Statin, Ezetimibe, or Fibrate Initiation and Subsequent Use for the Primary and Secondary Prevention of Cardiovascular Diseases among Japanese Patients Aged ≥55 Years: A Nationwide Cohort Study.

The use of lipid-modifying agents (LMAs) other than statins has rarely been reported in real clinical settings. We aimed to compare the initiation and subsequent use of LMA classes for prevention of cardiovascular diseases. Using the national claims database, this retrospective cohort study was conducted on patients aged ≥55 years who initiated to use statins, ezetimibe, or fibrates between Fiscal Years (FYs) 2014 and 2017 as the first pharmacotherapy for dyslipidemia in Japan. A permissible gap for defining persistence was set as the median days of supply of a class to an individual. Kaplan-Meier estimates were calculated for rates. Cohorts for primary prevention without/with risk and secondary prevention comprised 1307438, 908378, and 503059 initiators for statins; 44116, 34206, and 11373 for ezetimibe; and 124511, 96380, and 27751 for fibrates. The persistence rates declined shortly after the therapy initiation regardless of the classes, which was approximately 50% at 1 year for any class for primary prevention without risk. A notable sex difference in terms of persistence rates was observed only for statins of secondary prevention. The restarting rates were similar between prevention settings: approximately 50-60% for statins and 30-40% for ezetimibe and fibrates 1 year after first discontinuation. For ezetimibe and fibrates, approximately 10% of initiators were added or switched to statins within 1 year of initiation. Collectively, any class tended to be discontinued early and some restarted; however, there were some unique classes. The findings are useful for improvement of dyslipidemia therapy.

Statin persistence and adherence among older initiators: A nationwide cohort study using the national health insurance claims database in Japan.

PURPOSE: This study clarifies the reality of persistence and adherence to statins in older Japanese people who initiated statin use and compares it between primary and secondary prevention cohorts. METHODS: The nationwide study using the national claims database targeted statin initiators aged ≥55 years from FY2014 to FY2017 in Japan. Persistence and adherence to statins were analyzed overall and according to subgroups based on sex, age stratum, and prevention cohorts. Permissible gap of median days that statins were supplied per prescription to an individual was employed. Persistence rates were estimated as Kaplan-Meier estimates. Poor adherence during persistence was evaluated and defined as <0.8 of the proportion of days covered. RESULTS: Of 3 675 949 initiators, approximately 80% initiated statin use with strong variants. The persistence rate at 1 year was 0.61. Poor adherence to statins during persistence was 8.0% in all patients and this value gradually improved with increasing age. Persistence rate and adherence were lower for the primary prevention cohort than for the secondary prevention cohort, and a notable sex difference was observed for the secondary prevention cohort, which was lower in females but was almost never and slightly observed in the primary prevention cohorts without and with high-risk factors, respectively. CONCLUSIONS: Many statin initiators discontinued statins shortly following statin initiation but adherence while on statin therapy was good. Attentively watching older patients not to discontinue statins and listening to their reasons for discontinuation are required, especially for initiators in primary prevention and females in secondary prevention.

Fracture risk increased by concurrent use of central nervous system agents in older people: Nationwide case-crossover study.

BACKGROUND: Multiple medication use among older patients is reported to increase fracture risk. But this association is unclear in different subgroups and has not been confirmed by a case-crossover study, which can eliminate measurable and unmeasurable time-invariant confounders. OBJECTIVE: To estimate the fragility fracture risk associated with concurrent use of multiple central nervous system (CNS) agents in older patients using a case-crossover design. METHODS: This study targeted almost all patients aged ≥65 years in Japan who incurred fragility fractures from May 2013 to September 2014, based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB Japan). Conditional logistic regression analysis estimated the risk of fragility fracture associated with the daily number of CNS agents, including subgroup analyses stratified by sex, age, and fracture location. RESULTS: For 446,101 patients, the adjusted odds ratios (ORs) of fragility fracture increased almost linearly with number of CNS agents; 0, 0-1, 1-2, 2-3, 3-4, 4-5, and >5: OR reference, 1.21 (95% confidence interval, 1.18-1.23), 1.40 (1.35-1.46), 1.58 (1.49-1.67), 1.89 (1.74-2.05), 1.80 (1.60-2.03), and 1.90 (1.61-2.23; trend p < 0.001), respectively. A similar trend was observed for several subgroups, especially in males and those aged ≥85 years, showing marked linearity. CONCLUSIONS: The increased risk of fragility fracture associated with the use of multiple CNS agents was robust in older people in Japan.

Central Nervous System Agent Classes and Fragility Fracture Risk among Elderly Japanese Individuals in a Nationwide Case-Crossover Design Study.

Central nervous system (CNS) agents cause fractures among the elderly, but fracture risks of a wide range of CNS agent classes have not been analyzed in a study with the same population and definitions of variables. This study aimed to estimate the degree of fragility fracture risk of a wide range of CNS agent classes in elderly Japanese people. A case-crossover design study, with a case window and three control windows of 3 d each, as well as longer windows up to 15 d, was conducted among opioid non-users who lived without hospitalization for ≥13 months and incurred fragility fractures at ≥65 years of age, using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Conditional logistic regression estimated adjusted odds ratios (ORs) of CNS agent classes for fragility fractures for groups including and excluding users of pro re nata CNS agents (PRN-CNS agents) and for windows of 3-15 d. Antiepileptic agents had the highest adjusted ORs, 2.4 (95% confidence interval 2.3-2.5) for the group including PRN-CNS agent users (n = 446101). The next-highest classes were anti-dementia agents 1.5 (1.5-1.6), antipsychotics 1.5 (1.4-1.6), anti-Parkinson agents 1.3 (1.2-1.5), and antidepressants 1.1 (1.1-1.2). Similar ORs were found when PRN-CNS agent users were excluded (n = 352828), and slightly higher ORs were found for longer windows, with almost the same order of classes. Elderly individuals who use antiepileptic agents or a combination of antiepileptic agents and CNS agent classes with the next-highest ORs should be carefully monitored.

Fragility Fractures in Older People in Japan Based on the National Health Insurance Claims Database.

Fragility fractures associated with age-related bone loss are of urgent concern worldwide because they reduce QOL and pose financial burdens for health care services. Currently, national data in Japan are limited. This study provides quantitative data for older patients throughout Japan who, although otherwise relatively healthy, sustained fragility fractures and were hospitalized for them. The National Database of Health Insurance Claims and Specific Health Checkups of Japan was accessed to target patients aged 65 years or older who sustained fractures between May 2013 and September 2014 and were not hospitalized for at least 13 months prior to fracture. We investigated whether the first fracture sustained was fragility related at any of four locations (proximal humerus, distal radius, vertebra, or femoral neck) and whether it necessitated hospitalization. Fragility fractures were identified in 490138 of 1188754 patients (41.2%, 345980 patients/year; 1 : 4 male-to-female ratio). Regardless of gender, vertebral fractures were most common across the age cohorts studied (43286 males and 162767 females/year), and femoral neck fractures increased markedly with increased patient age. Approximately 80% of patients with femoral neck fractures were hospitalized (62.3% of males, 71.1% of females) compared with up to 10.4% of patients with other fragility fractures. Data provided in this study can be used as a baseline for evaluating the health economy and establishing health policy in Japan.