Clinical Question
What are the best pharmacologic therapies for patients with different severity levels of stable chronic obstructive pulmonary disease (COPD)?
Bottom Line
These guidelines recommend stepping up from long-acting muscarinic antagonists (LAMAs) or long-acting beta2 agonists (LABAs) to a LAMA/LABA combination, and then to a LAMA/LABA/inhaled corticosteroid (ICS) combination as the severity and number of acute exacerbations increases. (Level of Evidence = 1a)
Synopsis
The guideline from the Canadian Thoracic Society provides clear, actionable guidance for primary care physicians regarding the management of COPD. Its strengths include an evidence-based methodology, including systematic reviews and meta-analyses, to inform recommendations and evidence grading. Its limitations include the large number of financial and other conflicts of interests among panel members and the inclusion of only one primary care physician and one pharmacologist on the 16-member panel. The systematic reviews were organized around three outcomes: alleviating symptoms, reducing the risk of acute exacerbations, and reducing mortality. The panelists assessed severity based on the validated COPD Assessment Test (CAT; range = 0 to 40) and assessed dyspnea via the modified Medical Research Council (mMRC) scale: 1 = shortness of breath when hurrying on level ground or walking up a slight hill; 2 = walking slower because of shortness of breath or having to stop to catch breath; 3 = having to stoop after walking approximately 100 meters or after a few minutes; and 4 = too short of breath to leave the house.
The guideline had several key recommendations. Patients should use a short-acting bronchodilator, such as albuterol, as needed, whereas an ICS should never be used as monotherapy. For patients with mild COPD (defined as a CAT score of less than 10, an mMRC score of 1, a low symptom burden, and forced expiratory volume in 1 second [FEV1] of at least 80%), a LAMA or LABA is recommended. Patients with moderate to severe COPD (defined as a CAT score of at least 10, an mMRC score of 2 or more, and FEV1 of less than 80%) are stratified based on their risk of acute exacerbations and, therefore, mortality. Those at low risk of acute exacerbations (i.e., no more than one moderate acute exacerbation in the past year) should receive a combined LAMA/LABA and, if needed, progress to a LAMA/LABA/ICS combination, preferably in a single inhaler (number needed to treat [NNT] = 4 at 1 year to prevent one moderate to severe exacerbation but with a higher risk of pneumonia; number needed to harm = 33). Those at high risk of acute exacerbations (i.e., at least two moderate or one severe exacerbation in the past year) should be given a combined LAMA/LABA/ICS because it has been shown to reduce mortality. Additional medications may be considered if the patient remains symptomatic and can include prophylactic macrolide antibiotics, phosphodiesterase-4 inhibitors (e.g., roflumilast [Daliresp]), and mucolytic agents (N-acetylcysteine). The recommendation regarding macrolides should include a warning that they have been shown to reduce exacerbations (NNT = 8) but not hospitalizations and can cause hearing loss and QT elongation with prolonged use.
Study design: Practice guideline
Funding source: Foundation
Setting: Outpatient (any)
Reference: Bourbeau J, Bhutani M, Hernandez P, et al. 2023 Canadian Thoracic Society guideline on pharmacotherapy in patients with stable COPD. Chest. 2023;164(5):1159-1183.
Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.
