Original Article| Volume 154, P136-145, February 2023

No short-term mortality from benzodiazepine use post-acute ischemic stroke after accounting for bias

Published:December 22, 2022DOI:


      • Quantifying the effect of benzodiazepines on mortality is not straightforward.
      • Immortal time bias threatens the validity of benzodiazepine effect estimates.
      • A process of cloning, weighting, and censoring is used to avoid immortal time bias.
      • The observed benzodiazepine-related 30-day mortality was largely due to confounding.


      Background and Objectives

      Older adults receive benzodiazepines for agitation, anxiety, and insomnia after acute ischemic stroke (AIS). No trials have been conducted to determine if benzodiazepine use affects poststroke mortality in the elderly.


      We examined the association between initiating benzodiazepines within 1 week after AIS and 30-day mortality. We included patients ≥65 years, admitted for new nonsevere AIS (NIH-Stroke-Severity[NIHSS]≤ 20), 2014–2020, with no recorded benzodiazepine use in the previous 3 months and no contraindication for use. We linked a stroke registry to electronic health records, used inverse-probability weighting to address confounding, and estimated the risk difference (RD). A process of cloning, weighting, and censoring was used to avoid immortal time bias.


      Among 2,584 patients, 389 received benzodiazepines. The crude 30-day mortality risk from treatment initiation was 212/1,000 among patients who received benzodiazepines, while the 30-day mortality was 34/1,000 among those who did not. When follow-up was aligned on day of AIS admission and immortal time was assigned to the two groups, the estimated risks were 27/1,000 and 22/1,000, respectively. Upon further adjustment for confounders, the RD was 5 (−12 to 19) deaths/1,000 patients.


      The observed higher 30-day mortality associated with benzodiazepine initiation within 7 days was largely due to bias.

      Graphical abstract


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