D Layton, M Davies, V Osborne, SAW Shakir
The UK National Institute for Health and Care Excellence recommends that APs can be used in elderly patients (pts) under strict guidelines, however use is associated with serious safety concerns (incl cerebrovascular accidents (CVA)). Modified Prescription-Event Monitoring (M-PEM) study was conducted as part of the Risk Management Plan for Seroquel XL© to examine safety and use as prescribed in primary care in England.
A post hoc 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 Sep2008-Feb2013; data on events from forms completed by physicians 12+ months(m) post each pt’s start date. Age & sex adjusted (adj) Mantel-Haenszel Odds Ratios (ORs) and 95%CI were calculated for all cause deaths and CVA (MedDRA PT: CVA, Cerebellar infarction, Cerebral haemorrhage, Haemorrhagic stroke) in elderly pts with/without dementia, and with/without psychosis.
Final elderly cohort= 3127; median age 77 yrs (IQR 69,84); 62% (1940) female; 892 (29%) had indications associated with dementia, of which 148 (17%) had concomitant psychosis. Within 12m of starting Seroquel XL© 10% (301) died; commonly from bronchopneumonia (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 pts with psychosis vs those without [14% (21/148) vs 15% (115/744); adjOR 1.0 (0.6,1.6)]. 23 (1%) had at least 1 report of CVA; 17 fatal. CVA events were twice as likely in pts 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 +/- psychosis. A higher rate of death was observed in elderly pts 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).