Arana A, Varas-Lorenzo C, McQuay LJ, Ziemiecki R, Bui CL, Gilsenan AW, Rothman KJ, Atsma WJ, Appenteng K, Franks B, de Vogel S, D'Silva M, Margulis AV, Perez Gutthann S. Do individual antimuscarinic drugs to treat overactive bladder have different cardiovascular risks? A UK CPRD cohort study. 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):534-5.


BACKGROUND: Users of drugs to treat overactive bladder (OAB) have been reported to have a higher prevalence of cardiovascular (CV) comorbidities.

OBJECTIVES: We investigated whether the risk of acute myocardial infarction (AMI), stroke, major adverse cardiovascular events (MACE), CV mortality, and all-cause mortality differed by antimuscarinic OAB drug

METHODS:
The study cohort consisted of new users of oxybutynin, tolterodine, solifenacin, fesoterodine, trospium, or darifenacin greater than or equal to 18 years old in the Clinical Practice Research Datalink (CPRD), 2004-2012. Follow-up ended with a study endpoint, cancer, HIV, death, disenrollment, or end of study. Exposure was ascertained from general practitioner (GP) prescriptions, and outcomes and covariates from GOLD, HES, ONS, and questionnaires completed by GPs. We estimated age-sex–standardized incidence rates (IRs) per 1,000 person-years and adjusted incidence rate ratios (IRRs) compared with current use of any other OAB drug. We first estimated propensity scores for drug use at baseline, stratified on deciles of propensity score among the exposed, and pooled the stratified IRRs using the Mantel-Haenszel approach.

RESULTS:
The study cohort included 119,912 new users of OAB drugs: mean age at cohort entry, 62 years; 70% female; mean follow-up, 3.3 years (range, 1 day to 9 years). Of all index therapy episodes, 33% were for oxybutynin, 31% for tolterodine and 27% for solifenacin. For current use of any OAB drug, the standardized IR (95% confidence interval [CI]) was 4.9 (4.5-5.3) for AMI, 6.0 (5.6-6.4) for stroke, 4.5 (4.2-4.9) for CV mortality, 12.2 (11.6-12.8) for MACE, 19.9 (19.1-20.6) for all-cause mortality. IRRs for CV endpoints were generally ∼1 for individual antimuscarinic OAB drugs except for oxybutynin and solifenacin. The IRR (95% CI) for current use of oxybutynin was 1.3 (1.1-1.4) for MACE and 1.4 (1.3-1.5) for all-cause mortality; for current use of solifenacin, 0.7 (0.6-0.8) for MACE, 0.7 (0.6-0.7) for all-cause mortality.

CONCLUSIONS:
Compared to current use of other study drugs combined, the risk for MACE and all-cause mortality was increased in users of oxybutynin and decreased in users of solifenacin.

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