Variation in Cardiovascular Risk Related to Individual Antimuscarinic Drugs Used to Treat Overactive Bladder: A UK Cohort Study

Abstract

BackgroundBlocking muscarinic receptors could have an effect on cardiac function, especially among elderly patients with overactive bladder (OAB).Study ObjectiveTo investigate the risk of cardiovascular (CV) events in users of antimuscarinic drugs to treat OAB.Design, Setting, and ParticipantsCohort study of new users of darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium, 18 years or older, in the United Kingdom's Clinical Practice Research Datalink (CPRD), 2004–2012.Outcome Measurements and Main ResultsUsing tolterodine as the reference, we estimated propensity‐score–stratified incidence rate ratios (IRRs) for acute myocardial infarction, stroke, CV mortality, major adverse cardiac events (MACE, a combined end point of the previous three), and all‐cause death for individual antimuscarinic drugs. The study cohort included 119,912 new users of OAB drugs. The mean age at cohort entry was 62 years, 70% were female, and the mean follow‐up was 3.3 years. The adjusted IRR for MACE and current use of oxybutynin compared with current use of tolterodine was 1.14 (95% confidence interval [CI] 1.01–1.30). In contrast, the IRR was 0.65 (CI 0.56–0.76) for current use of solifenacin compared with tolterodine. In this study, performed with health care data, the distribution of risk factors was relatively similar across users of different OAB drugs and, although our analyses controlled for a range of measured potential confounders, residual confounding cannot be ruled out.ConclusionsIn an observational comparative study of users of medications to treat OAB conducted in routine clinical practice, the risk for CV side effects was increased in users of oxybutynin and decreased in users of solifenacin compared with users of tolterodine.

Validation of cardiovascular outcomes and risk factors in the Clinical Practice Research Datalink in the United Kingdom

“…This validation study was conducted in a population of patients treated for overactive bladder because this validation effort was part of a broader study on the safety of antimuscarinic drugs. 8,9,15 We do not expect that these CV outcomes and risk factors would be better or less well recorded among these patients than in the general population. Furthermore, CV risk factors investigated here might have been recorded in patients' electronic records before treatment started.…”

“…This study was the validation component of a drug safety study 8 ("parent study") that included patients aged ≥18 years who were continuously enrolled in the UK CPRD primary care database (GOLD) for ≥12 months and were newly exposed to antimuscarinic medications to treat overactive bladder (darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, or trospium) in 2004 to 2012. Patients with a diagnosis of cancer other than nonmelanoma skin cancer were excluded, as were HIV+ patients because their health service utilization might not be fully captured.…”

“…6,7 Moreover, the impact of misclassification of myocardial infarction and stroke on effect measures when using primary care data that cannot be linked to hospital or mortality data has not yet been evaluated. The validation component of a larger drug safety study 8 provided an opportunity to evaluate the validity of algorithms for identifying CV risk factors from primary care data and to examine the effect of various outcome-identification strategies reliant on those algorithms when estimating the incidence of CV outcomes. This article has two parts.…”

Risk of Mortality Associated with Non-selective Antimuscarinic medications in Older Adults with Dementia: a Retrospective Study

“…Medications with strong anticholinergic properties such as antimuscarinics have been associated with cognitive and other adverse effects including risk of mortality in diverse samples of older adults [14][15][16][17][18][19][20][21][22][23][24][25] . Two recent studies have evaluated the risk of cardiovascular events and overall mortality with antimuscarinics and provided conflicting findings 26,27 . Arana et al found increased risk of cardiovascular events and mortality among adults using oxybutynin compared to tolterodine 26 .…”

“…Two recent studies have evaluated the risk of cardiovascular events and overall mortality with antimuscarinics and provided conflicting findings 26,27 . Arana et al found increased risk of cardiovascular events and mortality among adults using oxybutynin compared to tolterodine 26 . However, Margulis et al found no differential risk of cardiovascular events and overall mortality among adults using antimuscarinic agents for OAB 27 .…”