β-Blockers in COPD

Background Cardiovascular disease is a frequent comorbidity in patients with COPD. Many physicians, particularly pulmonologists, are reluctant to use β-adrenoceptor blocking agents (β-blockers) in patients with COPD, despite their proven effectiveness in preventing cardiovascular events. Methods The large (5,162 patients) phase III TONADO 1 and 2 studies assessed lung function and patient-reported outcomes in patients with moderate to very severe COPD receiving long-acting bronchodilator treatment across 1 year. This post hoc analysis characterized lung-function changes, patient-reported outcomes, and safety in the subgroup of patients receiving β-blockers in the studies. Results In total, …

Effect of long-acting β2-agonists olodaterol and formoterol on heart rate and blood pressure in chronic obstructive pulmonary disease patients

Abstract Background Cardiovascular comorbidities are common in chronic obstructive pulmonary disease (COPD), and elevated heart rate reflects increased cardiovascular risk over time, which is associated with unfavourable neurohumoral activation. Long-acting β 2 -agonists (LABAs) are established treatments in COPD, but potentially increase heart rate. We report a post hoc pooled analysis of the effect of olodaterol (5 or 10 μg) or formoterol (12 μg) on heart rate and blood pressure (BP) in Global Initiative for Chronic Obstructive Lung Disease Stage 2–4 COPD patients. Methods Four randomised, double-blind, placebo-controlled, Phase III studies were analysed. Changes in heart rate and systoli…

Long-Term Safety of Tiotropium/Olodaterol Respimat in Patients with Moderate-to-Very Severe COPD and Renal Impairment in the TONADO Studies

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…

Lung function and long-term safety of tiotropium/olodaterol in East Asian patients with chronic obstructive pulmonary disease

Background and purpose While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials. Materials and methods In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tio…

Long-term safety of tiotropium/olodaterol Respimat<sup>®</sup> in patients with moderate-to-very severe COPD and renal impairment in the TONADO<sup>®</sup> studies

Introduction: The safety, lung function efficacy, and symptomatic benefits of combined tiotropium and olodaterol in patients with COPD were established in the 1-year TONADO (R) studies (NCT01431274; NCT01431287). As tiotropium is predominantly excreted by the kidneys, the long-term safety profile of tiotropium/olodaterol was investigated in patients with renal impairment in a prespecified safety analysis of the TONADO studies. Methods: These were 2 replicate, randomized, double-blind, parallel-group, 52-week Phase III studies that assessed tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat (R)) in patients with moderate-to-very severe COPD. In this analysis…

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…

Long-Term Safety of Tiotropium/Olodaterol Respimat in Elderly Patients with Moderate to Very Severe COPD in the TONADO Studies

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…

Long-term general and cardiovascular safety of tiotropium/olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease

Abstract Background Long-term safety, particularly cardiovascular safety, is of special interest in maintenance treatment of chronic obstructive pulmonary disease (COPD) with long-acting β 2 -agonists and long-acting muscarinic antagonists, given potential cardiovascular effects. Methods Two 52-week Phase III trials (TONADO ® ) investigated tiotropium/olodaterol (5/5 and 2.5/5 μg) versus tiotropium 2.5, 5 μg and olodaterol 5 μg. In a pre-specified safety analysis, investigator-reported treatment-emergent adverse events (AEs), electrocardiogram and laboratory data were pooled. All serious AE (SAE) reports were reviewed by an independent Adjudication Committee, which assessed whether deaths, …