Deprescribing preventive medications in older adults with advanced frailty, dementia, or limited life expectancy: a systematic review and meta-analysis

Polypharmacy and long-term preventive medication use are common in frail older adults with limited life expectancy, despite uncertain benefits and potential risks. This systematic review and meta-analysis synthesized evidence on the effect of deprescribing preventive medications (antihypertensives, statins, anticoagulants, and antidiabetic agents) compared to continuation on clinical, physiological, safety, and patient-centered outcomes among older adults with advanced frailty, dementia, or limited life expectancy. PubMed, Embase, Cochrane Library, Web of Science, CINAHL, and ProQuest Dissertations & Theses Global were searched for eligible randomized controlled trials and observational studies. The primary outcome was all-cause mortality. Secondary outcomes were hospitalization, major adverse cardiovascular events (MACE), changes in blood pressure, risks of fractures and falls, and quality of life. Data were pooled (relative risk [RR] or mean difference or standardized mean difference) using random-effects models (RevMan version 5.4). The evidence certainty was evaluated by the GRADE framework (PROSPERO ID: CRD420251147086). From 10,397 records, 15 studies (> 33,000 participants) were included. Overall, deprescribing was not associated with increased risk of all-cause mortality (RR: 1.15, 95% CI: 0.98–1.35, I2: 93%), hospitalization (RR: 0.93, 95% CI: 0.82–1.07, I2: 68%), or MACE (RR: 1.37, 95% CI: 0.70–2.70, I2: 95%) (certainty: very low GRADE). Deprescribing was also not associated with increased risks of fracture, fall, or deterioration of quality of life, but with slightly increased systolic blood pressure (deprescribing antihypertensives). Deprescribing preventive medications in frail or palliative older adults was not associated with worse outcomes; however, evidence certainty was very low, and further studies are needed.