Cardiovascular outcomes in patients with atrial fibrillation concomitantly treated with antiarrhythmic drugs and non-vitamin k antagonist oral anticoagulants.

AIMS: Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the study. METHODS AND RESULTS: National health insurance database were retrieved during 2012-17 for study. We excluded patients not taking AADs, bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Outcomes were compared in Protocol 1, dronedarone vs. non-dronedarone; Protocol 2, dronedarone vs. amiodarone; and Protocol 3, dronedarone vs. propafenone. Outcomes were acute myocardial infarction (AMI), ischaemic stroke/systemic embolism, intracranial haemorrhage (ICH), major bleeding, cardiovascular death, all-cause mortality, and major adverse cardiovascular event (MACE) (including AMI, ischaemic stroke, and cardiovascular death). In Protocol 1, 2298 dronedarone users and 6984 non-dronedarone users (amiodarone = 4844; propafenone = 1914; flecainide = 75; sotalol = 61) were analysed. Dronedarone was associated with lower ICH (HR = 0.61, 95% CI = 0.38-0.99, P = 0.0436), cardiovascular death (HR = 0.24, 95% CI = 0.16-0.37, P < 0.0001), all-cause mortality (HR = 0.33, 95% CI = 0.27-0.42, P < 0.0001), and MACE (HR = 0.56, 95% CI = 0.45-0.70, P < 0.0001). In Protocol 2, 2231 dronedarone users and 6693 amiodarone users were analysed. Dronedarone was associated with significantly lower ICH (HR = 0.53, 95%=CI 0.33-0.84, P = 0.0078), cardiovascular death (HR = 0.20, 95% CI = 0.13-0.31, P < 0.0001), all-cause mortality (HR 0.27, 95% CI 0.22-0.34, P < 0.0001), and MACE (HR = 0.53, 95% CI = 0.43-0.66, P < 0.0001), compared with amiodarone. In Protocol 3, 812 dronedarone users and 2436 propafenone users were analysed. There were no differences between two drugs for primary and secondary outcomes. CONCLUSION: The use of dronedarone with NOACs was associated with cardiovascular benefits in an Asian population, compared with non-dronedarone AADs and amiodarone.

Surgical volume and outcomes of surgical ablation for atrial fibrillation: a nationwide population-based cohort study.

BACKGROUND: Atrial fibrillation is the most common cardiac arrythmia and causes many complications. Sinus rhythm restoration could reduce late mortality of atrial fibrillation patients. The Maze procedure is the gold standard for surgical ablation of atrial fibrillation. Higher surgical volume has been documented with favorable outcomes of various cardiac procedures such as mitral valve surgery and aortic valve replacement. We aimed to determine the volume-outcome relationship (i.e., association between surgical volume and outcomes) for the concomitant Maze procedure during major cardiac surgeries. METHODS: This nationwide population-based cohort study retrieved data from the Taiwan National Health Insurance Research Database. Adult patients undergoing concomitant Maze procedures during 2010-2017 were identified; consequently, 2666 patients were classified into four subgroups based on hospital cumulative surgery volumes. In-hospital outcomes and late outcomes during follow-up were analyzed. Logistic regression and Cox proportional hazards model were used to analyze the volume-outcome relationship. RESULTS: Patients undergoing Maze procedures at lower-volume hospitals tended to be frailer and had higher comorbidity scores. Patients in the highest-volume hospitals had a lower risk of in-hospital mortality than those in the lowest-volume hospitals [adjusted odds ratio, 0.30; 95% confidence interval (CI), 0.15-0.61; P < 0.001]. Patients in the highest-volume hospitals had lower rates of late mortality than those in the lowest-volume hospitals, including all-cause mortality [adjusted hazard ratio (aHR) 0.53; 95% CI 0.40-0.68; P < 0.001] and all-cause mortality after discharge (aHR 0.60; 95% CI 0.44-0.80; P < 0.001). CONCLUSIONS: A positive hospital volume-outcome relationship for concomitant Maze procedures was demonstrated for in-hospital and late follow-up mortality. The consequence may be attributed to physician skill/experience, experienced multidisciplinary teams, and comprehensive care processes. We suggest referring patients with frailty or those requiring complicated cardiac surgeries to high-volume hospitals to improve clinical outcomes. TRIAL REGISTRATION: the institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502).

Long-term Outcomes of Concomitant Surgical Ablation for Atrial Fibrillation.

BACKGROUND: The long-term outcomes of surgical ablation for atrial fibrillation (AF) during cardiac surgery remain unclear. METHODS: This nationwide population-based retrospective cohort study used data from Taiwan's National Health Insurance Research Database. Overall, 11,459 patients undergoing coronary artery bypass graft, valve, or aortic surgery and diagnosed as having AF between January 1, 2001, and December 31, 2016, were included. To reduce possible selection bias, we created a propensity score-matched cohort and compared outcomes between groups. The outcomes of interest were long-term survival and late ischemic stroke. RESULTS: The surgical ablation group had a significantly lower risk of all-cause mortality (5.74 and 7.69 events per 100 patient-years, respectively; hazard ratio, 0.75; 95% CI, 0.69-0.81) and ischemic stroke after discharge (1.88 and 2.52 events per 100 patient-years, respectively; subdistribution hazard ratio, 0.78; 95% CI, 0.67-0.91). AF ablation performed concomitantly with coronary artery bypass graft surgery, tissue aortic valve replacement, tissue mitral valve replacement, or mitral valve repair led to significantly better long-term survival (P = .0176, P = .0001, P < .0001, P < .0001, respectively). The surgical ablation group also had better long-term survival than the matched general AF population (log-rank test, P < .001). CONCLUSIONS: Concomitant AF ablation during cardiac surgery is safe, does not increase the rate of perioperative complications, and confers the benefit of long-term survival after cardiac surgery in adults. AF ablation also improved cardiac surgery patients' long-term survival compared with the matched general AF population.

Effectiveness of aftercare program for suicide ideators: Real-world evidence from National Suicide Surveillance System in Taiwan.

Aftercare programs' effectiveness for suicide ideators has seldom been reported. This study assessed rates and factors related to the recurrence of suicide-related episodes after the index suicidal ideation episode, index cases, and family members receiving aftercare. This is a secondary data analysis of 1787 suicidal ideation episodes from 1557 individuals reported to the National Suicide Surveillance System in New Taipei City, Taiwan, from January 2012 to June 2013 and followed up until September 2013. Among 1787 index suicidal ideations, 19.1% had recurrences of suicide-related episodes, including suicidal ideation (11.9%), attempt (6.7%), and death (0.5%) within 2 years after index ideation. These recurrences were significantly reduced after the index cases received aftercare twice, three, and four or higher. Family members receiving aftercare twice or more were associated with reduced suicidality in the index cases. Receiving aftercare among index cases was associated with being a woman, suicide due to occupation/finance, and reporting from suicide hotlines. Receiving aftercare among family members was associated with the index cases aged ≤ 19 years old, suicide reasons related to school, occupation/finance, and reporting from schools and hospitals. Aftercare programs for suicide ideators and family members of adolescent suicide ideators (aged ≤ 19 years old) decreased subsequent episodes of suicidal behavior.

Electrocardiographic changes associated with SGLT2 inhibitors and non-SGLT2 inhibitors: A multi-center retrospective study.

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors has been shown with cardiovascular benefit in type 2 diabetes mellitus (T2DM) patients. However, its osmotic diuresis still concern physicians who may look for possible electrolyte imbalance. We therefore aimed to investigate electrocardiographic (ECG) changes associated with SGLT2 inhibitors. Methods: Electronic medical records from Chang Gung Research Database between January 1, 2001 and January 31, 2019 were searched for patients with ECG reports and patients on an oral hypoglycemic agent (OHA). We then separate these T2DM patients with EKG into those taking either SGLT2 inhibitors or non-SGLT2 inhibitors. We excluded patients with OHA use <28 days, age <18 years, baseline ECG QTc > 500 ms, and ECG showing atrial fibrillation or atrial flutter. Propensity score matching (PSM) was performed between groups by age, sex, comorbidities, and medications (including QT prolonging medications). Conditional logistic regression and Firth's logistic regression for rare events were employed to compare the difference between SGLT2 and non-SGLT2 inhibitor patients. Results: After exclusion criteria and PSM, there remained 1,056 patients with ECG on SGLT2 inhibitors and 2,119 patients with ECG on non-SGLT2 inhibitors in the study. There were no differences in PR intervals, QT prolongations by Bazett's or Fridericia's formulas, new onset ST-T changes, new onset CRBBB or CLBBB, and ventricular arrhythmia between the group of patients on SGLT2 inhibitors and the group of patients on non-SGLT2 inhibitors. There were no differences between the two groups in terms of cardiovascular death and sudden cardiac death. In addition, there were no differences between the two groups in terms of electrolytes. Conclusions: Compared with T2DM patients on non-SGLT2 inhibitors, there were no differences in PR interval, QT interval, ST-T changes, bundle-branch block, or ventricular arrhythmia in the patients on SGLT2 inhibitors. There were no differences in cardiovascular mortality between these two groups. In addition, there were no electrolyte differences between groups. SGLT2 inhibitors appeared to be well-tolerated in terms of cardiovascular safety.

Concurrent use of statins decreases major bleeding and intracerebral hemorrhage in non-valvular atrial fibrillation patients taking direct oral anticoagulants-A nationwide cohort study.

Background: Statins are frequently prescribed with direct oral anticoagulants (DOACs), and previous studies have raised concerns about the increased risk of intracerebral hemorrhage or other major bleeding in concurrent statins and DOACs use. The objective of this study is to evaluate the risk of major bleeding in non-valvular atrial fibrillation patients taking DOACs with or without statins. Methods: This nationwide, retrospective cohort study used data from the Taiwan National Health Insurance Research Database, enrolled a total of 90,731 non-valvular atrial fibrillation patients receiving rivaroxaban, dabigatran, apixaban or edoxaban from January 1st, 2012 to December 31st, 2017. Major bleeding was defined as a hospitalization or emergency department visit with a primary diagnosis of intracerebral hemorrhage, gastrointestinal tract bleeding, urogenital tract bleeding, or other sites of bleeding. Adjusted incidence rate ratios (IRR) and differences of major bleeding between person-quarters of DOACs with or without statins were estimated using a Poisson regression and inverse probability of treatment weighting using the propensity score. Results: 50,854 (56.0%) of them were male with a mean age of 74.9 (SD, 10.4) years. Using DOACs without statins as a reference, the adjusted IRR for all major bleedings in concurrent use of DOACs and statins was 0.8 (95% CI 0.72-0.81). Lower major bleeding risk was seen in both low-to-moderate-intensity statins (IRR: 0.8, 95% CI 0.74-0.84) and high-intensity statins (IRR: 0.8, 95% CI 0.74-0.88). Concurrent use of DOACs and statins decreased the risk for intracerebral hemorrhage with an IRR of 0.8 (95% CI 0.66-0.93), and gastrointestinal tract bleeding with an IRR of 0.7 (95% CI 0.69-0.79). The protective effect of statins on intracerebral hemorrhage was observed only in female patients (IRR 0.67, 95% CI 0.51-0.89), but not in male patients (IRR 0.87, 95% CI 0.70-1.08). Conclusions: Among non-valvular atrial fibrillation patients who were taking DOACs, concurrent use of statins decreased major bleeding risk, including intracerebral hemorrhage and gastrointestinal tract bleeding. Considering this and other cardioprotective effects, statins should be considered in all eligible patients prescribed with DOACs.

Major Bleeding Risk in Atrial Fibrillation Patients Co-Medicated With Non-Vitamin K Oral Anticoagulants and Antipsychotics.

Major bleeding risks associated with non-vitamin K oral anticoagulants (NOACs) used with and without concurrent antipsychotics in patients with non-valvular atrial fibrillation (AF) were assessed. A total of 98,863 patients with non-valvular AF receiving at least one NOAC prescription from Taiwan's National Health Insurance database were enrolled. Major bleeding was defined as a primary diagnosis of intracranial or gastrointestinal hemorrhage or bleeding at other sites. The adjusted incidence rate difference (AIRD) per 1,000 person-years and adjusted rate ratio of major bleeding were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. A total of 8,037 major bleeding events occurred during 705,521 person-quarters with NOAC prescriptions. Antipsychotics were used in 26.35% of NOAC-exposed patients. Compared to using NOAC alone, co-medication of either typical (AIRD: 79.18, 95% confidence interval [CI]: 70.63-87.72) or atypical (AIRD: 40.5, 95% CI: 33.64-47.35) antipsychotic with NOAC had a significant increase in the adjusted incidence rate per 1,000 person-years of major bleeding. The concomitant use of a NOAC with chlorpromazine (AIRD: 103.87, 95% CI: 51.22-156.52), haloperidol (AIRD: 149.52, 95% CI: 125.03-174.00), prochlorperazine (AIRD: 90.43, 95% CI: 78.55-102.32), quetiapine (AIRD: 44.6, 95% CI: 37.11-52.09), or risperidone (AIRD: 41.55, 95% CI: 22.86-60.24) (All p < 0.01) showed a higher adjusted incidence rate of major bleeding than using NOACs alone. The concomitant use of typical (chlorpromazine, haloperidol, or prochlorperazine) or atypical (quetiapine or risperidone) antipsychotic with NOACs was associated with a significantly increased risk of major bleeding.

Association of Glucagon-Like Peptide-1 Receptor Agonist vs Dipeptidyl Peptidase-4 Inhibitor Use With Mortality Among Patients With Type 2 Diabetes and Advanced Chronic Kidney Disease.

IMPORTANCE: Glucagon-like peptide-1 (GLP-1) receptor agonist use is associated with reduced mortality and improved cardiovascular outcomes in the general population with diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used antidiabetic agents for patients with advanced-stage chronic kidney disease (CKD). The association of these 2 drug classes with outcomes among patients with diabetes and advanced-stage CKD or end-stage kidney disease (ESKD) is not well understood. OBJECTIVE: To assess whether use of GLP-1 receptor agonists in a population with diabetes and advanced-stage CKD or ESKD is associated with better outcomes compared with use of DPP-4 inhibitors. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data on patients with type 2 diabetes and stage 5 CKD or ESKD obtained from the National Health Insurance Research Database of Taiwan. The study was conducted between January 1, 2012, and December 31, 2018. Data were analyzed from June 2020 to July 2021. EXPOSURES: Treatment with GLP-1 receptor agonists compared with treatment with DPP-4 inhibitors. MAIN OUTCOMES AND MEASURES: All-cause mortality, sepsis- and infection-related mortality, and mortality related to major adverse cardiovascular and cerebrovascular events were compared between patients treated with GLP-1 receptor agonists and patients treated with DPP-4 inhibitors. Propensity score weighting was used to mitigate the imbalance among covariates between the groups. RESULTS: Of 27 279 patients included in the study, 26 578 were in the DPP-4 inhibitor group (14 443 [54.34%] male; mean [SD] age, 65 [13] years) and 701 in the GLP-1 receptor agonist group (346 [49.36%] male; mean [SD] age, 59 [13] years). After weighting, the use of GLP-1 receptor agonists was associated with lower all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.63-0.98) and lower sepsis- and infection-related mortality (HR, 0.61; 95% CI, 0.40-0.91). Subgroup analysis demonstrated a lower risk of mortality associated with use of GLP-1 receptor agonists compared with DDP-4 inhibitors among patients with cerebrovascular disease (HR, 0.33; 95% CI, 0.12-0.86) than among those without cerebrovascular disease (HR, 0.89; 95% CI, 0.71-1.12) (P = .04 for interaction). CONCLUSIONS AND RELEVANCE: Treatment with GLP-1 receptor agonists was associated with lower all-cause mortality among patients with type 2 diabetes, advanced-stage CKD, and ESKD than was treatment with DPP-4 inhibitors. Additional well-designed, prospective studies are needed to confirm the potential benefit of GLP-1 receptor agonist treatment for patients with advanced CKD or ESKD.

Major Bleeding Risk in Patients With Non-valvular Atrial Fibrillation Concurrently Taking Direct Oral Anticoagulants and Antidepressants.

Direct oral anticoagulants (DOACs) are commonly prescribed with antidepressants that may increase bleeding risk. Here we assessed the association between DOACs with and without concurrent antidepressants and major bleeding risk in patients with atrial fibrillation (AF) by a retrospective cohort study included patients with AF who received prescriptions of DOACs in Taiwan's National Health Insurance database between 2012 and 2017. Adjusted rate ratio (ARR) of major bleeding was calculated by comparing incidence rate adjusted with Poisson regression and inverse probability of treatment weighting using the propensity score between patient-times with and without antidepressants. Among 98863 patients with AF, concurrent use of bupropion with DOACs increased the risks of all major bleeding (ARR: 1.49, 95% CI: 1.02-2.16) and gastrointestinal hemorrhage (ARR: 1.57, 95% CI: 1.04-2.33). An increased risk of intracerebral hemorrhage (ICH) was associated with the combinations of DOACs with selective serotonin reuptake inhibitors (SSRIs, ARR: 1.38, 95% CI: 1.08-1.76), particularly in paroxetine (ARR: 2.11, 95% CI: 1.17-3.81), and tetracyclic antidepressants (TeCAs, ARR: 1.34, 95% CI: 1.01-1.78). In subgroup analyses stratified by individual NOACs, SSRIs increased the risk of ICH in the dabigatran-treated patients (ARR: 1.55, 95% CI: 1.04-2.33). The combinations of apixaban and serotonin-norepinephrine reuptake inhibitors (SNRIs) were associated with a higher risk of all major bleeding (ARR: 1.63, 95% CI: 1.04-2.55). These results clearly indicate the drug-drug interactions between DOACs and antidepressants, which should be carefully considered when prescribing DOACs in adult patients. Careful monitoring for bleeding should be performed while concurrently prescribing DOACs with bupropion, SSRI, SNRI, and TeCA. Concomitant use of DOACs and TCAs may be a relatively safe strategy for patients with AF.

Risk of major bleeding associated with concomitant use of anticancer drugs and direct oral anticoagulant in patients with cancer and atrial fibrillation.

This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan's National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer.

Hypoglycemia Associated With Drug-Drug Interactions in Patients With Type 2 Diabetes Mellitus Using Dipeptidylpeptidase-4 Inhibitors.

Background: Dipeptidylpeptidase-4 inhibitors (DPP-4i's) are considered to be safe for patients with type 2 diabetes mellitus (T2DM). However, little is known about drug-drug interactions between DPP-4i's and concurrent medications. Methods: Data on patients using DPP-4i's for T2DM during 2011-2017 were retrieved from Chang Gung Research database provided by Chang Gung Memorial Hospital. Patients were excluded if they were aged <30 years or >90 years; had incomplete demographic data; had insulinoma; or had records of concomitant insulin use. A generalized estimating equation-based Poisson model was employed for statistical analysis. The primary outcome was hypoglycemia events. Results: We retrieved data on a total of 97,227 patients using DPP-4i's. After patients were excluded according to the mentioned criteria, the remaining 77,047 DPP-4i users were studied (mean age 64 ± 12 years, men 54.4%). The most common medications coprescribed with DPP4is over all person-quarters were acetaminophen, simvastatin, fluvastatin, and colchicine (all >20,000 person-quarters). The combinations of a DPP-4i with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were associated with an increased risk of hypoglycemia. Compared with the ratios observed for person-quarters of DPP-4i use alone (reference category), the adjusted prevalence ratios per 100 person-years of hypoglycemia for person-quarters of DPP-4i use in combination with bumetanide, captopril, colchicine, acetaminophen, cotrimoxazole, and pantoprazole were 2.44 (95% confidence interval [CI], 1.78-3.36), 2.97 (95% CI, 2.26-3.90), 1.87 (95% CI, 1.44-2.42), 2.83 (95% CI, 2.44-3.29), 2.27 (95% CI, 1.27-4.04), and 3.03 (95% CI, 1.96-4.68), respectively. Conclusion: Among patients taking DPP-4i's for T2DM, concurrent use of such inhibitors with bumetanide, captopril, acetaminophen, and pantoprazole was associated with an increased risk of hypoglycemia compared with the use of DPP-4i's alone. Physicians prescribing DPP-4i's should consider the potential risks associated with their concomitant use with other drugs.

Bleeding associated with co-administration of clopidogrel and ACEi in patients undergoing PCI and DAPT.

BACKGROUND AND AIMS: The coprescription of an angiotensin-converting enzyme inhibitor (ACEi) with clopidogrel reportedly increases bleeding risk. However, studies have not described such an increase in cases of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). METHODS: We analyzed electronic medical records of patients with discharge records of having undergone DAPT after PCI from a national health insurance claims database for January 1, 2006 to December 31, 2014. The date of PCI was the index date, and the primary outcome was major bleeding. The unit of analysis was one person-quarter. We compared patients who were prescribed with those not prescribed an ACEi in the cohort. A Poisson model with inverse probability of treatment weighting was fitted using generalized estimating equations to measure the risk of outcomes. RESULTS: In total, 193,258 patients underwent DAPT after PCI; 46% had a coprescription of an ACEi. After screening, 170,775 patients (479,263 person-quarters) remained for analysis. The mean patient age was 65 ± 13 years, and 73.43% were men. In total, 79,739 prescriptions of an ACEi were written: 57%, 14.21%, 8.88%, 7.17%, and 4.68% were for captopril, ramipril, enalapril, perindopril, and imidapril, respectively. A concomitant prescription of an ACEi with clopidogrel was not associated with increased bleeding risk (adjusted rate ratio: 1.08, 99% confidence interval: 0.99-1.17). CONCLUSIONS: The coadministration of an ACEi with clopidogrel after PCI is common. In this real-world cohort study, such coadministration was not associated with an increased risk of major bleeding in patients undergoing DAPT after PCI.

Reduced Risk of Sepsis and Related Mortality in Chronic Kidney Disease Patients on Xanthine Oxidase Inhibitors: A National Cohort Study.

BACKGROUND: Advanced chronic kidney disease (CKD) patients are at higher risk of sepsis-related mortality following infection and bacteremia. Interestingly, the urate-lowering febuxostat and allopurinol, both xanthine oxidase inhibitors (XOis), have been suggested to influence the sepsis course in animal studies. In this study, we aim to investigate the relationship between XOis and infection/sepsis risk in pre-dialysis population. METHODS: Pre-dialysis stage 5 CKD patients with gout were identified through the National Health Insurance Research Database (NHIRD) in Taiwan from 2012 to 2016. Outcomes were also compared with national data. RESULTS: In our nationwide, population-based cohort study, 12,786 eligible pre-dialysis stage 5 CKD patients were enrolled. Compared to non-users, febuxostat users and allopurinol users were associated with reduced sepsis/infection risk [hazard ratio (HR), 0.93; 95% confidence interval (CI), 0.87-0.99; P = 0.0324 vs. HR, 0.92; 95% CI, 0.86-0.99; P = 0.0163]. Significant sepsis/infection-related mortality risk reduction was associated with febuxostat use (HR, 0.68; 95% CI, 0.52-0.87). Subgroup analysis demonstrated preference of febuxostat over allopurinol in sepsis/infection-related mortality among patients younger than 65 years of age, stain users, non-steroidal anti-inflammatory drug non-users, and non-diabetics. There was no significant difference in major adverse cardiac and cerebrovascular event (MACCE) risk between users and non-users while reduced risk of all-cause mortality was observed for XOi users. CONCLUSIONS: Use of XOi in pre-dialysis stage 5 CKD patients may be associated with reduced risk of sepsis/infection and their related mortality without increased MACCE and overall mortality.

Novel oral anticoagulant vs. warfarin in elderly atrial fibrillation patients with normal, mid-range, and reduced left ventricular ejection fraction.

AIMS: Patients with concomitant atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF) have poor prognosis. Outcomes of novel oral anticoagulant (NOAC) in elderly AF patients with normal, mid-range, and reduced LVEF were investigated. METHODS AND RESULTS: Data were retrieved from Chang Gung Research Database during 2010-2017 for patients with AF. We excluded patients with venous thromboembolism within 6 months, total knee/hip replacement and heart valve replacement within 6 months, end-stage renal disease, stroke/systemic embolism (SE)/death within 7 days, age <65 years old, or no records of LVEF. Primary outcomes were ischaemic stroke (IS)/SE, major bleeding, and death from any cause. There was a total of 50 035 elderly AF patients retrieved. After exclusion criteria, 9615 patients with normal LVEF ≥ 50%, 737 with mid-range LVEF 41-49%, and 908 with reduced LVEF ≤ 40% were studied. At end of follow-up, patients on NOAC had significantly reduced IS/SE compared with warfarin in LVEF ≥ 50% [adjusted hazard ration (aHR) 0.80, 95% confidence interval (CI) 0.71-0.89] and LVEF 41-49% (aHR 0.57, 95% CI 0.36-0.88) after adjusting for covariates, while there was no difference in LVEF ≤ 40%. Patients on NOAC had significantly reduced major bleeding in all LVEF groups. In addition, patients on NOAC had significantly reduced death compared with warfarin in LVEF ≥ 50% (aHR 0.81, 95% CI 0.67-0.98). CONCLUSIONS: In elderly AF patients ≥65 years, using NOAC was associated with lower IS/SE compared with warfarin in normal and mid-range LVEF but not in reduced LVEF. Using NOACs was associated with lower death compared with warfarin in normal LVEF.

All-cause mortality and the risk of stroke with selective aspiration thrombectomy in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: A nationwide retrospective cohort study.

Few data exist on the clinical outcomes of selective aspiration thrombectomy during primary percutaneous coronary intervention (PPCI).This was a nationwide retrospective cohort study. Patients who were diagnosed with ST-elevation myocardial infarction (STEMI) and received primary percutaneous coronary intervention (PCI) from July 2009 to December 2011 were identified from the National Health Insurance Research Database of Taiwan. Propensity score weighting was used to balance the covariates between the 2 study groups. The primary endpoints were all-cause mortality and stroke during hospitalization and at 30 days and 1 year of follow-up. Subgroup analyses were performed based on the hospital and physician volume of primary PCI.A total of 9100 ST-elevation myocardial infarction patients (29.4% of patients receiving aspiration thrombectomy and conventional PPCI vs 70.6% receiving PPCI alone) were identified. The incidence rates of all-cause mortality were comparable between the 2 groups during hospitalization (21.0 vs 27.37/100 person-months; P = .29) and 1-year follow-up (0.81 vs 1.26/100 person-months; P = .85). There were no significant differences in the stroke rates between the 2 groups during hospitalization (1.1 vs 2.34/100 person-months; P = .3) and 1-year follow-up (0.09 vs 0.15/100 person-months; P = .85). For the patients who survived to discharge, the post-discharge 1-year mortality was lower in the aspiration thrombectomy group of patients in whom the procedures were performed by physicians with a high volume of PPCI (hazard ratio: 0.47; 95% confidence interval: 0.24-0.94; P = .03).In this nationwide cohort study, selective aspiration thrombectomy at the operation's discretion had a comparable mortality rate compared with PCI alone and did not increase the risk of stroke. In the patients treated by physicians with a high volume of PPCI, aspiration thrombectomy appeared to have a beneficial effect on post-discharge survival at 1 year.

Assessing major bleeding risk in atrial fibrillation patients concurrently taking non-vitamin K antagonist oral anticoagulants and antiepileptic drugs.

AIMS: This study compared the risk of major bleeding between atrial fibrillation (AF) patients who took non-vitamin K antagonist oral anticoagulants (NOACs) and antiepileptic drugs (AEDs) concurrently and those who took only NOACs. METHODS AND RESULTS: We performed a retrospective cohort study using Taiwan National Health Insurance database and included AF patients who received NOAC prescriptions from 1 June 2012 to 31 December 2017. The major bleeding risks of person-quarters exposed to NOAC and 11 concurrent AEDs (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, valproic acid, and zonisamide) were compared with person-quarters exposed to NOAC alone. Adjusted incidence rate differences between NOAC with or without concurrent AEDs were estimated using Poisson regression models weighted by the inverse probability of treatment. Among 104 319 patients (age 75.0 ± 10.3 years; men, 56.2%), 8546 major bleeding events occurred during 731 723 person-quarters with NOAC prescriptions. Concurrent AED use was found in 15.3% of NOAC-treated patients. Concurrent use of NOAC with valproic acid, phenytoin, or levetiracetam increased adjusted incidence rates per 1000 person-years of major bleeding more significantly than NOAC alone: 153.49 for NOAC plus valproic acid vs. 55.06 for NOAC alone [difference 98.43, 95% confidence interval (CI) 82.37-114.49]; 135.83 for NOAC plus phenytoin vs. 54.43 for NOAC alone (difference 81.4, 95% CI 60.14-102.66); and 132.96 for NOAC plus levetiracetam vs. 53.08 for NOAC alone (difference 79.88, 95% CI 64.47-95.30). CONCLUSION: For AF patients, the concurrent use of NOACs and valproic acid, phenytoin, or levetiracetam was associated with a higher risk of major bleeding.

Effectiveness and Safety of Four Direct Oral Anticoagulants in Asian Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Whether four direct oral anticoagulants (DOACs) are superior to warfarin in Asian patients with nonvalvular atrial fibrillation (NVAF) remains unclear. METHODS: This nationwide retrospective cohort study was based on data from Taiwan's National Health Insurance Research Database from June 1, 2012, to December 31, 2017, covering patients with NVAF taking edoxaban (n = 4,577), apixaban (n = 9,952), rivaroxaban (n = 33,022), dabigatran (n = 22,371), and warfarin (n = 19,761). Propensity score weighting was used to balance covariates across study groups. Patients were followed up until occurrence of study outcomes or end date of study. RESULTS: Edoxaban, apixaban, and rivaroxaban were associated with a lower risk of ischemic stroke/systemic embolism than warfarin. All DOACs had a lower risk of major bleeding than warfarin. Apixaban was associated with a lower risk of major bleeding than rivaroxaban and dabigatran, whereas the risk of major bleeding was comparable between edoxaban and apixaban. The reduced risks of thromboembolism/major bleeding for the four DOACs persisted in high-risk subgroups, including those with chronic kidney disease, elderly patients (age ≥ 75 years), secondary stroke prevention, or CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65-74 years, and female sex) ≥ 4. A total of 2,924 (64%), 6,359 (64%), 31,108 (94%), and 19,821 (89%) patients received low-dose edoxaban (15-30 mg/d), apixaban (2.5 mg bid), rivaroxaban (10-15 mg/d), and dabigatran (110 mg bid), respectively. The effectiveness/safety outcomes with the four low-dose DOACs compared with warfarin were consistent with the main analysis. CONCLUSIONS: In the largest real-world practice study among Asian patients with NVAF, four DOACs were associated with a comparable or lower risk of thromboembolism, and a lower risk of bleeding than warfarin. There was consistency even among high-risk subgroups and whether standard-or low-dose regimens were compared.

Temporal Trends of Severe Hypoglycemia and Subsequent Mortality in Patients with Advanced Diabetic Kidney Diseases Transitioning to Dialysis.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at higher risk of hypoglycemia than diabetic patients without DKD. We aimed to investigate the temporal trends of severe hypoglycemia in advanced DKD patients transitioning to dialysis and examine risk factors associated with severe hypoglycemia. We also investigated the association of severe hypoglycemia episodes with one-year mortality after initiation of dialysis in patients with advanced DKD. METHODS: Using the Taiwan National Health Insurance Research Database, 46,779 advanced DKD patients transitioning to dialysis (Peritoneal dialysis 4216, hemodialysis 42,563) between 1997 and 2011 were enrolled. We calculated the rates of severe hypoglycemia from 5 years before dialysis until 10 years after dialysis. Cox proportional hazard model was used to examine the risk factors of post end stage renal disease (ESRD) one-year hypoglycemia and post ESRD one-year mortality in advanced DKD patients transitioning to dialysis. RESULTS: We found that 11.5% of advanced DKD patients had at least one episode of severe hypoglycemia the year leading up to dialysis initiation. Multivariate analysis revealed hemodialysis compared with peritoneal dialysis, stroke, use of sulfonylurea, glinide, and insulin were associated with higher risk of severe hypoglycemia one year after transitioning to dialysis. Increased frequency of severe hypoglycemia-related hospitalizations was associated with incrementally higher mortality risk one year after transitioning to dialysis (Pre-ESRD hypoglycemia: Hazard ratios: 1.28 (1.18⁻1.38, p < 0.001), 1.64 (1.49⁻1.81, p < 0.001) for one, two hypoglycemia-related hospitalizations, respectively; post-ESRD hypoglycemia: HRs of 1.56 (1.40⁻1.73, p < 0.001), 1.72 (1.39⁻2.12, p < 0.001) for one, two hypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia related hospitalization)). CONCLUSIONS: Among advanced DKD patients, we observed a progressive elevated risk of hypoglycemia during the critical dialysis transition period. Increased frequency of severe hypoglycemia-related hospitalizations was associated with higher mortality risk one year after transitioning to dialysis. Further study of glycemic management strategies which prevent hypoglycemia during the critical transition period are warranted.

Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulant and Warfarin in Cirrhotic Patients With Nonvalvular Atrial Fibrillation.

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 ( NOAC s) 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 NOAC s may be considered for such patients.

The CHA2DS2-VASc Score Predicts Major Bleeding in Non-Valvular Atrial Fibrillation Patients Who Take Oral Anticoagulants.

BACKGROUND: Patients with atrial fibrillation (AF) are at a substantial risk of ischemic stroke. The CHA2DS2-VASc score predicts the risk of thromboembolism, but its role in predicting major bleeding in patients taking oral anticoagulants is unclear. METHODS: We used the National Health Insurance Research Database (NHIRD) of Taiwan to identify patients with AF from 2010 to 2016. They were divided into four groups according to the oral anticoagulants. The outcomes were ischemic stroke/systemic thromboembolism, and major bleeding. RESULTS: A total of 279,776 patients were identified. Ischemic stroke or systemic embolism events were observed in 1.73%, 3.62%, 4.36%, and 5.02% of the patients in the apixaban, rivaroxaban, dabigatran, and warfarin groups, respectively. Major bleeding was recorded in 1.18%, 2.66%, 3.23%, and 4.70% of the patients in the apixaban, rivaroxaban, dabigatran, and warfarin groups, respectively. The highest rates for both ischemic stroke and bleeding events occurred in the patients with a CHA2DS2-VASc score of five or more. CONCLUSION: Non-valvular AF patients with high CHA2DS2-VASc scores are susceptible to both systemic thromboembolism and major bleeding. The trend was consistently observed in patients who took non-vitamin K oral anticoagulants (NOACs) or warfarin. NOACs might be potentially more effective in reducing overall events.