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

Moura, Lidia M.V.R.; Yan, Zhiyu; Donahue, Melanie; Smith, Leanne; Schwamm, Lee H; Hsu, John; Newhouse, Joseph P.; Haneuse, Sebastien; Blacker, Deborah; Hernández–Dı́az, Sonia

doi:10.1016/j.jclinepi.2022.12.013

Cited by 3 publications

(3 citation statements)

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“…We examined patterns of missing data for all relevant variables to confirm that the analysis had minimal missing information with less than 5% missingness on all variables 10,13 . The sedating effects of benzodiazepines on ambulation dexterity might be more pronounced among AIS survivors who can walk during the early days of recovery (e.g., those with mild AIS) and are therefore at risk for falls or FRIs.…”

Section: Missing Data and Pre-planned Stratified Analysismentioning

confidence: 99%

“…While risks associated with long-term benzodiazepine use are well established, avoidance is yet to be reflected in clinical practice and there remain conflicting views on whether short-term use carry similar risks [7][8][9] . Perhaps as a result, guidelines have failed to specifically address this issue, and some physicians dispute whether short-term prescriptions would represent a real public health problem 3,10,11 .…”

Section: Introductionmentioning

confidence: 99%

“…Implementation of randomized clinical trials to determine the safety of short-term benzodiazepine usage during the acute AIS recovery phase is practically difficult and ethically challenging. Given the context of safety warnings associated with benzodiazepine use, the debatable safety of shortterm administration, and the variability in initiation patterns, we employed a range of novel analytical methods to investigate whether early use of inpatient benzodiazepines within three days of an AIS, a threshold chosen to denote short-term inpatient use, results in net harm for adults 65 years and older 8,10,[12][13][14][15][16] .To mitigate the influence of confounding and selection biases in the context of non-randomized studies, we used a target trial methodology to emulate a pragmatic randomized clinical trial to assess the effect of short term inpatient benzodiazepine use on falls or fall related injuries (FRIs) for this population.…”

Section: Introductionmentioning

confidence: 99%

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Benzodiazepine Initiation and the Risk of Falls or Fall-Related Injuries in Older Adults Following Acute Ischemic Stroke

Sun,

Lomachinsky,

Smith

et al. 2024

Preprint

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BackgroundBenzodiazepine use in older adults following acute ischemic stroke (AIS) is common, yet short-term safety concerning falls or fall-related injuries remains unexplored.MethodsWe emulated a hypothetical randomized trial of benzodiazepine use during the acute post stroke recovery period to assess incidence of falls or fall related injuries in older adults. Using linked data from the Get With the Guidelines Registry and Mass General Brigham’s electronic health records, we selected patients aged 65 and older admitted for Acute Ischemic Stroke (AIS) between 2014 and 2021 with no documented prior stroke and no benzodiazepine prescriptions in the previous 3 months. Potential for immortal-time and confounding biases was addressed via separate inverse-probability weighting strategies.ResultsThe study included 495 patients who initiated inpatient benzodiazepines within three days of admission and 2,564 who did not. After standardization, the estimated 10-day risk of falls or fall-related injuries was 694 events per 1000 (95% confidence interval CI: 676-709) for the benzodiazepine initiation strategy and 584 events per 1000 (95% CI: 575-595) for the non-initiation strategy. Subgroup analyses showed risk differences of 142 events per 1000 (95% CI: 111-165) and 85 events per 1000 (95% CI: 64-107) for patients aged 65 to 74 years and for those aged 75 years or older, respectively. Risk differences were 187 events per 1000 (95% CI: 159-206) for patients with minor (NIHSS≤ 4) AIS and 32 events per 1000 (95% CI: 10-58) for those with moderate-to-severe AIS.ConclusionsInitiating inpatient benzodiazepines within three days of AIS is associated with an elevated 10-day risk of falls or fall-related injuries, particularly for patients aged 65 to 74 years and for those with minor strokes. This underscores the need for caution with benzodiazepines, especially among individuals likely to be ambulatory during the acute and sub-acute post-stroke period.

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Section: Missing Data and Pre-planned Stratified Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Benzodiazepine Initiation and the Risk of Falls or Fall-Related Injuries in Older Adults Following Acute Ischemic Stroke

Sun,

Lomachinsky,

Smith

et al. 2024

Preprint

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The Clone-Censor-Weight Method in Pharmacoepidemiologic Research: Foundations and Methodological Implementation

Gaber,

Hanson,

Kim

et al. 2024

Curr Epidemiol Rep

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

Sankaranarayanan,

Donahue,

Sun

et al. 2024

Preprint

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RationaleDespite 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.MethodsUsing 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.ResultsIn 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.ConclusionInitiating 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.

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

Cited by 3 publications

References 46 publications

Benzodiazepine Initiation and the Risk of Falls or Fall-Related Injuries in Older Adults Following Acute Ischemic Stroke

Benzodiazepine Initiation and the Risk of Falls or Fall-Related Injuries in Older Adults Following Acute Ischemic Stroke

The Clone-Censor-Weight Method in Pharmacoepidemiologic Research: Foundations and Methodological Implementation

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

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