Triple inhaler therapy should be reserved for patients with COPD with a history of asthma, multiple recent exacerbations, and poor lung function.


In COPD treatment, the step up from a dual bronchodilator to triple inhaler therapy is an important clinical decision, explains Samy Suissa, PhD. “Randomized trials on triple therapy reported surprisingly remarkable benefits on mortality compared with dual bronchodilators,” he says. “However, most patients in these studies were already using an inhaled corticosteroid (ICS) that they had to discontinue at randomization, making these findings ambiguous. Indeed, these trials found that mortality was not lower but, in fact, tended to be higher with triple therapy among those patients who were not previously on ICS.

For a study published in COPD: Journal of Chronic Obstructive Pulmonary Disease, Dr. Suissa and colleagues compared triple therapy with dual bronchodilator combinations on mortality and other major COPD outcomes in a real-word general clinical practice setting. They evaluated a cohort of patients with COPD aged 50 and older, comparing more than 117,000 new users of triple therapy with more than 26,000 new users of dual bronchodilators, with the comparisons adjusted by propensity scores. The comparative effectiveness of the two therapies was assessed based on patients’ history of asthma, lung function, previous exacerbations, and blood eosinophil levels.

All-Cause Mortality Was Not Lower With Triple Therapy

“Overall, we found that all-cause mortality was not lower with triple therapy but was, in some patients, slightly higher than with two bronchodilators,” Dr. Suissa notes. “However, mortality was not higher in certain subgroups of patients, namely those who also have asthma, those with two or more recent exacerbations, and those with very poor lung function.”

The study group also observed that the overall, slightly higher mortality with triple therapy was gradual over the 1-year treatment follow-up. With triple therapy, 4,277 deaths were recorded; with dual bronchodilator therapy, 591 deaths were reported during the 1-year follow-up. With triple therapy, the weighted cumulative incidence of death over 1 year was 7.0% compared with 5.8% for dual bronchodilators (Figure).

 Triple Therapy Best for Patients With Asthma, Multiple Exacerbations

“We observed that for half the patients who initiated triple therapy in our study, COPD treatment guidelines would not recommend it,” Dr. Suissa says. “Our data suggest that such non-recommended use of triple therapy may be associated with higher mortality. Thus, in line with treatment guidelines, triple therapy should be reserved for patients with COPD with a history of asthma, multiple recent exacerbations, and poor lung function, after treatment with dual bronchodilators. Our research suggests that the use of triple therapy may be harmful for other patients.”

Dr. Suissa and colleagues would like to see future studies focus on evaluating COPD treatments targeting specific clinical profiles to optimize effectiveness and avoid such inappropriate use. “In essence, we would like to see studies that will result in the right drug for the right patient rather than the potentially harmful ‘one drug for all,’” Dr. Suissa says.