Submitted on April 1, 2008
Accepted on September 5, 2008
The Safety of Long Acting Beta Agonists Among Patients with Asthma Using Inhaled Corticosteroids
Roman Jaeschke1*, Paul M O'Byrne2, Filip Mejza3, Parameswaran Nair2, Wiktoria Lesniak3, Jan Brozek4, Lehana Thabane5, Ji Cheng6, Holger J Schunemann7, Malcom R Sears2, and Gordon Guyatt8
1 Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Polish Institute of EBM, Krakow, Poland,
2 Department of Medicine, McMaster University, Hamilton, Ontario, Canada,
3 Polish Institute of EBM, Krakow, Poland; II Katedra Chorob Wewnetrznych, Jagiellonian University School of Medicine, Krakow, Poland,
4 Polish Institute of EBM, Krakow, Poland; II Katedra Chorob Wewnetrznych, Jagiellonian University School of Medicine, Krakow, Poland; Italian National Cancer Institute, Rome, Italy,
5 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; Biostatistics Unit, Father Sean O'Sullivan Research Centre, St Joseph's Healthcare, Hamilton, Ontario, Canada,
6 Biostatistics Unit, Father Sean O'Sullivan Research Centre, St Joseph's Healthcare, Hamilton, Ontario, Canada,
7 Italian National Cancer Institute, Rome, Italy; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; CLARITY Research Group in the Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada,
8 Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; CLARITY Research Group in the Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
* To whom correspondence should be addressed. E-mail: Jaeschke{at}mcmaster.ca.
Background: Inhaled long acting beta agonists (LABAs) when usedas monotherapy in asthma may increase asthma-related hospitalizations,life threatening events requiring intubation/mechanical ventilationand asthma-related deaths, but concomitant use of inhaled corticosteroids(ICS) may modify this effect.
Methods: We conducted a systematicreview and meta-analysis of parallel group, blinded, randomizedcontrolled trials with at least 12 weeks of treatment addressingthe impact of LABA on asthma-related and total morbidity andmortality in patients concomitantly using ICS. We searched MEDLINE,EMBASE, ACPJC, and Cochrane (Central) databases and contactedauthors and sponsors. We used random effects model to pool resultsfrom different studies as odds ratio [OR] (95% confidence interval)(OR < 1.0 favors LABA).
Findings: The search yielded 62relevant studies included in this analysis. Among over 29,000participants (15,710 taking LABA with over 8,000 patient-yearsobservation in LABA groups) there were 3 asthma-related deathsand 2 asthma-related non-fatal intubations (all in LABA groups,no more than one event per study). Differences in asthma-relatedhospitalizations (OR 0.74, 95% CI 0.53 - 1.03) and asthma-relatedserious adverse events (mostly hospitalizations, OR 0.75, 95%CI 0.54 - 1.03) failed to reach statistical significance. TheOR for total mortality was 1.26, 95% CI 0.58 - 2.74 reflecting14 deaths in LABA groups and 8 deaths in control groups respectively.
Interpretation:In patients with asthma using inhaled corticosteroids LABA didnot increase the risk of asthma-related hospitalizations. Therewere very few asthma-related deaths and intubations, and eventswere too infrequent to establish LABA's relative effect on theseoutcomes.
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