Introduction: Long-acting beta2-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((R)) study. Methods: The TONADO((R)) 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 mug and 2.5/5 mug) with tiotropium (5 mug and 2.5 mug) and olodaterol (5 mug) 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 microg 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.
- Andreas, S.
- McGarvey, L.
- Bothner, U.
- Trampisch, M.
- de la Hoz, A.
- Flezar, M.
- Buhl, R.
- Alter, P.
Keywords
- *blood pressure
- *chronic obstructive pulmonary disease
- *heart rate
- *olodaterol
- *tiotropium
- 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.
