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Original research article
Cardiovascular outcomes with an inhaled beta2-agonist/corticosteroid in patients with COPD at high cardiovascular risk
  1. Robert D Brook1,
  2. Julie A Anderson2,
  3. Peter MA Calverley3,4,
  4. Bartolome R Celli5,
  5. Courtney Crim6,
  6. Martin A Denvir7,
  7. Sheldon Magder8,
  8. Fernando J Martinez9,
  9. Sanjay Rajagopalan10,
  10. Jørgen Vestbo11,
  11. Julie Yates6,
  12. David E Newby12
  13. on behalf of the SUMMIT Investigators
  1. 1 Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA
  2. 2 Research & Development, GlaxoSmithKline, Uxbridge, UK
  3. 3 Department of Medicine, University of Liverpool, Liverpool, UK
  4. 4 Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK
  5. 5 Pulmonary and Critical Care Division, Brigham and Womens Hospital, Harv’ard Medical School, Boston, Massachusetts, USA
  6. 6 Research & Development, GSK, Research Triangle Park, North Carolina, USA
  7. 7 Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
  8. 8 Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada
  9. 9 Joan and Sandy Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA
  10. 10 Cardiovascular Medicine, University of Maryland, College Park, Maryland, USA
  11. 11 Centre for Respiratory Medicine and Allergy, Manchester Academic Health Science Centre, The University of Manchester and South Manchester University Hospital NHS Foundation Trust, Manchester, UK
  12. 12 British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
  1. Correspondence to Dr Robert D Brook, Division of Cardiovascular Medicine, University of Michigan, 24 Frank Lloyd Wright Dr., PO Box 322, Ann Arbor, MI 48106, USA; robdbrok{at}umich.edu

Abstract

Objectives Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) often coexist. We assessed the effect of inhaled COPD treatments on CVD outcomes and safety in patients with COPD and at heightened CVD risk.

Methods The SUMMIT (Study to Understand Mortality and MorbidITy) was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial in 16 485 patients with moderate COPD who had or were at high risk of CVD. Here, we assessed the prespecified secondary endpoint of time to first on-treatment composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD adverse events across the four groups: once-daily inhaled placebo (n=4111), long-acting beta2-agonist (vilanterol (VI) 25 µg; n=4118), corticosteroid (fluticasone furoate (FF) 100 µg; n=4135) and combination therapy (FF/VI; n=4121).

Results Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with overt CVD (66%). The composite CVD endpoint occurred in 688 patients (first event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%), and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI 0.80 to 1.22), FF (HR 0.90, 95% CI 0.72 to 1.11) and their combination (HR 0.93, 95% CI 0.75 to 1.14). Outcomes were similar among all subgroups. Adverse events, including palpitations and arrhythmias, did not differ by treatment.

Conclusions In patients with COPD with moderate airflow limitation and heightened CVD risk, treatment with inhaled VI, FF or their combination has an excellent safety profile and does not impact CVD outcomes.

Trial registration number NCT01313676.

  • pulmonary disease
  • cardiovascular disease
  • inhaler therapies

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Acknowledgements The authors acknowledge the work of Veramed employees: Matthew Jones, Abigail Fuller and Nick Cowans on statistical analysis and programming.

  • Contributors RDB, PMAC, BRC, FJM, JV, DEN, JAA, CC and JY conceived and designed the research; JAA performed statistical analysis; JAA, CC and JY handled funding and supervision; RDB drafted the manuscript; JAA, PMAC, BRC, CC, MAD, SM, FJM, SR, JV, JY and DEN made critical revisions of the manuscript for key intellectual content.

  • Funding Funded by GSK Study 113782 (NCT01313676).

  • Competing interests RDB, PMAC, BRC, FJM, JV and DEN are external members of the SUMMIT Steering Committee. JAA, CC and JY are employed by GSK and are members of the SUMMIT Steering Committee. MAD and SM are members of the SUMMIT Clinical Endpoint Committee, and SR is a member of the SUMMIT Independent Data Monitoring Committee.

  • Ethics approval The study was approved by local ethics committees and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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