Linder M, Margulis AV, Anveden-Berglind I, Bahmanyar S, Bui CL, Atsma WJ, Appenteng K, Franks B, de Vogel S, D'Silva M, Perez-Gutthann S, Arana A. Cardiovascular risk in users of antimuscarinic drugs for overactive bladder: a cohort study in the Swedish National Registers. Poster presented at the 32nd ICPE International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 28, 2016. Dublin, Ireland. [abstract] Pharmacoepidemiol Drug Saf. 2016 Aug; 25(Suppl 3):491-2.

BACKGROUND: It has been noted that patients with overactive bladder (OAB) may have increased cardiovascular (CV) risks, but we lack information on risks in users of individual OAB drugs.

OBJECTIVES: In preparation for a postauthorization safety study for mirabegron, a drug with a novel mechanism of action to treat OAB, we assessed the risk of acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality in users of individual antimuscarinic OAB drugs.

METHODS: We identified new users of tolterodine, solifenacin, fesoterodine, darifenacin, and oxybutynin aged greater than or equal to 18 years without cancer or HIV from the Swedish National Registers in years 2006-2012. We estimated age-sex-standardized incidence rates per 1,000 person-years (IRs) and incidence rate ratios (IRRs). For the latter, we used propensity scores with a large number of variables, we trimmed the distribution tails, estimated IRRs in deciles of scores, and pooled IRRs using Mantel-Haenzel methods. We report point estimates and 95% confidence intervals.

RESULTS: The cohort of 130,944 patients had a mean age of 66 years; 60% were women. The most commonly used OAB drugs were tolterodine, solifenacin and fesoterodine. During follow-up, 4% had an AMI, 5% had a stroke, 3% died of CV causes and 8% died of any cause. For current use of the three most commonly used OAB drugs, the standardized IR (95% CI) for AMI was lowest for fesoterodine, 8.2 (6.6-9.8), and greatest for tolterodine, 13.3 (12.3-14.3). For stroke, it was lowest for solifenacin, 16.9 (15.6-18.1), and greatest for tolterodine, 21.0 (19.7-22.3). For CV mortality, it was lowest for fesoterodine, 4.2 (3.0-5.4), and greatest for tolterodine, 7.8 (7.0-8.5). For all-cause mortality, it was lowest for fesoterodine, 12.4 (10.4-14.4), and greatest for tolterodine, 21.4 (20.1-22.6). With reference to current use of tolterodine, IRRs for current use of solifenacin and fesoterodine for all endpoints were lower than one, between 0.69 (95% CI, 0.48-0.99) and 0.88 (0.79-0.98). Other point estimates were close to one, generally below.

CONCLUSIONS: We observed higher CV risks with tolterodine than with solifenacin and fesoterodine.