Association between holiday and weekend admissions and mortality outcomes among patients with acute myocardial infarction receiving percutaneous coronary intervention in Taiwan.

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93-1.42 or aOR 1.23; 95% CI 0.96-1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90-1.58 or aOR 1.24; 95% CI 0.90-1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions.

Off-hours Surgery and Mortality in Patients With Type A Aortic Dissection Repair: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The impact of off-hours admission (such as weekends, nighttime, and non-working hours) vs. regular hours (weekdays and daytime working hours) on the mortality risk of patients undergoing surgery for type A aortic dissection (TAAD) repair is still uncertain. To address this uncertainty, we undertook a comprehensive systematic review and meta-analysis. We aimed to assess the potential link between off-hours admission and the risk of mortality in patients undergoing TAAD repair surgery. METHODS: We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases, covering the period from their inception to May 20, 2023. Our inclusion criteria encompassed all studies that examined the potential relationship between off-hour admission and mortality in individuals who had undergone surgery for TAAD repair. The odds ratios (ORs) were extracted and combined utilizing a random effects model for our synthesis. RESULTS: Nine studies with 16,501 patients undergoing TAAD repair surgery were included in the meta-analysis. Overall, patients who underwent surgery during the weekend had higher in-hospital mortality (pooled OR, 1.41; 95% confidence interval [CI], 1.14-1.75; p=0.002) than those treated on weekdays. However, the mortality risks among patients who underwent TAAD surgery during nighttime and non-working hours were not significantly elevated compared to daytime and working hours admission. CONCLUSIONS: Weekend surgery for TAAD was associated with a higher in-hospital mortality risk than weekday surgery. However, further studies are warranted to identify and develop strategies to improve the quality of round-the-clock care for patients with TAAD.

Sodium-glucose co-transporter-2 inhibitors and the risk of venous thromboembolism: A nationwide population-based study and meta-analysis.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have off-target effects on haemoconcentration and anti-inflammation. The impact of SGLT-2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT-2i in comparison to dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA). MATERIALS AND METHODS: In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20 years or older who received SGLT-2i, DPP-4i, or GLP-1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT-2i users were compared with those of DPP-4i and GLP-1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta-analysis of relevant articles published before 23 May 2023, was conducted. RESULTS: Data from 136,530 SGLT-2i, 598,280 DPP-4i, and 5760 GLP-1RA users were analysed. SGLT-2i use was associated with a lower risk of VTE than DPP-4i (HR, 0.70; 95% CI, 0.59-0.84; p < 0·001), but not with GLP-1RA (HR, 1.39; 95% CI, 0.32-5.94; p = 0.66). Our meta-analysis further supported these findings (SGLT-2i vs. DPP-4i: HR, 0.71; 95% CI, 0.62-0.82; p < 0·001; SGLT-2i vs. GLP-1RA: HR, 0.91; 95% CI, 0.73-1.15; p = 0.43), suggesting the robustness of our retrospective analysis. CONCLUSIONS: In patients with DM, SGLT-2i was associated with a lower risk of VTE compared to DPP-4i, but not GLP-1RA.

Risk of serious hypoglycaemia in patients with atrial fibrillation and diabetes concurrently taking antidiabetic drugs and oral anticoagulants: a nationwide cohort study.

AIMS: Evidence regarding the risks of serious hypoglycaemia for patients with atrial fibrillation (AF) and diabetes mellitus (DM) taking antidiabetic medications with concurrent non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin is limited. This study aimed to investigate this knowledge gap. METHODS AND RESULTS: This retrospective cohort study used nationwide data from Taiwan's National Health Insurance Research Database and included a total of 56 774 adult patients treated with antidiabetic medications and oral anticoagulants between 1 January 2012 and 31 December 2020. The incidence rate ratios (IRRs) of serious hypoglycaemia were estimated for patients taking antidiabetic drugs with NOACs vs. warfarin. Poisson regression models with generalized estimating equations accounting for intra-individual correlation across follow-up periods were used. Stabilized inverse probability of treatment weighting was used to create treatment groups with balanced characteristics for comparisons. Compared to concurrent use of antidiabetic drugs with warfarin, those with NOACs showed a significantly lower risk of serious hypoglycaemia (IRR = 0.73, 95% CI: 0.63-0.85, P < 0.001). In the analyses of each NOAC, patients taking dabigatran (IRR = 0.76, 95% CI: 0.63-0.91, P = 0.002), rivaroxaban (IRR = 0.72, 95% CI: 0.61-0.86, P < 0.001), and apixaban (IRR = 0.71, 95% CI: 0.57-0.89, P = 0.003) showed a significantly lower risk of serious hypoglycaemia than those taking warfarin. CONCLUSION: In patients with AF and DM taking antidiabetic drugs, concurrent use of NOACs was associated with a lower risk of serious hypoglycaemia than concurrent use of warfarin.

Risk of heart failure in elderly patients with atrial fibrillation and diabetes taking different oral anticoagulants: a nationwide cohort study.

BACKGROUND: Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin. METHODS: A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models. RESULTS: The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74-0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80-0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74-0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68-0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60-0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings. CONCLUSIONS: This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.

Long-Term Risks of Stroke in Patients With Type A Aortic Dissection: A Nationwide Cohort Study.

Background Patients with type A aortic dissection (TAAD) have a high short-term risk of stroke. However, whether patients with TAAD have an increased long-term risk of stroke is still undetermined, and our study aims to address this knowledge gap. Methods and Results A nationwide retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database. We included patients with TAAD as well as age- and sex-matched aortic disease-free individuals between 2003 and 2016. Inverse probability of treatment weighting was performed to balance patient characteristics between the groups. The primary outcome was the development of stroke, regardless of subtype; the secondary outcomes were the risk of developing either ischemic or hemorrhagic stroke. The hazard ratios (HRs) of stroke were estimated using the Cox proportional hazards model. After inverse probability of treatment weighting, 3556 and 7023 patients were categorized into the TAAD and aortic disease-free cohorts, respectively. The mean follow-up period was 5.71 years. The HRs for overall, ischemic, and hemorrhagic strokes in the TAAD cohort were 3.01 (95% CI, 2.40-3.78), 3.18 (95% CI, 2.47-4.10), and 2.32 (95% CI, 1.58-3.41), respectively, compared with the aortic disease-free cohort. Consistent trends of higher stroke risk in patients with TAAD were revealed in the analyses stratified by age; sex; antiplatelet use; and history of hypertension, diabetes, or dyslipidemia. Conclusions Our study findings revealed that patients with TAAD had an increased long-term risk of both ischemic and hemorrhagic strokes. Further studies are warranted to establish optimal strategies for stroke prevention in these patients.

Oral anticoagulant decreases stroke recurrence in patients with atrial fibrillation detected after stroke.

Background: Atrial fibrillation detected after stroke (AFDAS) has a lower risk of ischemic stroke recurrence than known atrial fibrillation (KAF). While the benefit of oral anticoagulants (OAC) for preventing ischemic stroke recurrence in KAF is well established, their role in patients with AFDAS is more controversial. This study aimed to evaluate the association between OAC use and the risk of recurrent ischemic stroke in patients with AFDAS in a real-world setting. Methods: This nationwide retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients hospitalized with a first-ever ischemic stroke and AFDAS confirmed within 30 days after hospitalization were assigned to OAC and non-OAC cohorts. Inverse probability of treatment weighting was applied to balance the baseline characteristics of the cohorts. The primary outcome was ischemic stroke recurrence. Secondary outcomes were intracranial hemorrhage (ICH), death, and the composite outcome of "ischemic stroke recurrence, ICH, or death." Multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: A total of 4,508 hospitalized patients with stroke and AFDAS were identified. Based on OAC use, 2,856 and 1,652 patients were assigned to the OAC and non-OAC groups, respectively. During the follow-up period (median duration, 2.76 years), the OAC cohort exhibited a lower risk of ischemic stroke recurrence (aHR, 0.84; 95% CI, 0.70-0.99), death (aHR, 0.65; 95% CI, 0.58-0.73), and composite outcome (aHR, 0.70; 95% CI, 0.63-0.78) than did the non-OAC cohort. The risk of ICH (aHR, 0.96; 95% CI, 0.62-1.50) was not significantly different between the two cohorts. Conclusion: OAC use in patients with AFDAS was associated with reduced risk of ischemic stroke recurrence, without an increased risk of ICH. This supports current guidelines recommending OACs for secondary stroke prevention in patients with AF, regardless of the time of diagnosis.

Association between Hyperosmolar Hyperglycemic State and Venous Thromboembolism in Diabetes Patients: A Nationwide Analysis in Taiwan.

BACKGROUND: Previous studies in Western countries have shown that a hyperosmolar hyperglycemic state (HHS) is associated with an increased risk of venous thromboembolism (VTE); in these cases, prophylactic anticoagulant treatment is suggested. However, the association between HHS and VTE in Asian populations remains undetermined. Therefore, we aimed to evaluate whether HHS is associated with an increased risk of VTE in diabetic Taiwanese patients. METHODS: This nationwide, population-based, retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. We enrolled a total of 4,723,607 admission records of patients with diabetes diagnosed with one or more of seven common diseases (pneumonia, urinary tract infection, sepsis, heart disease, stroke, malignancy, and respiratory tract disease) between 2001 and 2018 in Taiwan. The patients were divided into two groups based on the presence (n = 46,000) or absence (n = 4,677,607) of HHS. We estimated the adjusted odds ratio (aOR) for developing VTE within 90 days after the index hospitalization using multivariable logistic regression with generalized estimating equations accounting for repeated measures. RESULTS: Overall, patients admitted with HHS had a similar risk of VTE compared with those admitted without HHS (408/46,000 vs. 39,345/4,677,607; aOR = 1.06, 95% CI: 0.97-1.17, p = 0.190). A similar non-significant association between HHS and VTE was found regardless of age and sex subgroups. CONCLUSIONS: There was no significant association between HHS and overall VTE risk in patients with diabetes in Taiwan. The results of our study may not support the use of prophylactic anticoagulant therapy in diabetic Taiwanese patients with HHS.

Diabetes-Related Complications and Mortality in Patients With Atrial Fibrillation Receiving Different Oral Anticoagulants : A Nationwide Analysis.

BACKGROUND: Evidence about the association between types of oral anticoagulants and hazards of diabetes complications is limited in patients with atrial fibrillation (AF) and diabetes mellitus (DM). OBJECTIVE: To compare the hazards of diabetes complications and mortality between patients with AF and DM receiving non-vitamin K antagonist oral anticoagulants (NOACs) and those receiving warfarin. DESIGN: A retrospective cohort study. SETTING: Nationwide data obtained from Taiwan's National Health Insurance Research Database. PATIENTS: Patients with AF and DM receiving NOACs or warfarin between 2012 and 2017 in Taiwan were enrolled. Treatment groups were determined by patients' first initiation of oral anticoagulants. MEASUREMENTS: Hazards of diabetes complications (macrovascular complications, microvascular complications, and glycemic emergency) and mortality in the NOAC and warfarin users were investigated with a target trial design. Cause-specific Cox proportional hazards models were used to estimate hazard ratios (HRs). Propensity score methods with stabilized inverse probability of treatment weighting were applied to balance potential confounders between treatment groups. RESULTS: In total, 19 909 NOAC users and 10 300 warfarin users were included. Patients receiving NOACs had significantly lower hazards of developing macrovascular complications (HR, 0.84 [95% CI, 0.78 to 0.91]; P < 0.001), microvascular complications (HR, 0.79 [CI, 0.73 to 0.85]; P < 0.001), glycemic emergency (HR, 0.91 [CI, 0.83 to 0.99]; P = 0.043), and mortality (HR, 0.78 [CI, 0.75 to 0.82]; P < 0.001) than those receiving warfarin. Analyses with propensity score matching showed similar results. Several sensitivity analyses further supported the robustness of our findings. LIMITATION: The claims-based data did not allow for detailed data on patients' lifestyles and laboratory examinations to be obtained. CONCLUSION: Non-vitamin K antagonist oral anticoagulants were associated with lower hazards of diabetes complications and mortality than warfarin in patients with AF and DM. PRIMARY FUNDING SOURCE: Hualien Tzu Chi Hospital.

Dynamic Changes and Temporal Association with Ambient Temperatures: Nonlinear Analyses of Stroke Events from a National Health Insurance Database.

BACKGROUND: The associations between ambient temperatures and stroke are still uncertain, although they have been widely studied. Furthermore, the impact of latitudes or climate zones on these associations is still controversial. The Tropic of Cancer passes through the middle of Taiwan and divides it into subtropical and tropical areas. Therefore, the Taiwan National Health Insurance Database can be used to study the influence of latitudes on the association between ambient temperature and stroke events. METHODS: In this study, we retrieved daily stroke events from 2010 to 2015 in the New Taipei and Taipei Cities (the subtropical areas) and Kaohsiung City (the tropical area) from the National Health Insurance Research Database. Overall, 70,338 and 125,163 stroke events, including ischemic stroke and intracerebral hemorrhage, in Kaohsiung City and the Taipei Area were retrieved from the database, respectively. We also collected daily mean temperatures from the Taipei and Kaohsiung weather stations during the same period. The data were decomposed by ensemble empirical mode decomposition (EEMD) into several intrinsic mode functions (IMFs). There were consistent 6-period IMFs with intervals around 360 days in most decomposed data. Spearman's rank correlation test showed moderate-to-strong correlations between the relevant IMFs of daily temperatures and events of stroke in both areas, which were higher in the northern area compared with those in the southern area. CONCLUSIONS: EEMD is a useful tool to demonstrate the regularity of stroke events and their associations with dynamic changes of the ambient temperature. Our results clearly demonstrate the temporal association between the ambient temperature and daily events of ischemic stroke and intracranial hemorrhage. It will contribute to planning a healthcare system for stroke seasonally. Further well-designed prospective studies are needed to elucidate the meaning of these associations.

Evaluating the "holiday season effect" of hospital care on the risk of mortality from pulmonary embolism: a nationwide analysis in Taiwan.

We aimed to determine whether hospital admissions during an extended holiday period (Chinese New Year) and weekends were associated with increased mortality risk from pulmonary embolism (PE), compared to admissions on weekdays. We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Data of newly diagnosed PEs during the months of January and February from 2001 to 2017 were obtained from patient records and classified into three admission groups: Chinese New Year (≥ 4 consecutive holiday days), weekends, and weekdays. The adjusted odds ratios (aORs) (95% confidence intervals [CIs]) for 7-day and in-hospital mortality were calculated using multivariable logistic regression models. The 7-day and in-hospital mortality risks were higher for patients admitted during the Chinese New Year holiday (10.6% and 18.7%) compared to those admitted on weekends (8.4% and 16.1%) and weekdays (6.6% and 13.8%). These higher mortality risks for holiday admissions compared to weekday admissions were confirmed by multivariable analysis (7-day mortality: aOR = 1.68, 95% CI 1.15-2.44, P = 0.007; in-hospital mortality: aOR = 1.41, 95% CI 1.05-1.90, P = 0.022), with no subgroup effects by sex or age. Hospital admission for PE over an extended holiday period, namely Chinese New Year, was associated with an increased risk of mortality.

Mortality risk from acute aortic dissection among hospital admissions during weekends and holiday season.

BACKGROUND: Acute aortic dissection is a life-threatening condition associated with high mortality rate. Findings from previous studies addressing the "weekend effect" on the mortality rate from an acute aortic dissection mortality have been inconsistent. Furthermore, the effect of admission for acute aortic dissection during the holiday season has not been previously investigated. OBJECTIVE: Our aim was to evaluate the effect of admission for acute aortic dissection during holiday season or weekends on the risk of mortality. METHODS: We conducted a retrospective analysis of nationwide cohort data from the Taiwan's National Health Insurance Research Database. We collected data on all adult patients hospitalized for acute aortic dissection between 2001 and 2017 in Taiwan and classified them into the following three groups based on day of admission: holiday season (at least 4 consecutive days; n = 280), weekend (n = 1 041), and weekday (n = 3 109). The following three outcomes were evaluated: in-hospital mortality, 7-day mortality, and 180-day mortality. RESULTS: A multivariable logistic regression was used to adjust for possible cofounders on the measured outcomes. Compared to weekday admissions for acute aortic dissection, weekend admissions resulted in a 29% increase in the risk of in-hospital death (aOR = 1.29; 95% CI, 1.05-1.59; P = 0.0153), with a 25% increase in the 7-day (aOR = 1.25; 95% CI, 1.001-1.563; P = 0.0492) and 20% increase in the 180-day mortality risk (aOR = 1.20; 95% CI, 1.01-1.42; P = 0.0395). Of note, admission over the holiday season did not result in a higher mortality risk than for weekday admissions; this finding, however, might reflect insufficient statistical power on subgroup analysis. CONCLUSION: Patients admitted for acute aortic dissection during the weekends are at higher risk of mortality compared to those admitted on weekdays. Our finding likely reflects inadequate staffing and team experience of weekend staff and can guide healthcare policy makers to improve patient outcomes.

High 1-year risk of stroke in patients with hepatocellular carcinoma: a nationwide registry-based cohort study.

Patients with hepatocellular carcinoma (HCC) might be more vulnerable to develop stroke than other cancer patients because of HCC-associated coagulation dysfunction. However, limited studies have investigated the relationship between HCC and stroke. This nationwide population-based cohort study enrolled all patients with HCC diagnosed between 2011 and 2015 from the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database; an age- and sex-matched cohort without cancer was included. The primary outcome was the 1-year risk for first-ever stroke after the index date. The Fine and Gray competing risk regression model was used to estimate the 1-year stroke risk with adjusted hazard ratios (aHRs). After propensity score matching, each cohort has 18,506 patients with similar baseline characteristics. Compared with the cancer-free cohort, the aHRs in the HCC cohort for overall, ischemic, and hemorrhagic strokes were 1.59 [95% confidence interval (CI), 1.35-1.88], 1.38 [95% CI, 1.15-1.65], and 2.62 [95% CI, 1.79-3.84], respectively. On subgroup analysis, HCC patients without cirrhosis, those with stage 3 or 4 cancer had a higher stroke risk than cancer-free cohort. Therefore, stroke prevention should be considered in patients with HCC, especially in those without cirrhosis and with stage 3 or 4 cancer.

Fracture Risks in Patients Treated With Different Oral Anticoagulants: A Systematic Review and Meta-Analysis.

Background Evidence on the differences in fracture risk associated with non-vitamin K antagonist oral anticoagulants (NOAC) and warfarin is inconsistent and inconclusive. We conducted a systematic review and meta-analysis to assess the fracture risk associated with NOACs and warfarin. Methods and Results We searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov from inception until May 19, 2020. We included studies presenting measurements (regardless of primary/secondary/tertiary/safety outcomes) for any fracture in both NOAC and warfarin users. Two or more reviewers independently screened relevant articles, extracted data, and performed quality assessments. Data were retrieved to synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin. Random-effects models were used for data synthesis. We included 29 studies (5 cohort studies and 24 randomized controlled trials) with 388 209 patients. Patients treated with NOACs had lower risks of fracture than those treated with warfarin (pooled RR, 0.84; 95% CI, 0.77-0.91; P<0.001) with low heterogeneity (I2=38.9%). NOACs were also associated with significantly lower risks of hip fracture than warfarin (pooled RR, 0.89; 95% CI, 0.81-0.98; P=0.023). A nonsignificant trend of lower vertebral fracture risk in NOAC users was also observed (pooled RR, 0.74; 95% CI, 0.54-1.01; P=0.061). Subgroup analyses for individual NOACs demonstrated that dabigatran, rivaroxaban, and apixaban were significantly associated with lower fracture risks. Furthermore, the data synthesis results from randomized controlled trials and real-world cohort studies were quite consistent, indicating the robustness of our findings. Conclusions Compared with warfarin, NOACs are associated with lower risks of bone fracture.

Lower Risk of Dementia in Patients With Atrial Fibrillation Taking Non-Vitamin K Antagonist Oral Anticoagulants: A Nationwide Population-Based Cohort Study.

Background A higher risk of developing dementia is observed in patients with atrial fibrillation (AF). Results are inconsistent regarding the risk of dementia when patients with AF use different anticoagulants. We aimed to investigate the risk of dementia in patients with AF receiving non-vitamin K antagonist oral anticoagulants (NOACs) compared with those receiving warfarin. Methods and Results We conducted a nationwide population-based cohort study of incident cases using the Taiwan National Health Insurance Research Database. We initially enlisted all incident cases of AF and then selected those treated with either NOACs or warfarin for at least 90 days between 2012 and 2016. First-ever diagnosis of dementia was the primary outcome. We performed propensity score matching to minimize the difference between each cohort. We used the Fine and Gray competing risk regression model to calculate the hazard ratio (HR) for dementia. We recruited 12 068 patients with AF (6034 patients in each cohort). The mean follow-up time was 3.27 and 3.08 years in the groups using NOACs and warfarin, respectively. Compared with the HR for the group using warfarin, the HR for dementia was 0.82 (95% CI, 0.73-0.92; P=0.0004) in the group using NOACs. Subgroup analysis demonstrated that users of NOAC aged 65 to 74 years, with a high risk of stroke or bleeding were associated with a lower risk of dementia than users of warfarin with similar characteristics. Conclusions Patients with AF using NOACs were associated with a lower risk of dementia than those using warfarin. Further randomized clinical trials are greatly needed to prove these findings.

Risk of developing diabetes in patients with atrial fibrillation taking non-vitamin K antagonist oral anticoagulants or warfarin: A nationwide cohort study.

AIM: To compare the risk of diabetes development in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. MATERIALS AND METHODS: We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Adult patients with new onset of AF, treated with NOACs or warfarin between 2012 and 2016, were included. The NOAC cohort was further divided into dabigatran, rivaroxaban and apixaban groups. The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. Fine and Gray subdistribution hazards models were used to estimate the adjusted hazard ratio (aHR). Propensity score matching was performed for each head-to-head comparison. RESULTS: A total of 10 746 new-onset AF patients were included in our study. During the mean 2.4-year follow-up, NOACs were associated with a lower risk of developing diabetes than warfarin (aHR = 0.80, 95% confidence interval [CI]: 0.68-0.94, P = .007). Subgroup analyses confirmed that dabigatran, rivaroxaban and apixaban each had a reduced diabetes risk. Stratified analyses showed that the lower risk of diabetes associated with NOAC treatment was specific to patients aged 65 years or older (aHR = 0.74, 95% CI: 0.62-0.89, P = .002) and those with good medication adherence (aHR = 0.70, 95% CI: 0.58-0.84, P < .001). CONCLUSIONS: Taking an NOAC was associated with a lower risk of developing diabetes than taking warfarin in patients with AF.

Fracture risks among patients with atrial fibrillation receiving different oral anticoagulants: a real-world nationwide cohort study.

AIMS: To evaluate the fracture risk among patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. METHODS AND RESULTS: We conducted a real-world nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. All adult patients in Taiwan newly diagnosed with AF between 2012 and 2016 who received NOACs or warfarin were enrolled and followed up until 2017. Patients treated with NOACs were sub-grouped according to the NOAC used (dabigatran, rivaroxaban, and apixaban). Propensity score matching was performed for each head-to-head comparison. Cox regression analysis, with a shared frailty model, was used to calculate the adjusted hazard ratios (aHRs) for hip, vertebral, and humerus/forearm/wrist fractures. After matching, 19 414 patients were included (9707 in each NOAC and warfarin groups). The median follow-up time was 2.4 years. Compared with warfarin, NOACs were associated with a reduced fracture risk [aHR = 0.84, 95% confidence interval (CI) = 0.77-0.93; P < 0.001]. Sub-analyses revealed that each NOAC, namely dabigatran (aHR = 0.88, 95% CI = 0.78-0.99; P = 0.027), rivaroxaban (aHR = 0.81, 95% CI = 0.72-0.90; P < 0.001), and apixaban (aHR = 0.67, 95% CI = 0.52-0.87; P = 0.003), had a reduced fracture risk. Analyses including all eligible patients, without propensity score matching, generated similar results. CONCLUSION: Compared with warfarin, NOAC was associated with a reduced fracture risk among AF patients. Therefore, if oral anticoagulants are indicated, NOACs rather than warfarin should be considered to lower the risk of fractures. However, further studies are needed to investigate the underlying mechanisms and elucidate causality.

Risk of Osteoporosis in Patients With Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants or Warfarin.

Background Warfarin, a vitamin K antagonist, has been shown to affect bone mineral density and cause osteoporosis. However, studies investigating the relationship between non-vitamin K antagonist oral anticoagulants (NOACs) and osteoporosis are limited. We thus compared the risk of osteoporosis in patients with atrial fibrillation treated with either NOACs or warfarin. Methods and Results This nationwide, retrospective cohort study used Taiwan's National Health Insurance Research Database. All adult patients in Taiwan who were newly diagnosed with atrial fibrillation and treated with NOACs or warfarin between January 2012 and December 2015 were included and classified into their respective cohorts. Patients who received NOACs were subcategorized into the rivaroxaban, dabigatran, and apixaban subgroups. Propensity score matching was performed for each head-to-head comparison. Adjusted hazard ratios (aHRs) for the risk of osteoporosis were calculated using Cox proportional hazards regression models, with adjustment for confounders. Overall, 17 008 patients were included, with 8504 in each cohort. NOACs were associated with a lower osteoporosis risk than warfarin (aHR=0.82; 95% CI=0.68-0.97). A subgroup effect of treatment duration was identified (namely, the lower osteoporosis risk with NOAC compared with warfarin became stronger in those with longer treatment duration [P for interaction <0.001]). Furthermore, significantly lower risks of osteoporosis were observed in the rivaroxaban (aHR=0.68; 95% CI=0.55-0.83) and apixaban (aHR=0.38; 95% CI=0.22-0.66) subgroups, but not in the dabigatran subgroup (aHR=1.04; 95% CI=0.85-1.27). Conclusions Compared with warfarin, rivaroxaban and apixaban were associated with a significantly lower risk of osteoporosis in patients with atrial fibrillation.

Long-term stroke incidence in proximal thoracic aorta aneurysm survivors.

BACKGROUND: Aneurysm of proximal thoracic aorta (pTAA) is an often indolent, yet fatal disease. Although advancements in aneurysmal repair techniques have increased long-term survival rates, studies have proven that there are increases in perioperative risk for stroke incidence after pTAA surgery. Conversely, there is little evidence regarding the long-term stroke incidence in pTAA individuals, which strongly influences the morbidity, mortality, and usage of antithrombotic agents. METHODS: Using the Taiwan National Health Insurance Research Database, a nationwide population-based cohort, we recruited 3013 pTAA survivors hospitalized from 1 January 2000 to 31 December 2012. To ensure study cohort quality, only patients aged 20 years and above who underwent aneurysmal repair surgery are included. The control cohort is identified by matching background features (comorbidities, age, gender) at a 1:4 ratio through the use of frequency matching. The primary outcomes include incidence of ischemic stroke and intracranial hemorrhage one month after aneurysmal repair surgery. RESULTS: The mortality of pTAA survivors is nearly twice of the matched controls despite aneurysmal repair (28.5 % vs. 15.2%, p < 0.001). Long-term follow-up of participants indicated that pTAA survivors had a higher risk for hemorrhage stroke (adjusted hazard ratio (aHR): 1.93; 95% confidence interval (CI): 1.47-2.53), but no significant increase in risk for ischemic stroke (aHR: 1.07; 95% CI: 0.92-1.25). Hemorrhagic stroke occurrence was found to be associated with age and diabetes mellitus. Comparison on hemorrhagic stroke subtypes between study and matched cohorts showed no statistical differences in intracerebral hemorrhage and subarachnoid hemorrhage. CONCLUSIONS: Despite the advancement of aneurysmal repair surgery, this study suggests that pTAA patients may still face an increased risk of hemorrhage stroke. Further investigation is warranted to provide better long-term care for the pTAA population.

Anticoagulants for cancer-associated ischemic stroke.

Patients with cancer-associated ischemic stroke pose similar clinical manifestations and image characteristics, mainly embolic infarction, as patients with atrial fibrillation do. D-dimer, a degraded product of fibrin polymer, is a useful indicator of hypercoagulability, which frequently increases in cancer-associated stroke, but not in stroke resulted from atrial fibrillation. The level of serum D-dimer is associated with mortality, prognosis, and recurrence of systemic thromboembolism in these patients. Theoretically, drugs block coagulation cascade, such as heparin and low-molecular-weight-heparin (LMWH), oral direct anticoagulants, could attenuate the status of hypercoagulation and decrease the amount of D-dimer. These drugs may be helpful to prevent thromboembolic events in patients with cancer-associated hypercoagulability. Vitamin K antagonist, warfarin, decreases the production of coagulation factors, but not interrupts coagulation cascade may not be helpful to decrease hypercoagulability, but increase the risk of bleeding. However, the treatment of cancer-associated embolic stroke is still controversial. This article reviews relevant clinical studies and proposes the applicability of direct oral anticoagulants from the pathophysiological mechanism.