The safety of dual bronchodilation on cardiovascular serious adverse events in COPD

Introduction: Long-acting β2-adrenoceptor (β2-AR) agonists (LABAs) plus long-acting muscarinic antagonists (LAMAs) is the cornerstone for treating chronic obstructive pulmonary disease (COPD). LABA/LAMA combinations elicit clinical and functional synergistic interaction, and such an interaction should permit to reduce the dose of each monocomponent in the drug mixture to minimize the risk of adverse events (AEs). Overall, currently available LABA/LAMA fixed-dose combinations (FDCs) combine the drugs at the same doses of formulations designed for a single drug. Therefore, concerns regarding the possible risk of cardiovascular AEs have been raised related to the use of LABA/LAMA FDCs in COPD patients. Areas covered: LABAs and LAMAs have a high potential to induce cardiovascular AEs by stimulating the β2-AR receptors and inhibiting the muscarinic M2receptors expressed in the heart. This review will explore the data published on the cardiovascular safety of dual bronchodilation therapy in COPD patients. Expert opinion: LABA/LAMA FDCs are characterized by an acceptable cardiovascular safety profile, at least in the COPD population enrolled in randomized clinical trials. Nevertheless, large real life studies suggest that dual bronchodilation therapy may increase the risk of cardiovascular AEs. Post-marketing surveillance and observational studies are needed to adequately define the real cardiovascular safety profile of LABA/LAMA FDCs.