Patient-Oriented Evidence That Matters

Triple Inhaled Therapy Provides a Small Reduction in Moderate COPD Exacerbations, No Effect on Severe Exacerbations


Am Fam Physician. 2021 Jan 15;103(2):online.

Clinical Question

Is triple inhaled therapy for chronic obstructive pulmonary disease (COPD) more effective than dual inhaled therapy?

Bottom Line

Triple inhaled therapy, with budesonide (Pulmicort) in a dose of either 160 mcg or 320 mcg daily plus a long-acting muscarinic antagonist (LAMA) and a long-acting beta2 agonist (LABA), reduces moderate exacerbations (a need for an antibiotic or steroid for three or more days) more than either a LAMA plus a LABA or inhaled corticosteroid plus a LABA, but the difference is small and of questionable clinical significance. There is no clinically important difference in severe exacerbations and no difference in mortality. Another study found a mortality reduction for triple therapy, with numbers needed to treat for one year of 120 (vs. a LAMA plus a LABA) and 358 (vs. an inhaled corticosteroid plus a LABA). (Level of Evidence = 1b)


Triple inhaled therapy for COPD consists of an inhaled corticosteroid, a LAMA, and a LABA. The inhaled corticosteroid in this study was budesonide, the LAMA was glycopyrrolate, 9 mcg twice daily, and the LABA was formoterol (Breztri Aerosphere), 4.8 mcg twice daily. The study randomized 8,588 patients to one of four regimens: triple therapy with 320 mcg of budesonide daily, triple therapy with budesonide, 160 mcg daily, dual therapy with a LAMA plus a LABA, and dual therapy with an inhaled corticosteroid plus a LABA. Participants had COPD that was not well-controlled (forced expiratory volume in one second [FEV1] less than 0.70 postbronchodilator, and already taking at least two inhaled agents) and had experienced at least one moderate or severe exacerbation in the past year. Participants had a mean age of 64 years, approximately 60% were men, and 41% were current smokers. Approximately 30% of participants had a postbronchodilator FEV1 of 50% to 80% of predicted, 60% were at 30% to 50% of predicted, and 10% were less than 30% of predicted.

The primary outcome was the rate of moderate or severe ex

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

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This series is coordinated by Sumi Sexton, MD, editor-in-chief.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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