ICS therapy shows most CV benefit in COPD patients with eosinophilia 


COPD patients with higher levels of eosinophils are more at risk of experiencing a cardiac event if not receiving an inhaled corticosteroid (ICS) as part of their therapy, according to a post hoc analysis of data from the ETHOS trial.

Presenting the findings at ERS 2021, Professor Mona Bafadhel, Respiratory Physician and COPD research group lead at Oxford University, said rates of total confirmed major adverse cardiac events (MACE) and CV death were lower in patients taking ICS containing triple therapy with BGF (budesonide/glycopyrronium/formoterol fumarate) compared to dual bronchodilator therapy with GFF (glycopyrronium/formoterol fumarate).

The difference between the triple and dual therapies in rates of total confirmed MACE and CV death were found to generally increase as the baseline level of eosinophils increased. For example, the MACE rate (per 1,000 patient years) was 16.9 with the BGF 320 dose and 26.6 for GFF, while the figures for the subgroup of patients with a blood eosinophil level of over 300/μL were 3.6 and 39.8, respectively.

Interestingly, with regard to CV death, the analysis showed the mid dose of BGF 160 to be the most effective in patients with the highest eosinophil levels, with a rate of 3.5 compared to 3.6 for the higher dose and 13.3 in the group taking the dual bronchodilator.

A reduction in non-fatal myocardial infarction (MI) was also observed with BGF triple therapy compared to GFF, but again this was most pronounced with elevated eosinophil levels, with 0 for BGF 320, 10.5 for BGF 160 and 26.6 for GFF.

A similar effect was not seen for non-fatal stroke, though Prof Bafadhel said she presumed that this was “likely a consequence of very low event numbers of non-fatal stroke in the study”.

Overall, the findings are “consistent with the reduction in the risk of all cause mortality with BGF versus GFF that increased with increasing eosinophil count previously reported ETHOS,” she said, and “support the potential benefit of ICS in reducing CV death and non-fatal MI in patient with COPD and high risk of exacerbation burden”.

Commenting on the analysis, Professor Guy Brusselle, Chair of the European Respiratory Society (ERS) Science Council, said the observations on mortality were particularly intriguing.

“The triple combination with medium dose of budesonide had lowest all cause mortality and the LABA/LAMA the highest. This raises the question, should we base the entire treatment algorithm only on the exacerbations? Many drugs which reduce exacerbations do not decrease COPD mortality.”

“The main focus of RCTs in COPD is short improvement in lung function and prevention of exacerbations. However, the respiratory community should be ambitious and aim to develop treatments for COPD which significantly improve the long-term course of the disease and decrease mortality.”

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