(ASPOT43) Fall risk increasing adverse reactions (FRIARs) and fracture risk: A nested case control study

Background: The cumulative effect of simultaneously administered Fall Risk Increasing Drugs (FRIDs) has been scarcely investigated. A promising approach is the definition of scores that quantify, at the patient level, the overall burden of specific Fall Risk Increasing Adverse Reactions (FRIARs).

Objectives: To examine whether and to which extent FRIAR Scores based on Summary of product characteristics (SmPC) adverse reactions listings of (1) "visual impairment," (2) "dizziness," (3) "impaired vigilance," (4) "hypotension," (5) "weakness," and (6) "propensity to fall" are associated with fracture risk?

Methods: The data source consists of anonymized population-based data from the Tayside/Fife Region in Scotland, UK. The study design is a nested case-control study of patients aged ≥65 years. Cases are defined as patients hospitalized due to fractures. Controls are matched by gender, age, and date of cohort entry. FRIAR Scores correspond to the number of concurrently prescribed active substances whose drug information lists the respective FRIAR as an adverse effect. FRIAR Scores are determined for cases and controls within the 3-month window preceding the index date (i.e. date of case defining event or date of selection as control). The risk of fall injuries associated with FRIAR Scores was quantified using conditional logistic regression.

Results: A total of 18,456 cases and up to 10 matched controls per case were included. In multivariate analyses, the risk of fall injuries increased particularly for FRIAR Scores (1) "visual impairment," (3) "impaired vigilance," and (6) "propensity to fall" (adjusted odds ratio for FRIAR Score >= 3 versus 0: 1.58 (95% CI 1.35–1.85), 1.70 (1.57–1.85), and 2.39 (1.35–4.22), respectively). In contrast, FRIAR scores for (2) “dizziness”, (4) “hypotension”, and (5) “weakness” appeared not or only weakly associated with fractures. In comparison, the association with the use of >= 3 versus 0 drugs known as FRIDS in the literature was 1.70 (95% CI 1.60–1.82).

Conclusions: The study suggests that FRIAR Scores based on SmPC information for "visual impairment", "impaired vigilance," and "propensity to fall" provide meaningful information regarding fracture risk in older people. SmPC listings of “Propensity to fall” may be more strongly associated with fracture risk than use of drug classes known as FRIDS in the literature.