In a nested case-control study published in the journal JAMA Internal Medicine, researchers have reported that in patients with chronic obstructive pulmonary disease (COPD), new use of inhaled long-acting β2-agonists (LABAs) or long-acting antimuscarinic antagonists (LAMAs) is associated with an approximate 1.5-fold increased cardiovascular risk within one month of initiation therapy.

The associations between cardiovascular disease (CVD) and inhaled long-acting β2-agonists (LABAs) or long-acting antimuscarinic antagonists (LAMAs) in chronic obstructive pulmonary disease (COPD) are greatly debated. Pivotal and relevant randomized clinical trials included prior LABA or LAMA users and excluded patients with baseline CVD; therefore, cardiovascular events arising from first-time LABA or LAMA use, if any, could not be observed.

The research team said there is an urgent requirement to examine whether new use of and duration since initiating LABAs and LAMAs could act as important determinants of cardiovascular events. The study aimed to investigate risk of CVD associated with LABAs and LAMAs, focusing on the initiation and duration of LABA and LAMA therapies.

The nested case-control study included 284?220 LABA-LAMA–naïve patients with COPD at least 40 years old (mean age, 71.4 years; 68.9% men), retrieved from the Taiwan National Health Insurance Research Database for health care claims. LABA or LAMA use was measured in the year preceding the event or index date, stratified by duration since initiation of LABA or LAMA treatment, new and prevalent users, concomitant COPD medications, and individual agents.

Cases with inpatient or emergency care visits for coronary artery disease, heart failure, ischemic stroke, or arrhythmia were identified and individually matched to 4 randomly selected controls. Conditional logistic regressions were performed to estimate odds ratios of CVD from LABA and LAMA treatment.

During a mean follow-up of 2.0 years, 37?719 patients with CVD (mean age, 75.6 years; 71.6% men) and 146?139 matched controls (mean age, 75.2 years; 70.1% men) were identified. New LABA and LAMA use in COPD was associated with a 1.50-fold (95% CI, 1.35-1.67; P < .001) and a 1.52-fold (95% CI, 1.28-1.80; P < .001) increased cardiovascular risk within 30 days of initiation, respectively, whereas the risk was absent, or even reduced with prevalent use.

Individual inhaled long-acting β2-agonists (LABAs) agents, long-acting antimuscarinic antagonists (LAMAs) dosage forms, and concomitant COPD regimens did not differ in the cardiovascular disease (CVD) risks. The risk persisted in an alternative case-crossover study and remained across subgroups without CVD history or prior exacerbations.

The team showed that new initiation of LABAs or LAMAs in patients with COPD is associated with an approximate 1.5-fold increased severe cardiovascular risk, irrespective of prior CVD status and history of exacerbations. Hence, health care professionals need to be very cautious with regard to any cardiovascular symptoms within one month of initiating LABA or LAMA treatment for COPD.