ArticlePloS one2025
Associations of high-risk drug patterns with mortality among community-dwelling older adults: A 23-year prospective cohort study.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundData on drug safety in multimorbid older-adults are limited, as clinical trials often apply upper age limits and focus on individual drugs or specific combinations. We aimed to explore high-risk drug patterns in community-dwelling older-adults, and their associations with long-term mortality.
methodsWe included 1,048 participants from a longitudinal population-based cohort, all taking at least one medication. Participants were examined in 1999-2007 and followed for mortality through March 2022. Individuals with similar profiles of high-risk drugs, identified using Beers criteria as potentially inappropriate for most older adults or requiring caution, were grouped using agglomerative hierarchical clustering. Cox and competing-risk regressions were used to examine the associations of the high-risk drug patterns with all-cause and non-cancer mortality.
resultsThe most prevalent morbidities among participants (mean age 73.3 ± 7.3 years, 55.9% women) were hypertension (55.3%) and cardiovascular diseases (45.5%), and 77.7% took at least one high-risk drug. Five distinct patterns were identified: 'None' cluster (no dominant high-risk drug); 'Calcium channel blockers' (CCBs) cluster, with high nonsteroidal anti-inflammatory drug (NSAID) prevalence; 'Renin-angiotensin-aldosterone system (RAAS) inhibitors' cluster, with a high concomitant use of sulfonylureas compared to other clusters; 'Diuretics' cluster, with a relatively high prevalence of antithrombotics and proton pump inhibitors; and 'Benzodiazepines' cluster, with a relatively high antidepressant prevalence. Clusters differed by age, sex, ethnicity, and health characteristics. In multivariable analysis, the 'Diuretics' cluster was associated with increased all-cause (HR = 1.33, 95%CI: 1.03-1.72) and non-cancer (HR = 1.41, 95%CI: 1.03-1.93) mortality compared to the 'None' cluster. The 'CCBs' cluster was associated with a greater risk for non-cancer mortality. Several drug combinations were identified as potential contributors to the increased risk observed in these clusters, including the concomitant use of NSAIDs and antihypertensives and a possible CCB-diuretic prescribing cascade.
conclusionsExamining high-risk drug patterns offers a patient-centered approach to improving evidence-based medication guidelines and facilitating early interventions for vulnerable older-adults.
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