Effects of Changes in Number of Medications and Drug Burden Index Exposure on Transitions Between Frailty States and Death: The Concord Health and Ageing in Men Project Cohort Study

OBJECTIVES: To investigate the effects of number of medications and Drug Burden Index (DBI) on transitions between frailty stages and death in community-dwelling older men. DESIGN: Cohort study. SETTING: Sydney, Australia. PARTICIPANTS: Community-dwelling men aged 70 and older (N = 1,705). MEASUREMENTS: Self-reported questionnaires and clinic visits were conducted at baseline and 2 and 5 years. Frailty was assessed at all three waves according to the modified Fried frailty phenotype. The total number of regular prescription medications and DBI (a measure of exposure to sedative and anticholinergic medications) were calculated over the three waves. Data on mortality over 9 years were obtained. Multistate modeling was used to characterize the transitions across three frailty states (robust, prefrail, frail) and death. RESULTS: Each additional medication was associated with a 22% greater risk of transitioning from the robust state to death (adjusted 95% confidence interval (CI) = 1.06-1.41). Every unit increase in DBI was associ-ated with a 73% greater risk of transitioning from the robust state to the prefrail state (adjusted 95% CI = 1.302.31) and a 2.75 times greater risk of transitioning from the robust state to death (adjusted 95% CI = 1.60-4.75). There was no evidence of an adjusted association between total number of medications or DBI and the other transitions. CONCLUSION: Although the possibility of confounding by indication cannot be excluded, additional medications were associated with greater risk of mortality in robust community-dwelling older men. Greater DBI was also associated with greater risk of death and transitioning from the robust state to the prefrail state.