Comparative cardiovascular safety of LABA/LAMA FDC versus LABA/ICS FDC in patients with chronic obstructive pulmonary disease: a population-based cohort study with a target trial emulation framework

Respir Res. 2023 Sep 29;24(1):239. doi: 10.1186/s12931-023-02545-9.

Abstract

Background: Use of combinations of long-acting β2 agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant.

Aim: The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies.

Methods: We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017-2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS).

Results: Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78-1.01) for the composite events, 0.80 (95% CI, 0.61-1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68-3.25) for unstable angina, 1.00 (95% CI, 0.80-1.24) for congestive heart failure, 0.62 (95% CI, 0.37-1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66-1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses.

Conclusion: Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.

Keywords: Cardiovascular events; Chronic obstructive pulmonary disease; Cohort study; Fixed-dose combinations (FDC); Long-acting β2 agonists/inhaled corticosteroids (LABA/ICS); Long-acting β2 agonists/long-acting muscarinic antagonists (LABA/LAMA); Target trial emulation framework.

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / adverse effects
  • Angina, Unstable / chemically induced
  • Angina, Unstable / drug therapy
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / drug therapy
  • Bronchodilator Agents / adverse effects
  • Clinical Trials as Topic
  • Cohort Studies
  • Drug Therapy, Combination
  • Heart Failure* / drug therapy
  • Humans
  • Ischemic Stroke* / chemically induced
  • Ischemic Stroke* / drug therapy
  • Muscarinic Antagonists / adverse effects
  • Myocardial Infarction* / diagnosis
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / epidemiology
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / epidemiology

Substances

  • Adrenal Cortex Hormones
  • Bronchodilator Agents
  • Muscarinic Antagonists