Spironolactone use and the risk of upper gastrointestinal bleeding: a population‐based case–control study

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Recent studies have suggested an increased risk of upper gastrointestinal bleeding (UGB) in spironolactone users. • We conducted this population‐based case–control study to confirm the association between spironolactone use and acute nonvaricose UGB alone or in combination with low‐dose aspirin and other antithrombotic drugs. WHAT THIS STUDY ADDS • The current use of spironolactone is associated with an increased risk of nonvaricose UGB. • The effect is most pronounced for cases aged 55–74 years. • Persons with a high current dose have a higher risk. • The risk is not modified by high cumulative doses or by concurrent use of antithrombotic or nonsteroidal anti‐inflammatory drugs. 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.