Absence of Adverse Effects of Tiotropium/Olodaterol Compared with the Monocomponents on Long-Term Heart Rate and Blood Pressure in Patients with Moderate-to-Very-Severe COPD

• Published in: International journal of chronic obstructive pulmonary disease Vol. 15; pp. 1935 - 1944
• Main Authors: Andreas, Stefan, McGarvey, Lorcan, Bothner, Ulrich, Trampisch, Matthias, de la Hoz, Alberto, Fležar, Matjaz, Buhl, Roland, Alter, Peter
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2020; Dove Medical Press Ltd; Dove; Dove Medical Press
• Subjects: Benzoxazines - adverse effects; Blood Pressure; Bronchodilator Agents - adverse effects; Cardiac arrhythmia; Cardiac patients; Cardiovascular disease; Care and treatment; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Clinical trials; Comorbidity; Comparative analysis; Complications and side effects; Confidence intervals; Double-Blind Method; Electrocardiography; Forced Expiratory Volume; Heart Rate; Humans; Mortality; Olodaterol; Original Research; Patients; Pharmaceutical industry; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Tiotropium; Tiotropium Bromide - adverse effects; Treatment Outcome; United Kingdom; Switzerland; Germany; blood pressure; heart rate; chronic obstructive pulmonary disease; olodaterol; tiotropium
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S246348

Long-acting β -agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are established maintenance bronchodilator treatments for chronic obstructive pulmonary disease (COPD) with the potential to increase heart rate (HR) and impact blood pressure (BP). While previous studies indicate that HR and BP are not negatively influenced by tiotropium or olodaterol monotherapy, the effect of tiotropium/olodaterol has not been evaluated. We report a post hoc analysis of the effect of dual bronchodilation with tiotropium/olodaterol versus monocomponents on HR and BP in patients with moderate-to-very-severe COPD included in the large TONADO study. The TONADO trials (1237.5 [NCT01431274] and 1237.6 [NCT01431287]) were two replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials that compared tiotropium/olodaterol (5/5 μg and 2.5/5 μg) with tiotropium (5 μg and 2.5 μg) and olodaterol (5 μg) in patients with moderate-to-very-severe COPD. Patients with cardiovascular comorbidities were included. Changes in HR and systolic/diastolic BP were measured before and after dosing with the study medication at each visit (baseline, Week 12, Week 24 and Week 52). Overall, 3,100 patients were included in this analysis. Over 52 weeks, small changes from baseline in mean HR (<2 beats per minute [bpm]) and small changes from pre- to post-dose (<1 bpm) were evident at different time points. There was a non-significant increase from baseline in mean diastolic and systolic BP (<2 mmHg) observed over 52 weeks of treatment. The short-term (1 hour pre- to 1 hour post-dose) mean changes in systolic and diastolic BP over 52 weeks in the tiotropium/olodaterol 5/5 µg group were comparable with those observed for the monocomponents at all time points. There were no differences in HR or BP among patients on tiotropium/olodaterol when compared with monocomponents. This supports the already demonstrated cardiovascular safety profile of tiotropium/olodaterol as long-acting maintenance bronchodilator treatment for COPD, including patients with cardiovascular comorbidities.