Leukotriene receptor antagonists and lower risk of major adverse cardiovascular events in patients with asthma
J Q Le Van, S Beradid, S Suissa, P Ernst, C RenouxAbstract
Background
Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality worldwide and is characterized by inflammatory processes involved in plaque development. The leukotriene pathway contributes to vascular inflammation and may play a role in atherosclerosis. By modulating this pathway, leukotriene receptor antagonists (LTRA), currently used in asthma, could potentially reduce inflammatory mechanisms relevant to plaque formation and have potential for repurposing in cardiovascular prevention.
Objective
To evaluate whether LTRA use is associated with lower risk of major adverse cardiovascular events (MACE) in patients with asthma compared with long-acting beta-agonist (LABA) use.
Methods
We first formed a base cohort of patients aged ≥40 years with active asthma between 2000 and 2023 from the United Kingdom Clinical Practice Research Datalink. Using a prevalent new-user design, all patients initiating LTRAs (montelukast or zafirlukast) were identified to create time-based exposure sets including all eligible LABA comparators with the same age, sex, prior coronary artery disease status, and prior LABA use. Each LTRA initiator was then matched 1:1 without replacement to a comparator LABA user with the closest time-conditional propensity score. Patients were followed until outcome occurrence, treatment discontinuation or switch to the other exposure group, end of registration, death, or end of the study period, whichever occurred first. We used a Cox proportional hazards model to estimate hazard ratio (HR) with 95% confidence interval (CI) for MACE, defined as myocardial infarction, ischaemic stroke, or cardiovascular death. We also assessed the individual components of MACE and MACE+, defined as an extended composite of MACE plus transient ischaemic attack and unstable angina, as secondary outcomes.
Results
The study cohort included 55,997 patients LTRA users matched to 55,997 LABA users. Mean age was 59.4 (standard deviation 11.0) years, 66.8% were female and 5.0% had prior coronary artery disease. During 123,810 years of follow-up, 891 MACE occurred. LTRA use was associated with lower risk of MACE compared with LABA use, with adjusted incidence rates of 6.64 vs 7.91 events per 1,000 person-years (HR 0.83; 95% CI 0.73–0.95). For individual components of the MACE, myocardial infarction (HR 0.90; 95% CI 0.74–1.10), ischaemic stroke (HR 0.88; 95% CI 0.69–1.11), and cardiovascular death (HR 0.67; 95% CI 0.51–0.88) showed similar patterns. LTRA use was also associated with lower risk of MACE+ (HR 0.89; 95% CI 0.79–1.00). Findings did not differ by age and sex. Results using an intention-to-treat approach with follow-up restricted to 1 year were consistent with the primary analyses.
Conclusion
LTRA use was associated with a lower risk of MACE compared with LABA use in patients with asthma and supports further evaluation of LTRA for cardiovascular prevention.Primary analyses