P656Risk of major gastrointestinal bleed in relation to vascular disease risk in 0.5M UK Biobank participants

Abstract

Abstract Background Low-dose aspirin is of established benefit for secondary prevention of cardiovascular events but in primary prevention the benefit is finely balanced with the hazard of major bleeds, and in particular gastrointestinal (GI) bleeds. Purpose To investigate non-vascular, non-genetic risk factors for major GI bleeds and derive a score for GI bleed risk which may help identify who will receive most net benefit from aspirin. Methods In the UK Biobank prospective study of 0.5M participants aged 40–69 at recruitment, prior history of cardiovascular disease, bleeds and other medical conditions was ascertained from self-reported diagnoses and electronic heath records (EHR) prior to recruitment. Major GI bleed during 6 years of follow-up was defined based on coded diagnoses and duration of hospital stay. Non-vascular risk factors for bleed were identified from amongst 100 baseline and prior disease factors using a stepwise regression with adjustment for established vascular risk factors, aspirin and warfarin use. 10-way cross-validation was used when making risk scores. Results Among the primary prevention population without prior intracranial bleed, serious extracranial bleed or gastrointestinal ulcer in the 6 months prior to recruitment, 1682 (0.06%/y) participants had a major GI bleed (1006 upper GI, 676 lower GI) with a mean stay in hospital of 3.2 days. Antiplatelet use (in 11%) and anticoagulant use (in 1%), were associated with 1.5 and 4 fold risks of GI bleed, respectively. Stepwise regression identified a non-vascular risk score for major bleed with a 4-fold risk ratio across fifths (Figure). But the score was also associated with a 2-fold risk ratio for major vascular events. Conclusions Major GI bleeds cause substantial morbidity. A 4-fold difference in bleed risk across quintiles was distinguishable by a score based largely on EHR prior disease information and frailty measures. This score is applicable in other contexts and will be applied in the ASCEND randomised trial of daily aspirin to provide randomized evidence of the net benefit of aspirin in different risk categories. However, vascular risk factors predicted risk of GI bleeds, and non-vascular risk factors for GI bleed predicted risk of major vascular events; so the net benefit from aspirin may vary only modestly across categories by vascular and bleed risks.