Wise Robert A, Chapman Kenneth R, Scirica Benjamin M, Schoenfeld David A, Bhatt Deepak L, Daoud Sami Z, Seoane Beatriz, Reisner Colin, Garcia Gil Esther
1-Johns Hopkins University School of Medicine, Baltimore, Maryland.
2-University of Toronto, Ontario, Canada.
Chronic Obstr Pulm Dis. 2018 Jan 24;5(1):5-15. doi: 10.15326/jcopdf.5.1.2017.0149.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous illness characterized by persistent airflow obstruction and exacerbations. Patients typically experience a decline in lung function, increasingly impaired health-related quality of life, and high mortality. Poor lung function and exacerbations are associated with an increased risk of cardiovascular (CV) and cerebrovascular events, and approximately 30% of patients with COPD die from CV‑related disease. Treatment with inhaled long-acting bronchodilators, such as long-acting muscarinic antagonists (LAMAs), is recommended; however, some studies have suggested that LAMAs may increase the risk of CV events. As patients with CV and cerebrovascular conditions are often excluded from clinical trials, an evaluation of the safety of COPD treatments in an at-risk population is vital. Aclidinium bromide is a LAMA approved for the long-term maintenance treatment of COPD. The Phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group clidinium Bromide on Long-Term Cardiovascular afety and OPD xacerbations in Paties with Moderate to Very Severe (ASCENT COPD) study (NCT01966107) is being conducted at 500 sites in the United States and Canada. The primary objectives are to evaluate the long-term effects of twice-daily aclidinium bromide 400 µg on CV safety and exacerbations in patients with moderate to very severe COPD with a history of cerebrovascular, coronary, or peripheral artery disease, or the presence of ≥2 atherothrombotic risk factors. The primary safety and efficacy variables are time to first major adverse CV event (MACE) (on-study analysis) and rate of moderate to severe COPD exacerbations during the first year of treatment (on-treatment analysis), respectively. The study will be terminated after approximately 122 MACE have occurred.
慢性阻塞性肺疾病（COPD）是一种异质性疾病，其特征为持续性气流受限和病情加重。患者通常会出现肺功能下降、与健康相关的生活质量日益受损以及高死亡率。肺功能差和病情加重与心血管（CV）和脑血管事件风险增加相关，约30%的COPD患者死于与CV相关的疾病。推荐使用吸入长效支气管扩张剂进行治疗，如长效毒蕈碱拮抗剂（LAMA）；然而，一些研究表明LAMA可能会增加CV事件风险。由于患有CV和脑血管疾病的患者通常被排除在临床试验之外，因此评估COPD治疗在高危人群中的安全性至关重要。阿地溴铵是一种被批准用于COPD长期维持治疗的LAMA。正在美国和加拿大的500个地点开展4期、多中心、双盲、随机、安慰剂对照、平行组的阿地溴铵对中重度COPD患者长期心血管安全性及病情加重影响的研究（ASCENT COPD）（NCT01966107）。主要目的是评估每日两次400µg阿地溴铵对有脑血管、冠状动脉或外周动脉疾病病史或存在≥2个动脉粥样硬化血栓形成危险因素的中重度COPD患者的CV安全性和病情加重情况的长期影响。主要安全性和有效性变量分别是首次发生主要不良CV事件（MACE）的时间（研究期间分析）和治疗第一年中重度COPD病情加重率（治疗期间分析）。在发生约122例MACE后，该研究将终止。
