Statin (mis)use in older people: A cross-sectional study using French health insurance databases.

PURPOSE: To describe the occurrence of potential statin misuse, its characteristics and associated factors in older people. METHODS: A retrospective cross-sectional study was conducted in Alsace and Lorraine (France) using French health insurance databases. Study population comprised community-dwelling patients and nursing homes residents aged 80 and over, who received at least one statin prescription between January 1, 2017 to April 30, 2017 (N = 38 268). Potential statin misuse was identified considering off-label uses, high-intensity doses, drug contraindications and statin-drug interactions. RESULTS: At least one potential statin misuse was detected for 19 468 patients (50.9%). Off-label prescription was the most frequent misuse observed (53.6%), followed by high-intensity statin dose (30.5%). Polypharmacy (five to nine drugs) and excessive polypharmacy (10 or more drugs) were the main risk factors associated with potential statin misuse (adjusted OR = 2.6 and 4.7 respectively). Nursing home, multi-morbidity and the presence of multiple prescriptions from different doctors for the same patient were other risk factors significantly associated. Two sensitivity analyzes (reconsiderations of off-label and high statin dose definitions) revealed the same statistical trend. CONCLUSION: Potential statin misuse is frequent in people aged 80 and over. These findings should serve as a warning to health care professionals and hopefully will contribute to ensure an appropriate and safe use of statin in aged population.

Potential Statin Overuse in Older Patients: A Retrospective Cross-Sectional Study Using French Health Insurance Databases.

BACKGROUND: Although compelling evidence exists supporting statins (HMG-CoA reductase inhibitors) for secondary prevention in older patients with clinical atherosclerotic diseases, the same cannot be said for primary prevention. OBJECTIVES: The objectives of this study were to estimate the frequency of potential statin overuse in older patients, the potential drug cost savings if corrected, and the associated factors. METHODS: A retrospective cross-sectional study was conducted in Alsace and Lorraine (France) from 1 January to 30 April 2017. All statin users aged 80 years or over living in the community (including nursing homes) and identified from the French health insurance database were analyzed. Potential statin overuse was defined according to the STOPP/START (Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment) criteria. RESULTS: Among the 38,268 aged insured, 23,228 (60.7%) had potential statin overuse. Of those living in the community, 22,132 (60.0%) patients had potential statin overuse: 12,352 (55.8%) for primary and 9780 (44.2%) for secondary prevention. Among nursing home residents, 1096 (79.0%) had potential statin overuse: 394 (35.9%) for primary and 702 (64.1%) for secondary prevention. The potential drug cost savings associated with the adjustment of potential statin overuse were €924,100 for the study period. Living in nursing home [adjusted odds ratio (ORadjusted) 3.91, 95% confidence interval (CI) 2.82-5.41] and being a female (ORadjusted 2.84, 95% CI 2.54-3.17) were the main risk factors associated with potential statin overuse. CONCLUSION: The frequency of potential statin overuse is very high among older people aged 80 years or over, highlighting the need to re-evaluate statin therapy and consider deprescribing, particularly for primary prevention and in nursing homes.

Testosterone down-regulates ornithine aminotransferase gene and up-regulates arginase II and ornithine decarboxylase genes for polyamines synthesis in the murine kidney.

The enzymes ornithine aminotransferase (OAT) and ornithine decarboxylase (ODC) share L-ornithine as a common substrate and arginase II produces this amino acid. In the murine kidney, testosterone induced ODC gene expression and polyamine production, but it is unknown how OAT gene is expressed under androgen treatment. These experiments were designed to study the influence of testosterone on the renal expression of OAT gene. Pharmacological and physiological doses of testosterone were injected into female and castrated male mice. Total RNA and soluble proteins extracted from whole kidneys were analyzed by Northern and Western blots, respectively. The results clearly indicate that pharmacological doses of testosterone simultaneously down-regulated the level of OAT protein and up-regulated the expression of arginase II and ODC genes. Variations of the levels of OAT protein and arginase II mRNA and protein were strongly correlated with testosteronemia. Orchidectomy increased the renal level of OAT protein and decreased that of ODC and arginase II. These effects were reversed by injecting a physiological dose of testosterone into castrated male mice. In conclusion, OAT and ODC genes are inversely regulated by testosterone in the mouse kidney. Consequently, in kidneys of testosterone-treated mice, L-arginine-derived ornithine produced by arginase II might be preferentially used by ODC for putrescine production rather than by OAT. This metabolic fate of L-ornithine was facilitated by decreasing OAT gene expression. In contrast, in female and castrated male mice devoided of testosterone, OAT gene is highly expressed and L-ornithine is converted into L-glutamate.