Increased all-cause mortality during severe exacerbations in COPD patients

A posthoc analysis of the phase 3 IMPACT trial demonstrated that the risk of all-cause mortality increased more than 40-fold in COPD patients with severe exacerbations. This highlights the importance of the prevention of these events as a COPD treatment goal.

Exacerbations of chronic obstructive pulmonary disease (COPD) result in acute worsening of respiratory symptoms, necessitating additional treatment. In particular, severe exacerbations have shown to be a key contributor to the clinical and economic burden of COPD. Previously, the IMPACT study 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 [1,2].

During this year's ATS meeting, a posthoc analysis was presented that investigated the risk of all-cause mortality during and following a moderate or severe exacerbation in patients enrolled in the IMPACT trial [1].

Overall, 42.5% of patients experienced an on-treatment moderate exacerbation and 11.4% an on-treatment severe exacerbation. The most common cause of death in the analysis was cardiovascular during 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 by 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, New York, USA) pointed out, these results show that severe exacerbations are the driver of mortality risk in these patients. This emphasises the need to optimise treatment in patients at risk of exacerbations.

1. 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.
2. Lipson DA et al. N Engl J Med 2018;378:1671-80.

Posted on 17 May 20214 August 2021