TABLE 3

Characteristics of studies using long-acting β-agonists (LABAs) and/or long-acting muscarinic receptor antagonists (LAMAs) in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidities

First author [ref.]YearDesignPopulationSafety outcome
Tricco [22]2015Systematic review and network meta-analysis of 208 randomised clinical trials134 692 adults with COPDNo statistically significant differences in risks of serious arrhythmia across any of the compared agents
Tashkin [23]2015Post hoc analysis of all-cause mortality and serious cardiac adverse events using data from the UPLIFT study6562 patients with COPD with recent myocardial infarction, heart failure or unstable rhythm disorderRisk of cardiac events, mortality or SAEs was not increased by tiotropium versus placebo in patients experiencing cardiac events
Oba [24]2016Systematic review and network meta-analysis of 23 trials27 172 patients older than 35 or 40 years with a diagnosis of COPDCombination therapy had similar effects on safety outcomes, including mortality, total SAEs, cardiac SAEs and dropouts, compared with monotherapy
Calzetta [25]2016Systematic review and meta-analysis of 22 randomised clinical trials23 168 with a diagnosis of COPDNo evidence of any significant difference concerning the cardiac safety profile of combination therapy compared with monocomponents
Lahousse [26]2016Review of 93 studies about cardiac safety of bronchodilatator therapy in COPD>700 000 patients with a diagnosis of COPDLAMAs and/or LABAs are safe when used in the appropriate dose in adherent patients with COPD without uncontrolled cardiovascular disease or other notable comorbidities; cardiac safety is less evident when used inappropriately (e.g. overdosing) or in patients with COPD and substantial cardiovascular disease, prolonged QTc interval or polypharmacy

UPLIFT: Understanding Potential Long-term Impacts on Function with Tiotropium; SAEs: severe adverse effects.