Mortality among patients due to adverse drug reactions that lead to hospitalization: a meta-analysis

The aim of this study was to estimate the prevalence of mortality among patients due to adverse drug reactions that lead to hospitalisation (fatal ADR_Ad), to explore the heterogeneity in its estimation through subgroup analysis of study characteristics, and to identify system-organ classes involved and causative drugs for fatal ADR_Ad.

We identified prospective ADR_Ad-related studies via screening of the PubMed and Google Scholar databases with appropriate key terms. We estimated the prevalence of fatal ADR_Ad using a double arcsine method and explored heterogeneity using the following study characteristics: age groups, wards, study region, ADR definitions, ADR identification methods, study duration and sample size. We examined patterns of fatal ADR_Ad and causative drugs.

Among 312 full-text articles assessed, 49 studies satisfied the selection criteria and were included in the analysis. The mean prevalence of fatal ADR_Ad was 0.20% (95% CI: 0.13-0.27%; I² = 93%). The age groups and study wards were the important heterogeneity modifiers. The mean fatal ADR_Ad prevalence varied from 0.01% in paediatric patients to 0.44% in the elderly. Subgroup analysis showed a higher prevalence of fatal ADR_Ad in intensive care units, emergency departments, multispecialty wards and whole hospitals. Computer-based monitoring systems in combination with other methods detected higher mortality. Intracranial haemorrhage, renal failure and gastrointestinal bleeding accounted for more than 50% of fatal ADR_Adcases. Warfarin, aspirin, renin-angiotensin system (RAS) inhibitors and digoxin accounted for 60% of fatal ADR_Ad.

ADR_Ad is an important cause of mortality. Strategies targeting the safer use of warfarin, aspirin, RAS inhibitors and digoxin could reduce the large number of fatal ADR_Adcases.