Polypharmacy is a risk factor for mortality, severe chronic kidney disease, and liver disease among privately insured adults with cerebral palsy

BACKGROUND: Adults with cerebral palsy (CP) have an increased risk for polypharmacy, premature mortality, and early development of several morbidities, including conditions associated with excess medication exposure, such as chronic kidney disease (CKD) and liver disease. To date, very little is known about the consequence of polypharmacy for adults with CP. OBJECTIVE: To determine if polypharmacy is associated with an increased risk for mortality, severe CKD, and liver disease among adults with CP, before and after adjusting for comorbid neurodevelopmental disabilities (NDDs) and multimorbidity. METHODS: This is an exploratory treatment effectiveness study. Data from the Optum Clinformatics Data Mart were used for this retrospective cohort study. Adults aged 18 years or older with a diagnosis of CP and without severe CKD (stages IV+) and liver disease were identified from the calendar year 2013 and were subsequently followed from January 1, 2014, to death, severe CKD, liver disease, loss to follow-up, or end of study period (December 31, 2017). Diagnosis codes were used to identify NDDs (intellectual disabilities, epilepsy, autism spectrum disorders, spina bifida) and 24 relevant morbidities at baseline (i.e., calendar year 2013). Polypharmacy was defined as ≥ 5 medications and hyperpolypharmacy was defined as ≥ 10 medications at baseline. Cox regression models were developed to examine the association (as HR and 95% CI) between polypharmacy and hyperpolypharmacy with mortality, severe CKD, and liver disease separately, before and after adjusting for covariates (demographics, NDDs, multimorbidity). Exploratory analyses examined the mediating effect of incident severe CKD or liver disease on the association between the exposure (polypharmacy or hyperpolypharmacy) on outcomes. RESULTS: Of the 9,238 adults with CP, 58.5% had polypharmacy and 29.5% had hyperpolypharmacy. The fully adjusted HR for mortality was 2.14 (95% CI = 1.59-2.89) for polypharmacy and 1.65 (95% CI = 1.31-2.09) for hyperpolypharmacy. The fully adjusted HR for severe CKD was 1.66 (95% CI = 1.17-2.36) for polypharmacy and 1.67 (95% CI = 1.27-2.19) for hyperpolypharmacy. The fully adjusted HR for liver disease was 1.57 (95% CI = 1.27-1.94) for polypharmacy and 1.72 (95% CI = 1.42-2.08) for hyperpolypharmacy. Incident liver disease mediated 5.37% (polypharmacy) and 7.54% (hyperpolypharmacy) of the association between the exposure with incident severe CKD for nonelderly (aged < 65 years), while incident severe CKD mediated 7.05% (polypharmacy) and 6.64% (hyperpolypharmacy) of the association between the exposure with incident liver disease for elderly (aged ≥ 65 years). CONCLUSIONS: Polypharmacy and hyperpolypharmacy are robust risk factors for risk of mortality, severe CKD, and liver disease among privately insured adults with CP. While incidence of severe CKD and liver disease had negligible effects on the association between polypharmacy with mortality, there is evidence that they mediate a considerable portion of one another and require further examination.