Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

CVD Risk with LABAs and LAMAs in COPD

JAMA Intern Med; ePub 2018 Jan 2; Wang, et al

In patients with chronic obstructive pulmonary disease (COPD), new initiation of inhaled long-acting bronchodilators is associated with an approximate 1.5-fold increased severe cardiovascular (CV) risk. This risk is irrespective of prior CVD status and history of exacerbations. The nested case-control study included 284,220 patients (mean age 71.4 years, 69% men) with COPD on long-acting β2-agonisits (LABAs) or long-acting antimuscarinic antagonists (LAMAs) and examined risk of CVD associated with LABAs and LAMAs. Researchers found:

  • During a follow-up of 2.0 years, 37,719 patients with CVD and 146,139 matched controls were identified.
  • New LABA and LAMA use in COPD was associated with a 1.50-fold and a 1.52-fold increased CV risk within 30 days of initiation, respectively.
  • With continued use the risk was absent and even reduced below comparator risk.
  • LAMA dosage forms, and concomitant COPD regimens did not differ in the CVD risks.


Wang M, Liou J, Lin CW, et al. Association of cardiovascular risk with inhaled long-acting bronchodilators in patients with chronic obstructive pulmonary disease. A nested case-control study. [Published online ahead of print January 02, 2018]. JAMA Intern Med. doi:10.1001/jamainternmed.2017.7720.


Long-acting bronchodilators (LABAs and LAMAs) are the mainstay of treatment for patients with COPD. The signal about increased CV risk in patients with COPD has had incredibly contradictory evidence in the literature, with some studies suggesting increase in risk and others suggesting that there is not an increased risk. Two large randomized trials, the UPLIFT (tiotropium) and TORCH (Salmeterol and fluticasone propionate) showed a reduction in or no increase in CVD risk.1,2 The study reviewed above uses case-control methodology which increases the power of the study to detect a signal if one exists and eliminates the potential bias that may be existent in a randomized trial if patients who had a negative previous event on a bronchodilator were not included in the study. As a case-control study it cannot control for potential confounding variables which may influence the results. The results of the study showed an initial increase in risk that lasted approximately 30 days, followed by a decrease in risk over time. — Neil Skolnik, MD

  1. Calverley PM, Anderson JA, Celli B, et al; TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356(8):775- 789.
  2. Tashkin DP, Celli B, Senn S, et al; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543-1554.