A strategy utilizing ambulatory monitoring and home and clinic blood pressure measurements to optimize the safety evaluation of noncardiovascular drugs with potential for hemodynamic effects: a report from the SYNERGY trial.

Abstract:

OBJECTIVE:The aim of this study was to perform a blood pressure (BP) safety evaluation in patients with an overactive bladder receiving solifenacin (an antimuscarinic agent), mirabegron (a β3-adrenoceptor agonist), or both compared with placebo in the SYNERGY trial. PATIENTS AND METHODS:Patients were randomized to receive solifenacin 5 mg+mirabegron 50 mg (combination 5+50 mg); solifenacin 5 mg+mirabegron 25 mg (combination 5+25 mg); solifenacin 5 mg; mirabegron 50 mg; mirabegron 25 mg; or placebo for a double-blind 12-week treatment period. Systolic BP, diastolic BP, and heart rate were measured by ambulatory BP monitoring, and in the clinic or home. RESULTS:A total of 715 patients were analyzed in an ambulatory BP monitoring substudy. At the end of treatment, ambulatory BP monitoring measurements showed no consistent increases from baseline in the mean 24-h systolic BP or diastolic BP for combination versus monotherapy groups or for monotherapy groups versus placebo. Analysis of 1-h BP averages during the 6 h range that included the Tmax values of both study drugs showed no significant BP effects. Shift analysis (switch between different normotension/hypertension stages) did not show differences among the active and placebo groups, nor did outlier analysis of major BP changes differ between placebo and active treatment. Similarly, there were no significant signals in the 24-h heart rate. Office and home measurements were consistent with ambulatory BP monitoring findings. CONCLUSIONS:A paradigm of ambulatory BP monitoring analysis designed to test BP safety of noncardiovascular drugs showed that solifenacin plus mirabegron combination therapy during 12 weeks produced no meaningful changes in BP or heart rate.

journal_name

Blood Press Monit

authors

Weber MA,Chapple CR,Gratzke C,Herschorn S,Robinson D,Frankel JM,Ridder AM,Stoelzel M,Paireddy A,van Maanen R,White WB

doi

10.1097/MBP.0000000000000320

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

153-163

issue

3

eissn

1359-5237

issn

1473-5725

journal_volume

23

pub_type

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