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. 2024 Sep 13;24(1):450.
doi: 10.1186/s12890-024-03277-2.

Trends in COPD severe exacerbations, and all-cause and respiratory mortality, before and after implementation of newer long-acting bronchodilators in a large population-based cohort

Charles-Antoine Guay  1   2   3   4 , François Maltais  5   6 , Claudia Beaudoin  7 , Pierre-Hugues Carmichael  8 , Elhadji Anassour Laouan Sidi  7 , Laurie Perreault  5 , Caroline Sirois #  7   8   9 , Steeve Provencher  5   6
Affiliations

Trends in COPD severe exacerbations, and all-cause and respiratory mortality, before and after implementation of newer long-acting bronchodilators in a large population-based cohort

Charles-Antoine Guay et al. BMC Pulm Med. .

Abstract

Background: Little is known about the trends in morbidity and mortality at the population level that followed the introduction of newer once-daily long-acting bronchodilators for COPD. The purpose of the study was to evaluate whether the availability of new bronchodilators was associated with changes in the temporal trends in severe COPD exacerbations and mortality between 2007 and 2018 in the older population with COPD; and whether this association was homogeneous across sex and socioeconomic status classes.

Methods: We used an interrupted time-series and three segments multivariate autoregressive models to evaluate the adjusted changes in slopes (i.e., trend effect) in monthly severe exacerbation and mortality rates after 03/2013 and 02/2015 compared to the tiotropium period (04/2007 to 02/2013). Cohorts of individuals > 65 years with COPD were created from the nationally representative database of the Quebec Integrated Chronic Disease Surveillance System in the province of Quebec, Canada. Whether these trends were similar for men and women and across different socioeconomic status classes was also assessed.

Results: There were 130,750 hospitalizations for severe exacerbation and 104,460 deaths, including 24,457 (23.4%) respiratory-related deaths, over the study period (928,934 person-years). Significant changes in trends were seen after 03/2013 for all-cause mortality (-1.14%/month;95%CI -1.90% to -0.38%), which further decreased after 02/2015 (-1.78%/month;95%CI -2.70% to -0.38%). Decreases in respiratory-related mortality (-2.45%/month;95%CI -4.38% to -0.47%) and severe exacerbation (-1,90%/month;95%CI -3.04% to -0.75%) rates were only observed after 02/2015. These observations tended to be more pronounced in women than in men and in higher socioeconomic status groups (less deprived) than in lower socioeconomic status groups (more deprived).

Conclusions: The arrival of newer bronchodilators was chronologically associated with reduced trends in severe exacerbation, all-cause and respiratory-related mortality rates among people with COPD > 65 years. Our findings document population benefits on key patient-relevant outcomes in the years following the introduction of newer once-daily long-acting bronchodilators and their combinations, which were likely multifactorial. Public health efforts should focus on closing the gap between lower and higher socioeconomic status groups.

Keywords: COPD exacerbations; Fixed-dose combination; Interrupted time series.

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Conflict of interest statement

Charles-Antoine Guay reports financial support was provided by Quebec Health Research Fund. Francois Maltais reports a relationship with GlaxoSmithKline that includes: funding grants and speaking and lecture fees. Francois Maltais reports a relationship with AstraZeneca that includes: consulting or advisory and funding grants. Francois Maltais reports a relationship with Sanofi that includes: funding grants. Francois Maltais reports a relationship with Novartis that includes: funding grants and speaking and lecture fees. Francois Maltais reports a relationship with Boehringer Ingelheim that includes: funding grants and speaking and lecture fees. Francois Maltais reports a relationship with Grifols that includes: funding grants and speaking and lecture fees. Francois Maltais reports a relationship with Oxynov that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Proportion of ultra-LABAs/newer-LAMAs and FDC users between April 2007 and August 2018. The first ultra-LABAs (indacaterol) was introduced on the list of drugs covered by the public drug plan in February 2013 and was first reimbursed in March 2013. The first FDC (indacaterol/glycopyrronium) was introduced on the list of drugs covered by the public drug plan in February 2015 and was first reimbursed in February 2015. Listed ultra-LABAs/newer-LAMAs in the public drug plan: indacaterol (ultra-LABA), glycopyrronium and umeclidinium (newer-LAMAs). Listed FDCs in the public drug plan: indacaterol/glycopyrronium, vilanterol/umeclidinium, olodaterol/tiotropium
Fig. 2
Fig. 2
Severe AE-COPD and mortality trends before and after the introduction of ultra-LABAs/newer-LAMAs and FDCs. Vertical dashed line indicates March 2013 when ultra-LABAs/newer LAMAs were introduced in Quebec, Canada. Grey areas show the period from March 2013 (ultra-LABAs/newer-LAMAs’ introduction) to February 2015 (FDCs’ introduction). Solid regression lines show the observed adjusted trends after the introduction of ultra-LABAs/newer-LAMAs and FDCs, whereas dashed regression lines are the predicted adjusted trends after March 2013 assuming no change in the trends observed before introduction of new bronchodilators. AE-COPD = acute exacerbation of chronic obstructive pulmonary disease; ultra-LABA = ultra-long-acting beta2-agonist; LAMA = long-acting antimuscarinic; FDC = fixed-dose combinations
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