net clinical benefit analyses also favored the use of warfarin in different weighted models., Conclusions: In this Asian atrial fibrillation cohort, the mCHA2DS2-VASc score performed better than the CHA2DS2-VASc and would further identify atrial fibrillation patients who may derive a positive net clinical benefit from oral anticoagulation., (© 2016 American Heart Association, Inc.)

Objective: To investigate the impact on outcomes of changing treatment guideline recommendations by comparing the proportion of patients with atrial fibrillation (AF) recommended oral anticoagulants (OACs) under the 2011 and 2014 American College of Cardiology/American Heart Association (ACC/AHA) guidelines., Patients and Methods: We used the "National Health Insurance Research Database" in Taiwan, which included 354,649 patients with AF from January 1, 1996 through December 31, 2011. Patients with a CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score of 2 or more and a CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) score of 2 or more were considered to have a definitive indication for receiving OACs according to the 2011 and 2014 ACC/AHA guidelines, respectively., Results: The percentages of patients with AF recommended OACs increased from 69.3% (n=245,598) under the 2011 guideline to 86.7% (n=307,640) under the new 2014 guidelines, an increment of 17.5% (95% CI, 17.4-17.6). Most women with AF (94.1%) and patients older than 65 years (97.2%) would receive OACs on the basis of the 2014 guidelines. Among patients previously not being recommended OACs in older guidelines, OAC use under the new guidelines was associated with a lower risk of adverse outcomes (ischemic stroke or intracranial hemorrhage or bleeding requiring blood transfusion or mortality) with an adjusted hazard ratio of 0.89 (95% CI, 0.85-0.94)., Conclusion: In this nationwide cohort study, use of the 2014 guidelines led more patients with AF to receive OACs for stroke prevention, and this increased OAC use was associated with better outcomes. Better efforts to implement guidelines would lead to improved outcomes for patients with AF., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is associated with an increased risk of cognitive impairment and functional decline, and may contribute to development of dementia., Objectives: Data from a nationwide large-scale population-based cohort study are lacking. Besides, how best to predict the occurrence of incident dementia among AF subjects remains uncertain., Methods: A total of 332,665 AF subjects without dementia were identified as the study group from the "National Health Insurance Research Database" in Taiwan. For each study patient, one age- and sex-matched subject without AF and dementia was selected as the control group. The study end point was occurrence of dementia, and the usefulness of CHADS2 and CHA2DS2-VASc scores in predicting dementia was analyzed., Results: During the follow-up, 29,012 AF patients experienced dementia with an annual incidence of 2.12%, higher than non-AF subjects (1.50%). Patients with AF possessed a higher risk of dementia with a hazard ratio (HR) of 1.420 after adjustments for age, gender, baseline differences and medication use. Among AF patients, the CHADS2 and CHA2DS2-VASc scores were significant predictors of dementia with an adjusted HR of 1.520 and 1.497 per 1 increment of the CHADS2 and CHA2DS2-VASc scores, respectively. The c-index for CHA2DS2-VASc in predicting dementia (0.611, 95% confidence interval [CI]=0.608-0.614) was significantly higher than the CHADS2 score (0.589, 95% CI=0.586-0.592) (DeLong test p<0.001)., Conclusions: In this nationwide cohort study, AF was independently associated with a higher risk of dementia. The CHA2DS2-VASc score can be used to estimate the risk of dementia in AF patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Recent studies from Asia have suggested that the risk of ischemic stroke for patients with atrial fibrillation (AF) with a "low-risk" congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65 to 74, female (CHA2DS2-VASc) score of 0 (for males) or 1 (for females) might be higher than that for non-Asians., Objectives: This study hypothesized that the age threshold (65 years) used in the CHA2DS2-VASc system for initiating oral anticoagulants (OACs) might be lower in Taiwanese AF patients than in non-Asians., Methods: We used the National Health Insurance Research Database in Taiwan to study 186,570 nonanticoagulated AF patients. There were 9,416 males with a CHA2DS2-VASc score of 0 and 6,390 females with a CHA2DS2-VASc score of 1. Their risk of ischemic stroke was analyzed with stratification on the basis of age., Results: The annual risks of ischemic stroke for males (score 0) and females (score 1) were 1.15% and 1.12%, respectively, and continuously increased from younger to older age groups, with an increment in stroke risk evident for patients >50 years of age. At a cutoff of 50 years, patients could be further stratified into 2 subgroups with different stroke risks (>50 years of age: 1.78%/year; vs. <50 years of age: 0.53%/year). This observation was consistent for males (1.95%/year vs. 0.46%/year, respectively) and females (1.58%/year vs. 0.64%/year, respectively) with AF. In a subgroup analysis, the annual risks of ischemic stroke for males and females with AF 50 to 54 years of age were 1.47% and 1.07%, respectively., Conclusions: For Taiwanese patients 50 to 64 years of age, the annual stroke risk was 1.78%, which may exceed the threshold for OAC use for stroke prevention. The annual risk of ischemic stroke for AF patients <50 years of age was 0.53%, which was truly low-risk, and OACs could be omitted. Whether resetting the age threshold to 50 years could refine current clinical risk stratification for Asian AF patients deserves further study., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Data on the use of oral anticoagulation (OAC) and antiplatelet therapy and the risk of bleeding and stroke amongst Asian patients with atrial fibrillation (AF) are limited. We investigated the risks of bleeding and stroke with use of oral anticoagulation (OAC) and antiplatelet therapy as mono- or combination therapy, in patients with AF from a Chinese nationwide cohort study., Methods: We studied a cohort of 10384 patients (57.2% men, age 67.8 ± 13.2 yrs) between 1999 and 2010 from the National Health Insurance Research Database in Taiwan. Records of prescriptions were obtained during follow-up. The main outcome was a recurrent stroke during the follow-up period. Time-dependent Cox proportional hazards models were used for this analysis., Results: We documented 1009 events for bleeding, as well as 224 hemorrhagic stroke and 1642 ischemic stroke events during a median 3.2 (interquartile range, 1.05-6.54) years' follow-up. Compared with warfarin users, patients with antiplatelet therapy had a lower risk of bleeding (adjusted relative risk [RR], 0.59, 95% confidence interval [CI], 0.49-0.71, p<0.001) whilst combination therapy had a non-statistically significant higher bleeding risk (RR, 1.33, 95%, 0.91-1.94, p = 0.20). Patients on antiplatelet monotherapy had a similar risk for ischemic stroke compared with OAC (RR 1.05, 95% CI, 0.89-1.25, p = 0.50), whilst those on combination therapy had a significantly higher risk (RR 1.90, 95% CI, 1.34-2.70, p<0.001)., Conclusion: In a national representative cohort, antiplatelet therapy had no significant difference in ischemic stroke risk to warfarin. For bleeding, aspirin had a lower risk compared to warfarin. This may reflect poor anticoagulation control, highlighting important missed opportunities for improved stroke prevention, especially in countries where anticoagulation management is suboptimal.

Background: Although the CHA2DS2-VASc (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female) score is recommended by both American and European guidelines for stroke risk stratification in atrial fibrillation (AF), the treatment recommendations for a CHA2DS2-VASc score of 1 are less clear., Objectives: This study aimed to investigate the risk of ischemic stroke in patients with a single additional stroke risk factor (i.e., CHA2DS2-VASc score = 1 [males] or 2 [females]) and the impact of different component risk factors., Methods: We used the National Health Insurance Research Database in Taiwan. Among 186,570 AF patients not on antiplatelet or anticoagulant therapy, we evaluated males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2. The clinical endpoint was the occurrence of ischemic stroke., Results: Among 12,935 male AF patients with a CHA2DS2-VASc score of 1, 1,858 patients (14.4%) experienced ischemic stroke during follow-up (5.2 ± 4.3 years), with an annual stroke rate of 2.75%. Ischemic stroke risk ranged from 1.96%/year for men with vascular disease to 3.50%/year for those 65 to 74 years of age. For 7,900 females with AF and a CHA2DS2-VASc score of 2, 14.9% experienced ischemic stroke for an annual stroke rate of 2.55%. Ischemic stroke risk increased from 1.91%/year for women with hypertension to 3.34%/year for those 65 to 74 years of age., Conclusions: Not all risk factors in CHA2DS2-VASc score carry an equal risk, with age 65 to 74 years associated with the highest stroke rate. Oral anticoagulation should be considered for AF patients with 1 additional stroke risk factor given their high risk of ischemic stroke., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The risk of acute myocardial infarction (AMI) in patients with atrial fibrillation (AF) with a CHA2DS2-VASc score of 0 (for men) or 1 (for women) has not been previously investigated., Objective: The objective of the present study was to compare the risk of AMI in AF and non-AF subjects with a low (0 or 1) CHA2DS2-VASc score., Methods: By using the National Health Insurance Research Database in Taiwan, we identified 7254 men with AF (with a CHA2DS2-VASc score of 0) and 4860 women with AF (with a CHA2DS2-VASc score of 1). For each study patient, 1 age-, sex-, and CHA2DS2-VASc score-matched subject without AF was randomly selected to constitute the control group (n = 12,114). The clinical end point was the occurrence of AMI., Results: During a mean follow-up period of 5.7 ± 3.6 years, 258 patients (1.1%) suffered an AMI, with an annual incidence of 0.29% and 0.10% for patients with and without AF. AF was an independent risk factor of AMI, with an adjusted hazard ratio (HR) of 2.93 (95% confidence interval 2.21-3.87; P < .001). The risk of AMI was higher in men with AF than in women with AF, with a hazard ratio of 2.24 (95% confidence interval 1.61-3.11; P < .001) after adjustment for age and other comorbidities., Conclusion: In patients with a CHA2DS2-VASc score of 0 or 1, AF was an independent risk factor of AMI. The risk of AMI was higher in men with AF than in women with AF. Cardiovascular risk prevention should be performed as part of the holistic management of AF to minimize the risks of AMI associated with AF., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: A new scoring system, the anticoagulation and risk factors in atrial fibrillation (ATRIA) score, was proposed for risk stratification in patients with atrial fibrillation (AF). Whether the ATRIA scheme can adequately identify patients who are at low risk of ischemic stroke remains unknown., Objectives: The goal of the present study was to compare the performance of ATRIA to that of CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65 to 74, female) scores for stroke prediction., Methods: This study used the National Health Insurance research database in Taiwan. A total of 186,570 AF patients without antithrombotic therapy were selected as the study cohort. The clinical endpoint was the occurrence of ischemic stroke., Results: During the follow-up of 3.4 ± 3.7 years, 23,723 patients (12.7%) experienced ischemic stroke. The CHA2DS2-VASc score performed better than ATRIA score in predicting ischemic stroke as assessed by c-indexes (0.698 vs. 0.627, respectively; p < 0.0001). The CHA2DS2-VASc score also improved the net reclassification index by 11.7% compared with ATRIA score (p < 0.0001). Among 73,242 patients categorized as low-risk on the basis of an ATRIA score of 0 to 5, the CHA2DS2-VASc scores ranged from 0 to 7, and annual stroke rates ranged from 1.06% to 13.33% at 1-year follow-up and from 1.15% to 8.00% at 15-year follow-up. The c-index of CHA2DS2-VASc score (0.629) was significantly higher than that of the ATRIA score (0.593) in this "low-risk" category (p < 0.0001)., Conclusions: Patients categorized as low-risk by use of the ATRIA score were not necessarily low-risk, and the annual stroke rates can be as high as 2.95% at 1-year follow-up and 2.84% at 15-year follow-up. In contrast, patients with a CHA2DS2-VASc score of 0 had a truly low risk of ischemic stroke, with an annual stroke rate of approximately 1%., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Renal dysfunction is a significant risk factor for ischemic stroke in atrial fibrillation (AF). However, the incidence of ischemic stroke and how to predict its occurrence among AF patients with end-stage renal disease (ESRD) are unclear., Objective: The purpose of this study was to compare the CHADS2 and CHA2DS2-VASc scores for stroke risk stratification in AF patients with ESRD., Methods: A total of 10,999 AF patients with ESRD undergoing renal replacement therapy who were not receiving oral anticoagulants or antiplatelet agents were identified from Taiwan's National Health Insurance Research Database. The study end-point was occurrence of ischemic stroke., Results: The median (interquartile) CHADS2 and CHA2DS2-VASc scores for the study cohort were 3 (2-5) and 5 (4-7), respectively. During follow-up, 1217 patients (11.7%) experienced ischemic stroke, with an incidence rate of 6.9 per 100 person-years. In Cox regression models, the CHADS2 and CHA2DS2-VASc scores both were significant predictors of ischemic stroke. C-indexes for CHADS2 and CHA2DS2-VASc were 0.608 and 0.682, respectively (P < .001). CHA2DS2-VASc improved the net reclassification index by 4.8% compared with CHADS2 (P < .0001). Among 1409 patients with a CHADS2 score of 0 or 1, the CHA2DS2-VASc score ranged from 1 to 4, with event rates ranging from 2.1 to 4.7 per 100 person-years., Conclusion: The CHA2DS2-VASc score was useful in predicting ischemic stroke in AF patients with ESRD undergoing dialysis and was superior to the CHADS2 score. The net clinical benefit balancing stroke reduction against major bleeding with anticoagulation in these high-risk patients remains to be defined., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The HAS-BLED score is a validated bleeding risk model for predicting major bleeding events in anticoagulated individuals with atrial fibrillation (AF). It remains uncertain whether the HAS-BLED score could identify non-AF individuals at risk of developing intracranial haemorrhage (ICH), which is the most intractable and devastating major bleeding complication., Methods: We assessed the predictive value of a modified HAS-BLED and other bleeding risk scoring models to predict the risk for ICH in the Chin-Shan Community Cohort, which followed 1899 women and 1703 men, aged >35 years, for a median of 15.9 years. ICH events (including haemorrhagic strokes) were ascertained according to questionnaires and the national register database., Results: Of 3524 individuals without baseline AF, 54 ICH events occurred during follow-up. The risk for ICH was raised with increasing HAS-BLED scores, and was significantly associated with uncontrolled hypertension and older age (Odds Ratios [95% confidence interval (CI)], 4.2[2.3-7.6] and 1.9[1.1-3.4], respectively). Among the five bleeding risk scoring schemes tested, HAS-BLED had highest general discrimination performance (c-statistic [95% CI], 0.72 [0.67-0.78]), and better ability to discriminate between those who were at risk for ICH and who were not (NRI, net reclassification improvement, all p<0.05, compared to other four scoring schemes)., Conclusion: The HAS-BLED score had the highest general discrimination performance and best ability to discriminate risk for ICH. This score may be of clinical use in predicting the risk for occurrence of ICH among non-AF individuals., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)