title: Cardio- and cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD.
abstract: OBJECTIVE
  As COPD patients commonly suffer cardio- and cerebrovascular (CCV) co-morbidities, our purpose was to establish the CCV safety profile of indacaterol, a novel, inhaled, long-acting β(2)-agonist for COPD.
  
  
  METHODS
  The indacaterol clinical trial database comprised 4635 patients with moderate-to-severe COPD enrolled into studies of ≥6 months' duration treated with indacaterol, placebo or other bronchodilators (formoterol, salmeterol, tiotropium). Adverse events (AEs) were analysed overall and according to Anti-Platelet Trialists' Collaboration (APTC) criteria and baseline cardiovascular risk factors. A subset of patients had Holter monitoring.
  
  
  RESULTS
  Compared with placebo, indacaterol did not increase the risk of CCV AEs; relative risks were not significantly different for indacaterol versus other treatments. In all treatment groups, including placebo, most CCV AEs occurred in patients with pre-existing cardiovascular risk factors. The risk of APTC events (e.g. myocardial infarction, stroke, cardiovascular-related death) was not significantly increased for indacaterol versus placebo. The incidence of notable QTc interval increases >60 ms was low with all active treatments (0-0.5%, versus 0.3% with placebo). Holter monitoring in the subset of patients receiving indacaterol, tiotropium or placebo showed no clinically relevant effect of indacaterol or tiotropium relative to placebo on the development of arrhythmias. The number of deaths adjusted for exposure was lower with all active treatments than with placebo, with a trend to reduced risk with indacaterol (relative risk 0.30, p = 0.054).
  
  
  CONCLUSIONS
  The overall CCV safety profile of indacaterol was similar to placebo and comparable with other long-acting bronchodilators, providing reassurance for regular long-term use of indacaterol in COPD. Data for this analysis were pooled from three studies, registered at ClinicalTrials.gov as: NCT00393458, NCT00463567 and NCT00567996.
authors.affiliation: Medical Department I, Klinikum Fürth, Jakob-Henle-Str. 1, D-90766 Fürth, Germany. med1@klinikum-fuerth.de
authors.forename: Heinrich
authors.initials: H
authors.lastname: Worth
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: James M
authors.initials: JM
authors.lastname: Felser
authors.forename: Huilin
authors.initials: H
authors.lastname: Hu
authors.forename: Peter
authors.initials: P
authors.lastname: Rueegg
mesh_terms: D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000401:mortality; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D000068759:Formoterol Fumarate; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects / Q000401:mortality / Q000503:physiopathology; D000069447:Tiotropium Bromide
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D007189:Indans; D010919:Placebos; D015363:Quinolones; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; C510790:indacaterol; D000420:Albuterol; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide