Exploring high priority potentially inappropriate prescribing cascades in older adults: population level retrospective cohort study

Objective — To identify and prioritise potentially inappropriate prescribing cascades based on population prevalence, incidence, and temporal association between the initial and subsequent drug.

Design  — Population level retrospective cohort study.

Setting — Health administrative data from a source population of community dwelling older adults in Ontario, Canada.

Participants — 2 297 942 community dwelling older adults alive on 1 January 2022.

Main outcome measures — 65 potentially inappropriate prescribing cascades were identified through a 2025 international expert Delphi consensus. For each prescribing cascade, the analytic cohort comprised incident users of the initial and subsequent drug combination during the accrual period. The population prevalence of the drug starting the prescribing cascade and the incidence of the initial and subsequent drug combination were measured, and the strength of the temporal association between the initial and subsequent drug was evaluated using adjusted sequence ratios derived from prescription sequence symmetry analyses. Prioritised cascades were those with a population drug prevalence of the initial drug ≥5%, prescribing cascade incidence of ≥1%, and adjusted sequence ratio >1, with the lower limit of the 95% confidence interval (CI) above the corresponding threshold for each measure. Results were stratified by sex.

Results — The cohort comprised 2 297 942 people (54.3% female) aged ≥66 years. Twenty four prescribing cascades (37%) met all three prioritisation criteria. From the prioritised list, cardiovascular drugs were the most prevalent drugs starting the prescribing cascade (drug class range 19.0-65.9%). The highest incidence cascades were iron supplement to laxative (11.9%, 95% CI 11.7% to 12.1%), hydroxymethylglutaryl coenzyme A reductase inhibitor to pain reliever (10.9%, 10.7% to 11%), and cholinesterase inhibitor to sleep agent (10.3%, 9.9% to 10.7%). Temporal association, reported as adjusted sequence ratios, was highest for corticosteroid to antipsychotic (2.55, 95% CI 2.47 to 2.64), laxative to antidiarrheal (2.53, 2.43 to 2.65), and cholinesterase inhibitor to antiemetic drug treatment (2.24, 1.90 to 2.65). The adjusted sequence ratios were consistent when stratified by sex except for the selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor to overactive bladder drug cascade, which was stronger for male older adults (1.21, 1.10 to 1.33) than for female older adults (1.02, 0.96 to 1.09).

Conclusions — This prioritised list of 24 potentially inappropriate prescribing cascades could inform prescribing and deprescribing initiatives and policy development to improve drug safety in older adults at individual patient and population levels.