Prevalence of Drug-Drug Interactions in Older Community-Dwelling Individuals: A Systematic Review and Meta-analysis

Abstract

Background: Drug-drug interactions (DDIs) can lead to medication-related harm, and the older population is at greatest risk. We conducted a systematic review and meta-analysis to estimate DDI prevalence and identify common DDIs in older community-dwelling adults.

Methods: PubMed and EMBASE were searched for observational studies published between 01/01/2010 and 10/05/2021 reporting DDI prevalence in community-dwelling individuals aged ≥ 65 years. Nursing home and inpatient hospital studies were excluded. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool. Meta-analysis was performed using a random-effects model with logit transformation. Heterogeneity was evaluated using Cochran's Q and I². DDI prevalence and 95% confidence intervals (CIs) are presented. All analyses were performed in R (version 4.1.2).

Results: There were 5144 unique articles identified. Thirty-three studies involving 17,011,291 community-dwelling individuals aged ≥ 65 years met inclusion criteria. Thirty-one studies reported DDI prevalence at the study-participant level, estimates ranged from 0.8% to 90.6%. The pooled DDI prevalence was 28.8% (95% CI 19.3-40.7), with significant heterogeneity (p < 0.10; I² = 100%; tau² = 2.13) largely explained by the different DDI identification methods. Therefore, 26 studies were qualitatively synthesised and seven studies were eligible for separate meta-analyses. In a meta-analysis of three studies (N = 1122) using Micromedex^®, pooled DDI prevalence was 57.8% (95% CI 52.2-63.2; I² = 69.6%, p < 0.01). In a meta-analysis of two studies (N = 809,113) using Lexi-Interact^®, pooled DDI prevalence was 30.3% (95% CI 30.2-30.4; I² = 6.8%). In a meta-analysis of two studies (N = 947) using the 2015 American Geriatrics Society Beers criteria^®, pooled DDI prevalence was 16.6% (95% CI 5.6-40.2; I² = 97.5%, p < 0.01). Common DDIs frequently involved cardiovascular drugs, including ACE inhibitor-potassium-sparing diuretic; amiodarone-digoxin; and amiodarone-warfarin.

Conclusions: DDIs are prevalent among older community-dwelling individuals; however, the methodology used to estimate these events varies considerably. A standardised methodology is needed to allow meaningful measurement and comparison of DDI prevalence.

Fig. 1

Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flow diagram of systematic literature search and study selection process for the prevalence of drug-drug interactions (DDIs) in older (aged ≥ 65 years) community-dwelling adults. ADRs adverse drug reactions

Fig. 2

Forest plot showing the proportion [95% confidence interval (CI)] of older (aged ≥ 65 years) community-dwelling individuals potentially exposed to a drug–drug interaction (DDI)^*‡, identified using the 2015 American Geriatrics Society Beers criteria^®. n, numerator (number aged ≥65 years with a DDI ); N, denominator (sample size, aged ≥ 65 years). ^*Denominator (N): total number of participants aged ≥ 65 years included in the study; ^‡DDI classification: “Potentially Clinically Important Non-Anti-infective Drug–Drug Interactions That Should Be Avoided in Older Adults”.

Fig. 3

Forest plot showing the proportion [95% confidence interval (CI)] of older (aged ≥ 65 years) community-dwelling individuals potentially exposed to a drug–drug interaction (DDI)^*‡, identified using the Lexi-Interact^® database. n, numerator (number aged ≥65 years with a DDI ); N, denominator (sample size, aged ≥ 65 years). ^*Denominator (N): study participants ≥ 65 years dispensed/prescribed two or more drugs (< 20% of the population in Steinman et al. used one to two medications); ^‡DDI classification: clinically significant DDIs, classified as type D or X per Lexi-Interact^®

Fig. 4

Forest plot showing the proportion [95% confidence interval (CI)] of older (aged ≥ 65 years) community-dwelling individuals potentially exposed to a drug–drug interaction (DDI)^*†‡, identified using the Micromedex^® database. n, numerator (number aged ≥ 65 years with a DDI); N, denominator (sample size, aged ≥ 65 years). *Denominator (N): study participants aged ≥65 years dispensed/prescribed two or more drugs; ^‡DDI classification: potentially clinically important DDIs, classified as moderate, major, high or contraindicated per Micromedex^®; ^†mild DDIs were identified in < 10% of the overall study population aged ≥ 60 years for Secoli et al. and Teixeira et al.