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Adherence of Elderly Patients with Cardiovascular Disease to Statins and the Risk of Exacerbation of Chronic Obstructive Pulmonary Disease: Evidence from an Italian Real-World Investigation

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Abstract

Objective

The objective of this study was to investigate the relationship between adherence to statin therapy and the risk of exacerbation among elderly individuals affected by chronic obstructive pulmonary disease and cardiovascular disease.

Methods

Using the healthcare utilisation databases of five Italian territorial units accounting for nearly 35% of the Italian population, we recruited a cohort of 6263 elderly persons (i.e. aged 65 years or older) with co-existing chronic obstructive pulmonary disease and cardiovascular disease who initiated statin therapy. Exposure was adherence to statins measured by the proportion of days of follow-up covered. Outcome was the first hospital admission for chronic obstructive pulmonary disease occurring in the period of observation. A proportional hazards model was used to estimate the hazard ratio and 95% confidence intervals for the exposure–outcome association, after adjusting for several covariates. A set of sensitivity analyses was performed to account for sources of systematic uncertainty.

Results

During an average follow-up of about 4 years, 1307 cohort members experienced the outcome. Compared with patients with low adherence (proportion of days of follow-up covered ≤ 40%), those with intermediate (proportion of days of follow-up covered 41–80%) and high (proportion of days of follow-up covered > 80%) adherence exhibited a lower risk of exacerbation of 16% (95% confidence interval 3–27) and 23% (95% confidence interval 10–34).

Conclusions

In a real-world setting, we observed evidence that adherence to statin therapy markedly reduced the risk of chronic obstructive pulmonary disease exacerbations in elderly patients with co-existing chronic obstructive pulmonary disease and cardiovascular disease. Given the limited and controversial evidence from trials, more randomised controlled trials are urgently needed to better examine the potential benefits of statins as adjunct therapy in chronic obstructive pulmonary disease.

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Acknowledgements

I-GrADE members: Nera Agabiti, Claudia Bartolini, Roberto Bernabei, Alessandra Bettiol, Stefano Bonassi, Achille Patrizio Caputi, Silvia Cascini, Alessandro Chinellato, Francesco Cipriani, Giovanni Corrao, Marina Davoli, Massimo Fini, Rosa Gini, Francesco Giorgianni, Ursula Kirchmayer, Francesco Lapi, Niccolò Lombardi, Ersilia Lucenteforte, Alessandro Mugelli, Graziano Onder, Federico Rea, Giuseppe Roberto, Chiara Sorge, Michele Tari, Gianluca Trifirò, Alfredo Vannacci, Davide Liborio Vetrano, Cristiana Vitale.

Author information

Authors and Affiliations

  1. National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy

    Federico Rea, Giulia Calusi, Matteo Franchi & Giovanni Corrao

  2. Dipartimento di Statistica e Metodi Quantitativi, Sezione di Biostatistica, Epidemiologia e Sanità Pubblica, Università degli Studi di Milano-Bicocca, Via Bicocca degli Arcimboldi, 8, Edificio U7, 20126, Milan, Italy

    Federico Rea, Giulia Calusi, Matteo Franchi & Giovanni Corrao

  3. Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet, Stockholm University, Stockholm, Sweden

    Davide Liborio Vetrano

  4. Department of Geriatrics, Catholic University of Rome, Rome, Italy

    Davide Liborio Vetrano

  5. Epidemiology Unit, Regional Agency for Healthcare Services of Tuscany, Florence, Italy

    Giuseppe Roberto

  6. Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy

    Stefano Bonassi

  7. Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy

    Stefano Bonassi

  8. Department of Epidemiology, Lazio Regional Health Service, Rome, Italy

    Ursula Kirchmayer

  9. Treviso Local Health Unit, Treviso, Italy

    Alessandro Chinellato

  10. Department of Neurosciences, Psychology, Drug Research and Children’s Health, University of Florence, Florence, Italy

    Alessandra Bettiol & Alessandro Mugelli

  11. Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy

    Janet Sultana

Authors
  1. Federico Rea
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Consortia

the I-GrADE Investigators

  • Nera Agabiti
  • , Claudia Bartolini
  • , Roberto Bernabei
  • , Alessandra Bettiol
  • , Stefano Bonassi
  • , Achille Patrizio Caputi
  • , Silvia Cascini
  • , Alessandro Chinellato
  • , Francesco Cipriani
  • , Giovanni Corrao
  • , Marina Davoli
  • , Massimo Fini
  • , Rosa Gini
  • , Francesco Giorgianni
  • , Ursula Kirchmayer
  • , Francesco Lapi
  • , Niccolò Lombardi
  • , Ersilia Lucenteforte
  • , Alessandro Mugelli
  • , Graziano Onder
  • , Federico Rea
  • , Giuseppe Roberto
  • , Chiara Sorge
  • , Michele Tari
  • , Gianluca Trifirò
  • , Alfredo Vannacci
  • , Davide Liborio Vetrano
  •  & Cristiana Vitale

Corresponding author

Correspondence to Federico Rea.

Ethics declarations

Funding

This study was funded by a research grant from the Italian Medicines Agency (AIFA, project AIFA-FARM9LBBBL), Rome, Italy. Data analyses were performed at the Laboratory of Healthcare Research & Pharmacoepidemiology, University of Milano-Bicocca with grants from the Italian Ministry of Education, Universities and Research (MIUR) [’Fondo d’Ateneo per la Ricerca’ portion, year 2015].

Conflict of interest

Alessandro Mugelli received research support from the Italian Medicines Agency (AIFA), the Italian Ministry of Education, Universities and Research (MIUR), Gilead and Menarini. In the last 2 years, he received personal fees as a speaker/consultant for the Menarini Group, IBSA, Molteni, Angelini and Pfizer Alliance. Giovanni Corrao received research support from the European Community, AIFA and MIUR. He participated in a variety of projects funded by pharmaceutical companies (i.e. Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria as a member of an advisory board for Roche. Federico Rea, Giulia Calusi, Matteo Franchi, Davide Liborio Vetrano, Giuseppe Roberto, Stefano Bonassi, Ursula Kirchmayer, Alessandro Chinellato, Alessandra Bettiol and Janet Sultana have no conflicts of interest that are directly relevant to the contents of this study.

Ethics Approval

This study was approved by the Ethics Committee of “Azienda Ospedaliera Universitaria di Careggi”, Florence, Italy, on 26 March, 2012; Protocol Number: 2012/0012643.

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Rea, F., Calusi, G., Franchi, M. et al. Adherence of Elderly Patients with Cardiovascular Disease to Statins and the Risk of Exacerbation of Chronic Obstructive Pulmonary Disease: Evidence from an Italian Real-World Investigation. Drugs Aging 35, 1099–1108 (2018). https://doi.org/10.1007/s40266-018-0600-0

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  • DOI: https://doi.org/10.1007/s40266-018-0600-0

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