{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T17:12:07Z","timestamp":1758042727544,"version":"3.44.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004375","name":"Tel Aviv University","doi-asserted-by":"publisher","award":["Through the Albert and Alba Cuenca Institute for Therapeutical-Approaches to Age Related Disease"],"award-info":[{"award-number":["Through the Albert and Alba Cuenca Institute for Therapeutical-Approaches to Age Related Disease"]}],"id":[{"id":"10.13039\/501100004375","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003976","name":"Israel National Institute for Health Policy Research","doi-asserted-by":"publisher","award":["180\/2018"],"award-info":[{"award-number":["180\/2018"]}],"id":[{"id":"10.13039\/501100003976","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Data 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We included 1,048 participants from a longitudinal population-based cohort, all taking at least one medication. Participants were examined in 1999\u20132007 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The most prevalent morbidities among participants (mean age 73.3\u2009\u00b1\u20097.3 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: \u2018None\u2019 cluster (no dominant high-risk drug); \u2018Calcium channel blockers\u2019 (CCBs) cluster, with high nonsteroidal anti-inflammatory drug (NSAID) prevalence; \u2018Renin-angiotensin-aldosterone system (RAAS) inhibitors\u2019 cluster, with a high concomitant use of sulfonylureas compared to other clusters; \u2019Diuretics\u2019 cluster, with a relatively high prevalence of antithrombotics and proton pump inhibitors; and \u2019Benzodiazepines\u2019 cluster, with a relatively high antidepressant prevalence. Clusters differed by age, sex, ethnicity, and health characteristics. In multivariable analysis, the \u2018Diuretics\u2019 cluster was associated with increased all-cause (HR\u2009=\u20091.33, 95%CI: 1.03\u20131.72) and non-cancer (HR\u2009=\u20091.41, 95%CI: 1.03\u20131.93) mortality compared to the \u2018None\u2019 cluster. The \u2018CCBs\u2019 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Examining high-risk drug patterns offers a patient-centered approach to improving evidence-based medication guidelines and facilitating early interventions for vulnerable older-adults.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0332210","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:38:47Z","timestamp":1757612327000},"page":"e0332210","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations of high-risk drug patterns with mortality among community-dwelling older adults: A 23-year prospective cohort study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9464-9123","authenticated-orcid":true,"given":"Liat","family":"Orenstein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Chetrit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronen","family":"Fluss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keren","family":"Laufer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moyses","family":"Szklo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Dankner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"issue":"1","key":"pone.0332210.ref001","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12889-020-10084-x","article-title":"Trends of multimorbidity in 15 European countries: a population-based study in community-dwelling adults aged 50 and over","volume":"21","author":"DLB Souza","year":"2021","journal-title":"BMC Public Health"},{"issue":"6","key":"pone.0332210.ref002","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1001\/jama.294.6.716","article-title":"Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance","volume":"294","author":"CM Boyd","year":"2005","journal-title":"JAMA"},{"issue":"11","key":"pone.0332210.ref003","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1111\/jgs.14833","article-title":"Exclusion of elderly people from randomized clinical trials of drugs for ischemic heart disease","volume":"65","author":"FT Bourgeois","year":"2017","journal-title":"J Am Geriatr Soc"},{"issue":"7267","key":"pone.0332210.ref004","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1136\/bmj.321.7267.992","article-title":"Unjustified exclusion of elderly people from studies submitted to research ethics committee for approval: descriptive study","volume":"321","author":"A Bayer","year":"2000","journal-title":"BMJ"},{"issue":"11","key":"pone.0332210.ref005","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1001\/jama.297.11.1233","article-title":"Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review","volume":"297","author":"HGC Van Spall","year":"2007","journal-title":"JAMA"},{"issue":"4","key":"pone.0332210.ref006","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/bcp.12596","article-title":"Adverse drug reactions in special populations - 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