Use of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients With Type 2 Diabetes and the Incidence of Retinal Vein Occlusion in Taiwan.

Purpose: The purpose of this study was to evaluate the risk of newly diagnosed retinal vein occlusion (RVO) in patients with type 2 diabetes (T2D) using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i). Methods: Claims data from the National Health Insurance Research Database of Taiwan were used in this nationwide retrospective cohort study. A target trial emulation framework was applied. Patients with T2D with no prior diagnosis of RVO who had newly commenced treatment with SGLT-2i or DPP-4i between May 1, 2016, and December 31, 2020, were included. Potential systematic differences in baseline characteristics between the paired groups were controlled using stabilized inverse probability of treatment weighting. The outcome of interest was incident RVO. The hazard ratio (HR) for SGLT-2i compared with that of DPP-4i was estimated using a Cox regression model. Results: Data from 123,567 and 578,665 patients receiving SGLT-2i and DPP-4i, respectively, were analyzed. The incidence of RVO was lower in patients newly receiving SGLT-2i (0.59 events per 1000 person-years) compared to those receiving DPP-4i (0.77 events per 1000 person-years) over a mean follow-up of 1.61 years. SGLT-2i users had a significantly lower risk of developing RVO compared with DPP-4i users (HR = 0.76, 95% confidence interval [CI] = 0.59-0.98). In the individual outcome analysis, SGLT-2i use was significantly associated with a lower risk of branch RVO (HR = 0.71, 95% CI = 0.52-0.96), but not central RVO (HR = 0.84, 95% CI = 0.57-1.24). Conclusions: The risk of developing RVO was lower in patients with T2D receiving SGLT-2i compared with that in those receiving DPP-4i.

MACE and Hyperthyroidism Treated With Medication, Radioactive Iodine, or Thyroidectomy.

Importance: Excessive thyroid hormones from hyperthyroidism increase cardiovascular risks. Among 3 available treatments for hyperthyroidism, comparisons of long-term outcomes associated with antithyroid drugs (ATDs), radioactive iodine (RAI), and surgery to treat newly diagnosed hyperthyroidism are lacking. Objective: To compare risks of major adverse cardiovascular events (MACE) and all-cause mortality among patients with hyperthyroidism treated with ATDs, RAI, or surgery. Design, Setting, and Participants: This nationwide cohort study used the Taiwan National Health Insurance Research Database. Patients aged 20 years or older with newly diagnosed hyperthyroidism between 2011 and 2020 were enrolled. Treatment groups were determined within 18 months from diagnosis, with follow-up until the development of MACE, death, or the end date of the database, whichever came first. Data were analyzed from October 2022 through December 2023. Exposures: The ATD group received ATDs only. RAI and surgery groups could receive ATDs before treatment. Anyone who underwent thyroid surgery without RAI was classified into the surgery group and vice versa. Main Outcomes and Measures: The primary outcomes included MACE (a composite outcome of acute myocardial infarction, stroke, heart failure, and cardiovascular mortality) and all-cause mortality. Results: Among 114 062 patients with newly diagnosed hyperthyroidism (mean [SD] age, 44.1 [13.6] years; 83 505 female [73.2%]), 107 052 patients (93.9%) received ATDs alone, 1238 patients (1.1%) received RAI, and 5772 patients (5.1%) underwent surgery during a mean (SD) follow-up of 4.4 (2.5) years. Patients undergoing surgery had a significantly lower risk of MACE (hazard ratio [HR] = 0.76; 95% CI, 0.59-0.98; P = .04), all-cause mortality (HR = 0.53; 95% CI, 0.41-0.68; P < .001), heart failure (HR = 0.33; 95% CI, 0.18-0.59; P < .001), and cardiovascular mortality (HR = 0.45; 95% CI, 0.26-0.79; P = .005) compared with patients receiving ATDs. Compared with ATDs, RAI was associated with lower MACE risk (HR = 0.45; 95% CI, 0.22-0.93; P = .03). Risks for acute myocardial infarction and stroke did not significantly differ between treatment groups. Conclusions and Relevance: In this study, surgery was associated with lower long-term risks of MACE and all-cause mortality, while RAI was associated with a lower MACE risk compared with ATDs.

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.

Association between bisphosphonate use and stroke risk: a meta-analysis.

Previous studies have suggested that bisphosphonates may reduce stroke risk. This meta-analysis, which included 21 studies with 741,274 participants, revealed that bisphosphonates might be associated with lower stroke risk. However, evidence derived from randomized controlled trials identified no statistically significant association. Future high-quality studies are still required to determine causality. PURPOSE: Whether bisphosphonates may reduce the risk of stroke remains inconclusive. We conducted a systematic review and meta-analysis to evaluate the association between bisphosphonate use and the risk of stroke based on up-to-date evidence. METHODS: We searched for studies evaluating the effects of bisphosphonate on the risk of stroke from inception until January 3, 2022, on PubMed, Embase, Scopus, and Cochrane libraries and updated our search until August 22, 2022, using PubMed to identify any new potential published studies. Two or more reviewers independently screened articles, extracted data, and assessed the study quality. We retrieved the data to synthesize the pooled relative risk (RR) of stroke associated with bisphosphonate use compared with controls; random-effects models were used for meta-analysis. RESULTS: A total of 21 studies (7 randomized controlled trials [RCTs] and 14 observational studies) involving 741,274 participants were included in our meta-analysis. Overall, bisphosphonate use was associated with a lower risk of stroke, but the result was only borderline significant (pooled RR = 0.87, 95% confidence interval [CI]: 0.76-0.99, p = 0.048), and high between-study heterogeneity was found (I2 = 83.7%). Subgroup analyses showed that the evidence derived from RCTs suggested no significant association between bisphosphonate use and stroke risk (pooled RR = 0.93, 95% CI: 0.76-1.13, p = 0.462; I2 = 13.4%). CONCLUSION: Our results suggest that bisphosphonate use is associated with a lower risk of stroke. However, the current evidence does not lead to a definite conclusion due to the borderline statistical significance and high between-study heterogeneity. Future studies, especially RCTs, are necessary to assess causality.

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.

Association of bisphosphonates with diabetes risk and glycemic control: a meta-analysis.

Previous evidence suggests that bisphosphonates may improve glycemic control. The present meta-analysis, comprising seven studies with 1,233,844 participants, demonstrated that bisphosphonate use was significantly associated with a lower risk of diabetes. However, in the randomized controlled trial subgroup, a non-significant association was found. Further studies are needed to determine causality. PURPOSE: This study aimed to evaluate the impact of bisphosphonates on glycemic control and the risk of incident diabetes. METHODS: MEDLINE, Embase, and Cochrane Library were searched from inception to February 15, 2022. Experimental or observational studies that compared fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels and the diabetes risk with and without bisphosphonates were included. Studies without relevant outcomes, only providing crude estimates, or the absence of a control group were excluded. Two reviewers independently screened the articles, extracted data, and appraised studies. The pooled relative risk (RR) and weighted mean difference (WMD) were calculated using random effects models. RESULTS: Seven studies (n = 1,233,844) on diabetes risk were included, including two post hoc analyses of randomized controlled trials (RCTs) and five observational studies. Compared with controls, bisphosphonates (BPs) were associated with a significant decrease in the risk of diabetes (RR = 0.77; 95% CI, 0.65 to 0.90; P = 0.002). However, in the subgroup of post hoc analyses of RCTs, the association was non-significant (RR = 0.93; 95% CI, 0.74 to 1.18; P = 0.576). Moreover, three studies (n = 4906) on FBG and one (n = 60) on HbA1c were included. We observed non-significant association between BPs and changes in FBG (WMD = - 0.61 mg/dL; 95% CI, - 2.72 to 1.49; P = 0.567) and HbA1c (WMD = - 0.11%; 95% CI, - 0.23 to 0.01; P = 0.083). CONCLUSION: Patients taking BPs may have a lower risk of incident diabetes than those without BPs. However, due to the high between-study heterogeneity and inconsistent findings between post hoc analyses of RCTs and observational studies, further rigorous RCTs are required to determine whether the findings are causal.

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.

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.

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.

Cataract and the increased risk of depression in general population: a 16-year nationwide population-based longitudinal study.

Cataract is the primary cause of visual impairment and can be corrected by cataract surgery. We investigated the impact of cataract on the risk of depression along with the benefits of cataract surgery. Patients newly diagnosed with cataract by ophthalmologists between 2001 and 2015 were identified from the National Health Insurance Research Database (NHIRD) in Taiwan. Non-cataract individuals were recruited by 1:1 matching for age, sex and index year. After propensity score matching, 233,258 patients in total were included in our study: 116,629 in each of the cataract and non-cataract cohorts. The primary outcome was the new diagnosis of depression by psychiatrists. In a mean follow-up period of 7.8 years, cataract was significantly associated with increased risk of developing depression (adjusted hazard ratio [aHR] = 1.78, 95% confidence interval [CI] 1.70-1.87, p < 0.001). We further divided the cataract cohort into surgery and non-surgery groups. Notably, cataract surgery group was associated with a decreased risk of depression compared with non-surgery patients (aHR = 0.75, 95% CI 0.71-0.79, p < 0.001). Our results emphasise the importance of regular screening for depression among cataract patients and the beneficial effect of cataract surgery in reducing the risk of depression.

Exercise Capacity and Ventricular Remodeling After Transcatheter Ventricular Septal Defect Closure in Asymptomatic or Minimally Symptomatic Adolescents and Adults.

BACKGROUND: Transcatheter ventricular septal defect (VSD) closure is a safe and efficacious alternative to surgery. However, its benefits in asymptomatic or minimally symptomatic patients remain unknown. METHODS: Sixty patients with VSD aged 12 to 60 years underwent cardiopulmonary exercise test and echocardiography 1 day before transcatheter VSD closure and 6 months after intervention (closure group). Thirty patients who did not receive the intervention underwent the same evaluations over 6 months (observation group). RESULTS: No significant change in exercise function was observed after VSD closure, except for increased peak oxygen (O2) pulse (absolute increase: 0.4±1.4 mL/beat). Left ventricular end-diastolic dimension and mitral peak early filling velocity-to-early diastolic annular velocity ratio decreased (absolute decrease: 0.3±0.6 cm and 0.7±1.9, respectively). Despite unchanged overall peak O2 consumption, 33% of closure group patients exhibited clinically significant improvements in peak O2 consumption (>10% increase relative to baseline). This was not related to the pulmonary flow-to-systemic flow ratio or baseline exercise capacity. By contrast, all exercise function parameters deteriorated significantly in the observation group. Subgroup analysis revealed that patients with a baseline left ventricular end-diastolic dimension Z score of >2 exhibited a significantly greater improvement in peak O2 consumption, peak O2 pulse, and oxygen uptake efficiency slope than did the observation group. CONCLUSIONS: Compared with conservative management, transcatheter VSD closure prevents deterioration in exercise capacity and promotes left ventricular reverse remodeling in asymptomatic or minimally symptomatic patients. These benefits are most prominent in patients whose left ventricular end-diastolic dimension Z score before intervention is >2, irrespective of baseline peak O2 consumption and pulmonary flow/systemic flow ratio. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03127748.

Hypothyroidism and the Risk of Venous Thromboembolism: A Nationwide Cohort Study.

BACKGROUND: Previous studies have shown that hypothyroidism may have an impact on blood coagulation. However, how hypothyroidism and thyroxine replacement therapy (TRT) affect the risk of venous thromboembolism (VTE) remains controversial. This study aimed to examine the associations of hypothyroidism and TRT with VTE risks. MATERIALS AND METHODS: This nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. We enrolled 10,818 hypothyroid patients (the exposed cohort) and 21,636 non-hypothyroid subjects (the unexposed cohort) between 2001 and 2014 after 1:2 exact matching according to age, sex, and index year. Hypothyroid patients were further divided into two groups depending on whether they received TRT or not. Adjusted hazard ratios (aHRs) for VTE were calculated using Fine and Gray competing risk models. RESULTS: The mean follow-up period was 7.5 years. Hypothyroidism was significantly associated with a higher risk of VTE (aHR = 1.83 [95% confidence interval [CI]: 1.44-2.33, p < 0.001]). Among hypothyroid patients, the TRT subgroup had a non-significant trend of lower VTE risk than the non-TRT subgroup (aHR = 0.73 [95% CI: 0.52-1.01, p = 0.058]). The analysis for individual events revealed a significant association between TRT use and a lower risk of pulmonary embolism among hypothyroid patients (aHR = 0.34 [95% CI: 0.13-0.88, p = 0.026]). CONCLUSION: The data suggest that hypothyroidism was significantly associated with an increased risk of VTE. Among hypothyroid patients, a non-significant trend of lower VTE risk in patients treated with TRT was observed. Further prospective studies or clinical trials are necessary to confirm causality.

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.