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
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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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