Examining Risks of Adverse Drug Reactions in Multimorbidity and Polypharmacy in Chronic Obstructive Pulmonary Disease: A UK Biobank Study

Problem

Multimorbidity is common in Chronic Obstructive Pulmonary Disease (COPD). There is evidence that multimorbidity is associated with increased polypharmacy increasing the risk of adverse drug reactions (ADRs). However, less is known about risk of adverse drug reactions in the context of multimorbidity in COPD. It is not yet clear what what patterns of comorbidity contribute most to increased risk of ADRs. This study aims to: 1) describe the pattern and extent of comorbidity and polypharmacy in UK Biobank participants with COPD; 2) identify which comorbidities are associated with increased risk of ADRs resulting from polypharmacy.

Approach

Prevalence of multimorbidity (≥4 comorbid conditions) and polypharmacy (≥5 prescribed medications) was calculated for UK Biobank participants with COPD (n=8317) and compared to the rest of the cohort without COPD (n=494,323). Medications with similar ADRs were identified from the Scottish Intercollegiate Guidelines Network Polypharmacy Guideline. The proportion of participants with COPD taking ≥ 3 medications with similar ADRs was compared with the proportion in those without COPD. Logistic regression analyses were used to compare the odds of taking ≥3 medications with similar adverse effects between those with or without COPD, adjusting for age, sex and socioeconomic deprivation.

Findings

Multimorbidity was more common in participants with COPD that those without (17% vs. 4% having ≥4 or more comorbid conditions). Compared with those without COPD, participants with COPD were more likely to report comorbid cardiovascular disease, mental illness, gastrointestinal disease, cancer and painful conditions after adjusting for potential confounders of age, sex, socioeconomic deprivation, smoking and BMI.Polypharmacy was highly prevalent (52% with COPD taking ≥5 medications vs 18% in those without COPD). After adjusting for age, sex and socioeconomic deprivation, those with COPD were significantly more likely than those without to be prescribed ≥3 medications contributing to falls (Odds ratio (OR) 2.27, 95% confidence interval (CI) 2.13-2.42), constipation (OR 3.42, 95% CI 3.10-3.77), urinary retention (OR 3.38, 95% CI 2.94-3.87), central nervous system (CNS) depression (OR: 3.75, 95% CI 3.31-4.25), bleeding (OR 4.61, 95% CI 3.35-6.19) and renal injury (OR 2.22, 95% CI 1.86-2.62). Comorbid cardiovascular disease was associated with the greatest risk of taking multiple medications associated with falls and renal injury, while comorbid mental health problems were associated with medications associated with CNS depression, urinary retention and bleeding.

Consequences

COPD is associated with a range of comorbidities leading to high levels of polypharmacy. In the context of COPD, co-prescription of drugs with a range of ADRs is common. The medications contributing to this risk are largely indicated for the management of the associated comorbidities rather than COPD itself. Clinical guidelines for COPD should place greater emphasis on the need for assessment of associated comorbidities and the risk of associated ADRs.