Aims: Recent studies have suggested an increased risk of upper gastrointestinal bleeding (UGB) in spironolactone users. The aim was to confirm the association, identify the risk factors and quantify the absolute risk.
Methods: A population based case-control study was conducted in the County of Funen, Denmark. Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB during the period 1995 to 2006. Age- and gender-matched controls (10 for each case) (n = 36 502) were selected by risk set sampling. Data on all subjects' drug exposure and past medical history were retrieved from a prescription database and from the County's patient register. Confounders were controlled by conditional logistic regression.
Results: The adjusted odds ratio (OR) associating current use of spironolactone with UGB was 2.7 [95% confidence interval (CI) 2.2, 3.2]. The risk increased with higher doses of spironolactone (5.4; 3.4, 8.6) for 100-mg tablets. No trend was found with increasing cumulative dose. The strongest association was found among users aged 55-74 years (OR 13.1; 6.5, 26.3). Current use of loop diuretics was also associated with an increased risk of UGB (1.9; 1.7, 2.1).
Conclusion: The use of spironolactone is associated with increased risk of UGB. The risk increases with higher doses.