PMID- 30261995
OWN - NLM
STAT- MEDLINE
DCOM- 20191002
LR  - 20191002
IS  - 1532-3064 (Electronic)
IS  - 0954-6111 (Linking)
VI  - 143
DP  - 2018 Oct
TI  - Safety of tiotropium/olodaterol in chronic obstructive pulmonary disease: pooled 
      analysis of three large, 52-week, randomized clinical trials.
PG  - 67-73
LID - S0954-6111(18)30278-6 [pii]
LID - 10.1016/j.rmed.2018.08.012 [doi]
AB  - 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 mug 
      or tiotropium 5 mug (via Respimat((R))) 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 patients discontinued due 
      to AEs with tiotropium/olodaterol (5.9%) versus tiotropium (7.9%; rate ratio [RR] 
      0.72; 95% confidence interval [CI] 0.62-0.84). There was no significant 
      difference in the incidence of AEs, SAEs, cardiovascular AEs or central nervous 
      system vascular AEs between treatments. Incidences of major adverse 
      cardiovascular events (MACE) were 2.11 per 100 patient-years with 
      tiotropium/olodaterol and 2.22 with tiotropium (RR 0.95; 95% CI 0.72-1.25), and 
      incidences of fatal MACE (including death with undetermined cause) were 0.91 and 
      1.00 per 100 patient-years with tiotropium/olodaterol and tiotropium, 
      respectively (RR 0.91; 95% CI 0.60-1.37). Respiratory AEs were generally balanced 
      between treatment groups. CONCLUSIONS: These results provide robust evidence that 
      the benefits of tiotropium/olodaterol versus tiotropium are not at the expense of 
      an increased risk of safety events. The combination is a suitable option for 
      patients with COPD, even in the presence of cardiovascular risk factors. CLINICAL 
      TRIALS REGISTRATION: clinicaltrials. gov (TONADO 1 and 2: NCT01431274, 
      NCT01431287; DYNAGITO: NCT02296138).
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Ferguson, Gary T
AU  - Ferguson GT
AD  - Pulmonary Research Institute of Southeast Michigan, Suite A, 29255 W 10 Mile 
      Road, Farmington Hills, MI, 48336, USA. Electronic address: 
      garytferguson@msn.com.
FAU - Buhl, Roland
AU  - Buhl R
AD  - Johannes Gutenberg University Hospital Mainz, Langenbeckstrasse 1, 55131, Mainz, 
      Germany. Electronic address: Roland.Buhl@unimedizin-mainz.de.
FAU - Bothner, Ulrich
AU  - Bothner U
AD  - TA/Respiratory Biosimilars Medicine, Boehringer Ingelheim International GmbH, 
      Binger Strasse 173, 55216, Ingelheim am Rhein, Germany. Electronic address: 
      ulrich.bothner@boehringer-ingelheim.com.
FAU - Hoz, Alberto de la
AU  - Hoz A
AD  - TA/Respiratory Biosimilars Medicine, Boehringer Ingelheim International GmbH, 
      Binger Strasse 173, 55216, Ingelheim am Rhein, Germany. Electronic address: 
      alberto.de_la_hoz@boehringer-ingelheim.com.
FAU - Voss, Florian
AU  - Voss F
AD  - Biostatistics & Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger 
      Strasse 173, 55216, Ingelheim am Rhein, Germany. Electronic address: 
      florian.voss@boehringer-ingelheim.com.
FAU - Anzueto, Antonio
AU  - Anzueto A
AD  - Department of Pulmonary Medicine and Critical Care, University of Texas Health 
      Sciences Center and South Texas Veterans Health Care System, 4242 Medical Drive, 
      Suite 111E, San Antonio, TX, 78229, USA. Electronic address: anzueto@uthscsa.edu.
FAU - Calverley, Peter M A
AU  - Calverley PMA
AD  - Clinical Science Centre, Institute of Ageing and Chronic Disease, University of 
      Liverpool, 6 West Derby Street, Liverpool, L7 8TX, UK. Electronic address: 
      pmacal@liverpool.ac.uk.
LA  - eng
SI  - ClinicalTrials.gov/NCT01431274
SI  - ClinicalTrials.gov/NCT01431287
SI  - ClinicalTrials.gov/NCT02296138
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180828
PL  - England
TA  - Respir Med
JT  - Respiratory medicine
JID - 8908438
RN  - 0 (Benzoxazines)
RN  - 0 (Drug Combinations)
RN  - 0 (tiotropium-olodaterol)
RN  - XX112XZP0J (Tiotropium Bromide)
SB  - IM
MH  - Benzoxazines/*administration & dosage/*adverse effects
MH  - Cardiovascular Diseases/chemically induced/epidemiology
MH  - Central Nervous System Diseases/chemically induced/epidemiology
MH  - Drug Combinations
MH  - Female
MH  - Humans
MH  - Incidence
MH  - Male
MH  - Pulmonary Disease, Chronic Obstructive/*drug therapy
MH  - *Randomized Controlled Trials as Topic
MH  - Risk
MH  - Risk Factors
MH  - Safety
MH  - Time Factors
MH  - Tiotropium Bromide/*administration & dosage/*adverse effects
OTO - NOTNLM
OT  - COPD
OT  - Cardiovascular
OT  - Long-acting muscarinic antagonist
OT  - Long-acting beta(2)-agonist
OT  - Safety
EDAT- 2018/09/29 06:00
MHDA- 2019/10/03 06:00
CRDT- 2018/09/29 06:00
PHST- 2018/07/06 00:00 [received]
PHST- 2018/08/27 00:00 [accepted]
PHST- 2018/09/29 06:00 [entrez]
PHST- 2018/09/29 06:00 [pubmed]
PHST- 2019/10/03 06:00 [medline]
AID - S0954-6111(18)30278-6 [pii]
AID - 10.1016/j.rmed.2018.08.012 [doi]
PST - ppublish
SO  - Respir Med. 2018 Oct;143:67-73. doi: 10.1016/j.rmed.2018.08.012. Epub 2018 Aug 
      28.