A comparison of scales to quantify anticholinergic medication burden: does prevalence of anticholinergic burden and association with adverse outcomes differ depending on scale used?

Problem

Many medications are recognised to have anticholinergic effects. The cumulative effect of anticholinergic medications (termed anticholinergic burden) has been linked to adverse outcomes. Studies have focused on elderly people and impact on younger patients is unclear. Several scales have attempted to quantify anticholinergic burden by assigning scores (0, 1, 2 or 3) to medications, which can be summed to give an overall score. These scales vary in the medications they include and the scores assigned to specific medications. Scales have not previously been systematically compared in the same population. We aim to compare the prevalence of anticholinergic burden using different anticholinergic scales in UK Biobank participants, and assess the association of each scale with adverse outcomes.

Approach

Scales quantifying anticholinergic burden were identified through systematic literature review (searching three electronic databases, hand-searching references, citation searches). Using baseline data from UK Biobank participants (n=520,640, age 37-73 years) we calculated each participant’s anticholinergic burden using each of the identified scales. National mortality registers and Hospital Episode Statistics were then used to assess outcomes over a median 7 years follow-up. Primary outcome: composite outcome of all-cause mortality or major adverse cardiovascular event (MACE). Secondary outcomes: all-cause mortality; MACE; fall or fracture resulting in hospital admission; admission with dementia or delirium. For each scale, Cox-proportional hazard models calculated hazard ratios (HR) and 95% confidence intervals (CI) comparing those with low (1-2) and high (3 or more) scores to those scoring zero. Model 1 adjusted for age, sex, socioeconomic status. Model 2 adjusted for age, sex, socioeconomic status, multimorbidity count, smoking, alcohol, body mass index and physical activity (model 2).

Findings

Ten anticholinergic scales were identified. Number of included medications ranged from 49 to 128. Percentage of participants identified as taking any anticholinergic medication ranged from 5.5% to 13.1% depending on scale used. Each scale was associated significantly with increased risk of mortality and/or MACE, falls, and delirium/dementia. Participants with high scores had significantly greater risk than low scores in model 1. In model 2, only 4/10 scales (those including more medications) showed a statistically significant difference between low and high scores in risk of mortality and/or MACE. A score of 3 or more using the “Anticholinergic Drug Scale” had greatest risk of death or MACE (HR 1.66, CI 1.54-1.78), death (HR 1.72 CI 1.59-1.85), MACE (HR 2.18 CI 1.94-2.46) and falls (HR 1.67, CI 1.46-1.92).

Consequences

Anticholinergic burden associated with a range of adverse outcomes in middle-aged and older people. The number of people identified as at risk varied widely depending on the scale used. All scales were associated with adverse outcomes, however those including more medications showed greater discrimination between low and high burden. Such scales may better aid clinical decision-making in a primary care context.