Objectives: To assess the applicability of Electronic Frailty Index (eFI) and Hospital Frailty Risk Score (HFRS) algorithms to Japanese administrative claims data and to evaluate their association with long-term outcomes. Study Design and Setting: A cohort study using a regional government administrative healthcare and long-term care (LTC) claims database in Japan 2014–18. Participants: Plan enrollees aged ≥50 years. Methods: We applied the two algorithms to the cohort and assessed the scores’ distributions alongside enrollees’ 4-year mortality and initiation of government-supported LTC. Using Cox regression and Fine–Gray models, we evaluated the association between frailty scores and outcomes as well as the models’ discriminatory ability. Results: Among 827,744 enrollees, 42.8% were categorised by eFI as fit, 31.2% mild, 17.5% moderate and 8.5% severe. For HFRS, 73.0% were low, 24.3% intermediate and 2.7% high risk; 35 of 36 predictors for eFI, and 92 of 109 codes originally used for HFRS were available in the Japanese system. Relative to the lowest frailty group, the highest frailty group had hazard ratios [95% confidence interval (CI)] of 2.09 (1.98–2.21) for mortality and 2.45 (2.28–2.63) for LTC for eFI; those for HFRS were 3.79 (3.56–4.03) and 3.31 (2.87–3.82), respectively. The area under the receiver operating characteristics curves for the unadjusted model at 48 months was 0.68 for death and 0.68 for LTC for eFI, and 0.73 and 0.70, respectively, for HFRS. Conclusions: The frailty algorithms were applicable to the Japanese system and could contribute to the identifications of enrollees at risk of long-term mortality or LTC use.

A population pharmacokinetic (PK) analysis was conducted to characterize the voriconazole pharmacokinetic profiles in immunocompromised Japanese pediatric subjects and to compare them to those in immunocompromised non-Japanese pediatric subjects. A previously developed two-compartment pharmacokinetic model with first-order absorption and mixed linear and nonlinear elimination adequately described the voriconazole intravenous and oral data from Japanese pediatric subjects with few modifications. Bayesian priors were applied to this analysis by using the NONMEM routine NWPRI, which allowed priors for the fixed-effect parameter vector and variance matrix of the random-effect parameters to be a normal distribution and an inverse Wishart distribution, respectively. Large intersubject variabilities in oral bioavailability and voriconazole exposure were observed in these pediatric subjects. The mean oral bioavailability estimated in Japanese pediatric subjects was 73% (range, 17% to 99%), which is consistent with the reported estimates of 64% in the previous model and less than what was originally estimated for healthy adults—96%. Voriconazole exposures in Japanese pediatric subjects were generally comparable to those in non-Japanese pediatric subjects receiving the same dosing regimens, given the large intersubject variability. Consistent with the previous findings, the CYP2C19 genotyping status did not have a clinically relevant effect on voriconazole exposure in Japanese pediatric subjects, although it was identified as a covariate in the model to help explain the intersubject variability in voriconazole exposure. The CYP2C19 genotyping status alone does not warrant dose adjustment of voriconazole. No other factors besides age and weight were identified to explain the PK variability of voriconazole.

Aims: The long-term outcome in patients with heart failure (HF) after hospitalization may vary substantially depending on their age and left ventricular ejection fraction (LVEF). We aimed to assess the relative rates of cardiovascular death (CVD) and non-CVD based on the age and how the rates differ under the updated LVEF classification system. Methods and results: Consecutively registered hospitalized patients with HF (N = 3558; 39.7% women with a mean age of 73.9 ± 13.3 years) were followed for a median of 2 (interquartile range, 0.8–3.1) years. The CVDs and non-CVDs were evaluated based on age [young (<65 years), older (65–84 years), and very old (≥85 years)] and LVEF classification [HF with preserved EF (HFpEF; LVEF ≥50%) and non-HFpEF (LVEF <50%)]. The adverse clinical events were adjudicated independently by a central committee. Overall, 1505 (42.3%) had HFpEF [young: n = 182 (12.1%), older: n = 894 (59.4%), very old: n = 429 (28.5%)], and 2053 (57.7%) had non-HFpEF [young: n = 575 (28.0%), older: n = 1159 (56.5%), very old: n = 319 (15.5%)]. During the follow-up, the crude incidence of all-cause death was higher in non-HFpEF than in HFpEF across all age groups (non-HFpEF vs. HFpEF, young: 10.4% vs. 5.5%, log-rank P = 0.10; older: 26.6% vs. 20.9%, log-rank P = 0.002; very old: 36.7% vs. 31.7%, log-rank P = 0.043). CVDs accounted for more than half of all deaths in non-HFpEF (young 65.0%, older 64.2%, and very old 55.6%), whereas the proportion of CVDs remained less than half in HFpEF (young 50.0%, older 41.2%, very old 38.2%). HF readmission was associated with subsequent all-cause death in non-HFpEF [hazard ratio (HR): 1.72, 95% confidence interval (CI): 1.41–2.09, P < 0.001], but not in HFpEF (HR: 1.12, 95% CI: 0.87–1.43, P = 0.39). Conclusions: The probability of a non-CVD increases in both LVEF categories with advancing age, but that it is greater in the HFpEF category. The findings indicate that mitigating CV-related outcomes alone may be insufficient for treating HF in older population, particularly in the HFpEF category.

Background: Significant gap remains in the implementation of guideline‐directed medical therapy (GDMT) in patients with heart failure after a hospitalization. We aimed to evaluate the use and titration of GDMT at discharge and over a 12‐month period after hospital discharge and to identify factors associated with GDMT use and titration. Methods and Results: The CONNECT‐HF (Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure) trial evaluated the effect of a hospital and postdischarge quality improvement intervention in participants with heart failure with reduced ejection fraction. In this secondary analysis, we examined use and titration to at least 50% of the target dose of GDMTs at hospital discharge and over time. Among 4646 participants (mean age 63 years, 34% women), GDMT use did not numerically improve from discharge to 12 months: beta blockers (84%–78%), angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor‐neprilysin inhibitors (73%–65%), mineralocorticoid receptor antagonists (39%–36%), and sodium‐glucose cotransporter 2 inhibitors (1.5%–2.1%). Achieving ≥50% of the target dose also showed little change over 12 months: beta blockers (35%–32%), angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor‐neprilysin inhibitors (28%–25%). For all medications, use of GDMT at discharge was associated with the use and achieving ≥50% of the target dose at 12 months. Conclusions: Following a hospitalization for heart failure, GDMT use remained low and did not numerically improve over 12 months. Use of GDMT at discharge was significantly associated with the use of GDMT over time, highlighting the importance of initiating GDMT during hospitalization.

Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention has become the standard of care, particularly in patients with acute coronary syndrome (ACS). Current clinical guidelines recommend novel P2Y12 inhibitors (e.g., prasugrel or ticagrelor) in addition to aspirin based on the results of representative randomized controlled trials conducted predominantly in Western countries. These agents were superior to clopidogrel in reducing the composite ischemic events, with a trade-off of the increased bleeding events. However, multiple differences exist between East Asian and Western patients, especially with respect to their physique, thrombogenicity, hemorrhagic diathesis, and on-treatment platelet reactivity. Recent studies from East Asian countries (e.g., Japan or South Korea) have consistently demonstrated that use of novel P2Y12 inhibitors is associated with a higher risk of bleeding events than use of clopidogrel, despite borderline statistical difference in the incidence of composite ischemic events. Additionally, multiple studies have shown that the optimal duration of DAPT may be shorter in East Asian than Western patients. This review summarizes clinical studies of antithrombotic strategies in East Asian patients with ACS. Understanding these differences in antithrombotic strategies including DAPT and their impacts on clinical outcomes will aid in selection of the optimal tailored antithrombotic therapy for patients with ACS.

BACKGROUND: The increasing prevalence of frailty has gained considerable attention due to its profound influence on clinical outcomes. However, our understanding of the progression of frailty and long-term clinical outcomes in older individuals with atrial fibrillation remains scarce. METHODS: Using data from 2012 to 2018 from a comprehensive claims database incorporating primary and hospital care records in Shizuoka, Japan, we selected patients aged ≥65 years with atrial fibrillation who initiated oral anticoagulant therapy. The trajectory of frailty was plotted using Sankey plots, illustrating the annual changes in their frailty according to the electronic frailty index during a 3-year follow-up after oral anticoagulant initiation, along with the incidence of clinical adverse outcomes. For deceased patients, we assessed their frailty status in the year preceding their death. RESULTS: Of 6247 eligible patients (45.1% women; mean age, 79.3±8.0 years) at oral anticoagulant initiation, 7.7% were categorized as fit (electronic frailty index, 0–0.12), 30.1% as mildly frail (>0.12–0.24), 35.4% as moderately frail (>0.24–0.36), and 25.9% as severely frail (>0.36). Over the 3-year follow-up, 10.4% of initially fit patients transitioned to moderately frail or severely frail. Conversely, 12.5% of severely frail patients improved to fit or mildly frail. Death, stroke, and major bleeding occurred in 23.4%, 4.1%, and 2.2% of patients, respectively. Among the mortality cases, 74.8% (N=1183) and 3.5% (N=55) had experienced moderately or severely frail and either a stroke or major bleeding in the year preceding their death, respectively. CONCLUSIONS: In a contemporary era of atrial fibrillation management, a minor fraction of older patients on oral anticoagulants died following a stroke or major bleeding. However, their frailty demonstrated a dynamic trajectory, and a substantial proportion of death was observed after transitioning to a moderately or severely frail state.