Association of Opioid and Benzodiazepine Use with Adverse Respiratory Events in Older Adults with Chronic Obstructive Pulmonary Disease

<b>Rationale:</b> Older adults with chronic obstructive pulmonary disease (COPD) are at substantially increased risk for medication-related adverse events. Two frequently prescribed classes of drugs that pose a particular risk to this patient group are opioids and benzodiazepines. Research on this topic has yielded conflicting findings.<b>Objectives:</b> The purpose of this study was to examine, among older adults with COPD, whether: <i>1</i>) independent or concurrent use of opioid and benzodiazepine medications was associated with hospitalizations for respiratory events, and <i>2</i>) this association was exacerbated by the presence of obstructive sleep apnea (OSA).<b>Methods:</b> We conducted a case-control study of Medicare beneficiaries aged ≥66 years, who were diagnosed with COPD in 2013, using the 5% national Medicare database. Cases (<i>n</i> = 3,232) were defined as patients hospitalized for a primary COPD-related respiratory diagnosis in 2014 and were matched with up to two control subjects (<i>n</i> = 6,247) on index date, age, sex, socioeconomic status, comorbidity, presence of OSA, COPD medication, and COPD complexity.<b>Results:</b> In comparison to the referent (no opioid or benzodiazepine use), opioid use alone (adjusted odds ratio [aOR], 1.73; 95% confidence interval [CI], 1.52-1.97), benzodiazepine use alone (aOR, 1.42; 95% CI, 1.21-1.66), and concurrent opioid/ benzodiazepine use (aOR, 2.32; 95% CI, 1.94-2.77) in the 30 days before the event/index date were all associated with an increased risk of hospitalization for a respiratory condition. Risk of hospitalization was higher with concurrent opioid and benzodiazepine use when compared with use of either medication alone. There was no statistically significant interaction between OSA and either of the drugs, alone or in combination. However, the adverse respiratory effects of concurrent opioid and benzodiazepine use were increased in patients with a high degree of COPD complexity. All of the above findings persisted using exposure windows that extended to 60 and 90 days before the event/index date.<b>Conclusions:</b> Among older adults with COPD, use of opioid and benzodiazepine medications alone or in combination were associated with increased adverse respiratory events. The adverse effects of these medications were not exacerbated in patients with COPD-OSA overlap syndrome. However, the adverse impact of dual opioid and benzodiazepine was greater in patients with high-complexity COPD.