Cardiovascular, Cerebrovascular Risk Examined for LABA/LAMA in COPD

According to a new study published in the Annals of Pharmacotherapy, the combination of long-acting β₂-agonist (LABA)/ and long-acting muscarinic antagonist (LAMA) is associated with a similar or lower risk of cardiovascular and cerebrovascular adverse events compared to treatment with LABA/inhaled corticosteroid (ICS).  

The FDA recently approved several fixed-dose combination LABA/LAMA products, leading to a rise of usage in patients with chronic obstructive pulmonary disease (COPD). However, with these approvals come concerns regarding safety as both LABAs and LAMAs can affect receptors in the cardiac muscle.

To investigate these risks, researchers at the University of Illinois, Chicago, conducted a retrospective, observational cohort study using the Truven Health MarketScan Commercial Claims and Encounters and the MarketScan Medicare Supplement database. Patients were identified from January 2004 through December 2014 and followed until they had a cardiovascular cerebrovascular event (CCV) or when they discontinued use of either medication or health insurance data was lost.

The authors matched patients 1:4 on propensity scores (PSs), leaving 3,842 in the LABA/LAMA cohort and 15,225 in the LABA/ICS cohort. 

Overall results demonstrated that for the LABA/LAMA cohort cardiovascular event frequency was 2.11% compared to 3.41% in the LABA/ICS cohort. Cerebrovascular event frequency was 0.42% for LABA/LAMA and 0.46% for LABA/ICS cohorts. The hazard ratio showed a lower risk of cardiovascular events in the LABA/LAMA cohort (0.79, 95% CI=0.62–0.99), while for cerebrovascular events the hazard ratio was not significantly different between cohorts (1.17, 95% CI = 0.65–1.96).

When the authors combined CCV events into one outcome they found a lower hazard ratio among LABA/LAMA when compared to the LABA/ICS cohort, however it was not significantly different (HR=0.85, 95% CI=0.66–1.04).

“This study showed a lower HR for time to cardiovascular events in the LABA/LAMA cohort,” the authors stated, ” Results were most prominent in patients at high risk for CCV events, although the effect was not observed in patients at low risk for cerebrovascular events given that the HR increased.”  Despite these findings, they concluded that given the increased use of fixed-dose LABA/LAMA treatments, more studies should be conducted in order to confirm these results.

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