Statins did not reduce the frequency of exacerbations in individuals with COPD and cardiovascular comorbidities in the COSYCONET cohort
Authors: Frantzi N. , Nguyen X. P. , Herr C. , Alter P. , Söhler S. , Soriano D. , Watz H. , Waschki B. , Trinkmann F. , Eichenlaub M. , Trudzinski F. C. , Michels-Zetsche J. D. , Omlor A. , Seiler F. , Moneke I. , Biertz F. , Rohde G. , Stolz D. , Welte T. , Kauczor H. U. , Kahnert K. , Jörres R. A. , Vogelmeier C. F. , Bals R. , Fähndrich S. ,   on behalf of the German COSYCONET Cohort, Andreas Stefan , Behr Jürgen , Bahmer Thomas , Bewig Burkhard , Ewert Ralf , Stubbe Beate , Ficker HJoachim , Grohé Christian , Held Matthias , Henke Markus , Herth Felix , Kirsten Anne-Marie , Koczulla Rembert , Kronsbein Juliane , Kropf-Sanchen Cornelia , Herzmann Christian , Pfeifer Michael , Randerath JWinfried , Seeger Werner , Studnicka Michael , Taube Christian , Timmermann Hartmut , Schmeck Bernd , Wirtz Hubert 
Published: May 2024

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