Antimuscarinics and Heart Rate: Results from a Randomized, Double-Blind, Placebo-Controlled, 3 Way Crossover Study in Subjects Over Age 50

Introduction and Objectives

OAB is common in older pts, as are comorbidities that can impact a pt’s risk for experiencing AEs.

Risk of AEs could also impact physician’s OAB treatment decisions. Most antimuscarinic agents used in OAB treatment are nonselective and may have adverse cardiovascular (CV) and central nervous system (CNS) effects. Our study objective was to identify the proportion of OAB pts potentially at risk for AEs by assessing important comorbidities (focus on CV and CNS) and concomitant drug use (focus on drugs with known CNS effects). We also sought to assess the impact on OAB treatment decisions, by evaluating the presence of comorbidities and concomitant drug use among treated and untreated OAB pts.

Materials

Adult pts (age ≥18) from the HealthCore Integrated Research (HIRD) database with a diagnosis of OAB (ICD9 codes: 596.51, 596.55, 596.59, 788.31) or a pharmacy claim between 1/1/2000 to 12/31/2006 for an OAB antimuscarinic agent (tolterodine, oxybutynin, trospium, solifenacin, or darifenacin), and with 12mths of continuous health plan eligibility, formed the OAB cohort. Based on the presence of at least 1 pharmacy claim for an OAB antimuscarinic agent, the OAB cohort was stratified as treated and untreated. A random sample of pts with neither a diagnosis of OAB, nor any urinary bladder dysfunction (ICD9 codes: 596.5x, 788.3x, 344.61, 625.6x), nor a pharmacy claim for an OAB antimuscarinic agent formed a comprehensive non-OAB control cohort. During the 12mths prior to OAB diagnosis/treatment, CV and CNS comorbidities and use of medications with known CNS effects (identified using a modified version of the revised Beers Criteria; excluding OAB antimuscarinic agents) were assessed across the treated OAB, untreated OAB, and non-OAB cohorts using t-tests for continuous variables and chi-square tests for categorical variables.

Results

All OAB pts (N: 6,632; 83% women; median age 51y), when compared to non-OAB pts (N: 67,478; 83% women; median age 48y), were more likely to have CV (39% vs 18%; p<0.0001) and CNS disorders (39% vs 16%; p<0.0001), as well as prior exposure to medications with CNS effects (47% vs 25%; p<0.0001). In treated vs untreated OAB pts (1:1 matched), CV comorbidities (40% vs 38%; p=0.3259) and CNS comorbidities (39% vs 38%; p=0.4194) did not differ. However, more treated pts had prior exposure to medications with CNS effects than the untreated pts (51% vs 43%; p<0.0001).

Conclusions

A large proportion of OAB pts have pre-existing CV/CNS comorbidities and prior exposure to medications with CNS effects, and significantly different from control pts without OAB. Lack of evidence that treated pts have fewer pre-existing CV/CNS comorbidities, and less prior exposure to medications with CNS effects relative to untreated pts suggests that physicians do not take these factors into consideration prior to prescribing OAB antimuscarinic agents.

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