Severe exacerbations: A key driver of all-cause mortality in COPD patients

All-cause mortality increases more than 40-fold in chronic obstructive pulmonary disease (COPD) patients who experience severe exacerbations: this dramatic increase was revealed by a posthoc analysis of the phase 3 IMPACT trial. This result emphasises the need to optimise treatment in patients at risk of exacerbations.

Exacerbations of result COPD in acute worsening of respiratory symptoms, necessitating additional treatment. In particular, severe exacerbations are a key contributor to the clinical and economic burden of COPD. Previously, the IMPACT study (NCT02164513), involving more than 10,000 symptomatic COPD patients, demonstrated that patients treated with 2 bronchodilators that still suffer from exacerbations will benefit from a triple combination: patients treated with the combination of fluticasone furoate, umeclidinium, and vilanterol experienced a 34% reduction in the annual rate of severe exacerbations and a 42% reduction in on-treatment all-cause mortality versus patients treated with the combination of umeclidinium plus vilanterol only [1].

During this year’s ATS meeting, a posthoc analysis was presented on the risk of all-cause mortality during and following a moderate or severe exacerbation in patients enrolled in the IMPACT trial [2]. Moderate exacerbations were defined as those requiring treatment with antibiotics or systemic/oral corticosteroids. Severe exacerbations were defined as those resulting in hospitalisation or death.

Overall, 42.5% of patients experienced an on-treatment moderate exacerbation and 11.4% on-treatment severe exacerbations. The most common cause of death in the analysis was cardiovascular in the exacerbation-free period and respiratory during the exacerbation. Moderate exacerbations did not significantly increase the risk of all-cause mortality during an exacerbation. In contrast, this risk increased 41-fold during a severe exacerbation event compared with the exacerbation-free period and decreased thereafter to levels not significantly different from the baseline period. As Prof. Manoj J. Mammen (Jacobs School of Medicine and Biomedical Sciences, NY, USA) pointed out, these results show that severe exacerbations are the driver of mortality risk in these patients. This highlights the importance of the prevention of these events as a COPD treatment goal.

1. Lipson DA et al. N Engl J Med 2018;378:1671-80.
2. Mammen MJ, et al. Risk of all-cause mortality during and after severe exacerbations in patients with chronic obstructive pulmonary disease (COPD): Post hoc analysis of the IMPACT trial. Session TP040: COPD clinical trials and therapies. ATS 2021 International conference, 14-19 May.

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Posted on 5 July 2021