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, …

Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4).

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0–3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patien…

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…

Benefits of Tiotropium + Olodaterol Over Tiotropium at Delaying Clinically Significant Events in Patients with COPD Classified as GOLD B

Safety of tiotropium and olodaterol fixed-dose combination for COPD in patients on β-blockers

Introduction: The TONADO studies (NCT01431274; NCT01431287) established the efficacy and safety of a new once-daily fixed-dose combination (FDC) with tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, for the treatment of COPD. This post hoc analysis evaluates T+O safety in the subgroup of patients (pts) receiving β-blockers (BBs) in these studies. Methods: These were randomised, double-blind, parallel-group, 52-week, Phase III trials comparing T+O FDC (2.5/5 µg; 5/5 µg) with the monocomponents. Adverse events (AEs) and serious AEs (SAEs) were recorded and SAEs independently adjudicated. Pooled safety data from pts receiving BBs at baseline …

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…

P256 Safety Of Once-daily Tiotropium And Olodaterol Fixed-dose Combination Via The Respimat In Chronic Obstructive Pulmonary Disease In Two 1-year Studies

Introduction The fixed-dose combination (FDC) of tiotropium (T), a once-daily long-acting muscarinic antagonist, and olodaterol (O), a once-daily long-acting β 2 -agonist, is currently being evaluated in chronic obstructive pulmonary disease (COPD). Two 52-week, Phase III replicate pivotal studies were conducted to assess the efficacy and safety of FDCs of T and O (T+O) delivered via Respimat® Soft Mist™ inhaler in patients (pts) with GOLD Stage 2–4 COPD. Pooled safety data from the two studies are presented here. Methods These were double-blind, randomised, parallel-group studies with 5 arms: O 5 µg, T 2.5 µg, T 5 µg, T+O 2.5/5 µg, T+O 5/5 µg. Key inclusion criteria were: age ≥40 years, di…

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, …

Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial

Chronic non-specific respiratory symptoms are difficult to manage. This trial aimed to evaluate the association between baseline fractional exhaled nitric oxide (FeNO) and the response to inhaled corticosteroids in patients with non-specific respiratory symptoms.In this double-blind randomised placebo-controlled trial, we enrolled undiagnosed patients, aged 18-80 years, with cough, wheeze, or dyspnoea and less than 20% bronchodilator reversibility across 26 primary care centres and hospitals in the UK and Singapore. Patients were assessed for 2 weeks before being randomly assigned (1:1) to 4 weeks of treatment with extrafine inhaled corticosteroids (QVAR 80 μg, two puffs twice per day, equi…

P294 Benefits of tiotropium/olodaterol over tiotropium at delaying clinically significant events in patients with copd classified as gold B

Rationale The once-daily combination of tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, has demonstrated efficacy and safety in COPD. Two large clinical studies (TONADO ® 1 + 2) have also demonstrated the benefits of T/O compared to the monocomponents in patients with moderate to very severe COPD. This post hoc analysis investigated whether T/O is more effective than T at delaying clinically significant events in patients with GOLD stage B COPD. Methods A total of 5162 patients were randomised to O 5 µg, T 2.5 µg, T 5 µg, T/O 2.5/5 µg or T/O 5/5 µg (delivered via Respimat ® inhaler) in two 52-week, parallel-group, double-blind studies (NC…

P128 Pooled safety analysis of adjudicated serious adverse events with the combination of tiotropium + olodaterol: Abstract P128 Table 1

Rationale This analysis aimed to obtain a comprehensive and objective safety assessment of the combination of tiotropium (T), a long-acting muscarinic antagonist, with olodaterol (O), a long-acting β2-agonist, (T+O) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Methods Data from two, 52-week, pivotal Phase III trials investigating T+O 5/5 µg and T+O 2.5/5 µg versus T 2.5 µg, 5 µg and O 5 µg were pooled, and patient narratives and profiles of serious adverse-event (SAE) reports were reviewed by an independent Adjudication Committee. The committee members independently assessed all SAEs to determine if any deaths, hospitalisations or intubations were r…

Late Breaking Abstract - Predictive value of FeNO in patients with non-specific respiratory symptoms: a randomised controlled trial

Background: Fractional exhaled nitric oxide (FeNO) can predict treatment response in asthma, but little is known of its utility in patients with non-specific respiratory symptoms (NSRS). Aims and objectives: To evaluate the association between baseline FeNO and response to treatment with inhaled corticosteroids (ICS) in patients with NSRS. Methods: This was a multi-centre randomised, placebo-controlled trial, carried out in UK and Singapore. It consisted of a 2-week assessment period to establish baseline measurements and a 4-week treatment period with either extrafine ICS (200 µ beclomethasone bid) or placebo. NIOX VERO (Circassia) was used to measure baseline FeNO. The primary endpoint wa…