D. Layton, M. Davies, V. Osborne, S. Shakir
The UK National Institute for Health & Care Excellence recommends that antipsychotics can be used in elderly patients under strict guidelines, however use is associated with serious safety concerns (including cerebrovascular accidents (CVA)). A Modified Prescription-Event Monitoring (M- PEM) study was conducted as part of the Risk Management Plan for Seroquel XL© to examine it’s safety and use, irrespective of indication, as prescribed in primary care in England.
An adhoc analysis to examine the risk of CVA in the elderly.
M-PEM uses an observational cohort design; data on exposure were derived from dispensed prescriptions that had been issued by primary care physicians (GPs) between September 2008 and February 2013; data on events were derived from forms completed by GPs sent 12+ months after the date of each patient’s first prescription. Age and sex adjusted Mantel-Haenszel Odds Ratios (ORs) plus 95% Confidence Intervals (CI) were calculated for all cause deaths and CVA (MedDRA PT: CVA, Cerebellar infarction, Cerebral haemorrhage, Haemorrhagic stroke) in elderly patients with or without dementia, and with or without psychosis.
Final elderly cohort comprised 3127 patients; median age 77 yrs (IQR 69,84); 62% (n=1940) female; 29% (n=892) had indications associated with dementia, of which 17% (n=148) had concomitant psychosis. Within 12 months of starting Seroquel XL© 10% (n=301) died; commonly from bronchopneumonia (n=44). Deaths were more likely in elderly with dementia than without [15% (136/892) vs 8% (165/2070); adjOR 1.5(1.2, 1.9)] but not for dementia patients with psychosis versus those without [14% (21/148) vs 15% (115/744); adjOR 1.0 (0.6,1.6)]. At least one report of CVA was reported in 23 (<1%) elderly patients, of which 17 had a fatal outcome. CVA events were twice as likely in patients with dementia than without [48% (11/23) vs 28% (881/3104); adjOR 2.8 (1.3, 6.2).
Approximately one-third (29%) of this elderly cohort had dementia with or without psychosis. A higher rate of death was observed in elderly patients with dementia than without, but concomitant psychosis with dementia did not appear to be a risk factor. CVA was uncommon (<1%), but more likely in elderly with dementia than those without. Study limitations include low CVA counts, possible misclassification of depression and delirium as dementia and limited information on other possible factors (other modifiable medical and environmental factors).