Patients with chronic obstructive pulmonary disease (COPD) who initiate treatment with inhaled long-acting beta2-agonists (LABAs) or long-acting antimuscarinic antagonists (LAMAs) may be at increased risk for cardiovascular disease (CVD), according to a new study.
Researchers in Taiwan performed a nested case-control study using national data from 2007 to 2011 to examine whether new LAMA or LABA therapy in patients with COPD was associated with CVD risk. Patients with COPD who had never taken either type of drug and who were at least 40 years of age were enrolled in the study and were followed for CVD events. Use of LAMAs or LABAs was measured in the year before a CVD event or the index date and was stratified by duration of treatment, new and prevalent use, concomitant medications for COPD, and individual agents.
Current use was defined as within 30 days or more recently, recent use was defined as within 31 to 90 days, past use was defined as within 91 to 180 days, and remote use was defined as more than 180 days ago. The current user category was further divided into new users (those with no other dispensing records noted in the 31 to 365 days preceding the index date) and prevalent users (all remaining current users). Patients with COPD who had had inpatient or emergency care for coronary artery disease, heart failure, ischemic stroke, or arrhythmia were individually matched to four randomly selected controls, and odds ratios for CVD were estimated according to treatment with LABAs and LAMAs. The study results were published online Jan. 2 by JAMA Internal Medicine.
Overall, 284,200 patients with COPD who were new to LABA and LAMA treatment were included in the study. The mean age was 71.4 years, and 68.9% were men. A total of 37,719 patients with CVD and 146,139 matched controls (mean age, 75.6 years and 75.2 years; 71.6% and 70.1% men, respectively) were identified over a mean follow-up of 2.0 years. New use of LABA and LAMA in COPD was associated with a 1.50-fold increase and a 1.52-fold increase in cardiovascular risk within 30 days of treatment initiation, respectively (P<0.001 for both comparisons), while patients with prevalent use had a reduction in CVD risk of 9% to 12%. In a duration-response analysis, CVD risk peaked at approximately the 30th day after new initiation of LABA or LAMA or therapy, decreased at 31 to 60 days, and decreased further below baseline risk from 71 to 240 days. No difference in CVD risk was seen by LABA agent, LAMA dosage form, or concomitant COPD regimen.
The authors noted that their results could have been affected by selection bias and by patients' CVD status at baseline and that data on other determinants of CVD, such as smoking and alcohol use, were not available, among other limitations. However, they concluded that new use of LABAs or LAMAs in patients with COPD was associated with increased CVD risk in the first 30 days of treatment. “We caution physicians to closely monitor new users of LABAs or LAMAs for cardiovascular symptoms,” the authors wrote.