Inhaled long-acting bronchodilators may carry an elevated cardiovascular risk in the first 30 days of use by patients with chronic obstructive pulmonary disease (COPD), but it tapers afterward, according to a randomized study.
At the 30-day mark, these patients had approximately 50% higher odds of a severe cardiovascular event — hospital admission for coronary heart disease, cardiac arrhythmia, heart failure, ischemic stroke — after initiating long-acting β2-agonist (LABA; adjusted OR 1.50, 95% CI 1.35-1.67) or long-acting antimuscarinic antagonist (LAMA; adjusted OR 1.52, 95% CI 1.28-1.80) therapy.
Yet those who had previously been on LABA/LAMAs had their cardiovascular risk reduced when they went back on these inhaled long-acting bronchodilators more than 30 days later (LABA: adjusted OR 0.91, 95% CI 0.85-0.98; LAMA: adjusted OR 0.88, 95% CI 0.79-0.98), investigators led by Meng-Ting Wang, PhD, of Taiwan’s National Defense Medical Center, found and reported in JAMA Internal Medicine.
It turned out that the cardiovascular risks peaked at around the 30th day after new initiation of LABA or LAMA therapy, waned from 31 to 60 days on, and reduced to a level even lower than the baseline risk from 71 to 240 days, they said.
“Based on our findings, we suggest that the use of inhaled long-acting bronchodilators in COPD need to be carefully assessed, and a thorough cardiovascular physical examination, especially heart rate measurement and electrocardiograms, need to be performed when prescribing LABAs and LAMAs to patients,” Wang’s group urged.
“Given that cardiovascular disease is highly prevalent among patients with COPD, clinicians should also pay attention to the management of cardiovascular disease risk factors throughout the duration of LABA or LAMA therapy,” they added. “We also suggest that physicians assess patients’ cardiovascular risk before initiation of LABAs or LAMAs, and, if needed, a preventive therapy for cardiovascular disease should be considered during the initial treatment of inhaled long-acting bronchodilators.”
In 2010, the FDA warned against use of single-agent LABA products in patients with asthma, because studies had indicated an increase in mortality risk. But that warning did not apply to LABAs used to treat COPD, and no formal warnings of any kind are in place for LAMA drugs.
From the Taiwan National Health Insurance Research Database, the investigators identified COPD patients ages 40 and older who were not on long-acting bronchodilators at baseline for their study (n=284,220). Drug use was gleaned from the most recent prescription date preceding the index cardiovascular disease event.
Of those, 37,719 had a cardiovascular disease event over 2 years requiring hospitalization or emergency care (6.6 per 100 person-years). Wang and colleagues matched them by cohort entry date and disease risk score to 146,139 controls.
Randomization still left room for unmeasured confounders such as smoking and alcohol use, the authors said. Moreover, they could not assess the impact of newer inhaled COPD drugs.
Wang declared no relevant conflicts of interest.