Peer Reviewed

Controversies in Clinical Care

Which COPD Treatment Options Are Considered Equivalent?

Eric A. Dietrich, PharmD, BCPS, and Kyle Davis, PharmD, BCPS

Eric A. Dietrich, PharmD, BCPS, and Kyle Davis, PharmD, BCPS

Dietrich EA, Davis K. Which COPD treatment options are considered equivalent?


Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the United States and accounted for 40.8 deaths per 100,000 person years in 2010.1 While the mortality rate for men has declined since 1999, death rates for women have remained essentially unchanged at 36 deaths per 100,00 person years during this same timeframe.1 Currently available pharmacotherapy has not been shown to alter disease progression, but rather reduce the rate of COPD exacerbations or delay the time to such an event. Mainstays of therapy include long-acting beta-2-agonists (LABA), long-acting muscarinic antagonists (LAMA), or an inhaled corticosteroid (ICS) in combination with a LABA. 

Based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines,2 monotherapy with a LABA or a LAMA is recommended for patients considered at a low-to-moderate risk for exacerbations based on a combined risk assessment. When evaluating patients at low-to-moderate risk practitioners must ask themselves, are these strategies considered equivalent?

A Case Study

CD is a 63-year-old white woman who presented for continued workup for shortness of breath and an ongoing cough. Her past medical history was significant for hypertension (controlled on amlodipine 5 mg daily) and a 60-pack-year history of smoking (2 packs per day for 30 years). She quit smoking 5 years ago. 

The patient was admitted to a local hospital for severe shortness of breath, cough, and sputum production. Her workup during the hospital admission was negative. Upon resolution of her symptoms, she was discharged and underwent pulmonary function testing, which showed a forced expiratory volume in 1 second (FEV1) of 56% predicted and an FEV1/forced vital capacity ratio of 64%.

Diagnosis. Based on the PFT results, symptoms, hospital admission, and smoking history, CD is given a diagnosis of COPD. After completing the COPD Assessment Test, she is placed into risk category B per the 2015 GOLD guidelines. Accordingly, a LABA or LAMA is recommended for initial therapy for CD. (Note: Combined LABA + ICS is not recommended until stage C or D, and therapy should not be routinely utilized in patients with stage A or B.2)

Treatment. The 2 treatment options are salmeterol (twice-daily LABA) or tiotropium (once-daily LAMA). Both are only available as brand, are dry powder inhalers, and have a long track record of clinical use and success. Additionally, each of these agents is well-tolerated and associated with only minor adverse effects. In the case of CD, are both treatment options considered equivalent?


The Evidence >>

The Evidence

Salmeterol and tiotropium were compared in the head-to-head Prevention of Exacerbations with Tiotropium in COPD (POET-COPD) study. Similar to CD, subjects in the study had an FEV1 <70% predicted, had at least 1 hospital admission for a COPD exacerbation in the last year, and at least a 10-pack per year history of smoking. 

Subjects were randomized in a double-blind fashion to receive salmeterol 50 mcg twice daily or tiotropium 18 mcg daily for 1 year. The primary end point was time to first COPD exacerbation, which was defined as the need for systemic antibiotics and/or corticosteroids (moderate exacerbation) or hospital admission (severe exacerbation).3 

Treatment with tiotropium lengthened the time to the first exacerbation by 42 days as compared to salmeterol (187 days vs 145 days, respectively). This translated into a 17% relative risk reduction to the primary endpoint with tiotropium (hazard ratio 0.83, P<0.001). (Note: As less than 50% of study participants had an exacerbation, the time points reflect the time to first exacerbation in the first quartile of patients.) 

Furthermore, tiotropium reduced the risk for moderate and severe exacerbations by 14% and 28%, respectively (P<0.001 for both comparisons). Benefits of tiotropium appeared as early as 1 month and continued through the duration of the study. An important consideration is that more subjects receiving salmeterol discontinued the study early, although the absolute difference between groups was small (1.9%). Finally, the rate of adverse events was not significantly different between groups.3

Clinical Application

Although neither salmeterol nor tiotropium has been shown to reduce the progression of COPD, exacerbations further worsen lung function and are associated with significant healthcare costs. Based on the results of the POET-COPD study, tiotropium appears to have a superior efficacy profile compared to salmeterol in terms of lengthening the time to a COPD exacerbation and also reducing the risk for both moderate and severe COPD exacerbations. Importantly, subjects enrolled in the POET-COPD study had a similar severity of disease as CD based on exacerbation history and FEV1, which suggests that CD is likely to receive similar benefit from the studied medications. 

Given the clinical superiority of tiotropium over salmeterol and a similar safety profile, and in the absence of a contraindication, CD would be recommended to initiate tiotropium as a monotherapy regimen for the treatment of her COPD. 

Outcome of the Case

After discussing the risks, benefits, and alternatives, CD was started on tiotropium 18 mcg once daily and also provided with an albuterol 90 mcg hydrofluoroalkane inhaler to be used for as needed symptoms. She was counseled on the proper, and different, inhaler techniques for both inhalers and on the proper use and indication of each medication. She was congratulated on her abstinence from smoking for 5 years and encouraged to continue avoiding cigarette smoking.

Eric A. Dietrich, PharmD, BCPS, graduated from UF College of Pharmacy in 2011 and completed a 2-year fellowship in family medicine where he was in charge of a coumadin clinic. He now works for the UF Colleges of Pharmacy and Medicine. 

Kyle Davis, PharmD, BCPS, graduated from the University of Florida College of Pharmacy in 2011 and completed a PGY-1 at Jackson Memorial Hospital and a PGY-2 in internal medicine at Indiana University Health and Butler College of Pharmacy. He currently works at Jackson Memorial Hospital in Miami, FL. 


  1. CDC. Chronic Obstructive Pulmonary Disease. Accessed August 11, 2015.
  2. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2015. Accessed August 11, 2015.
  3. Vogelmeier C, Hederer B, Glaab T, et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med. 2011;364(12):1093-1103.