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

ABSTRACT

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 M₂ receptors 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.

KEYWORDS:

• COPD
• LABA/LAMA FDCs
• cardiovascular safety

Article highlights

• LABA/LAMA FDCs represent the cornerstone for treating most COPD patients, by eliciting clinical and functional synergistic interaction.

• The cardiovascular toxicity of LABAs and LAMAs overlap, and thus concerns regarding the possible risk of cardiovascular AEs have been raised concerning the use of LABA/LAMA FDCs in COPD patients.

• Although the synergism between LABAs and LAMAs should permit to reduce the dose of each monocomponent in the drug mixture in order to minimize the risk of cardiovascular AEs, the currently available LABA/LAMA FDCs generally combine the drugs at the same full doses of formulations including only a single monocomponent.

• LABA/LAMA FDCs are characterized by a good cardiovascular safety profile in the COPD population enrolled in RCTs that are generally not affected by severe cardiovascular comorbidities, whereas 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 in COPD patients.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This review was not funded