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, …

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…

Efficacy of Tiotropium/Olodaterol Compared with Tiotropium in Patients Naïve to LAMA, LABA and ICS: Pooled Analysis of Four Clinical Trials

<p>Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO<sup>®</sup> and OTEMTO<sup>®</sup> studies: a subgroup analysis by age</p>

BACKGROUND Increasing age is associated with poor prognosis in patients with COPD. OBJECTIVE This analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years. METHODS In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 μg or 5/5 μg, tiotropium 5 μg or 2.5 μg (TONADO only), olodaterol 5 μg (TONADO only), or placebo (OTEMTO onl…

Benefits of tiotropium/olodaterol compared with tiotropium in patients receiving COPD LAMA at baseline: pooled analysis of 4 clinical trials

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…

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, …

Tiotropium+olodaterol chez les patients atteints de BPCO modérée à sévère avec la bronchite chronique et/ou l’emphysème

Introduction La bronchite chronique et l’emphyseme sont deux phenotypes de la BPCO qui peuvent influer sur les decisions de traitement pharmacologiques. Objectifs Tiotropium (T) + olodaterol (O) a ete etabli en tant que traitement de la BPCO dans deux grands essais de phase III. Cette analyse post hoc a evalue l’effet de T + O sur la fonction pulmonaire, les symptomes et la qualite de vie (QdV) chez les patients (pts) selon la definition de la bronchite et/ou l’emphyseme portee par l’investigateur ( Fig. 1 ). Methodes Tonado® 1 + 2 etait dupliquee en 2 etudes jumelles, en double aveugle, controles vs traitement actif, les patients Gold 2–4 etaient randomises en 5 groupes paralleles (ratio 1…

P123 Inhaled corticosteroid plus long-acting β2-agonist therapy is overused in the treatment of patients with chronic obstructive pulmonary disease: post hoc analyses of two 1-year studies: Abstract P123 Table 1

Rationale Inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) therapy is indicated for different patient groups with chronic obstructive pulmonary disease (COPD) in the USA and Europe. In the previous version of the Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations, the use of ICS plus LABA therapy was restricted to patients with severe and very severe lung-function impairment and frequent exacerbations, with overtreatment in milder patient populations well documented. The current GOLD document recommends the use of ICS plus LABA maintenance therapy for patients in categories C and D. Methods We present post hoc analyses from the two pivotal 1-year TO…

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…

Tiotropium + olodaterol in patients with moderate to severe COPD with chronic bronchitis and/or emphysema

Introduction: Chronic bronchitis and emphysema are two COPD phenotypes that can affect pharmacologic treatment decisions. Aims: Tiotropium (T) + olodaterol (O) was established for COPD treatment in two large Phase III trials. This post hoc analysis assessed the effect of T+O on lung function, symptoms and health-related quality of life (QoL) in patients (pts) with investigator-defined bronchitis and/or emphysema. Methods: TONADO ® 1+2 were replicate, randomised, double-blind, parallel-group trials. Pts with GOLD 2–4 COPD were randomised to once-daily T+O 2.5/5 or 5/5 µg, T 2.5 or 5 µg, or O 5 µg via Respimat ® inhaler. 1 End points included forced expiratory volume in 1 second (FEV 1 ) area…