Drugs & Aging最新文献

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management but are associated with nephrotoxicity, particularly in senior populations. While the acute nephrotoxicity of NSAIDs is well established, evidence on their long-term effects on renal function-particularly in community-dwelling older adults-has been mixed across studies.

Objectives: This study investigated the association between NSAID use and chronic kidney disease (CKD) risk in the general senior population.

Methods: Data from the National Health Insurance Service-Senior Cohort (NHIS-SC) in South Korea were analyzed, including 1812 participants (604 NSAID users and 1208 controls) matched 1:2 by propensity score. Kidney dysfunction was defined as glomerular filtration rate (eGFR) < 60 mL/min/1.73m² with a ≥ 10% decline from baseline. Hazard ratios (HRs) for CKD were estimated using Cox regression.

Results: NSAID use was associated with an increased CKD risk (HR 1.46; 95% confidence interval (CI) 1.11-1.93) and faster eGFR decline. Subgroup analysis showed elevated risks for Cox-1 (HR 1.53) and Cox-2 inhibitors (HR 1.61). End-stage renal disease (ESRD) incidence was rare and not significant.

Conclusions: NSAIDs increase CKD risk and accelerate kidney function decline in senior individuals. Cautious prescription and regular kidney monitoring are recommended, and further randomized trials are needed.

Background: Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), has become a cornerstone therapy for heart failure (HF) since its approval over a decade ago. However, concerns have emerged about potential cognitive risks, as neprilysin inhibition may contribute to the accumulation of amyloid-beta (Aβ) in the brain-a hallmark of Alzheimer's disease, the most common form of dementia.

Objective: Given the already elevated risk of dementia in patients with HF and the widespread use of sacubitril/valsartan, this meta-analysis aimed to evaluate whether its use is associated with an increased risk of all-cause dementia in HF populations.

Methods: A systematic literature search was conducted on 23 March 2025, to identify eligible studies comparing the risk of dementia in patients receiving sacubitril/valsartan versus those receiving placebo, no treatment, or other HF medications. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model.

Results: Six studies, comprising 101,074 participants and published between 2017 and 2024, were included in the meta-analysis. Treatment with sacubitril/valsartan was associated with a significant 15% reduction in the risk of all-cause dementia (RR = 0.85; 95% CI: 0.74-0.98; p = 0.02). Leave-one-out sensitivity and subgroup analyses confirmed the robustness of the findings.

Conclusions: This meta-analysis suggests that sacubitril/valsartan is associated with a reduced risk of dementia in patients with HF, helping to alleviate previous concerns about potential cognitive adverse effects. These findings support the continued use of sacubitril/valsartan as a foundational therapy in this high-risk population.

Managing diabetes in older adults requires balancing long-term glycaemic control with the prevention of hypoglycaemia, to which this population is particularly vulnerable owing to frailty, multimorbidity and cognitive decline. Guidelines recommend individualized glucose targets for older adults, particularly those with multimorbidity or increased hypoglycaemia risk. For individuals with frailty or cognitive impairment, relaxed HbA1c targets are often appropriate to reduce the risk of adverse events. While HbA1c is widely used, it has important limitations in this population due to its inability to reflect daily glucose fluctuations. Continuous glucose monitoring (CGM) or self-monitoring of blood glucose provide more granular data to guide therapy. This review explores the pathophysiology, complications, and management of hypoglycaemia in older adults, emphasizing individualized care, safer pharmacotherapies (e.g. DPP-4 inhibitors, GLP-1 receptor agonists, ultra-long-acting insulins), and emerging technologies (continuous glucose monitoring, artificial Intelligence-guided insulin delivery and telehealth).

Interleukin (IL)-6 plays a central role in amplifying inflammation, and its inhibition is beneficial in managing immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis (RA). IL-6 signaling inhibition is associated with a slightly increased risk of infections in patients with RA, and older age has been identified as a risk factor for severe adverse events, including infections. Therefore, the combination of an aging population and the increasing use of IL-6R inhibitors in RA treatment highlights the importance of carefully evaluating the safety and effectiveness of these therapies in older patients with RA. Recent postmarketing surveillance (PMS) data on the safety and effectiveness of sarilumab (SAR) in Japanese patients with RA, along with PMS data from Japan and registry data from France and Germany of tocilizumab (TCZ), provide valuable insights for both current and future management of RA. These data suggest that anti-IL-6R therapies are generally well tolerated among older patients with RA and do not appear to increase the risk of cardiovascular events or malignancies. While the effectiveness of TCZ was somewhat lower in older patients compared with younger ones, the effectiveness of SAR was similar across age groups. Consequently, the use of anti-IL-6R antibodies is anticipated to expand to other IMIDs beyond RA, particularly in increasingly superaged societies worldwide.

Background and objectives: Older adults living with dementia are a heterogeneous group, which can make studying optimal medication management challenging. Unsupervised machine learning is a group of computing methods that rely on unlabeled data-that is, where the algorithm itself is discovering patterns without the need for researchers to label the data with a known outcome. These methods may help us to better understand complex prescribing patterns in this population. The objective of our study was to use clustering methods to determine whether common prescribing clusters exist in older adults newly identified as living with dementia in Ontario, Canada and to examine the association between individual clinical and demographic characteristics and those clusters.

Methods: Data were derived from population-based health administrative databases, including medication dispensation data. The hierarchical clustering algorithm started with each individual and merged individuals with the most similar prescribing patterns into a group, continuing this process stepwise until only one cluster remained. The optimal number of clusters was selected through clinical review and fit statistics. We examined the association between individual characteristics and prescribing clusters using bivariate multinomial models.

Results: In 99,046 individuals living with new dementia, we identified six prevalent clusters of individuals with common medication subclass patterns: higher dispensation of angiotensin-converting enzyme-specific cardiovascular (22.6% of the population), central nervous system-active (21.3%), hypothyroidism (22.9%), respiratory (3.9%), and angiotensin receptor blocker-specific cardiovascular (6.1%), as well as a group with lower dispensation of medications in general (23.1%). Specific demographic, clinical, and health-service-use characteristics were associated with assigned clusters.

Conclusions: Within individuals living with dementia, prescribing clusters reflected meaningful differences in clinical and demographic characteristics. The results suggest that applying clustering methods to pharmacological data may be useful in estimating complex comorbidity patterns to better describe a heterogeneous population of people living with dementia. Future studies could examine whether these clusters better predict health service use, disease progression, or medication-related adverse events compared with other measures.

Cardiovascular disease remains the leading cause of morbidity and mortality among older adults, who often face unique challenges in preventive care due to multimorbidity, frailty, and polypharmacy. The polypill, a fixed-dose combination of multiple cardiovascular medications, has emerged as a promising strategy to improve adherence, simplify treatment, and reduce the burden of major cardiovascular events. This review aims to synthesize current evidence supporting polypill use in both primary and secondary prevention, with a particular focus on older populations. Landmark clinical trials such as TIPS, HOPE-3, PolyIran, and SECURE have demonstrated favorable outcomes related to blood pressure and lipid reduction, medication adherence, and cardiovascular event prevention. In addition, real-world data suggest improved cost-effectiveness and feasibility across diverse healthcare settings. Despite these benefits, implementation remains limited by barriers including inflexible dosing, provider hesitancy, variable guideline endorsements, and regulatory challenges. Special considerations in geriatric populations such as heightened sensitivity to adverse drug reactions and the need for individualized care further underscores the importance of thoughtful integration into practice. As the global population ages, strategic adoption of polypill-based prevention can help address health disparities, streamline cardiovascular care, and improve outcomes in older adults worldwide.

Osteoporosis is the most common metabolic bone disease and the main cause of fractures in older adults. Although it is commonly described as a silent disease, the bone pain caused by fragility fractures is its main symptom. Besides acute pain, fragility fractures may trigger a sequence of events that perpetuate and progress into chronic pain. The pathogenesis of musculoskeletal pain in patients with osteoporosis is complex and largely depends on skeletal and muscular changes, unbalanced bone turn-over, alterations in bone innervation, and central sensitization. Pain, in the context of bone fragility, represents an outstanding contributor to functional limitation, disability, and impaired quality of life. Pain prevention is closely related to identification of osteoporosis risk factors and early diagnosis and treatment of bone fragility. The management of pain in patients with severe osteoporosis also benefits from a multidimensional approach combining nonpharmacological with pharmacological therapies (e.g., physical exercise, nutrition, analgesics, and anti-osteoporotic drugs, as appropriate). This review aims to examine the mechanisms of pain in osteoporosis and provide an evidence-based overview of current and emerging treatment strategies.

Objectives: Gout is an inflammatory arthritis caused by monosodium urate crystal deposition in the joints. Its clinical presentation varies by age of onset. This study compared the clinical features and treatment patterns of older-onset gout and common-age-of-onset gout.

Methods: We analyzed data from the Urate Lowering TheRApy in Gout registry. Eligible participants were aged ≥ 18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism classification criteria for gout. Older-onset gout was defined as gout diagnosed at or after age 65 years, and common-age-of-onset gout as gout diagnosed before age 65 years. Demographics, clinical features, treatment patterns, quality of life, and laboratory findings were collected at baseline and 6 months.

Results: Among 477 patients, 105 (22.0%) had older-onset gout and 372 (78.0%) had common-age-of-onset gout. The older-onset group included more women (25.7 versus 2.4%, P < 0.001) and showed higher frequencies of radiographic gout-related joint damage (erosion) (30.5 versus 19.6%, P = 0.018), comorbidities (e.g., hypertension, cardiovascular disease, chronic kidney disease, and malignancy), and glucocorticoid use for flare prophylaxis. In contrast, the common-age-of-onset group had higher body mass index (BMI), more frequent flares, unhealthier lifestyle habits (e.g., smoking, alcohol), and higher rates of nonsteroidal anti-inflammatory drug (NSAID) and benzbromarone use. Febuxostat was more frequently prescribed in the older-onset group (71.4 versus 58.9%, P = 0.019), while benzbromarone use was more common in the common-age-of-onset group (7.3 versus 0%, P = 0.004). The febuxostat dose was lower in the older-onset group. After 6 months, both groups showed similar follow-up adherence, flare frequency, and healthcare utilization.

Conclusions: Older-onset gout and common-age-of-onset gout have distinct clinical characteristics, particularly in comorbidities, lifestyle factors, and treatment patterns. Gout management should be tailored on the basis of age at onset.