Antipsychotics and risk of cerebrovascular events in treatment of behavioural and psychological symptoms of dementia in Hong Kong: a hospital‐based, retrospective, cohort study

Chan, Man-chak; Chong, Catherine Shiu‐yin; Wu, A. Y. T.; Wong, Kai-choi; Dunn, Eva Lai-Wah; Tang, Orlando Wai-nang; Chan, Wah-Fat

doi:10.1002/gps.2347

Cited by 19 publications

(16 citation statements)

References 28 publications

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“…Gill et al followed patients with dementia for an average of eight months and found no difference in risk [11] (HR = 0.99; 95%CI 0.79 to 1.23) even among high-risk subgroups defined by history of stroke or long-term care residence. A study based in Hong Kong followed dementia patients for an average of 2.4 years and also found no difference in risk [16] (HR = 0.93; 95%CI 0.52 to 1.67). These results may be explained by these studies' longer periods of follow-up, particularly if high-risk FGA patients experience stroke only during the first few months after antipsychotic initiation or if such patients were more likely to discontinue or switch their antipsychotic medication, which were both treated as censoring events in these analyses.…”

Section: Resultsmentioning

confidence: 99%

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

et al. 2014

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BackgroundObservational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture.Objectives1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs.Data sourcesPubmed and Science Citation Index.Study eligibility criteria, participants, and interventionsStudies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a “new user” design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events.Study appraisal and synthesis methodsFor each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference—comparing FGAs to SGAs—mediated by their difference in risk for the medical event.ResultsWe provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference.ConclusionsThe current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs.

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Section: Resultsmentioning

confidence: 99%

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

et al. 2014

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“…The few studies that avoided these potential biases reported higher first-generation antipsychotic risk for ventricular arrhythmia 33 , myocardial infarction 33,34 and hip-fracture, 34,35 but lower risk for venous thromboembolism. But the evidence for stroke was mixed 33,34,36-39 and none reported a difference in risk for pneumonia or other bacterial infections. 33-35 The divergent evidence for hip fracture and pneumonia may be partly explained by our focus on community-dwelling older adults to improve internal validity for comparisons across events, whereas many other studies focused on or included nursing home residents.…”

Section: Discussionmentioning

confidence: 99%

Mediators of First- Versus Second-generation Antipsychotic-related Mortality in Older Adults

et al. 2015

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Background Observational studies of older adults showed higher mortality for first-generation antipsychotics than their second-generation counterparts which led to FDA warnings, but the actual mechanisms involved remain unclear. Methods A cohort of 9,060 initiators of first-generation antipsychotics and 17,137 of second-generation antipsychotics enrolled in New Jersey and Pennsylvania Medicare were followed for 180 days. Medical events were assessed using diagnostic and procedure codes on inpatient billing claims. For the individual and joint set of medical events (mediators), we estimated the total, direct, and indirect effects of antipsychotic type (first versus second generation) on mortality on the risk ratio scale (RR) and the proportion mediated on the risk difference scale, obtaining 95% confidence intervals (CI) through bootstrapping. We performed bias analyses for false negative mediator misclassification in claims data, with sensitivity ranging from 0.25 to 0.75. Results There were 3,199 deaths (outcomes), 862 cardiovascular events, 675 infectious events, and 491 hip fractures (potential mediators). Mortality was higher for first-than second-generation antipsychotic initiators (adjusted RR 1.14; 95%CI 1.06-1.22). In naïve analyses that ignored potential misclassification, less than 4% of this difference was explained by any particular medical event. In bias analyses the proportion mediated ranged from 6% to 16% for stroke, 3% to 9% for ventricular arrhythmia, 3% to 11% for myocardial infarction, 0% venous thromboembolism, 3% to 9% for pneumonia, 0% to 1% for other bacterial infection, and 1% to 3% for hip fracture. Conclusions Acute cardiovascular events and pneumonia may explain part of the mortality difference between first- and second-generation antipsychotic initiators in this analysis.

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“…25 All studies included adult participants, 8 of which focused on elderly patients, 16,19,36e39,41,42 and 5 of which included patients with dementia. 16,19,38,41,42 Characteristics of individual studies are summarized in Table 1.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

“…Only 1 study performed CVA diagnosis validation from reviewed medical records. 42 The studies also varied in the adjusted covariates. All studies comprehensively adjusted for potential confounders in their analysis.…”

Section: Study Qualitymentioning

confidence: 99%

Antipsychotics and the Risk of Cerebrovascular Accident: A Systematic Review and Meta-Analysis of Observational Studies

Hsu

Esmaily-Fard

Lai

et al. 2017

Journal of the American Medical Directors Association

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Antipsychotics and risk of cerebrovascular events in treatment of behavioural and psychological symptoms of dementia in Hong Kong: a hospital‐based, retrospective, cohort study

Cited by 19 publications

References 28 publications

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

Mediators of First- Versus Second-generation Antipsychotic-related Mortality in Older Adults

Antipsychotics and the Risk of Cerebrovascular Accident: A Systematic Review and Meta-Analysis of Observational Studies

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