Trends in heart failure prevalence in Japan 2014-2019: a report from healthcare administration databases.

AIMS: Contemporary estimates of heart failure (HF) prevalence in Japan are scarce. We aimed to estimate HF prevalence and trends in Japan using nationally representative, large administrative claims databases. METHODS AND RESULTS: This retrospective analysis used data from the Japan Medical Data Center (JMDC) (age ≤74 years) and the Medical Data Vision (MDV) (all ages) databases (study period: 1 January 2014-31 December 31 2019). We calculated HF prevalence using crude and sex-/age-standardized models (weighting based on Japanese census data, 2014-2019). Among 8 954 313 individuals aged ≤74 years from JMDC, and 27 920 174 of all ages from MDV, the cumulative 6 year (2014-2019) crude and sex-/age-standardized prevalence of HF per 1000 persons (95% confidence intervals) in Japan was 21.80 [21.70, 21.89] and 41.79 [30.25, 56.11] using JMDC and 65.09 [65.00, 65.18] and 60.95 [46.94, 77.62], respectively, using MDV. We observed an increasing yearly trend in crude HF prevalence per 1000 persons: 11.12 in 2014 and 14.69 in 2019 for JMDC; 58.09 and 77.18, respectively, for MDV. There was an overall increasing trend of comorbidities over time (2014-2019) among HF patients, especially in type 2 diabetes, malignant cancer, chronic kidney disease, and atrial fibrillation. From 2014 to 2019, the percentage of patients in JMDC with type 2 diabetes increased from 15.4% to 20.8% and 23.4% to 31.5% in MDV; malignant cancer frequency increased from 16.5% to 20.1% in JMDC and 18.8% to 23.9% in MDV; frequency of chronic kidney disease increased from 14.8% to 17.7% in JMDC and 18.2% to 22.7% in MDV; and frequency of atrial fibrillation increased from 13.6% to 15.6% in JMDC and 23.8% to 29.0% in MDV. CONCLUSIONS: We estimated that the prevalence of HF in Japan was 2.2-3.7% for patients aged ≤74 during the period 2014-2019 using the JMDC database, while the prevalence for patients of all ages was 6.5% using the MDV database.

Analysis of eGFR index category and annual eGFR slope association with adverse clinical outcomes using real-world Japanese data: a retrospective database study.

OBJECTIVES: Real-world clinical outcome data of patients with an above-normal estimated glomerular filtration rate (eGFR) and increasing eGFR over time (eGFR slope) are scarce. Although eGFR is commonly recorded, eGFR slopes are rarely used for adverse outcome risk categorisation in clinical practice. We investigated the association of above-normal/below-normal eGFR ranges and increasing/declining eGFR slopes with clinical outcomes in Japan. DESIGN: Observational cohort study. SETTING: Primary and acute care hospitals; 423 centres. PARTICIPANTS: 57 452 patients aged ≥16 years with ≥3 eGFR values (latest available January 2013-December 2016) from the Japanese Medical Data Vision database were stratified into six index eGFR and six eGFR slope groups (slopes calculated using a linear mixed model). PRIMARY AND SECONDARY OUTCOME MEASURES: Time-to-event analyses of cardiovascular mortality, all-cause mortality (ACM), all-cause hospitalisation (ACH) and cardiovascular and major kidney events. eGFR and slope groups were analysed by Cox proportional hazard models with multivariable adjustment, using normal eGFR/little-to-no slope groups as reference. RESULTS: Higher risk of clinical outcomes was observed with declining eGFR slope groups versus the reference group; the HR (95% CI) for slope ≤-5 mL/min/1.73 m2/year: cardiovascular events 1.8 (1.4 to 2.2), ACH 1.8 (1.5 to 2.1), and ACM 2.8 (1.9 to 4.2) and was non-significant for kidney events 1.5 (0.9 to 2.5). A similar, but non-significant, pattern was observed with increasing slope groups (slope >3 mL/min/1.73 m2/year HR (95% CI): cardiovascular events 1.2 (0.9 to 1.5), ACH 1.1 (0.9 to 1.4) and ACM 1.5 (0.9 to 2.3)).Above-normal and below-normal eGFR groups were associated with poorer outcomes versus the reference group, but kidney events were associated with below-normal eGFR only. CONCLUSION: Poorer clinical outcomes were observed not only for below-normal eGFR and declining eGFR slope groups but also for certain above-normal eGFR and increasing slope groups. eGFR and eGFR slope may, therefore, be useful for identifying patients at high risk of adverse clinical outcomes.

Incidence Rates of Bleeding and Emergency Surgery Due to Trauma or Fracture Among Japanese Patients with Non-valvular Atrial Fibrillation Receiving Oral Anticoagulation Therapy.

INTRODUCTION: In patients with nonvalvular atrial fibrillation (NVAF) receiving oral anticoagulants (OACs), reversal of coagulopathy can be achieved with specific reversal drugs such as idarucizumab, which is indicated for use in patients treated with dabigatran for cases of life-threatening or uncontrolled bleeding or during emergency procedures that may cause serious bleeding. This study examined the incidence rate (IR) of emergency surgeries and major bleeding episodes associated with fractures and trauma in Japanese patients with NVAF receiving OACs. METHODS: This retrospective, non-interventional analysis of health insurance claims was conducted using data from 62,888 OAC-naive adult patients with NVAF who initiated dabigatran, warfarin, apixaban, rivaroxaban, or edoxaban between March 2011 and June 2016. The primary endpoint was overall IR of emergency surgery or major bleeding due to fracture or trauma. RESULTS: Overall IR of emergency surgery or major bleeding due to fracture or trauma considering outcomes until OAC discontinuation was 0.489 per 100 patient-years (PY) (95% confidence interval [CI] 0.406-0.572). Considering first OAC exposure only, the IR was 0.483 per 100 PY (95% CI 0.394-0.573). Emergency surgery/major bleeding events due to fracture or trauma was highest in those aged ≥ 75 years (0.611 per 100 PY [95% CI 0.481-0.741]). CONCLUSIONS: Fewer than one in 200 patients per year with NVAF receiving OACs experience emergency surgeries and major bleeding episodes associated with fractures and trauma; however, the IR of these events is markedly higher in patients of advanced age. TRIAL REGISTRATION: ClinicalTrials.gov 207, NCT03254147.

Patients with an abnormal heart rhythm (nonvalvular atrial fibrillation [NVAF]) have a higher risk of blood clots and stroke (which is when the blood supply to part of the brain is blocked). To reduce these risks, patients can take anticoagulants that slow or prevent the formation of blood clots. However, if the patient needs major emergency surgery or has a severe injury, the anticoagulants can increase their risk of bleeding, which can sometimes be life-threatening. There are drugs (e.g., idarucizumab) that can be used to reverse the effects of anticoagulants in this type of emergency. What we don't know is how many NVAF patients in Japan who are on anticoagulants have emergency surgeries or major bleeding after an injury, and therefore may require a reversal drug. The authors looked at Japanese health insurance claim data from 62,888 adult patients with NVAF who started taking an anticoagulant. They found that, annually, approximately 0.5% of the patients had emergency surgery or a major bleed associated with a fracture or injury. In very elderly patients (aged at least 75 years), the annual percentage was approximately 0.6%, which was almost double the annual percentage in patients aged less than 65 years. The authors concluded that, even though the number of people requiring a reversal agent are quite small, it is important to have an effective reversal agent for patients on anticoagulants, particularly older patients.

Validity of Claims Diagnosis Codes for Cardiovascular Diseases in Diabetes Patients in Japanese Administrative Database.

BACKGROUND: Observational studies using large claims databases for diabetes patients have been increasingly conducted. While validation of outcomes is important in such studies, validation studies from Japan are still scarce and small in scale with questions remaining on the representativeness of their findings. We examined the positive predictive value (PPV) of outcomes that often develop in type 2 diabetes patients: cardiovascular outcomes including congestive heart failure (CHF), myocardial infarction (MI), stroke-related diseases, and renal outcomes including end stage renal disease (ESRD), and death using a large Japanese database containing administrative claims and electronic medical record (EMR) data. PATIENTS AND METHODS: We used patient-level administrative claims data from 2003 and EMR data from 1985 to the most recent data up to December 2018 provided by Real World Data Co., Ltd. The database consisted of data from over 200 hospitals including ≥12 million uniquely identifiable patients. Among patients who had ≥1 type 2 diabetes diagnosis in the EMR, those who had administrative claims for each outcome were identified, and then the PPV was calculated for each outcome using the EMR as the gold standard. RESULTS: The numbers of patients identified for each outcome were 1,700 for MI, 2,027 for hemorrhagic stroke, 3,722 for ESRD, 4,723 for ischemic stroke, 5,404 for CHF, 6,678 for any type of stroke, and 10,815 for death. PPVs ranged from 67.4% for ESRD, 78.7% for MI, 80.3% for death, 85.7% for ischemic stroke, 88.9% for any type of stroke, 89.9% for hemorrhagic stroke, and 95.7% for CHF. A post hoc analysis showed PPV for ESRD as 83.8%. CONCLUSION: This large-scale validation study on diagnosis in administrative claims showed reasonable PPVs for the outcomes. We believe that the definitions of outcomes can be considered to be appropriate for future studies using Japanese administrative claims data.

Comparative effectiveness and safety of warfarin and dabigatran in patients with non-valvular atrial fibrillation in Japan: A claims database analysis.

BACKGROUND: Antithrombotic therapy, including direct oral anticoagulants, is recommended in patients with non-valvular atrial fibrillation (NVAF) who are at intermediate-to-high risk of stroke. The aims of this study were to assess the patterns of oral anticoagulant (OAC) prescription in Japanese patients with NVAF and compare the effectiveness and safety of dabigatran and warfarin. METHODS: This was a retrospective observational study of adults with NVAF who initiated dabigatran or warfarin between March 14, 2011 and June 30, 2016, using electronic claims data of approximately 12.94 million patients from 230 hospitals. Propensity score matching was used to derive equal patient cohorts. Outcomes included the combined incidence of stroke, systemic embolism, and intracranial bleeding (primary endpoint) and the incidence of major bleeding (secondary endpoint). RESULTS: Overall, 400,884 patients were included. Among those prescribed an OAC, warfarin was the most common (34.3%). For the comparison of dabigatran and warfarin, 4606 patients were propensity-score matched in each cohort. Dabigatran recipients had lower incidences of stroke, systemic embolism, and intracranial bleeding [29.0 vs. 35.6 per 1000 patient-years; hazard ratio (HR), 0.72; 95% confidence interval (CI): 0.53-0.97; p=0.031] and major bleeding (6.4 vs. 11.3 per 1000 patient-years; HR, 0.55; 95% CI: 0.30-0.99; p=0.048). The most common type of bleeding in both groups was gastrointestinal and the incidence was lower in dabigatran recipients (1.6 vs. 6.4 per 1000 patient-years; HR, 0.24; 95% CI: 0.08-0.69; p=0.009). CONCLUSIONS: In Japan, dabigatran was associated with a lower risk of stroke, systemic embolism, and intracranial bleeding and major bleeding compared with warfarin in patients with NVAF.