Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children

Abstract

Background Long-acting inhaled ß2-adrenergic agonists (LABAs) are recommended as ’add-on’ medication to inhaled corticosteroids (ICS) in the maintenance therapy of asthmatic adults and children aged two years and above. Objectives To quantify in asthmatic patients the safety and efficacy of the addition of LABAs to ICS in patients insufficiently controlled on ICS alone. Search methods We identified randomised controlled trials (RCTs) through electronic database searches (the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers until May 2008. Selection criteria We included RCTs if they compared the addition of inhaled LABAs versus placebo to the same dose of ICS in children aged two years and above and in adults. Data collection and analysis Two review authors independently assessed studies for methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the relative risk (RR) of asthma exacerbations requiring rescue oral corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), rescue beta2-agonist use, symptoms, withdrawals and adverse events. Main results Seventy-seven studies met the entry criteria and randomised 21,248 participants (4625 children and 16,623 adults). Participants were generally symptomatic at baseline with moderate airway obstruction despite their current ICS regimen. Formoterol or salmeterol were most frequently added to low-dose ICS (200 to 400 μg/day of beclomethasone (BDP) or equivalent) in 49% of the studies. The addition of a daily LABA to ICS reduced the risk of exacerbations requiring oral steroids by 23% from 15% to 11% (RR 0.77, 95% CI 0.68 to 0.87, 28 studies, 6808 participants). The number needed to treat with the addition of LABA to prevent one use of rescue oral corticosteroids is 41 (29, 72), although the event rates in the ICS groups varied between 0% and 38%. Studies recruiting adults dominated the analysis (6203 adult participants versus 605 children). The subgroup estimate for paediatric studies was not statistically significant (RR 0.89, 95% CI 0.58 to 1.39) and includes the possibility of the superiority of ICS alone in children. Higher than usual dose of LABA was associated with significantly less benefit. The difference in the relative risk of serious adverse events with LABA was not statistically significant from that of ICS alone (RR 1.06, 95% CI 0.87 to 1.30). The addition of LABA led to a significantly greater improvement in FEV1 (0.11 litres, 95% 0.09 to 0.13) and in the proportion of symptom-free days (11.88%, 95% CI 8.25 to 15.50) compared to ICS monotherapy. It was also associated with a reduction in the use of rescue short-acting ß2-agonists (−0.58 puffs/day, 95% CI −0.80 to −0.35), fewer withdrawals due to poor asthma control (RR 0.50, 95% CI 0.41 to 0.61), and fewer withdrawals due to any reason (RR 0.80, 95% CI 0.75 to 0.87). There was no statistically significant group difference ...

The pharmacokinetics, safety, and tolerability of single, high-strength doses of fluticasone propionate and fluticasone propionate/salmeterol delivered via a novel multidose dry powder inhaler in adolescents and adults with persistent asthma

“…Studies have demonstrated that adding the LABA salmeterol to moderate doses of ICS provides greater clinical benefit than increased doses of ICS monotherapy (4,6,7). The combination of Fp/salmeterol (FS) was approved for asthma maintenance therapy in 2000 (8).…”

Cardiovascular safety of new inhaled medications for asthma and chronic obstructive pulmonary disease: a critical review from pharmacist perspective

“…9,31,32 Consequently, LABA is only recommended for use in combination with corticosteroids, especially among asthma patients. 3,5,9,18,26,29,31,33 In addition, ongoing concerns about the safety and its use in children has prompted the FDA to require more safety studies from drug companies, including 5 double blinded (DB) randomised controlled trial (RCT) by 2017. 34,35 Within the last few years, studies examined the utilisation of inhaled corticosteroids (ICS)+LABAs (salmeterol and efomoterol) in adult asthma patients and observed no significant increase in cardiovascular AEs, including electrocardiogram (ECG) changes, vital signs, and laboratory variables.…”

“…The reported AEs were considered relatively minor in clinical consequences, and showed no difference between the two LABAs. 5,26,37 However, the use of SABAs was permitted in many studies, and it may mask the true effect of LABAs. [38][39][40][41] Some studies also suggested that ICSs can contribute to dose-dependent reduction of cardiotoxicity from LABAs.…”

“…This critical review presents a pharmacist's perspective of the cardiovascular adverse effects (AE) of respiratory Beta-2 agonists are bronchodilators that are commonly used for asthma and COPD, which selectively bind to beta-2 receptors primarily found at the airways. [3][4][5][6] Nonselective beta-agonists (e.g. isoprenaline) will activate beta-1 receptors at the cardiovascular system, contributing to higher mortality.…”

“…7 Inhaled beta-2 agonists are generally categorised into short-acting (SABA) and long-acting (LABA). [3][4][5] Although highly selective, they are known to be associated with extra-pulmonary effects such as tremor, palpitations, headache, hyperglycaemia, and decreased serum potassium levels, as well as potentially contributing to ischemia and heart failure (HF). 6,[8][9][10][11][12][13][14] It is believed that these effects are related to systemic absorption of the drug.…”