Effect of Cancer on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- Substudy of the ANAFIE Registry.

BACKGROUND: Data on outcomes for patients with atrial fibrillation (AF) and active cancer are scarce. The effect of active cancer on thrombosis and bleeding risks in elderly (≥75 years) patients with non-valvular AF (NVAF) enrolled in the All Nippon AF In the Elderly (ANAFIE) Registry were prospectively analyzed.Methods and Results:In this subanalysis of the ANAFIE Registry, a prospective, multicenter, observational study conducted in Japan, we compared the incidence rates of clinical outcomes between active cancer and non-cancer groups. Relationships between primary outcomes and anticoagulation status were evaluated. Of the 32,725 patients enrolled in the Registry, 3,569 had active cancer at baseline; 92.0% of active cancer patients received anticoagulants (23.7%, warfarin; 68.2%, direct oral anticoagulants [DOACs]). Two-year probabilities of stroke/systemic embolic events (SEE) were similar in the cancer (3.33%) and non-cancer (3.16%) groups. Patients with cancer had greater incidences of major bleeding (2.86% vs. 2.04%), all-cause death (10.95% vs. 6.77%), and net clinical outcomes (14.63% vs. 10.00%) than those without cancer. In patients without cancer, DOACs were associated with a decreased risk of stroke/SEE, major bleeding, all-cause death, and net clinical outcome compared with warfarin. No between-treatment differences were observed in patients with active cancer. CONCLUSIONS: Active cancer had no effect on stroke/SEE incidence in elderly NVAF patients, but those with cancer had higher incidences of major bleeding events and all-cause death than those without cancer.

Two-year outcomes of more than 30 000 elderly patients with atrial fibrillation: results from the All Nippon AF In the Elderly (ANAFIE) Registry.

AIMS: To clarify the real-world clinical status and prognosis of elderly and very elderly non-valvular atrial fibrillation (NVAF) patients, more than 30 000 elderly patients with NVAF aged ≥75 years were enrolled in the ANAFIE Registry. METHODS AND RESULTS: This multicentre, prospective, observational study followed elderly NVAF patients in Japan for ∼2 years. Among 32 275 patients (mean age, 81.5 years; men, 57.3%; mean CHA2DS2-VASc score, 4.5), 2445 (7.6%) were not receiving oral anticoagulants (OACs) and 29 830 (92.4%) were given OACs. Of these, 21 585 (66.9%) were receiving direct OACs (DOACs) and 8233 (25.5%), warfarin (mean time in therapeutic range: ∼75%). In total, the 2-year incidence rate was 3.01% for stroke/systemic embolic events (SEE); 2.00%, major bleeding; and 6.95%, all-cause death. When compared with the warfarin group, the DOAC group had a lower hazard ratio (HR) for stroke/SEE, major bleeding, and all-cause death after adjusting for confounders. The group without OACs had a higher HR for stroke/SEE and all-cause death, with a lower HR for major bleeding. History of falls within 1 year at enrolment and of catheter ablation were positive and negative independent risk factors, respectively, for stroke/SEE, major bleeding, and all-cause death. CONCLUSION: In Japan, a large proportion of elderly and very elderly NVAF patients were receiving DOACs, which was significantly associated with lower rates of stroke/SEE, major bleeding, and all-cause death vs. well-controlled warfarin. History of falls and of catheter ablation were independently associated with stroke/SEE, major bleeding, and all-cause death.

Echocardiographic Structure and Function in Elderly Patients With Atrial Fibrillation in Japan　- The ANAFIE Echocardiographic Substudy.

BACKGROUND: Echocardiographic data on the cardiac structure and function in elderly patients with atrial fibrillation (AF) and heart failure (HF) are limited. This subcohort study of the ANAFIE Registry analyzed echocardiographic parameters to identify cardiac structural and functional characteristics.Methods and Results:Of 32,726 subjects in the ANAFIE population, 1,494 (4.6%) were entered as the echocardiography subcohort. Half of the patients, including those with persistent and permanent AF, older age (≥80 years), and CHADS2score ≥2, had left atrial (LA) volume index ≥48 mL/m2, indicating severe LA enlargement. LA enlargement significantly correlated with impaired LA reservoir function, regardless of age and CHADS2score. Types of AF and rhythm were strongly related to LA volume and reservoir function (P<0.0001). Moderate-to-severe mitral and tricuspid regurgitation were significantly more common, and the early diastolic mitral inflow velocity to mitral annulus velocity ratio was significantly higher among patients with than without HF history (all, P<0.0001). CONCLUSIONS: In this subcohort, LA enlargement correlated with impaired LA reservoir function. Elderly patients with non-valvular AF and a history of HF had LA enlargement and dysfunction, increased LV mass index, low LV ejection fraction, and high heart rate.

Background characteristics and anticoagulant usage patterns of elderly non-valvular atrial fibrillation patients in the ANAFIE registry: a prospective, multicentre, observational cohort study in Japan.

OBJECTIVE: To explore anticoagulant usage patterns stratified by stroke and bleeding risk in elderly patients with non-valvular atrial fibrillation (NVAF). DESIGN: Prospective, multicentre, observational cohort study. SETTING: The real-world All Nippon AF In the Elderly (ANAFIE) registry. PARTICIPANTS: Japanese patients aged ≥75 years with NVAF (n=32 726). OUTCOME MEASURES: The distribution of stroke and bleeding risk scores, and the selection of anticoagulant regimen for patients at high stroke and bleeding risk. RESULTS: Overall, 18 185 (55.6%) patients had a high risk of stroke (CHADS2 score ≥3). Of these, 12 561 (38.4% of the total ANAFIE population) had a low bleeding risk (HAS-BLED ≤2) and 5624 (17.2%) had a high bleeding risk (HAS-BLED ≥3). Significant differences were noted between the high versus low bleeding risk groups in sex, height, weight, systolic blood pressure and rates of abnormality of lipid metabolism, gastrointestinal disease, cerebrovascular disorders, chronic kidney disease, angina pectoris, respiratory disease, primary malignant tumour, dementia and fall history within the past year (all p<0.0001). Patients with high stroke and bleeding risks had a lower anticoagulant usage rate versus the low bleeding risk group, and 8.7% and 5.8%, respectively, were not receiving any anticoagulant (p<0.0001). Patients in the high bleeding risk group had a higher usage of warfarin versus the low bleeding risk group (p<0.0001); more patients (14.0%) in the high bleeding risk group receiving warfarin had time in the therapeutic range <40%, versus those in the low bleeding risk group (11.6%, p=0.0146). Direct-acting oral anticoagulants (DOACs) were used less in the high bleeding risk group, without notable differences in the DOAC dose distribution between the two groups. CONCLUSIONS: In elderly NVAF patients at high stroke risk, significant demographic and clinical differences were observed according to bleeding risk. Administration of low-dose DOACs was frequent, but the dose distribution was unaffected by bleeding risk. TRIAL REGISTRATION NUMBER: UMIN000024006 (http://www.umin.ac.jp/).

High prevalence of masked uncontrolled morning hypertension in elderly non-valvular atrial fibrillation patients: Home blood pressure substudy of the ANAFIE Registry.

In the ANAFIE Registry home blood pressure subcohort, we evaluated 5204 patients aged ≥75 years with non-valvular atrial fibrillation (NVAF) to assess blood pressure (BP) control, prevalence of masked hypertension, and anticoagulant use. Mean clinic (C) and home (H) systolic/diastolic BP(SBP/DBP) was 128.5/71.3 and 127.7/72.6 mm Hg, respectively. Overall, 77.5% of patients had hypertension; of these, 27.7%, 13.4%, 23.4%, and 35.6% had well-controlled, white coat, masked, and sustained hypertension, respectively. Masked hypertension prevalence increased with diabetes, decreased renal function, age ≥80 years, current smoker status, and chronic obstructive pulmonary disease. By morning/evening average, 59.0% of patients had mean H-SBP ≥ 125 mm Hg; 48.9% had mean C-SBP ≥ 130 mm Hg. Early morning hypertension (morning H-SBP ≥ 125 mm Hg) was found in 65.9% of patients. Although 51.1% of patients had well-controlled C-SBP, 52.5% of these had uncontrolled morning H-SBP. In elderly NVAF patients, morning H-BP was poorly controlled, and masked uncontrolled morning hypertension remains significant.

Current status of proton pump inhibitor use in Japanese elderly patients with non-valvular atrial fibrillation: A subanalysis of the ANAFIE Registry.

The real-world status of proton pump inhibitor (PPI) use in patients with atrial fibrillation (AF) receiving antithrombotic treatment is largely unknown. The All Nippon AF In the Elderly (ANAFIE) Registry, a prospective, multicenter, observational study, aimed to determine treatment patterns, risk factors, and outcomes among elderly (aged ≥75 years) Japanese non-valvular AF (NVAF) patients in the real-world clinical setting. The present subanalysis of the ANAFIE Registry determined the PPI prescription status of 32,490 elderly Japanese NVAF patients. Patients were stratified by PPI use (PPI+) or no PPI use (PPI-). Risk scores for stroke (CHADS2, CHA2DS2-VASc) and bleeding (HAS-BLED), anticoagulant use, time in therapeutic range (TTR) for warfarin, and anticoagulant/antiplatelet combination use were evaluated. PPIs were used in 11,981 (36.9%) patients. Compared with the PPI- group, the PPI+ group included a greater proportion of female patients (45.2% vs 41.3%; P <0.0001) and had significantly higher CHADS2, CHA2DS2-VASc, and HAS-BLED scores (P <0.0001 for each) as well as higher prevalences of several comorbidities. In the PPI+ group, 54.6% of patients did not have gastrointestinal (GI) disorders and were likely prescribed a PPI to prevent GI bleeding events. Most of the patients with a GI disorder in the PPI+ group had reflux esophagitis. Compared with patients not receiving anticoagulants, a significantly higher proportion of patients receiving anticoagulants received PPIs. For patients receiving anticoagulants, antiplatelet drugs, and both drugs, rates of PPI use were 34.1%, 44.1%, and 53.5%, respectively (P <0.01). Although the rate of PPI use was the highest for NVAF patients receiving both antiplatelet and anticoagulants, no clear differences were observed in the anticoagulants used. These data suggest that PPIs were actively prescribed in high-risk cases and may have been used to prevent GI bleeding among elderly NVAF patients receiving antithrombotic drugs. Trial registration: UMIN000024006.

Characteristics and anticoagulant treatment status of elderly non-valvular atrial fibrillation patients with a history of catheter ablation in Japan: Subanalysis of the ANAFIE registry.

BACKGROUND: Benefits of catheter ablation (CA) have been shown for patients with atrial fibrillation (AF), including elderly patients. However, data in patients aged ≥75 years who have undergone CA for non-valvular AF (NVAF) are lacking. This cross-sectional subanalysis of the ANAFIE registry determined the characteristics and status of anticoagulant treatment in elderly NVAF patients with a history of CA at enrollment. METHOD: The ANAFIE registry was a multicenter, prospective, non-interventional cohort study in which elderly ambulatory patients (≥75 years) diagnosed with NVAF by electrocardiogram were enrolled between October 2016 and January 2018. Treatment was prescribed per routine clinical practice by individual treating physicians. The patients were stratified into two groups: the CA and No-CA groups. RESULTS: Among 32,726 NVAF patients aged ≥75 years, 3002 (9.2%) underwent CA before enrollment. Patients who underwent CA were significantly younger (78.9 years vs 81.7 years; p < 0.0001), had significantly greater height and body weight, as well as creatinine clearance rate (CCr) compared with those who did not undergo CA. In both the CA and No-CA groups, the most common type of AF was paroxysmal AF (72.9% and 38.9%). In the CA group, a significantly larger proportion of patients did not receive anticoagulant therapy compared with the No-CA group (13.3% vs 7.6%; p < 0.0001). Direct oral anticoagulant (DOAC) use was similar in the CA (69.9%) and No-CA (66.0%) groups, and standard doses of DOACs were administered more frequently in the CA group than in the No-CA group. A lower proportion of patients in the CA group received warfarin (16.9% vs 26.4%) compared with the No-CA group. CONCLUSIONS: This ANAFIE registry subanalysis showed that patients with NVAF in the CA group tended to have paroxysmal AF; be significantly younger; have greater weight, height, and CCr; receive standard doses of DOACs; and have not used anticoagulant medication compared with No-CA patients.

Rhythm versus rate control strategies regarding anticoagulant use in elderly non-valvular atrial fibrillation patients: Subanalysis of the ANAFIE (All Nippon AF In the Elderly) Registry.

BACKGROUND: Data on real-world antiarrhythmic and anticoagulant therapy use in elderly atrial fibrillation (AF) patients are lacking; thus, we performed a subanalysis of data from the ANAFIE registry to clarify the current management of Japanese patients aged ≥75 years with non-valvular AF. METHODS: The ANAFIE registry was a multicenter, prospective, observational study. Patients were stratified into three groups: rhythm control group, rate control group, and no antiarrhythmic group. The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were used to estimate embolic and bleeding risk. RESULTS: Among 32,490 patients, the overall frequencies of AF by type were 42.0 % (paroxysmal), 30.1 % (persistent and long-standing persistent), and 27.9 % (permanent). Significant differences (p < 0.0001, each) in age were observed among the three groups; more patients aged 75-79 years received rhythm control (44.2 %) vs rate control (38.8 %). Patients aged ≥85 years received either rate control therapy or no antiarrhythmic agent (∼20 %, each). In the overall population, 36.9 % and 19.6 % of patients were receiving rate and rhythm control therapy, respectively; 43.4 % were not receiving antiarrhythmic therapy. The rate control group consisted mainly of patients with persistent (16.3 %) and permanent AF (38.6 %), and the rhythm control group, of patients with paroxysmal AF (79.0 %). Significantly lower embolic and bleeding risk scores and significantly higher embolic risk scores were observed in patients in the rhythm and rate control groups, respectively. In total, 92.1 % of elderly Japanese patients with AF were receiving anticoagulant therapy. The frequency of direct-acting oral anticoagulant (DOAC) use was similar (∼66 %) among the three groups. Significantly more patients in the rate control group (28.6 %) were being treated with warfarin than in the rhythm control group (21.6 %) (p < 0.0001). CONCLUSIONS: Use versus non-use and antiarrhythmic therapy varied significantly by age, stroke risk scores, type of AF, and DOAC use between subgroups.

Baseline Characteristics of Elderly Japanese Patients Aged ≥75 Years With Non-Valvular Atrial Fibrillation and a History of Stroke　- ANAFIE Registry.

BACKGROUND: Despite the well-established benefits in patients with non-valvular atrial fibrillation (NVAF), oral anticoagulants (OAC) have been underused in elderly patients. We investigated the characteristics and status of anti-thrombotic therapy in elderly NVAF patients in Japan according to a history of stroke or of transient ischemic attack (TIA).Methods and Results:In a multicenter, prospective, observational study, 32,726 Japanese patients aged ≥75 years with NVAF were enrolled, and divided into 3 groups for the present analysis: 6,543 patients with previous ischemic stroke (IS) or TIA (2,410 women), 275 with previous hemorrhagic stroke (HS; 113 women), and the other 25,908 without previous stroke or TIA (11,470 women). Median CHADS2score was 5 in patients with IS/TIA, 2 in those with HS and 2 in those without stroke/TIA (P<0.05). Anti-thrombotic agents were used in 97.1% of patients with IS/TIA (OAC alone in 73.0%; antiplatelets alone in 3.7%; and both in 23.4%), 90.2% of those with HS (84.7%, 3.2%, and 12.1%, respectively), and 94.1% of those without stroke/TIA (83.4%, 2.7%, and 13.9%, respectively; P<0.05 for any anti-thrombotic choice). Of patients taking OAC, 72.2% received direct OAC (DOAC). CONCLUSIONS: In this unique nationwide NVAF registry of >30,000 elderly patients, >90% of patients, even those with HS, received anti-thrombotic therapy, nearly always with OAC. DOAC were the major choice of OAC.

Age-Related Differences in the Clinical Characteristics and Treatment of Elderly Patients With Atrial Fibrillation in Japan　- Insight From the ANAFIE (All Nippon AF In Elderly) Registry.

BACKGROUND: Atrial fibrillation (AF) is increasing as the global population ages. Elderly AF patients (≥75 years) have a worse prognosis than younger patients, and effective management is often difficult due to multiple comorbidities. This analysis examined the age-related differences in clinical characteristics and treatment in real-world elderly Japanese AF patients.Methods and Results:The ANAFIE Registry is a multicenter, prospective, observational registry of 32,726 non-valvular AF patients aged ≥75 years. The present study assessed the age-related differences in baseline clinical status and anticoagulant therapy between age groups 75-<80, 80-<85, 85-<90, and ≥90 years. The prevalence of persistent or permanent AF increased, and that of paroxysmal AF decreased, with increasing age (trend P<0.0001). The risk of stroke, based on CHADS2and CHA2DS2-VASc scores, and bleeding, based on HAS-BLED score, increased with age. Both warfarin and apixaban were used more often as age increased (trend P<0.0001, for each), while other anticoagulants were used less. Anticoagulant doses were significantly lower in older patients. CONCLUSIONS: Permanent/persistent AF, comorbidities, and cardiovascular and bleeding risk all increased significantly with age. Furthermore, use of warfarin and apixaban increased with age, accompanied by a decrease in other oral anticoagulant usage.

Oral Anticoagulant Use in Elderly Japanese Patients With Non-Valvular Atrial Fibrillation　- Subanalysis of the ANAFIE Registry.

Background: Oral anticoagulants (OACs) are effective in preventing stroke in patients with atrial fibrillation (AF), but are challenging for elderly patients because of the higher risk of bleeding complications. Methods and Results: The ANAFIE Registry is a prospective multicenter observational study of elderly (≥75 years) Japanese AF patients. This subanalysis evaluated the current use of OACs. Of 32,713 patients (mean age 81.5 years), 30,068 (91.9%) were receiving OACs, including 8,354 (25.5%) on warfarin and 21,714 (66.4%) on direct OACs (DOACs); 2,645 (8.1%) were not receiving OACs. The most common prescribed dose was a reduced dose for all DOACs. A substantial proportion of patients receiving the reduced dose did not fulfill dose reduction criteria (underdosing): apixaban, 25.1%; rivaroxaban, 26.3%; and edoxaban, 13.7%. Some patients received a lower off-label dose rather than the reduced dose: apixaban, 5.9%; rivaroxaban, 0.3%; edoxaban, 5.3%; and dabigatran, 13.6%. In multivariate analyses, advanced age, history of hemorrhage, paroxysmal AF, and antiplatelet drug use were significantly associated with no OAC. Advanced age, persistent or permanent AF, chronic kidney disease, and concomitant antiplatelet drugs were associated with warfarin rather than DOAC use. Conclusions: In the ANAFIE Registry, >90% of elderly Japanese AF patients received OAC therapy, mostly DOACs. Inappropriate low doses of DOACs that did not fulfill dose reduction criteria were prescribed in 20-30% of patients.

The global Edoxaban Treatment in routine cliNical prActice (ETNA) noninterventional study program: rationale and design.

BACKGROUND: Randomized controlled trials showed the nonvitamin K oral anticoagulant (NOAC) edoxaban was effective and safe for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (AF) and for the prevention and treatment of venous thromboembolism (VTE; including pulmonary embolism and deep vein thrombosis). Additional research is needed to evaluate the effects of edoxaban in routine clinical practice. Therefore, the Edoxaban Treatment in routine cliNical prActice (ETNA) program is being conducted to provide routine clinical care data on characteristics and outcomes in patients with AF or VTE receiving edoxaban. METHODS: The Global ETNA program integrates prospectively collected data from edoxaban patients in regional ETNA noninterventional studies across Europe, Japan, and East and Southeast Asia into indication-specific databases for AF and VTE. Targeted enrollment is >31 000 patients (AF >26 000; VTE >4500), with a follow-up of 2 years for AF and 1 year for VTE. Data integration will be possible using consistent terminology, parameter definitions, and data collection across the regional noninterventional studies. Safety and effectiveness data will be assessed. Crude rates of outcomes including bleeding and thromboembolic events will be reported. RESULTS: Globally, enrollment began in early 2015 and is ongoing. CONCLUSIONS: Global ETNA will generate the largest integrated prospective repository of routine clinical care data for a single NOAC in patients with AF or VTE. It will provide important information on the safety of edoxaban in routine clinical care and gather further information on its effectiveness.

Design and rationale of the STroke secondary prevention with catheter ABLation and EDoxaban clinical trial in patients with non-valvular atrial fibrillation: The STABLED study.

BACKGROUND: Catheter ablation (CA) has been reported to reduce risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) in retrospective studies. However, the risks and benefits of CA have not been well elucidated in patients with NVAF and who have suffered a recent ischemic stroke in prospective randomized trials. Thus, the aim of the STABLED clinical trial is to investigate the efficacy and safety of CA with anticoagulant therapy using edoxaban in patients with NVAF and a history of recent ischemic stroke. METHODS AND DESIGN: The STABLED trial is a multicenter, prospective, randomized, open-label, standard medication-controlled study in Japan. The target patient number is 250, comprising 125 patients receiving standard medication and 125 receiving CA. For patients allocated to the CA group, ablation is to be performed between 1 to 6 months from the onset of index stroke. The observation period will be 3 years from the day of random allocation of the final patient to any of the groups. The primary outcome measure is the composite of recurrence of ischemic stroke, systemic embolism, all-cause death, and hospitalization for heart failure. CONCLUSION: This study will investigate the effectiveness and safety of CA and basic anticoagulation treatment with edoxaban for patients with NVAF who have suffered a recent ischemic stroke. The aim is to determine the best evidence for an optimal treatment strategy for patients with NVAF and recent stroke. TRIAL REGISTRATION: UMIN000031424/NCT03777631.

Baseline Demographics and Clinical Characteristics in the All Nippon AF in the Elderly (ANAFIE) Registry.

BACKGROUND: Despite the well-established benefits in patients with nonvalvular atrial fibrillation (NVAF), anticoagulants have been underused in elderly patients. The All Nippon AF In the Elderly (ANAFIE) Registry is a multicenter, prospective, observational study with 2-year follow-up of Japanese patients aged ≥75 years with a definitive diagnosis of NVAF, aiming to collect detailed information on clinical status and therapeutic challenges in this patient population.Methods and Results:Patients were enrolled from October 2016 to January 2018. A total of 32,726 patients (57.2% male) were included. The average age, CHADS2score, and creatinine clearance were 81.5±4.8 years (26.2% of patients were aged ≥85 years), 2.9±1.2, and 48.4±21.8 mL/min, respectively. Paroxysmal AF was the most common clinical AF type (42.0%), and most patients (97.2%) had comorbidities. Most patients (91.9%) were receiving anticoagulant therapy; of these, 27.8% and 72.2% were treated with warfarin and direct oral anticoagulants, respectively. The average number of concomitant drugs used was 6.6±3.2, including anticoagulants. CONCLUSIONS: The ANAFIE Registry is the largest prospective registry study of elderly Japanese patients with NVAF to date. Baseline data indicate that patients in this age group are treated in a manner similar to their younger counterparts.

Prospective observational study in elderly patients with non-valvular atrial fibrillation: Rationale and design of the All Nippon AF In the Elderly (ANAFIE) Registry.

BACKGROUND: Although anticoagulation effectively prevents stroke in patients with atrial fibrillation (AF), it has been underused in elderly AF patients for many reasons, mainly because of knowledge gaps regarding cardiovascular treatment of these populations with multiple comorbidities and poor prognosis. The objectives of the All Nippon AF In the Elderly (ANAFIE) Registry are to collect real-world information about the clinical status of patients with non-valvular AF (NVAF) aged ≥75 years, current status of anticoagulant therapy, and prognosis with/without anticoagulation to establish a database for this specific patient population that is increasing remarkably worldwide. METHODS AND DESIGN: The ANAFIE Registry is an observational, multicenter, prospective study of Japanese patients with NVAF aged ≥75 years that will include 30,000 patients and have the primary endpoint of composite of stroke and systemic embolism over a 2-year follow-up period. In parallel with the main study, seven sub-cohort studies will be conducted with assessments including coagulation-fibrinolysis markers, echocardiography, heart rate, hypertension, cognitive function, frailty, and medication adherence. Subgroup analyses will be performed, and stratified by renal function, HbA1c, and maximum number of drugs used. The study was started in October 2016, with a planned 2-year recruitment period. As of January 31, 2018, 33,213 patients were enrolled; the recruitment was therefore ended 8 months earlier than the original plan. CONCLUSIONS: The ANAFIE Registry will provide a valuable database for the clinical status, management, and outcomes of mortality, stroke, systemic embolism, and hemorrhagic events with/without anticoagulation in the increasing population of elderly NVAF patients, and will identify risk factors associated with these clinical events.

Recurrent Stroke and Bleeding Events after Acute Cardioembolic Stroke-Analysis Using Japanese Healthcare Database from Acute-Care Institutions.

BACKGROUND: To understand the reality of patients who experienced a cardioembolic stroke (CES) is important because of the high incidence of recurrent stroke and the need to account for bleeding risk in relation to the need for anticoagulation treatment. We elucidated the current real-world medical care in patients who had a CES and identified the risk factors for recurrent stroke. METHODS AND RESULTS: The study comprised 9804 patients who were diagnosed with CES between April 2008 and September 2013 as identified in a healthcare database used by acute-care institutions in Japan. We analyzed the incidence and risk factors of stroke and bleeding events in CES patients. The incidence of stroke was 10.3% during the median observation period of 68 days, mainly consisting of recurrent CES (8.5%). The incidence of bleeding events and intracranial bleeding was 10.3% and 7.0%, respectively. The recurrence of ischemic stroke was significantly lower, and brain hemorrhage was significantly higher in the anticoagulation treatment group. The factors related to an increased risk of stroke were a history of cerebral infarction or transient ischemic attack, diabetes, and increase of CHA2DS2-VASc and CHADS2 scores. The risk factors for bleeding events were hypertension, renal dysfunction, and use of proton pump inhibitors (PPIs). CONCLUSIONS: The patients who experienced CES had a high rate of recurrent stroke or CES, mainly consisting of recurrent CES. Although anticoagulation may be beneficial for reducing recurrence of ischemic stroke, careful management is required given consideration of increased risk of brain hemorrhage during anticoagulation treatment, especially for patients with hypertension, renal dysfunction, and use of PPIs.

Incidence of venous thromboembolism and bleeding events in patients with lower extremity orthopedic surgery: a retrospective analysis of a Japanese healthcare database.

BACKGROUND: Orthopedic surgeries of lower extremities such as total knee arthroplasty (TKA), total hip arthroplasty (THA), and hip fracture surgery (HFS) are widely considered to carry a high risk of developing deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE). Growing attention to epidemiological studies using a healthcare database led us to quantify the risks using a Japanese database to reveal recent medical care for such events. METHODS: The study comprised 36,947 patients who had undergone orthopedic surgeries of the lower extremities and whose medical information from April 2008 to September 2013 was available. The source population of the database was derived from 100 acute-care hospitals with Diagnosis Procedure Combination. The events were defined by diagnosis, medication, imaging, and laboratory tests. RESULTS: A breakdown of patients who underwent orthopedic surgeries by type of surgery showed 13.6% for TKA, 10.4% for THA, 56.8% for HFS, 1.5% for rupture of Achilles tendon, and 18.0% for simple fracture of lower extremities. The incidence for DVT, PTE, and bleeding events by type of surgery was 1.3, 0.2, and 1.0% for TKA; 0.9, 0.2, and 1.1% for THA; and 0.4, 0.1, and 1.8% for HFS, respectively. The population for risk factor analysis consisted of patients with similar background factors who underwent TKA, THA, or HFS. The statistically significant risk factors for PTE analyzed by the backward elimination procedure in a multivariate model were female sex, history of venous thromboembolism (VTE), thrombophilia, and varicose veins of lower extremity. CONCLUSIONS: The incidence of DVT, PTE, and bleeding events and the risk factors for DVT and PTE in patients by type of orthopedic surgeries of lower extremities found in our study are considered to be rational as they reflect evidence from real-world cases. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000012667.

Predictors of venous thromboembolism recurrence and the bleeding events identified using a Japanese healthcare database.

BACKGROUND: Treatment to prevent the recurrence of venous thromboembolism (VTE) and prevent bleeding events should be given to patients with VTE in an appropriate balance in relation to relevant predictors. We elucidated the current medical care in a real world setting and quantified predictors using a Japanese healthcare database. METHODS: The study included 3578 patients who were diagnosed with VTE between April 2008 and September 2013 at a Japanese acute-care hospital and included in the hospital database. Twenty-four patients who had a VTE event during the 180-day period after enrollment were excluded. We analyzed the incidence of recurrent VTE, incidence of bleeding events, and predictors in VTE patients. Events were defined by disease, medication, imaging, and laboratory testing, among other factors. RESULTS: The rate of recurrence of VTE events was 7.2 per 100 patient-years. The incidence rate of bleeding events was 8.3 per 100 patient-years. The presence of malignant disease, antipsychotic drugs, and nonsteroidal anti-inflammatory drugs increased the risk for recurrent VTE. The predictors for bleeding events were malignant disease, central venous catheterization, cancer chemotherapy, stroke, and diabetes. CONCLUSIONS: These findings obtained from healthcare database suggest predictors either for recurrent VTE and bleeding that should be considered when selecting treatment to reduce the risk of recurrent VTE and mitigate bleeding.