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

Affiliations

¹ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA. Electronic address: lidia.moura@mgh.harvard.edu.
² Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
⁵ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA; Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁶ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA; National Bureau of Economic Research, Cambridge, MA, USA; Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Harvard Kennedy School, Cambridge, MA, USA.
⁷ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

PMID: 36572369
PMCID: PMC10033385
DOI: 10.1016/j.jclinepi.2022.12.013

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

Lidia M V R Moura et al. J Clin Epidemiol. 2023 Feb.

. 2023 Feb:154:136-145.

doi: 10.1016/j.jclinepi.2022.12.013. Epub 2022 Dec 23.

Authors

Affiliations

¹ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA. Electronic address: lidia.moura@mgh.harvard.edu.
² Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
⁵ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA; Mongan Institute, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁶ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA; National Bureau of Economic Research, Cambridge, MA, USA; Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Harvard Kennedy School, Cambridge, MA, USA.
⁷ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

PMID: 36572369
PMCID: PMC10033385
DOI: 10.1016/j.jclinepi.2022.12.013

Abstract

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.

Methods: 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.

Results: 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.

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

Keywords: Acute ischemic stroke; Benzodiazepines; Mortality; Neurology; Polytherapy; Stroke.

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Conflict of interest statement

Conflicts of Interest:

The authors declare no conflict of interest.

Figures

**Figure 1.. Selection of eligible patients with new acute ischemic stroke (AIS) ≥65 years, 1/2014–12/2020**
Figure 1 describes the sampling process that resulted in a sample of 2,584 subjects, including patients ≥65 years, at the time of new acute ischemic stroke admission, patients with available data in the electronic health record system, and patients who had not received benzodiazepines in the months prior to admission.

**Figure 2.. Crude and standardized survival curves by benzodiazepine initiation strategy during the first 30 days post-stroke admission**
A. Crude - naïve crude comparison of 30-day mortality with misaligned time zero ^a ^a Red: No initiation of benzodiazepine within seven days post-AIS admission. Blue: initiation of benzodiazepine within seven days post-AIS admission. B. Survival curve that fixed the immortal person-time without confounders’ standardization ^{a, b} ^b Shaded area: 95% confidence intervals constructed using bootstrap with 500 replications. C. Survival curve fixed the immortal person-time with confounders’ standardization ^{b, c} ^c This survival curve includes weights for treatment initiation.

See this image and copyright information in PMC

References

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

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

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