COPD Combination Therapy May Improve Lung Hyperinflation

The combination of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) may improve cardiac function significantly in patients with chronic obstructive pulmonary disease (COPD), as measured by left ventricular end diastolic volume, according to a study published in The Lancet Respiratory Medicine.

Jens M. Hohfeld, MD, from the Fraunhofer Institute of Toxicology and Experimental Medicine in Hannover, Germany, and colleagues conducted a double-blind, randomized, 2-period crossover, placebo-controlled, single-center study (CLAIM; ClinicalTrials.gov Identifier: NCT02442206) at the Fraunhofer Institute, a specialty clinic. The investigators included individuals with COPD who were ≥40 years of age with pulmonary hyperinflation (baseline residual volume >135% of predicted), smoking history of ≥10 pack-years, and airflow limitation (forced expiratory volume in 1 second [FEV₁] <80% predicted and postbronchodilator FEV₁: forced vital capacity [FVC] ratio <0.7). Patients with stable cardiovascular disease were eligible for inclusion.

Between May 18, 2015, and April 20, 2017, the investigators randomly assigned 62 patients to receive a combined inhaled dual bronchodilator containing the LABA indacaterol plus the LAMA glycopyrronium once per day for 14 days followed by a 14-day washout period, then a matched placebo for 14 days, or the same treatment in reverse order. The primary end point was the effect of indacaterol-glycopyrronium vs placebo on left ventricular end diastolic volume as measured by magnetic resonance imaging. A total of 57 patients completed both treatment periods.

Left ventricular end diastolic volume increased from a mean 55.46 mL/m² at baseline to a least-squares mean of 61.76 mL/m² in patients treated with indacaterol-glycopyrronium compared with a change from 56.42 mL/m² at baseline to 56.53 mL/m² in patients who were given placebo (least-squares means treatment difference 5.23 mL/m²; 95% CI, 3.22-7.25; P <.0001). Combination therapy also significantly improved hyperinflation, FEV₁, and FVC compared with placebo. The most common adverse events with indacaterol-glycopyrronium were cough (15%) and throat irritation (12%).

The authors noted that CLAIM was a single-center study with an all-white population, which may limit the applicability of the findings. However, they argued that because this the first study to show that lung deflation and improvement in cardiac filling translated to a clinically relevant reduction of disease burden and dyspnea, these findings are still of considerable interest. Furthermore, they believe these results are important because of the known association of cardiovascular impairment with COPD and that they support the early use of dual bronchodilation in patients with COPD who show signs of pulmonary hyperinflation.

Disclosures: This study was funded by Novartis Pharma GmbH.

Reference

Hohfeld JM, Vogel-Claussen J, Biller H, et al. Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial [published online February 21, 2018]. Lancet Respir Med. doi:10.1016/S2213-2600(18)30054-7