Long-acting muscarinic antagonists

Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability worldwide. Inhaled bronchodilators are the mainstay of COPD pharmacological treatment. Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators. Some LAMA/device systems with different characteristics and dosing schedules are currently approved for maintenance therapy of COPD and a range of other products are being developed. They improve lung function and patient-reported outcomes and reduce acute bronchial exacerbations with good safety. LAMAs are used either alone or associated with long-acting β₂-agonists, eventually in fixed dose combinations. Long-acting β₂-agonist/LAMA combinations assure additional benefits over the individual components alone. The reader will obtain a view of the safety and efficacy of the different LAMA/device systems in COPD patients.

Effectiveness and safety of concurrent beta-blockers and inhaled bronchodilators in COPD with cardiovascular comorbidities

“…Tiotropium was associated with higher cardiovascular mortality risk. However, in another context, tiotropium was shown to be more effective in reducing exacerbations than salmeterol and indacaterol, regardless of association with inhaled corticosteroids [27,28]. Moreover, the UPLIFT study (Understanding Potential Long-term Impacts on Function with Tiotropium), a double-blind, randomised, placebo-controlled clinical trial conducted on >6000 patients (followed up for 4 years), revealed a reduced acute myocardial infarction and cardiovascular mortality incidence versus placebo [29].…”

Safety of long acting muscarinic antagonists: are all these drugs always and equally safe?

“…Until recently tiotropium was the only marketed LAMA, but other LAMAs are currently available, such as aclidinium and glycopyrronium. Umeclidinium bromide (UMEC) is also a newer LAMA, being a potent antagonist of M3 muscarinic receptors with long-term duration of bronchodilation 1 . Several controlled trials have suggested that the optimal dosing of UMEC is 62.5 mg once daily (OD).…”

“…Few head-to-head studies between LAMAs have been performed, but the current idea is that they are equivalent in efficacy. However, as more LAMAs are available, clinicians shall decide the first choice among LAMAs and possibly safety may have a key-role 1 . Even if inhaled LAMAs are generally considered to be safe, muscarinic receptors are expressed not only in the lungs, but also at the level of heart, digestive and urinary apparatus.…”

“…The most common adverse events of subjects receiving tiotropium compared to placebo were dry mouth, constipation and urinary retention, usually mild and seldom causing the stopping of treatment. Meta-analyses and some observational studies have shown that tiotropium, mainly when delivered via the Soft Mist Inhaler Respimat, increased the risk of nonfatal and fatal cardiovascular events 1,2 . Although this point is debated, it is important to add information from studies to establish the safety of newer agents 1,3 .…”

“…Meta-analyses and some observational studies have shown that tiotropium, mainly when delivered via the Soft Mist Inhaler Respimat, increased the risk of nonfatal and fatal cardiovascular events 1,2 . Although this point is debated, it is important to add information from studies to establish the safety of newer agents 1,3 . Overall, the risk of serious adverse events is increased at higher than recommended dosages.…”