Spironolactone use and the risk of upper gastrointestinal bleeding: a population-based case-control study.
OBJECTIVE
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).


CONCLUSIONS
The use of spironolactone is associated with increased risk of UGB. The risk increases with higher doses.
Gulmez
Sinem E
SE
Research Unit of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark. egulmez@health.sdu.dk
Lassen
Annmarie T
AT
Aalykke
Claus
C
Dall
Michael
M
Andries
Alin
A
Andersen
Birthe S
BS
Hansen
Jane M
JM
Andersen
Morten
M
Hallas
Jesper
J
D000368:Aged; D016022:Case-Control Studies; D003718:Denmark; D004232:Diuretics / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000139:chemically induced*; D004812:Epidemiologic Methods; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013148:Spironolactone / Q000009:adverse effects*; D013276:Stomach Ulcer / Q000139:chemically induced*; D016896:Treatment Outcome
D004232:Diuretics; D005343:Fibrinolytic Agents; D013148:Spironolactone