Benzodiazepine Initiation Effect on Mortality Among Medicare Beneficiaries Post Acute Ischemic Stroke

Despite guideline warnings, older acute ischemic stroke (AIS) survivors still receive benzodiazepines (BZD) for agitation, insomnia, and anxiety despite being linked to severe adverse effects, such as excessive somnolence and respiratory depression. Due to polypharmacy, drug metabolism, comorbidities, and complications during the sub-acute post-stroke period, older adults are more susceptible to these adverse effects. We examined the impact of receiving BZDs within 30 days post-discharge on survival among older Medicare beneficiaries after an AIS.

Using the Medicare Provider Analysis and Review (MedPAR) dataset, Traditional fee-for-service Medicare (TM) claims, and Part D Prescription Drug Event data, we analyzed a random 20% sample of TM beneficiaries aged 66 years or older who were hospitalized for AIS between July 1, 2016, and December 31, 2019. Eligible beneficiaries were enrolled in Traditional Medicare Parts A, B, and D for at least 12 months before admission. We excluded beneficiaries who were prescribed a BZD within 90 days before hospitalization, passed away during their hospital stay, left against medical advice, or were discharged to institutional post-acute care. Our primary exposure was BZD initiation within 30 days post-discharge, and the primary outcome was 90-day mortality risk differences (RD) from discharge. We followed a trial emulation process involving cloning, weighting, and censoring, plus we used inverse-probability-of-censoring weighting to address confounding.

In a sample of 47,421 beneficiaries, 826 (1.74%) initiated BZD within 30 days after discharge from stroke admission or before readmission, whichever occurred first, and 6,392 (13.48%) died within 90 days. Our study sample had a median age of 79, with an inter-quartile range (IQR) of 12, 55.3% female, 82.9% White, 10.1% Black, 1.7% Hispanic, 2.2% Asian, 0.4% American Native, 1.5% Other and 1.1% Unknown. After standardization based on age, sex, race/ethnicity, length of stay in inpatient, and baseline dementia, the estimated 90-day mortality risk was 159 events per 1,000 (95% CI: 155, 166) for the BZD initiation strategy and 133 events per 1,000 (95% CI: 132, 135) for the non-initiation strategy, with an RD of 26 events per 1,000 (95% CI: 22, 33). Subgroup analyses showed RDs of 0 events per 1,000 (95% CI: -4, 11) for patients aged 66-70, 3 events per 1,000 (95% CI: -1, 13) for patients aged 71-75, 10 events per 1,000 (95% CI: 3, 23) for patients aged 76-80, 27 events per 1,000 (95% CI: 21, 46) for patients aged 81-85, and 84 events per 1,000 (95% CI: 73, 106) for patients aged 86 years or older. RDs were 34 events per 1,000 (95% CI: 26, 48) and 20 events per 1,000 (95% CI: 11, 33) for males and females, respectively. RDs were 87 events per 1,000 (95% CI: 63, 112) for patients with baseline dementia and 18 events per 1,000 (95% CI: 13, 21) for patients without baseline dementia.

Initiating BZDs within 30 days post-AIS discharge significantly increased the 90-day mortality risk among Medicare beneficiaries aged 76 and older and for those with baseline dementia. These findings underscore the heightened vulnerability of older adults, especially those with cognitive impairment, to the adverse effects of BZDs.