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Background: The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF. Methods: An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022. Results: Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban. Conclusion: Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.

Abstract Background In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. Methods This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. Results The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052–1.158, p

Background Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium–glucose cotransporter‐2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. Methods and Results We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow‐up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of −3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28–9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78–3.95]) as well as hypokalemia events

BackgroundPrevious studies have shown that global constructive work (CW) and wasted work (WW) predict response to cardiac resynchronization therapy (CRT). This study evaluated the predictive value of regional CW and WW for reverse remodeling and clinical outcomes after CRT.MethodsWe performed a prospective study involving 134 CRT candidates with left bundle branch block and left ventricular ejection fraction ≤35%. Global and regional CW and WW were calculated using pressure-strain loop analysis. CRT response was defined by reverse remodeling as a reduction of ≥15% in left ventricular end-systolic volume after six months.ResultsAt six-month follow-up, 92 (69%) patients responded to CRT. Of the regional CW and WW measures, lateral wall (LW) CW and septal WW were most strongly and significantly correlated with reverse remodeling. At multivariate analysis, LW CW and septal WW were both independent determinants of reverse remodeling. When LW CW and septal WW were included in the model, global CW and WW were not independently associated with reverse remodeling. LW CW and septal WW predicted reverse remodeling with an area under the curve (AUC) of 0.783 (95% CI: 0.700–0.866) and 0.737 (95% CI: 0.644–0.831), respectively. Using both variables increased the AUC to 0.832 (95% CI: 0.755–0.908). Both LW CW ≤878 mmHg% (HR 2.01; 95% CI: 1.07–3.79) and septal WW ≤181 mmHg% (HR 2.60; 95% CI: 1.38–4.90) were significant predictors of combined death and HF hospitalization at two-year follow-up.ConclusionLW CW and septal WW before CRT are important determinants of reverse remodeling and clinical outcomes.

Introduction: Reduced-dose (Low-dose [LD]) apixaban is recommended in patients with atrial fibrillation (AF) who fulfill 2 of 3 criteria: age ≥ 80 years, body weight ≤ 60 kg, and a serum creatinine (sCr) ≥ 1.5 mg/dl. However, the suitable (appropriate) dose for Asian patients who have a sCr

Abstract Skepticism exists among healthcare workers and patients regarding the efficacy and safety of generic medication, despite its potential to lower healthcare costs. This study aimed to compare the outcomes of a generic clopidogrel and its brand‐name counterpart for secondary prevention in patients with acute myocardial infarction (AMI). Using the Taiwan National Health Insurance Research Database, we identified 49,325 patients who were hospitalized for AMI between January 1, 2008 and December 31, 2013 and prescribed either generic or brand‐name clopidogrel. Among them, 2419 (4.9%) were prescribed the generic clopidogrel. After propensity score matching, both the generic and brand‐name groups consisted of 2382 patients. The primary efficacy outcome was a composite of myocardial infarction, coronary revascularization, ischemic stroke, and all‐cause death. The primary safety outcome was major bleeding requiring hospitalization. At a mean follow‐up of 2.5 years, the generic and brand‐name clopidogrel groups had comparable risks of primary efficacy outcome (41.9% vs. 42%; hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.88–1.04), and the risks of the individual components were also similar. There were no significant differences between the two groups in major bleeding (7.9% vs. 7.9%; HR 0.99; 95% CI 0.81–1.21). Subgroup analyses also revealed no statistically significant interactions between the treatment effect and various subgroups. In this retrospective database analysis, the generic clopidogrel was comparable to its brand‐name counterpart regarding cardiovascular and bleeding outcomes for the treatment of patients with AMI.

Background: Premature ventricular complexes (PVCs) are common electrocardiographic abnormalities and may be a prognosticator in predicting mortality in patients with structurally normal hearts or chronic heart diseases. Whether PVC burden was associated with mortality in patients with chronic atrial fibrillation (AF) remained unknown. We investigated the prognostic value of PVC burden in patients with persistent AF. Methods: A retrospective analysis of 24 h Holter recordings of 1767 patients with persistent AF was conducted. Clinical characteristics, 24 h average heart rate (HR), and PVC measures, including 24 h PVC burden and the presence of consecutive PVCs (including any PVC couplet, triplet, or non-sustained ventricular tachycardia) were examined for the prediction of all-cause and cardiovascular mortality using the Cox proportional hazards model. Results: After a median follow-up time of 30 months, 286 (16%) patients died and 1481 (84%) patients survived. Multivariate analysis revealed that age, heart failure, stroke, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, digoxin, oral anticoagulant use, and estimated glomerular filtration rate were significant baseline predictors of all-cause mortality and cardiovascular mortality. Twenty-four-hour PVC burden and the presence of consecutive PVCs were significantly associated with all-cause and cardiovascular mortality after adjusting for significant clinical factors. When compared to the first quartile of PVC burden (0.3%/day) was significantly associated with an increased risk of all-cause mortality (hazard ratio, 2.46; 95% CI, 1.77–3.42) and cardiovascular mortality (hazard ratio: 2.67; 95% CI, 1.76–4.06). Conclusions: Twenty-four-hour PVC burden is independently associated with all-cause and cardiovascular mortality in patients with persistent AF.

Abstract Background Sustained, chronic activation of β-adrenergic receptor (β-AR) signaling leads to cardiac arrhythmias, with exchange proteins directly activated by cAMP (Epac1 and Epac2) as key mediators. This study aimed to evaluate whether CD44, a transmembrane receptor mediating various cellular responses, participates in Epac-dependent arrhythmias. Methods The heart tissue from CD44 knockout (CD44−/−) mice, cultured HL-1 myocytes and the tissue of human ventricle were used for western blot, co-immunoprecipitaiton and confocal studies. Line-scanning confocal imaging was used for the study of cellular Ca2+ sparks on myocytes. Optical mapping and intra-cardiac pacing were applied for arrhythmia studies on mice’s hearts. Results In mice, isoproterenol, a β-AR agonist, upregulated CD44 and Epac1 and increased the association between CD44 and Epac1. Isoproterenol upregulated the expression of phospho-CaMKII (p-CaMKII), phospho-ryanodine receptor (p-RyR), and phospho-phospholamban (p-PLN) in mice and cultured myocytes; these effects were attenuated in CD44−/− mice compared with wild-type controls. In vitro, isoproterenol, 8-CPT-cAMP (an Epac agonist), and osteopontin (a ligand of CD44) significantly upregulated the expression of p-CaMKII, p-RyR, and p-PLN; this effect was attenuated by CD44 small interfering RNA (siRNA). In myocytes, resting Ca2+ sparks were induced by isoproterenol and overexpressed CD44, which were prevented by inhibiting CD44. Ex vivo optical mapping and in vivo intra-cardiac pacing studies showed isoproterenol-induced triggered events and arrhythmias in ventricles were prevented in CD44−/− mice. The inducibility of ventricular arrhythmias (VAs) was attenuated in CD44−/− HF mice compared with wild-type HF controls. In patients, CD44 were upregulated, and the association between CD44 and Epac1 were increased in ventricles with reduced contractility. Conclusion CD44 regulates β-AR- and Epac1-mediated Ca2+-handling abnormalities and VAs. Inhibition of CD44 is effective in reducing VAs in HF, which is potentially a novel therapeutic target for preventing the arrhythmias and sudden cardiac death in patients with diseased hearts.

BackgroundRecently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR).MethodsA retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals.ResultsBefore exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48).ConclusionsThe findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease.

Background The widely used Bentall procedure is the criterion standard treatment for aortic root pathology. Studies comparing the long‐term outcomes of bioprosthetic and mechanical valves in patients undergoing the Bentall procedure are limited. Methods and Results Patients who underwent the Bentall procedure with a bioprosthetic or mechanical valve between 2001 and 2018 were identified from Taiwan's National Health Insurance Research Database. The primary outcome of interest was all‐cause mortality. Inverse probability of treatment weighting was performed to compare the 2 prosthetic types. In total, 1052 patients who underwent the Bentall procedure were identified. Among these patients, 351 (33.4%) and 701 (66.6%) chose bioprosthetic and mechanical valves, respectively. After inverse probability of treatment weighting, no significant differences in the in‐hospital mortality (odds ratio, 0.96 [95% CI, 0.77–1.19]; P=0.716) and all‐cause mortality (34.1% vs. 38.1%; hazard ratio, 0.90 [95% CI, 0.78–1.04]; P=0.154) were observed between the groups. The benefits of relative mortality associated with mechanical valves were apparent in younger patients and persisted until ≈50 years of age. Conclusions No differences in survival benefits were observed between the valves in patients who underwent the Bentall procedure. Additionally, bioprosthetic valves may be a reasonable choice for patients aged >50 years when receiving the Bentall procedure in this valve‐in‐valve era.

Abstract Aims The effectiveness and limb safety of sodium glucose co-transporter 2 inhibitors (SGLT2i) for patients with type-2 diabetes (T2D) who have received peripheral artery disease (PAD) revascularization are unknown. Methods and results In this nationwide retrospective cohort study, we identified a total of 2,455 and 8,695 patients with T2D who had undergone PAD revascularization and received first prescriptions for SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i), respectively, between May 1, 2016, and December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates between the two study groups. Patients were followed up from the drug index date until the occurrence of specified outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first. After PSM, we observed that compared with DPP4i, SGLT2i were associated with comparable risks of ischemic stroke, acute myocardial infarction, and heart failure hospitalization but were associated with a lower risk of cardiac death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.40–0.90]; p = 0.0126). Regarding major limb outcomes, SGLT2i were associated with comparable risks of repeated revascularization and lower limb amputation compared with DPP4i. SGLT2i were associated with a lower risk of composite renal outcomes (HR: 0.40; 95% CI: 0.27–0.59; p

Abstract Background Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients. Methods In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. Results After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84–0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63–0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86–1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02). Conclusions Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.

Abstract 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.

Abstract Clinical outcomes are unknown after ticagrelor treatment in patients with end-stage renal disease (ESRD) who are diagnosed with acute myocardial infarction (AMI). ESRD patients who were on hemodialysis and received dual antiplatelet therapy (DAPT) for AMI between July 2013 and December 2016 were identified in Taiwan's National Health Insurance Research Database. Using stabilized inverse probability of treatment weighting, patients receiving aspirin plus ticagrelor (n = 530) were compared with those receiving aspirin plus clopidogrel (n = 2462) for the primary efficacy endpoint, a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke, and bleeding, defined according to the Bleeding Academic Research Consortium. Study outcomes were compared between the two groups using Cox proportional hazards model or competing risk model for the hazard ratio or subdistribution hazard ratio (SHR). During 9 months of follow-up, ticagrelor was comparable to clopidogrel with respect to the risks of primary efficacy endpoint [11.69 vs. 9.28/100 patient-months; SHR, 1.16; 95% confidence interval (CI) 0.97–1.4] and bleeding (5.55 vs. 4.36/100 patient-months; SHR 1.14; 95% CI 0.88–1.47). In conclusion, among hemodialysis patients receiving DAPT for AMI, ticagrelor was comparable to clopidogrel with regard to the composite efficacy endpoint and bleeding.

Abstract Background There is a controversy over the association between obesity and the risk of renal events in patients with type 2 diabetes mellitus (T2DM). Furthermore, whether body weight (BW) loss following sodium glucose cotransporter 2 inhibitor (SGLT2i) treatment associated with risk of adverse renal events is unknown. Methods We used medical data from a multi-center healthcare provider in Taiwan, enrolling 8992 T2DM patients with a baseline/following-up BW data available after around 12 weeks of SGLT2i treatment, from June 1, 2016 to December 31, 2018. Patients were followed up until the occurrence of composite renal outcome (estimated glomerular filtration rate decline > 40% or end-stage kidney disease) or the end of study period, whichever occurred first. Results Participants were divided into six baseline BMI categories:

BackgroundAlthough atrial fibrillation (AF) is a risk factor for ischemic bowel disease, data regarding the incidence of ischemic bowel disease in patients with anticoagulated AF were limited.MethodsThe present study used the Taiwan NHIRD and included newly diagnosed patients with AF aged ≥ 20 years without ischemic bowel disease from 2012 to 2018. A total of 69,549 patients taking warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) constituted the final study group. We aimed to study the incidence of ischemic bowel disease in patients with AF receiving warfarin or NOACs. Secondary endpoints were also analyzed, including ischemic stroke, systemic embolism, myocardial infarction, mortality, intracranial hemorrhage (ICH), major bleeding, and composite adverse events (ischemic bowel disease or ICH or major bleeding).ResultsThere were 43,787 patients taking NOACs and 25,762 patients taking warfarin. The overall incidence rate of ischemic bowel disease was 0.036% per year and increased with the CHA2DS2-VASc scores [0.013% for patients with a CHA2DS2-VASc score of 0 (men) or 1 (women), 0.022% for those with a CHA2DS2-VASc score of 1 (men) or 2 (women), and 0.039% for those with a CHA2DS2-VASc score ≥ 2 (men) or ≥ 3 (women)]. The risk of ischemic bowel disease was similar between NOAC and warfarin groups (0.036%/year vs. 0.037%/year; adjusted hazard ratio 0.802, p = 0.430), whereas the NOAC group had a significantly lower risk of secondary endpoints compared to the warfarin group.ConclusionWe reported the incidence of ischemic bowel disease in patients with anticoagulated AF from a nationwide cohort database and observed a positive correlation between the increase of CHA2DS2-VASc scores and the incidence rate. Moreover, NOAC was as effective as warfarin for the risk of ischemic bowel disease.

Abstract Background Sodium–glucose cotransporter 2 inhibitor (SGLT2i) use reduces body weight (BW) in patients with type 2 diabetes mellitus (T2DM). Obesity and T2DM are strong risk factors of new-onset atrial fibrillation (AF). However, whether BW loss following SGLT2i treatment reduces AF risk in patients with T2DM remains unclear. Methods We used a medical database from a multicenter health care provider in Taiwan, which included 10,237 patients with T2DM, from June 1, 2016 to December 31, 2018, whose BW data at baseline and at 12 weeks of SGLT2i treatment were available. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the SGLT2i, or the end of the study period, whichever occurred first. Results The patients’ baseline body mass index (BMI) was 28.08 $$\pm$$ ± 4.88 kg/m2. SGLT2i treatment was associated with a BW loss of 1.35 $$\pm$$ ± 3.28 kg (1.78% $$\pm$$ ± 4.47%). There were 37.4%, 47.0%, and 15.6% of patients experienced no-BW loss (n = 3832), BW loss 0.0–4.9% (n = 4814), and $$\ge$$ ≥ 5.0% (n = 1591) following SGLT2i treatment, respectively. Compared with patients with baseline BMI 0.05). Conclusion BW loss of ≥ 5.0% following SGLT2i treatment was associated with a lower risk of new-onset AF in patients with T2DM in real-world practice.

Abstract Background Acute heart failure is a life-threatening clinical condition. Levosimendan is an effective inotropic agent used to maintain cardiac output, but its usage is limited by the lack of evidence in patients with severely abnormal renal function. Therefore, we analyzed data of patients with acute heart failure with and without abnormal renal function to examine the effects of levosimendan. Methods We performed this retrospective cohort study using data from the Chang Gung Research Database (CGRD) of Chang Gung Memorial Hospital (CGMH). Patients admitted for heart failure with LVEF ≤ 40% between January 2013 and December 2018 who received levosimendan or dobutamine in the critical cardiac care units (CCU) were identified. Patients with extracorporeal membrane oxygenation (ECMO) were excluded. Outcomes of interest were mortality at 30, 90, and 180 days after the cohort entry date. Results There were no significant differences in mortality rate at 30, 90, and 180 days after the cohort entry date between the levosimendan and dobutamine groups, or between subgroups of patients with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and eGFR

Introduction: The choice of an artificial mitral valve (MV) is a crucial clinical decision that affects the long-term survival and quality of life of patients. However, current guidelines recommend selecting MV based on patient age and life expectancy at the time of mitral valve replacement (MVR), without considering the etiology of MV disease. This study aimed to investigate whether MV disease etiology should be considered when choosing a valve for MVR and to evaluate the impact of MV disease etiology on long-term patient survival. Methods: Using data (2002-2018) from Taiwan's National Health Insurance Research Database, the authors conducted a nationwide retrospective cohort study to compare the biological and mechanical valves in terms of all-cause mortality as the primary outcome. The inverse probability of the treatment weighting method was used to reduce the effects of the confounding factors. The following etiologies were assessed: infective endocarditis, rheumatic heart disease, ischemic mitral regurgitation, and degenerative mitral regurgitation. Results: In patients aged below 70 years, it was observed that mechanical valves demonstrated an association with benefits compared to biological valves in the context of survival. In patients with infective endocarditis aged below 72 years, mechanical valves were associated with survival benefits, but not in those with stroke during hospitalization. These valves were also found to be linked with survival advantages for patients with rheumatic heart disease aged below 60 years and for those with degenerative mitral regurgitation aged below 72 years. However, no age-dependent effects of valve type on all-cause mortality were observed in patients with ischemic mitral regurgitation. Conclusion: The etiology of MV disease appears to be important in the selection of a suitable MV and determination of a cutoff age for mechanical and biological MVR. [ABSTRACT FROM AUTHOR]

Background/purpose: In-hospital cardiac arrest is a serious issue for hospitalized patients. The documented initial rhythm and detected medical events have been reported to influence the survival of cardiopulmonary resuscitation. This study aimed to identify the effect of continuous real-time electrocardiogram (ECG) monitoring on the prognosis of resuscitated patients in a general cardiac ward. Methods: We conducted this retrospective study using medical records of hospitalized patients in a cardiovascular ward who experienced an in-hospital cardiac arrest and received cardiopulmonary resuscitation from February 2015 to December 2018. The patients who were considered to be at high risk of cardiac events such as ventricular arrhythmia would receive continuous ECG monitoring. A wireless ECG telemonitoring system was introduced to replace traditional bedside ECG monitors. The outcome measures were the initial success of resuscitation, 24-h survival after resuscitation, and survival to discharge. Results: We enrolled 115 patients with a cardiac arrest during hospitalization, of whom 73 (63%) patients received wireless ECG telemonitoring. Patients receiving continuous ECG monitoring were associated with higher opportunities of initial success of resuscitation and 24-h survival after resuscitation (67.1% vs. 40.5%, p = 0.005; and 49.3% vs. 26.2%, p = 0.015, respectively) when comparing to the non-monitoring group; but no significant difference in survival to discharge (21.9% vs. 16.7%, p = 0.498) was observed. With adjustment of the covariates, the monitoring group was associated with a higher likelihood to reach the initial success of resuscitation (odds ratios [ORs], 3.21; 95% confidence interval [CI], 1.03–9.98). However, the effect of monitoring on 24-h survival and survival to discharge was close to null after adjusting for covariates. Conclusion: A wireless ECG telemonitoring system were beneficial to the initial success of resuscitation for patients at high risk of cardiovascular events suffering an in-hospital cardiac arrest; but had less impact on 24-h survival and survival to discharge.

Abstract Background Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitor (DPP4i) among a longitudinal cohort of diabetic patients. Methods We used medical data from a multi-center healthcare provider in Taiwan, which included a total of 15,606 and 12,383 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first. Results Overall, 55%, 45%, and 0% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (5%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [hazard ratio: 0.61; 95% confidential interval: 0.50–0.73; P

Abstract Aims Recent studies indicated that sodium glucose cotransporter‐2 inhibitors (SGLT2i) reduced heart failure hospitalization in patients with type 2 diabetes mellitus (T2DM). However, whether SGTL2i can improve left ventricular (LV) systolic and diastolic function remained unclear. This study aimed to compare the change in echocardiographic parameters in T2DM patients receiving SGLT2i with a different baseline LV ejection fraction (LVEF). The change in echocardiographic parameters was also compared between T2DM patients treated with SGLT2i and those treated with dipeptidyl peptidase‐4 inhibitor (DPP4i). Methods and results This multicentre cohort study consecutively enrolled 665, 119, and 132 T2DM patients treated with SGLT2i with a preserved (≥50%), moderately reduced (40–50%), and reduced baseline LVEF (

Abstract Background Whether sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a lower risk of cardiovascular as well as adverse lower limb events in patients with type-2 diabetes mellitus (T2DM) and concomitant peripheral artery disease (PAD) is unclear. We aimed to evaluate the risk of cardiovascular and limb events, and death associated with the use of SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal and national cohort of patients with T2DM. Methods In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, we identified a total of 11,431 and 93,972 consecutive T2DM patients with PAD taking SGLT2i and DPP4i, respectively, from May 1, 2016, to December 31, 2017. We used 1:1 propensity score matching (PSM) to balance covariates across study groups. Patients were followed from the drug index date until the occurrence of clinical outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first. Results Overall, 56% and 44% of the patients were treated with dapagliflozin and empagliflozin, respectively. The use of SGLT2i had comparable risks of ischemic stroke and acute myocardial infarction, and was associated with lower risks of congestive heart failure (CHF) [hazard ratio (HR): 0.66; 95% confidence interval (CI) 0.49–0.89; p = 0.0062], lower limb ischemia requiring revascularization (HR: 0.73; 95% CI 0.54–0.98; p = 0.0367) or amputation (HR: 0.43; 95% CI 0.30–0.62; p

Abstract 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

Abstract Background Studies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories. Methods We utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: 0.05). Conclusion For AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level

ObjectiveThe aim of this study is to evaluate the sex-related differences on the risks of perioperative and late outcomes for adult acute aortic dissection (AAD) patients following surgical management.Methods and resultsBy using Taiwan National Health Insurance Research Database, totally 1,410 female and 3,432 male patients were identified to first-ever receive type A AAD open surgery or type B AAD stenting treatment from 2004 to 2013. We assessed the sex-related difference on outcomes, including in-hospital mortality, all-cause mortality, aortic death, redo aortic surgery, ischemic stroke, and depression during the follow-up period. The analysis was done separately for type A and type B surgeries.ResultsOn average, female patients diagnosed with AAD were older than males. There was no significant sex difference of in-hospital mortality or all-cause mortality for both type A open and type B stent surgeries. The risk of redo aortic surgery was significantly greater in males than females (7.8% vs. 4%; unadjusted subdistribution hazard ratio [SHR] 0.51, 95% CI 0.38-0.69) for type A open surgery, but not for type B stent surgery. Noticeably, the risk of newly-diagnosed depression was significantly greater in females than males (8% vs. 5.1%; unadjusted SHR 1.6, 95% CI 1.24-2.06) for type A open surgery, but not for type B stent surgery.ConclusionsNo significant sex-related difference was found for the in-hospital mortality or accumulative all-cause mortality. However, there were more redo aortic surgeries for males and more postoperative depression for females in type A AAD population.

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 Background Insulin resistance (IR) is considered as a risk factor for atrial fibrillation (AF) even before diabetes develops. The pathophysiology and underlying mechanism are largely unclear. Methods We investigated the corresponding mechanism in two IR models of rats fed 15-week high-fat (HFa) and high-fructose/cholesterol (HFr) diets. AF was evaluated and induced by burst atrial pacing. Isolated atrial myocytes were used for whole-cell patch clamp and calcium assessment. Ex vivo whole heart was used for optical mapping. Western blot and immunofluorescence were used for quantitative protein evaluation. Results Both HFa and HFr rat atria were vulnerable to AF evaluated by burst atrial pacing. Isolated atrial myocytes from HFa and HFr rats revealed significantly increased sarcoplasmic reticulum calcium content and diastolic calcium sparks. Whole-heart mapping showed prolonged calcium transient duration, conduction velocity reduction, and repetitive ectopic focal discharge in HFa and HFr atria. Protein analysis revealed increased TGF-β1 and collagen expression; increased superoxide production; abnormal upregulation of calcium-homeostasis-related proteins, including oxidized CaMKIIδ, phosphorylated-phospholamban, phosphorylated-RyR-2, and sodium-calcium exchanger; and increased Rac1 activity in both HFa and HFr atria. We observed that inhibition of CaMKII suppressed AF in both HF and HFr diet-fed rats. In vitro palmitate-induced IR neonatal cardiomyocytes and atrial fibroblasts expressed significantly more TGF-β1 than did controls, suggesting paracrine and autocrine effects on both myocytes and fibroblasts. Conclusions IR engenders both atrial structural remodeling and abnormal intracellular calcium homeostasis, contributing to increased AF susceptibility. The inhibition of CaMKII may be a potential therapeutic target for AF in insulin resistance.

Background: Heart rate variability (HRV), a non-invasive measurement of the sympathetic-vagal balance, has been demonstrated as a predictor of long-term survival in various patient populations. However, its predictive value in patients with end-stage renal disease (ESRD) has not been evaluated in a long-term follow-up study. Methods: Prospective data collected for 41 patients with chronic hemodialysis (age 59 ± 10 years, men 51.3%, diabetes mellitus 31%, and duration of dialysis 64 ± 50 months) who underwent a 5-minute electrocardiogram (ECG) recording as a baseline for frequency domain HRV analysis. Results: During a median follow-up of 150.2 months from 2003 to 2014, 15 (35.7%) patients died (3 due to cardiac causes and 12 due to non-cardiac causes). The Cox proportional hazards model suggested that the low frequency versus high frequency signal (LF/HF) of a high ratio for the HRV and diabetes mellitus were two independent predictors of mortality (hazard ratios 3.028 and 3.494; p = 0.033 and 0.022, respectively). Less reduction in MAP during dialysis showed borderline significance of long-term survival than those with larger drop (p = 0.058). Conclusion: A short ECG recording and an analysis of the frequency domain of the HRV is clinically predictive of the long-term survival of patients with chronic hemodialysis. Keywords: Heart rate variability, Cardiorenal syndrome, Hemodialysis, Survival, End-stage renal disease

Background: The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Cai) handling and VA susceptibility by IL-17.Methods: The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, N = 6) and the IL-17 with neutralizer (0.4 μg/ml, N = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Cai transient duration (CaiTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed.Results: There were longer APD80, CaiTD80 and increased thresholds of APD and CaiTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na+/Ca2+ exchanger, phospholamban, and ryanodine receptor Ca2+ release channel were upregulated, and the subunit of L-type Ca2+ current and sarcoplasmic reticulum Ca2+-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group.Conclusions: IL-17 enhanced CaiTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.

ObjectiveSeveral serum biomarkers have been investigated for their potential as diagnostic tools in aortic disease; however, no study has investigated the association between serum biomarkers and outcomes after aortic surgery. This study explored the predictive ability of serum soluble lumican in postoperative outcomes after aortic surgery.MethodsIn total, 58 patients receiving aortic surgery for aortic dissection or aneurysm at Linkou Chang Gung Memorial Hospital in Taiwan in December 2011-September 2018 were enrolled. Blood samples were collected immediately upon patients' arrival in the intensive care unit after aortic surgery. The diagnostic properties of soluble lumican levels were assessed by performing receiver operating characteristic (ROC) curve analysis. The confidence interval (CI) of the area under the ROC curve (AUC) was measured using DeLong's nonparametric method and the optimal cutoff was determined using the Youden index.ResultsThe serum soluble lumican level distinguished prolonged ventilation (AUC, 73.5%; 95% CI, 57.7%-89.3%) and hospital stay for >30 days (AUC, 78.2%; 95% CI, 61.6%-94.7%). The optimal cutoffs of prolonged ventilation and hospital stay for >30 days were 1.547 and 5.992 ng/mL, respectively. The sensitivity and specificity were respectively 100% (95% CI, 71.5%-100%) and 40.4% (95% CI, 26.4%-55.7%) for prolonged ventilation and 58% (95% 27.7%-84.8%) and 91.3% (95% CI, 79.2%-97.6%) for hospital stay for >30 days.ConclusionsThe serum soluble lumican level can be a potential prognostic factor for predicting poor postoperative outcomes after aortic surgery. However, more studies are warranted in the future.

IntroductionAortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model.MethodsLUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum-/-) mice were challenged with β-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN-Ang II-challenged wildtype (WT) mice. Tgf-β/Smad2, Mmps, Lum, and Nox expression patterns were examined.ResultsLUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum-/- AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum-/- AD mice compared with the WT AD mice. The BAPN-Ang II-challenged WT and Lum-/- AD mice had higher Tgf-β, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II-challenged WT in comparison to the unchallenged WT mice.ConclusionLUM expression was altered in patients with AD display increased s-LUM in blood, and Lum-/- mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes.

Background The ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) evaluated rivaroxaban (20/15 mg/d) versus warfarin in patients with atrial fibrillation. A separate trial, J‐ROCKET AF (Japanese ROCKET AF), compared rivaroxaban (15/10 mg/d) and warfarin in Japanese patients with atrial fibrillation. Data about rivaroxaban following J‐ROCKET AF criteria compared with warfarin and ROCKET AF dosage were limited. Methods and Results This retrospective study used medical data from a multicenter healthcare provider in Taiwan that included 3162 patients taking rivaroxaban. Among 2320 patients with an estimated glomerular filtration rate (eGFR) ≥50 mL/min per 1.73 m2, 384 and 1936 patients followed the ROCKET AF (20 mg/d) and J‐ROCKET AF (15 mg/d) recommendation, respectively. Among 842 patients with an eGFR

Abstract Background Whether dipeptidyl peptidase-4 inhibitor (DPP4i) is associated with a lower risk of new-onset atrial fibrillation (AF) in patients with diabetes remains unclear. This study aimed to evaluate the risk of AF associated with use of DPP4i among a longitudinal cohort of patients with diabetes. Methods Over a 3-year period, 480,000 patients with diabetes were analyzed utilizing Taiwan’s National Health Insurance Research Database and 90,880 patients taking metformin as first-line therapy were enrolled. Patients were further divided into two groups: (1) DPP4i users: those taking DPP4i and (2) non-DPP4i users: those prescribed other hypoglycemic agents (HAs) as second-line drug. Study end point was defined by diagnosis of AF, addition of any third-line HA, or the end of the study period (December 31, 2013), whichever came first. Results A total of 16,017 DPP4i users and 74,863 non-DPP4i users were eligible for the study. For the DPP4i group, most patients were prescribed sitagliptin (n = 12,180; 76%). Among the non-DPP4i group, most patients took sulfonylurea (n = 60,606; 81%) as their second-line medication. DPP4i users were associated with a lower risk of new-onset AF compared with non-DPP4i users after propensity-score weighting (hazard ratio 0.65; P 65 years, presence of hypertension, and ischemic heart disease were independent risk factors for new-onset AF. Conclusions Among patients with diabetes prescribed with metformin, the patients with DPP4i as second HA were associated with a lower risk of AF compared with the patients with other drugs as second HAs in real-world practice.

Angiosarcoma is a rare soft tissue sarcoma of poor prognosis. A retrospective single-center study was conducted to characterize cutaneous angiosarcoma. Twenty patients were enrolled. The mean age was 76 years and male to female ratio 3:1. Ninety percent had primary angiosarcoma. Scalp was the most commonly involved site. Metastatic disease was noted in 20% when angiosarcoma was diagnosed. Median overall survival time was 20 months. In this single center series, cutaneous angiosarcoma was a disease of early metastasis and poor prognosis. Physician should be aware of vascular lesions on the scalp and face regions especially in male elderly patients. Keywords: Angiosarcoma, Primary cutaneous angiosarcoma, Metastasis, Treatment, Prognosis

Reconstruction to close a peripheral nerve gap continues to be a challenge for clinical medicine, and much effort is being made to develop nerve conduits facilitate nerve gap closure. Acellular dermal matrix (ADM) is mainly used to aid wound healing, but its malleability and plasticity potentially enable it to be used in the treatment of nerve gaps. Adipose-derived stem cells (ADSCs) can be differentiated into three germ layer cells, including neurospheres. We tested the ability of ADSC-derived neural stem cells (NSCs) in combination with ADM or acellular sciatic nerve (ASN) to repair a transected sciatic nerve. We found that NSCs form neurospheres that express Nestin and Sox2, and could be co-cultured with ADM in vitro, where they express the survival marker Ki67. Following sciatic nerve transection in rats, treatment with ADM+NSC or ASN+NSC led to increases in relative gastrocnemius weight, cross-sectional muscle fiber area, and sciatic functional index as compared with untreated rats or rats treated with ADM or ASN alone. These findings suggest that ADM combined with NSCs can improve peripheral nerve gap repair after nerve transection and may also be useful for treating other types of neurological gaps.

Background Liver cirrhotic patients with nonvalvular atrial fibrillation have been excluded from randomized clinical studies regarding oral anticoagulants for stroke prevention. Whether non–vitamin K antagonist oral anticoagulants (NOACs) are superior to warfarin for these patients remains unclear. Methods and Results This nationwide retrospective cohort study, with data collected from the Taiwan National Health Insurance Research Database, enrolled 2428 liver cirrhotic patients with nonvalvular atrial fibrillation taking apixaban (n=171), dabigatran (n=535), rivaroxaban (n=732), or warfarin (n=990) from June 1, 2012, to December 31, 2016. We used propensity score–based stabilized weights to balance covariates across study groups. Patients were followed until the occurrence of an event or the end date of study. The NOAC group (n=1438) showed risk of ischemic stroke/systemic embolism and intracranial hemorrhage comparable to that of the warfarin group (n=990) after adjustment. The NOAC group showed significantly lower risk of gastrointestinal bleeding (hazard ratio: 0.51 [95% CI, 0.32–0.79]; P=0.0030) and all major bleeding (hazard ratio: 0.51 [95% CI, 0.32–0.74]; P=0.0003) compared with warfarin group. Overall, 90% (n=1290) of patients were taking a low‐dose NOAC (apixaban 2.5 mg twice daily, rivaroxaban 10–15 mg daily, or dabigatran 110 mg twice daily). The subgroup analysis indicated that both dabigatran and rivaroxaban showed lower risk of all major bleeding than warfarin. The advantage of lower gastrointestinal and all major bleeding with NOACs over warfarin is contributed by those subgroups with either nonalcoholic or nonadvanced liver cirrhosis. Conclusions NOACs have a risk of thromboembolism comparable to that of warfarin and a lower risk of major bleeding among liver cirrhotic Asian patients with nonvalvular atrial fibrillation. Consequently, thromboprophylaxis with low‐dose NOACs may be considered for such patients.

BackgroundPrevious studies indicated low-intensity warfarin (INR target of 1.5-2.5) achieved reduced hemorrhage without increasing thromboembolism for Asians with non-valvular atrial fibrillation (NVAF). Whether non-vitamin K antagonist oral anticoagulant (NOAC) is superior to warfarin with good time in the therapeutic range (TTR) based on lower INR target among Asians with NVAF remains unknown.MethodsIn this retrospective study collected from Taiwan Chang Gung Memorial Hospital Database, there were 5,197, 3,396, and 9,898 consecutive patients taking warfarin, NOAC, and no-treatment, respectively, from January 1, 2000 to December 31, 2015. Propensity-score weighting was used across the study groups. Patients were followed until the first occurrence of study outcome or end date of study.ResultsAmong those patients taking warfarin, the mean"artificial" TTR (aTTR) based on a lower INR target of 1.5-2.5 was 44.4±33.3%. Total 79.2% (n = 2,690) patients took low-dose NOACs. Patients with aTTR in the range from 70%(24.9%) showed decremental risks of efficacy and composite outcome compared with no-treatment. The risk of major bleeding didn't increase among patients with top aTTR>70% compared to no-treatment. The NOAC group showed a comparable risk of composite outcome to the warfarin subgroup with aTTR of >70% (P = 0.485). The NOAC group had a lower risk of composite outcome than warfarin subgroup with TTR of>70% based on the INR target of 2.0-3.0 (P = 0.004).ConclusionsNOACs showed a comparable risk of efficacy, safety, and composite outcome to well-managed warfarin based on a lower INR target of 1.5-2.5 in Asians with NVAF taking oral anticoagulants.