Cardiovascular Outcomes with an Inhaled Beta2-agonist/Corticosteroid in COPD Patients at High Cardiovascular Risk

OBJECTIVES: Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) often co-exist. We assessed the effect of inhaled COPD treatments on CVD outcomes and safety in patients with COPD and at heightened CVD risk.
METHODS: The Study to Understand Mortality and MorbidITy (SUMMIT) was a multicenter, randomized, 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 pre-specified secondary endpoint of time to first on-treatment composite CVD event (CVD death, myocardial infarction, stroke, unstable angina, or transient ischemic attack [TIA]) by Cox regression and by clinician-reported CVD adverse events across the 4 groups: once-daily inhaled placebo (n =4,111), long-acting beta2-agonist (vilanterol [VI] 25 μg; n =4,118), corticosteroid (fluticasone furoate [FF] 100 μg; n =4,135) and combination therapy (FF/VI; n =4,121).
RESULTS: Participants were predominantly middle-aged (65±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: vilanterol (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.80–1.22), FF (HR 0.90, 95%CI 0.72–1.11) and their combination (HR 0.93, 95%CI 0.75–1.14). Outcomes were similar among all subgroups. Adverse events, including palpitations and arrhythmias, did not differ by treatment.
CONCLUSIONS: In COPD patients with moderate airflow limitation and heightened CVD risk, treatment with inhaled vilanterol, FF, or their combination has an excellent safety profile and does not impact CVD outcomes.