BACKGROUND Recent treatment guidelines for chronic obstructive pulmonary disease (COPD) have replaced the long-acting beta2-agonist and inhaled corticosteroid (LABA-ICS) combination with single-inhaler triple therapy that adds a long-acting muscarinic antagonist (LAMA-LABA-ICS). Yet, the corresponding trials reported numerically higher incidences of cardiovascular adverse events with triple therapy compared with LABA-ICS. RESEARCH QUESTION Does single-inhaler triple therapy increase the incidence of major adverse cardiovascular events, compared with LABA-ICS, in a real-world clinical practice setting? STUDY DESIGN AND METHODS We identified a cohort of COPD patients, 40 years or older, treated during 2017-2021, from the United Kingdom's Clinical Practice Research Datalink. Among LAMA-naïve 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 (MACE), defined as hospitalization for myocardial infarction or stroke, or all-cause-mortality, over one year. RESULTS The cohort included 10,255 initiators of triple therapy and 10,255 matched users of LABA-ICS. The incidence rate of MACE was 11.3 per 100 per year with triple therapy compared with 8.7 per 100 per year for LABA-ICS. The corresponding adjusted hazard ratio (HR) of MACE with triple therapy was 1.28 (95% CI: 1.05-1.55), relative to LABA-ICS, though the increase was mainly in the first four 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), while 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. INTERPRETATION In a real-world setting of COPD treatment, patients who initiated single-inhaler triple therapy had an increased incidence of MACE compared with similar patients treated with a LABA-ICS inhaler. This small increase was due to the all-cause mortality component, occurring mainly in the first four months after treatment initiation.

中文翻译：

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COPD 的单吸入器三联疗法与 LABA-ICS 疗法：实际临床实践中的比较安全性。


背景 最近的慢性阻塞性肺疾病 （COPD） 治疗指南已经用单吸入器三联疗法取代了长效 β2 受体激动剂和吸入皮质类固醇 （LABA-ICS） 联合疗法，该疗法增加了长效毒蕈碱拮抗剂 （LAMA-LABA-ICS）。然而，相应的试验报告称，与 LABA-ICS 相比，三联疗法的心血管不良事件发生率更高。研究问题 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？研究设计和方法 我们从英国的临床实践研究数据链中确定了一组 40 岁或以上的 COPD 患者，他们在 2017-2021 年期间接受了治疗。在未接受过 LAMA 治疗的患者中，单吸入器三联疗法的启动者在时间条件倾向评分上与 LABA-ICS 使用者 1：1 匹配。比较了他们一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。结果 该队列包括 10,255 名三联疗法的启动者和 10,255 名匹配的 LABA-ICS 用户。三联疗法的 MACE 发病率为每年 11.3/100，而 LABA-ICS 的年发病率为 8.7/100。相对于 LABA-ICS，三联疗法 MACE 的相应调整后风险比 （HR） 为 1.28 （95% CI： 1.05-1.55），尽管增加主要发生在前四个月 （HR 1.41;95% CI： 1.14-1.74）。相对于 LABA-ICS，全因死亡的 HR 为 1.31 （95% CI： 1.06-1.62），而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），相对于 LABA-ICS。 解释 在 COPD 治疗的真实环境中，与接受 LABA-ICS 吸入器治疗的类似患者相比，开始单吸入器三联疗法的患者 MACE 发生率增加。这种小幅增加是由于全因死亡率成分，主要发生在治疗开始后的前 4 个月。