Suissa Samy, Dell'Aniello Sophie, Ernst Pierre
Centre for Clinical Epidemiology, Lady Davis Institute-Jewish General Hospital; Montreal, QC; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada.
Centre for Clinical Epidemiology, Lady Davis Institute-Jewish General Hospital; Montreal, QC.
Chest. 2025 Mar;167(3):712-723. doi: 10.1016/j.chest.2024.10.025. Epub 2024 Oct 24.
Recent treatment guidelines for COPD have replaced the long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) combination with single-inhaler triple therapy that adds a long-acting muscarinic antagonist (LAMA). However, the corresponding trials reported numerically higher incidences of cardiovascular adverse events with triple therapy compared with LABA-ICS.
Does single-inhaler triple therapy increase the incidence of major adverse cardiovascular events, compared with LABA-ICS, in a real-world clinical practice setting?
We identified a cohort of patients with COPD aged ≥ 40 years treated during 2017-2021 from the UK's Clinical Practice Research Datalink. Among LAMA-naive patients, initiators of single-inhaler triple therapy were matched 1:1 to LABA-ICS users on time-conditional propensity scores. They were compared on the incidence of major adverse cardiovascular events (MACEs), defined as hospitalization for myocardial infarction or stroke, or all-cause-mortality, over 1 year.
The cohort included 10,255 initiators of triple therapy and 10,255 matched users of LABA-ICS. The incidence rate of MACEs was 11.3 per 100 per year with triple therapy compared with 8.8 per 100 per year for LABA-ICS. The corresponding adjusted hazard ratio (HR) of MACEs with triple therapy was 1.28 (95% CI, 1.05-1.55), relative to LABA-ICS; however, the increase was mainly in the first 4 months (HR, 1.41; 95% CI, 1.14-1.74). The HR of all-cause death was 1.31 (95% CI, 1.06-1.62), whereas for acute myocardial infarction and stroke hospitalization it was 1.00 (95% CI, 0.56-1.79) and 1.06 (95% CI, 0.48-2.36), respectively, with triple therapy, relative to LABA-ICS.
In a real-world setting of COPD treatment, patients who initiated single-inhaler triple therapy had an increased incidence of MACEs compared with similar patients treated with an LABA-ICS inhaler. This small increase was due to the all-cause mortality component, occurring mainly in the first 4 months after treatment initiation.
慢性阻塞性肺疾病（COPD）的最新治疗指南已将长效β受体激动剂（LABA）与吸入性糖皮质激素（ICS）联合用药替换为添加长效毒蕈碱拮抗剂（LAMA）的单吸入器三联疗法。然而，相应试验报告显示，与LABA-ICS相比，三联疗法的心血管不良事件发生率在数值上更高。
在真实世界的临床实践环境中，与LABA-ICS相比，单吸入器三联疗法是否会增加主要不良心血管事件的发生率？
我们从英国临床实践研究数据链中确定了一组2017年至2021年期间接受治疗的年龄≥40岁的COPD患者队列。在未使用过LAMA的患者中，根据时间条件倾向评分，将单吸入器三联疗法的起始者与LABA-ICS使用者按1:1进行匹配。比较他们在1年内主要不良心血管事件（MACE）的发生率，MACE定义为因心肌梗死或中风住院或全因死亡率。
该队列包括10255名单吸入器三联疗法的起始者和10255名匹配的LABA-ICS使用者。三联疗法的MACE发生率为每年每100人中有11.3例，而LABA-ICS为每年每100人中有8.8例。与LABA-ICS相比，三联疗法MACE的相应调整后风险比（HR）为1.28（95%CI，1.05-1.55）；然而，增加主要发生在开始的4个月内（HR，1.41；95%CI，1.14-1.74）。全因死亡的HR为1.31（95%CI，1.06-1.62），而三联疗法与LABA-ICS相比，急性心肌梗死和中风住院的HR分别为1.00（95%CI，0.56-1.79）和1.06（95%CI，0.48-2.36）。
在COPD治疗的真实世界环境中，与接受LABA-ICS吸入器治疗的类似患者相比，开始使用单吸入器三联疗法的患者MACE发生率有所增加。这种小幅增加是由于全因死亡率部分，主要发生在治疗开始后的前4个月。
