The safety of long-acting beta-agonists among patients with asthma using inhaled corticosteroids: systematic review and metaanalysis.
BACKGROUND
Inhaled long-acting beta-agonists (LABAs), when used as monotherapy in asthma, may increase asthma-related hospitalizations, life threatening events requiring intubation/mechanical ventilation, and asthma-related deaths, but concomitant use of inhaled corticosteroids (ICS) may modify this effect.


OBJECTIVE
To determine the safety of long-acting beta-agonists among patients with asthma using corticosteroids.


METHODS
We conducted a systematic review and metaanalysis of parallel-group, blinded, randomized, controlled trials with at least 12 weeks of treatment addressing the impact of LABA on asthma-related and total morbidity and mortality in patients concomitantly using ICS. We searched MEDLINE, EMBASE, ACPJC, and Cochrane (Central) databases, and contacted authors and sponsors.


RESULTS
We used a random effects model to pool results from different studies as odds ratios (ORs) (95% confidence interval [CI]) (OR < 1.0 favors LABA). The search yielded 62 relevant studies included in this analysis. Among over 29,000 participants (15,710 taking LABA, with over 8,000 patient-years observed in the LABA groups), there were three asthma-related deaths and two asthma-related, nonfatal intubations (all in LABA groups; <or= one event per study). Differences in asthma-related hospitalizations (OR, 0.74; 95% CI, 0.53-1.03) and asthma-related serious adverse events (mostly hospitalizations; OR, 0.75; 95% CI, 0.54-1.03) failed to reach statistical significance. The OR for total mortality was 1.26 (95% CI, 0.58-2.74), reflecting 14 deaths in LABA groups and eight deaths in control groups, respectively.


CONCLUSIONS
In patients with asthma using ICS, LABA did not increase the risk of asthma-related hospitalizations. There were very few asthma-related deaths and intubations, and events were too infrequent to establish LABA's relative effect on these outcomes.
Jaeschke
Roman
R
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. jaeschke@mcmaster.ca
O'Byrne
Paul M
PM
Mejza
Filip
F
Nair
Parameswaran
P
Lesniak
Wiktoria
W
Brozek
Jan
J
Thabane
Lehana
L
Cheng
Ji
J
Schünemann
Holger J
HJ
Sears
Malcolm R
MR
Guyatt
Gordon
G
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D000305:Adrenal Cortex Hormones; D000319:Adrenergic beta-Antagonists