Statins did not reduce the frequency of exacerbations in individuals with COPD and cardiovascular comorbidities in the COSYCONET cohort

Abstract

Background: The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities.

Methods: One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1-4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up.

Results: One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year.

Conclusion: These findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency.

Trial registration: Trial registration ClinicalTrials.gov, Identifier: NCT01245933. Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010-11, primary completion 2013-12, study completion 2023-09. https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3.

Keywords: COPD; Cardiovascular comorbidities; Exacerbations; Statins.

Fig. 1

Flow chart showing the selection process of patients for analysis

Fig. 2

A Forest plot displaying the adjusted odds ratios and their 95% confidence intervals for the association between each cardiovascular comorbidity (and a summary value for at least one disease and a summary value for the combination of two comorbidities) and the occurrence of at least one exacerbation per year at baseline. The numerical data can be found in Table 3 and were obtained by logistic regression analysis adjusted for sex, age, BMI, GOLD grade and pack-years. B Forest plot displaying the adjusted odds ratios and their 95% confidence intervals for the association between the medication with statins and the occurrence of at least one exacerbation per year at baseline for each of the cardiovascular comorbidities (and a summary value for at least one disease and a summary value for the combination of two comorbidities) shown in Fig. 2A. The numerical data can be found in Table 3 and were obtained by logistic regression analysis adjusted for sex, age, BMI, GOLD grade and pack-years

Fig. 3

A Forest plot displaying the adjusted odds ratios and their 95% confidence intervals for the association between each cardiovascular comorbidity (and a summary value for at least one disease and a summary value for the combination of two comorbidities) and the occurrence of at least one exacerbation per year between the investigated cardiovascular diseases and exacerbation occurrence during the 4.5 years of follow up. The numerical data can be found in Table 4 and were obtained by a GEE analysis adjusted for sex, age, BMI, GOLD grade and pack-years. B Forest plot displaying the adjusted odds ratios and their 95% confidence intervals for the association between the medication with statins and the occurrence of at least one exacerbation per year at baseline for each of the cardiovascular comorbidities (and a summary value for at least one disease and a summary value for the combination of two comorbidities) shown in Fig. 3A during the 4.5 years of follow up. The numerical data can be found in Table 4 and were obtained by a GEE analysis adjusted for sex, age, BMI, GOLD grade and pack-years

Fig. 4

A Forest plot displaying the adjusted odds ratios and their 95% confidence intervals for the association between each cardiovascular comorbidity and the occurrence of at least one severe exacerbation per year between the investigated cardiovascular diseases and exacerbation occurrence during the 4.5 years of follow up (and a summary value for at least one disease and a summary value for the combination of two comorbidities). The numerical data can be found in Table 5 and were obtained by a GEE analysis adjusted for sex, age, BMI, GOLD grade and pack-years. B Forest plot displaying the adjusted odds ratios and their 95% confidence intervals for the association between the medication with statins and the occurrence of at least one severe exacerbation per year at baseline for each of the cardiovascular comorbidities shown in Fig. 4A during the 4.5 years of follow up (and a summary value for at least one disease and a summary value for the combination of two comorbidities). The numerical data can be found in Table 5 and were obtained by an GEE analysis adjusted for sex, age, BMI, GOLD grade and pack-years