4.5 Article

Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease (COPD) Occurrence Frequency and the Effect of Treatment With the Inhaled Long-Acting Beta2-Agonists Arformoterol and Salmeterol

Journal

MEDICINE
Volume 87, Issue 6, Pages 319-328

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MD.0b013e31818fcc02

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Funding

  1. Sepracor Inc.. Marlborough, MA

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Beta-adrenergic stimulation may increase heart rate and the potential for cardiac arrhythmias. The effect of inhaled long-acting beta2-agonists (LABAs) on these outcomes was evaluated ill patients with chronic obstructive pulmonary disease (COPD) in 2 double-blind randomized clinical trials. The pretreatment arrhythmia Occurrence frequency in these patients was also described. In this analysis, 24-hour Holter monitoring data were pooled from 2 identically designed Phase III trials. patients were randomized to LABA treatment or placebo for 12 weeks: a) nebulized arformoterol 15 mu g BID, b) 25 mu g BID, or c) 50 mu g QD; d) salmeterol metered dose inhaler 42 mu g BID- or e) placebo. The 24-hour Holler monitoring was performed pretreatment and at Weeks 0 (first day of dosing), 6, and 12. We assessed the proportion of patients with each of 4 arrhythmias: atrial tachycardia. atrial fibrillation/flutter. and nonsustained (4-10 beats) and sustained (>10 beats) ventricular tachycardia. There were 5226 Holler recordings in 1429 treated patients. At baseline, there was low frequency of occurrence of atrial fibrillation,flutter (0.1%). nonsustained ventricular tachycardia (3.1%). and >10 beat ventricular tachycardia (0.3%). Atrial tachycardia occurred frequently (41.8%). The proportion of patients with treatment-emergent atrial tachycardia ranged front 27%, to 32 was non-significantly higher. by similar to 2%-5% (p = 0.70) in the LABA g groups compared with the placebo group. The rates of the other more serious arrhythmias did riot increase with LABA treatment and were similar to placebo. All treatment groups (LABA and placebo) had consistent small decreases from baseline in mean 24-hour and maximum hourly heart rate. In conclusion. in this large cohort of COPD patients with no or stable cardiac comorbidities. a high proportion (similar to 40%) of patients Were observed to have atrial tachycardia before treatment. which increased by 2%-5% with LABA treatment. More serious arrhythmias were Infrequent and did not increase with inhaled LABA therapy. LABA administration did not increase mean heart rate.

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