B-blocker therapy and clinical outcomes in patients with moderate chronic obstructive pulmonary disease and heightened cardiovascular risk an observational substudy of SUMMIT

Rationale: Cardiovascular disease is a common comorbidity in patients with chronic obstructive pulmonary disease. Although b-blockers can be used safely in patients with chronic obstructive pulmonary disease, concerns remain regarding safety and efficacy interactions in patients using concomitant inhaled long-acting b-agonists. Objectives: To compare the differential effects of long-acting b-agonist or inhaled corticosteroid use on clinical outcomes in patients with heightened cardiovascular risk treated and not treated with b-blockers. Methods: We examined data from 16,485 participants in the SUMMIT study (Study to Understand Mortality and Morbidity in COPD) who were randomized to once-daily inhaled fluticasone furoate, vilanterol, fluticasone furoate/vilanterol combination, or placebo and examined the associations between treatment allocation and lung function, chronic obstructive pulmonary disease exacerbations, cardiovascular events, and all-cause mortality, stratified by baseline b-blocker therapy. Results: Baseline b-blocker therapy was used by 31% (n = 5,159) of SUMMIT participants. There was no evidence of an interaction between baseline b-blocker therapy and the association between inhaled treatments and forced expiratory volume in 1 second at 3 months (P = 0.27), 6 months (P = 0.14), or 12 months (P = 0.33). The placebo-adjusted mean differences in post-bronchodilator forced expiratory volume in 1 second at 3 months in the vilanterol-alone group were 58 ml (95% confidence interval, 38-78) in those receiving baseline b-blocker therapy and 51 ml (95% confidence interval, 38-65) in those not receiving baseline b-blocker therapy. The placebo-adjusted mean differences in post-bronchodilator forced expiratory volume in 1 second at 3 months in the combination fluticasone furoate/vilanterol group were 85 ml (95% confidence interval, 65-105) in those receiving baseline b-blocker therapy and 68 ml (95% confidence interval, 54-82) in those not receiving baseline b-blocker therapy. Overall, there was no evidence of interaction by randomized treatment, including vilanterol alone or in combination with fluticasone furoate, for chronic obstructive pulmonary disease exacerbations (P = 0.18), cardiovascular composite events (P = 0.33), and all-cause mortality (P = 0.41). Conclusions: There is no evidence to suggest that baseline b-blocker therapy reduces the respiratory benefits or increases the cardiovascular risk of inhaled long-acting b-agonists in patients with chronic obstructive pulmonary disease and heightened cardiovascular risk.