Safety of tiotropium/olodaterol in chronic obstructive pulmonary disease: pooled analysis of three large, 52-week, randomized clinical trials.

Abstract Background An extensive clinical trial program supports the efficacy and safety of tiotropium/olodaterol in chronic obstructive pulmonary disease (COPD). We examined the safety of tiotropium/olodaterol compared with tiotropium in a large population of patients, focusing on cardiovascular and respiratory events. Methods Patients (n = 9942) who received once-daily tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (via Respimat®) in TONADO 1 & 2 and DYNAGITO were included. The number of patients and exposure-adjusted rate of events are presented for adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and cardiovascular and respiratory events. Findings Fewer patient…

Effect of tiotropium/olodaterol combination therapy on long-term heart rate and blood pressure in COPD patients

Introduction: Cardiovascular (CV) comorbidities are common in COPD, and associated with poor prognosis. LABAs and LAMAs are established COPD treatments whose pharmacology would suggest the potential to increase heart rate (HR) and impact blood pressure (BP). However, previous studies indicate that HR and BP are not negatively influenced by tiotropium (Tio) or olodaterol (Olo) monotherapy. Aims: To determine the effect of dual bronchodilation with Tio/Olo (T/O) on HR and BP. Methods: The 52-week, Phase III TONADO® studies (NCT01431274/NCT01431287) evaluated T/O 5/5 µg, Tio 5 µg or Olo 5 µg, via the Respimat® inhaler, in GOLD 2–4 COPD patients. In this post hoc analysis, long-term changes fro…

Efficacy of Once-Daily Tiotropium Respimat ® on Lung Function and Asthma Control in Adults with Asthma at GINA Steps 2–5

The effect of tiotropium/olodaterol versus tiotropium on COPD exacerbation rates in patients with/without frequent exacerbation history

Background: Patients with COPD with a history of frequent exacerbations are at increased risk of future exacerbations. There are limited data as to whether combining LAMA/LABA reduces exacerbation risk in all patients. We investigated whether tiotropium/olodaterol (T/O) reduced exacerbation rate versus tiotropium (tio) in patients with a range of exacerbation histories. Methods: TONADO 1+2 (NCT01431274/NCT01431287) and DYNAGITO (NCT02296138) were 52-week, parallel-group, randomised, double-blind, Phase III trials in COPD patients with FEV1 Results: There was a lower rate of moderate/severe exacerbations with T/O (0.68 per patient-year) than tio (0.77 per patient-year) (rate ratio [RR] vs ti…

The effect of tiotropium/olodaterol versus fluticasone propionate/salmeterol on left ventricular filling and lung hyperinflation in patients with COPD

This exploratory, randomised, double-blind, double-dummy, multicentre, cross-over study explored the effect of 6 weeks of treatment with tiotropium/olodaterol (T/O) versus fluticasone propionate/salmeterol (F/S) on left ventricular filling in patients with chronic obstructive pulmonary disease with functional residual capacity (FRC) >120% predicted and postbronchodilator improvement of FRC ≥7.5%. Overall, 76 patients were randomised across nine sites. Treatment with T/O or F/S increased left ventricular end-diastolic volume index from baseline (adjusted mean change: T/O: 2.317 mL/m2, F/S: 2.855 mL/m2), with no statistically significant difference between treatments. However, T/O resulted…

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,1,2 Lorcan McGarvey,3 Ulrich Bothner,4 Matthias Trampisch,4 Alberto de la Hoz,4 Matjaz Fležar,5 Roland Buhl,6 Peter Alter7 1Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; 2LungClinic Immenhausen, Immenhausen, Germany, Member of the German Center for Lung Research (DZL); 3Queen’s University Belfast, Belfast, UK; 4Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 5Klinika Golnik, Golnik, Slovenia; 6Pulmonary Department, Johannes Gutenberg University Mainz, Mainz, Germany; 7Department of Medicine, Pulmonary and Critical Care Medicine, Philipps University of Marburg (UMR); Member o…

Efficacy of once-daily tiotropium Respimat in adults with asthma at GINA Steps 2-5.

Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4–5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2–5, a post hoc analysis of five double-blind trials (12–48-weeks; patients aged 18–75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.5 μg, versus placebo, on peak forced expiratory volume in 1 s (FEV1) within 3 h post-dose (FEV1(0–3h)) response, and Asthma Control Questionnaire-7 (ACQ-7) responder rate. GINA step grouping was based on patients’ background treatment regi…