title: Cardiovascular safety of QVA149, a combination of Indacaterol and NVA237, in COPD patients.
abstract: This study assessed the cardiovascular safety of QVA149, an inhaled, once daily, bronchodilator combination containing two 24-hour bronchodilators, the long-acting β(2)-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237). In this randomised, double-blind, placebo-controlled, parallel-group study, 257 patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) were randomised to receive QVA149 (indacaterol/NVA237) 600/100 microg, 300/100 microg or 150/100 microg, indacaterol 300 μg or placebo, once daily for 14 days. The primary endpoint was change from baseline in 24-h mean heart rate versus placebo on Day 14. 255 patients were included in the safety analysis (mean age 63.8 years, 76.5% male, post-bronchodilator forced expiratory volume in one second [FEV(1)] 53.2% predicted, FEV(1)/FVC [forced vital capacity] 50.0%, mean 24-h heart rate 79.6 bpm). There were no clinically significant differences in the 24-h mean heart rate on Day 14 between the three doses of QVA149 and placebo or indacaterol. The confidence intervals of these treatment differences (contrasts) were within the pre-specified equivalence limit (-5 to 5 bpm). No clinically relevant differences in QTc interval (Fridericia's) were observed between groups on Days 1, 7 and 14. Once-daily QVA149 was well tolerated in COPD patients with a cardiovascular safety profile and overall adverse event rates similar to placebo.
authors.affiliation: AZ Sint Jan Brugge-Oostende AV, Campus H. Serruys, Oostende, Belgium. bvba.vandemaele@skynet.be
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Van de Maele
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Fabbri
authors.forename: Carmen
authors.initials: C
authors.lastname: Martin
authors.forename: Rachael
authors.initials: R
authors.lastname: Horton
authors.forename: Michael
authors.initials: M
authors.lastname: Dolker
authors.forename: Tim
authors.initials: T
authors.lastname: Overend
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001281:Atrial Fibrillation / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D015716:Electrocardiography, Ambulatory; D005260:Female; D006024:Glycopyrrolate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects*; D017180:Tachycardia, Ventricular / Q000139:chemically induced
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D007189:Indans; D015363:Quinolones; C554862:indacaterol-glycopyrronium combination; D006024:Glycopyrrolate