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

Stefan Andreas, Lorcan McGarvey, Ulrich Bothner, Matthias Trampisch, Alberto de la Hoz, Matjaz Fležar, Roland Buhl, Peter Alter, Stefan Andreas, Lorcan McGarvey, Ulrich Bothner, Matthias Trampisch, Alberto de la Hoz, Matjaz Fležar, Roland Buhl, Peter Alter

Abstract

Introduction: Long-acting β2-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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: blood pressure; chronic obstructive pulmonary disease; heart rate; olodaterol; tiotropium.

Conflict of interest statement

SA reports personal fees from Boehringer Ingelheim and GlaxoSmithKline, and payments for presenting from Boehringer Ingelheim, AstraZeneca, Berlin Chemie, Chiesi and Novartis, outside the submitted work. LM reports personal fees and non-financial support from Boehringer Ingelheim and personal fees from Applied Clinical Intelligence, during the conduct of the study; personal fees from Merck, Afferent, AstraZeneca, Bellus Health and European Union Interreg VA Health & Life Science Programme, grants, personal fees and non-financial support from Bionorica, grants and non-financial support from Chiesi, and personal fees and non-financial support from GlaxoSmithKline, outside the submitted work. UB, MT and AdlH are employees of Boehringer Ingelheim. RB reports grants to Mainz University and personal fees from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche, as well as personal fees from AstraZeneca, Chiesi, Cipla, Sanofi and Teva, outside the submitted work. PA reports grants from the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), AstraZeneca, GlaxoSmithKline, Grifols Deutschland, MSD Sharp & Dohme, Pfizer, Takeda, Boehringer Ingelheim and Novartis Deutschland, grants and non-financial support from Bayer Schering Pharma AG and Chiesi, grants, personal fees and non-financial support from Novartis Deutschland, and grants and personal fees from Novartis Deutschland, outside the submitted work. The authors report no other conflicts of interest in this work.

© 2020 Andreas et al.

Figures

Figure 1
Figure 1
Long-term mean change in HR from baseline over 52 weeks. *PAbbreviations: bpm, beats per minute; HR, heart rate; Olo, olodaterol; T/O, tiotropium/olodaterol; Tio, tiotropium.
Figure 2
Figure 2
Short-term (30 minutes pre- to 40 minutes post-dose) mean change in HR during dosing over 52 weeks. **PAbbreviations: bpm, beats per minute; HR, heart rate; Olo, olodaterol; T/O, tiotropium/olodaterol; Tio, tiotropium.
Figure 3
Figure 3
Long-term mean change in (A) systolic and (B) diastolic BP from baseline over 52 weeks. *P<0.05; **P<0.01. Error bars representing 95% confidence interval. Abbreviations: BP, blood pressure; Olo, olodaterol; T/O, tiotropium/olodaterol; Tio, tiotropium.
Figure 4
Figure 4
Short-term (1 hour pre- to 1 hour post-dose) mean change in (A) systolic and (B) diastolic BP during dosing over 52 weeks. *P<0.05. Error bars representing 95% confidence interval. Abbreviations: BP, blood pressure; Olo, olodaterol; T/O, tiotropium/olodaterol; Tio, tiotropium.

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