In patients with chronic obstructive pulmonary disease (COPD), long-acting muscarinic antagonists (LAMA)/long-acting beta-2 agonists (LABA) combinations are more effective than monotherapy or placebo for most exercise capacity and physical activity outcomes, according to study findings published in Respiratory Research.

Investigators conducted a systematic literature review and meta-analysis of randomized clinical trials to assess the effect of combination LAMA/LABA bronchodilators vs placebo or LAMA or LABA monotherapy on outcomes related to exercise capacity and physical activity in patients with COPD.

The literature search was performed in the MEDLINE, Central, and Embase databases for articles published between January 1, 2012, and December 31, 2021. Eligible trials included patients at least 40 years of age diagnosed with COPD who had a postbronchodilator forced expiratory volume at 1 second/forced vital capacity of less than 0.7.

A total of 17 randomized controlled, double-blind trials with 4041 patients were included. Of those patients, 2964 were treated with the LAMA/LABA combination, 1901 with placebo, 1070 with LAMA, and 755 with LABA.

The LAMA/LABA combination treatment was associated with significantly better physical endurance compared with placebo, based on the endurance shuttle walk test (ESWT) and constant work rate cycle ergometry (CWRCE). LAMA/LABA combinations had favorable results compared with monotherapy, although they were not statistically significant, according to use of ESWT (standardized mean differences [SMD], 0.16; 95% CI, -0.00 to 0.33) and CWRCE (SMD, 0.06; 95% CI, -0.00 to 0.13).

A meta-analysis of 4 studies that compared LAMA/LABA with monotherapies (n=634) found significant differences in the 6-minute walking test (6MWT) in favor of the LAMA/LABA therapy combination (SMD, 0.17; 95% CI, 0.02-0.33).

Our review showed that LAMA/LABA combination therapy was superior to placebo and monotherapy in terms of evaluating exercise capacity and physical activity in patients with COPD in almost every comparison.

LAMA/LABA combinations were significantly superior to placebo and monotherapy regarding steps per day. For daily duration activity, the LAMA/LABA combination significantly reduced the duration of at least 1.0 to 1.5 metabolic equivalent of task (MET) activities compared with monotherapy. For moderate physical activity, LAMA/LABA therapy increased the duration of 2.0 or more MET activities. Regarding vigorous physical activity (≥3.0 METs), LAMA/ LABA therapy was superior to monotherapy and placebo, although the latter findings were not statistically significant.

Daily activity-related energy expenditure was increased in the LAMA/LABA group compared with the placebo group (SMD, 0.28; 95% CI, 0.12-0.44). The placebo group had more inactive patients (<6000 steps/day) compared with the LAMA/LABA group (odds ratio, 0.27; 95% CI, 0.14-0.51; 1 study, n=267).

In sensitivity analysis stratified according to study design when heterogeneity was present, the LAMA/LABA combination’s favorable results vs monotherapy were confirmed in 6MWT and steps per day. For vigorous physical activity, LAMA/LABA therapy was superior to both monotherapies with a significant heterogeneity (I2 = 69%); owing to the inclusion of 2 studies, the sensitivity analysis was based on individual study results.

Limitations include differences among the studies on variables used to measure physical activity. In addition, in some analyses different LAMA/LABA combinations were compared with different LAMA or LABA monotherapies, and outcome evaluation times were different, ranging from 3 to 12 weeks. Also, statistical heterogeneity was high in some comparisons, which limited the validity and the generalizability of the findings.

“Our review showed that LAMA/LABA combination therapy was superior to placebo and monotherapy in terms of evaluating exercise capacity and physical activity in patients with COPD in almost every comparison,” stated the researchers. “Enhancing physical activity and exercise capacity in COPD patients might lead to improve their quality of life and minimize the burden of the disease.”

Disclosure: This study was funded by Boehringer Ingelheim Spain. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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