Summarizing the 2021 Updated GOLD Guideline for COPD

Mackenzie Laisure, PharmD Candidate 2022; Nicole Covill, PharmD Candidate 2022; Marissa L. Ostroff, PharmD, BCPS, BCGP; Jared L. Ostroff, PharmD, MBA, BCACP, BCGP


US Pharmacist. 2021;46(7):30-36. 

In This Article

Maintenance Treatment of COPD

GOLD classifications are used to determine initial treatment options for patients with COPD. Figure 2 shows the initial pharmacologic treatment for each GOLD group classification. Refer to Table 1 and Figure 2 for classifications. Importantly, all patients with COPD should be prescribed a rescue short-acting bronchodilator for immediate symptom relief.

Figure 2.

Initial Pharmacological Treatment
CAT: COPD Assessment Test; eos: eosinophil; ICS: inhaled corticosteroid; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic agonist; mMRC: modified British Medical Research Council. Source: Reference 1. Reprinted with permission.

Patients in Group A are recommended to be treated with either a short- or long-acting bronchodilator to address breathlessness. Initial therapy for patients in Group B consists of a long-acting bronchodilator, either a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA). There is no evidence to support a preference between the two classes of inhaled long-acting bronchodilators, so the choice may be patient-specific.

For patients in Group C, a LAMA is recommended. LAMAs were found to be superior to LABAs in terms of prevention of exacerbations.[7,8]

Vogelmeier et al conducted a randomized, double-blind, double-dummy, parallel-group study over 1 year to investigate superiority of tiotropium (LAMA) compared with salmeterol (LABA) in preventing COPD exacerbations in patients with COPD aged 40 years or older with at least a 10 pack-year smoking history and a history of at least one exacerbation requiring systemic glucocorticoids or hospitalization in the previous 12 months.[7] Enrollment included 7,376 patients randomly assigned to the tiotropium 18 μg once-daily intervention (3,707 patients) and the salmeterol 50 μg twice-daily intervention (3,669 patients). The primary endpoint was the time to first exacerbation of COPD. The results of the study show that tiotropium increased the time to first exacerbation (187 vs. 145 days) with a 17% reduction in risk of exacerbation (hazard ratio 0.83; confidence interval 0.77–0.90; P <.001). Tiotropium was also shown to reduce the annual number of moderate-to-severe exacerbations. The results of this study showed that in patients with COPD, tiotropium was more effective in preventing exacerbations.

Decramer et al also performed a randomized, blind, double-dummy, parallel-group study to compare the safety and efficacy of indacaterol (LABA) and tiotropium (LAMA) in patients aged 40 years or older with severe COPD and a history of at least one moderate-to-severe exacerbation in the previous year.[8] Patients were randomized 1:1, stratified by baseline to either indacaterol 150 μg or tiotropium 18 μg once daily for 52 weeks. Enrollment included 3,444 patients, with 1,723 patients in the indacaterol arm and 1,721 patients in the tiotropium arm. The primary endpoint was whether indacaterol was noninferior to tiotropium in terms of trough FEV1 at Week 12. The secondary endpoint was the rate of exacerbations at Week 52. The results showed that indacaterol was noninferior to tiotropium in terms of FEV1 improvement; however, indacaterol did not show noninferiority in terms of annual exacerbation rates. This study suggests that tiotropium offers more protection by reducing annual exacerbations.

Patients in Group D may be treated with a LAMA due to its effects on both breathlessness and prevention of exacerbations. If a patient is highly symptomatic, with greater dyspnea and/or exercise limitation, they may be treated with a combination of a LAMA and a LABA. The preferred treatment option for patients in Group D that present with eosinophils ≥300 cells per microliter or have a history of asthma is an inhaled corticosteroid (ICS) plus a LABA. Another update to the guidelines states that the level of efficacy and benefit on lung function with the use of an ICS is lower in heavy or current smokers in comparison to light or ex-smokers; however, this is not a reason to avoid ICS use in these patients.

When it comes to choosing an inhaler formulation, one may want to take into consideration the current COVID-19 pandemic. The SARS-CoV-2 virus has been shown to be viable in aerosols for up to 3 hours. For this reason, aerosol therapy, such as the use of a nebulizer, should be avoided if possible until the pandemic resolves. The use of pressurized metered-dose ihalers, dry powder inhalers, and soft mist inhalers should be used for drug delivery as an alternative to avoid the spread of infection. If a nebulizer must be used, it should be done so in the absence of other people and in an area with increased air circulation.

In terms of managing patient follow-up, the guidelines recommend modifying therapy based on two treatable targets: dyspnea or exacerbations. If a patient presents with both dyspnea and exacerbations, the guidelines recommend following the exacerbation treatment pathway as shown in Figure 3.

Figure 3.

Follow-Up Pharmacological Treatment
CAT: COPD Assessment Test; eos: eosinophil; ICS: inhaled corticosteroid; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic agonist; mMRC: modified British Medical Research Council. Source: Reference 1. Reprinted with permission.

The 2021 update to the GOLD guidelines included new findings on mortality reduction with triple therapy compared with dual bronchodilation based on the IMPACT and ETHOS randomized, controlled trials. Both trials showed similar results, finding that triple therapy significantly lowers mortality compared with dual bronchodilation. However, there were no differences between triple therapy and LABA/ICS.

A randomized, controlled trial by Lipson et al assessed the once-daily use of triple therapy (ICS/LAMA/LABA) compared with dual therapy (ICS/LABA or LAMA/LABA) in terms of exacerbations and hospitalizations.[9] A total of 10,355 patients with COPD were randomized into groups in which 4,151 received triple therapy with 100 μg fluticasone furoate, 62.5 μg umeclidinium, and 25 μg vilanterol; 4,134 participants received 100 μg fluticasone furoate/25 μg vilanterol; and 2,070 received 62.5 μg umeclidinium/25 μg vilanterol. The rates of moderate or severe exacerbations were 0.91 per year in the triple-therapy group, 1.07 per year in the fluticasone furoate/vilanterol group, and 1.21 per year in the umeclidinium/vilanterol group. The annual rates of hospitalization due to severe exacerbation were 0.13 with triple therapy and 0.19 in the umeclidinium/vilanterol group. These results were statistically significant with P <.001. The authors of this trial concluded that the use of triple therapy resulted in a lower rate in both moderate-severe COPD exacerbations and hospitalization.