Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis

Abstract

Objective:To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods:This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results:A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions:The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

POINT: Should LAMA/LABA Combination Therapy Be Used as Initial Maintenance Treatment for COPD? Yes

“…12 The available evidence seems to indicate that neither LAMAs nor LABAs show any significant benefit, relative to each other, in their effect on lung function, symptoms of breathlessness, mortality, and the overall number of hospitalizations, 13 but the exacerbation rates with the use of LAMAs are lower than those with the use of a LABA alone. 14 Nowadays, the evidence that dual bronchodilation is always more effective than a LAMA or LABA alone in improving lung function and controlling symptoms, 9 and also in reducing the risk of exacerbations 15 (a risk that is always possible even in patients with mild COPD as documented by the UNLOCK [Uncovering and Noting Long-Term Outcomes in COPD to Enhance Knowledge] study), 16 is the most solid reason to immediately start the treatment of COPD with dual bronchodilation.…”

Potential clinical and economic impact of optimised maintenance therapy on discharged patients with COPD after hospitalisation for an exacerbation in China

“…A total of 14 publications were identified, but only 2 were considered to fit our model concept. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] The two publications were by Mills et al 28 and Pavord et al 22 The publication by Mills et al 28 reported the annual number of exacerbations per year without long-acting maintenance treatment (1.21) and the associated relative risks of all maintenance treatments compared with placebo. The exacerbation rate without long-acting maintenance treatment was converted into a monthly exacerbation rate (0.1019) to fit the 1-month cycle length.…”

Pharmacology and Therapeutics of Bronchodilators Revisited

“…Conversely, LAMAs seem more effective than LABAs in the treatment of exacerbations, and this is regardless of whether LABAs are dosed once-or twice-a-day. LAMAs are able to significantly reduce the number of hospitalizations due to COPD exacerbations, and they also decrease the risk of severe adverse effects, but do not alter mortality (Maia et al, 2017). Therefore, if a single bronchodilator must be chosen for treating a patient with COPD, a LAMA seems to be a better option than a LABA, mainly for patients who are frequent exacerbators.…”