Associations of Opioid Prescriptions with Death and Hospitalization across the Spectrum of Estimated GFR

Abstract

Background and objectives: Most opioids undergo kidney excretion. The goal of this study was to evaluate opioid-associated risks of death and hospitalization across the range of eGFR.

Design, setting, participants, & measurements: The study population included adult primary care patients in Geisinger Health (Danville, PA) between 2008 and 2017. People receiving their first opioid prescription were propensity matched to people receiving NSAIDS (and, in sensitivity analysis, gabapentinoids) and the risk of death and hospitalization were compared, classifying opioid medication exposure as time-varying daily oral morphine milligram equivalents (MMEs) across time-varying eGFR.

Results: The propensity-matched cohort included 46,246 patients prescribed either opioids or NSAIDs between 2008 and 2017 (mean [SD] age, 54 [16] years; 56% female; 3% of black race). Prescriptions for 1-59 and ≥60 MMEs were associated with higher risk of death (HR, 1.70; 95% CI, 1.41 to 2.05 for 1-59 MMEs; HR, 2.25; 95% CI, 1.82 to 2.79 for ≥60 MMEs) and hospitalization (HR, 1.38; 95% CI, 1.30 to 1.46 for 1-59 MMEs; HR, 1.68; 95% CI, 1.56 to 1.81 for ≥60 MMEs) compared with NSAID prescriptions, when evaluated at eGFR 80 ml/min per 1.73 m². The relative risk of death associated with ≥60 MMEs was higher at lower GFR (e.g., eGFR, 40 ml/min per 1.73 m²; HR, 3.94; 95% CI, 2.70 to 5.75; P for interaction, 0.01). When gabapentinoids were used as the comparison medication, only ≥60 MMEs were significantly associated with higher risk of death (HR, 2.72; 95% CI, 1.71 to 4.34), although both 1-59 and ≥60 MMEs were associated with risk of hospitalization (HR, 1.22; 95% CI, 1.04 to 1.43 for 1-59 MMEs; HR, 1.54; 95% CI, 1.28 to 1.86 for ≥60 MMEs).

Conclusions: The receipt of prescription opioids was associated with a higher risk of death and hospitalization compared with other pain medications, particularly with higher doses and at lower eGFR.

Keywords: MME; Pennsylvania; adult; chronic kidney disease; cohort studies; female; goals; hospitalization; humans; morphine; non-steroidal anti-inflammatory agents; opioid analgesics; pain; prescriptions; primary health care; risk.