Evaluating the Impact of Triple Therapy on Mortality in Copd: The End is the Beginning?
Evaluating the Impact of Triple Therapy on Mortality in Copd: The End is the Beginning?
复制标题
评估三联疗法对慢性阻塞性肺病死亡率的影响：结束就是开始？
DOI：
10.1080/15412555.2021.1998410
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发表时间：
2022
期刊：
影响因子：
2.2
通讯作者：
Athena Gogali
中科院分区：
文献类型：
--
作者：
K. Kostikas;C. Kyriakopoulos;Athena Gogali
长期以来，死亡率一直是COPD管理的两个“圣杯”之一，第二个是疾病自然史的变化，如FEV 1下降率所示。关于吸入性皮质类固醇（ICS）在降低死亡率方面的作用的宣传由来已久，因为有证据表明这些药物可降低急性加重[1]和FEV 1的下降率[2]。然而，设计用于评价全因死亡率作为主要终点的ICS/长效β-激动剂（LABA）联合用药的两项大型试验未能显示这些联合用药与安慰剂相比的死亡率获益：TORCH试验显示沙美特罗/丙酸氟替卡松使死亡率降低17.5%，但未达到统计学显著性，P值为0.052 [3]，而SUMMIT试验未显示维兰特罗/糠酸氟替卡松对有心血管疾病史或心血管危险因素的COPD患者有任何生存获益[4]。其他没有把握度评价死亡率的试验提供了相反的结果，在COPD急性加重患者中进行的2年INSPIRE试验显示沙美特罗/氟替卡松相对于噻托溴铵具有死亡率获益[5]，而在比较沙美特罗/氟替卡松与LABA/长效毒蕈碱拮抗剂（LAMA）联合用药（茚达特罗/格隆溴铵）的FLAME试验中情况并非如此[6]，不允许得出明确的结论。最近，在大型IMPACT [7]和ETHOS [8]试验中重新讨论了这一主题，结果显示，
Mortality has long been one of the two “Holy Grails” of COPD management, the second being the change in the natural history of the disease, as expressed by the rate of decline of FEV 1 . The hype around the role of inhaled corticosteroids (ICS) in mortality reduction has been long-standing, as there is evidence that these drugs reduce exacerbations [1] and the rate of decline of FEV 1 [2]. However, the two mega-trials of combinations of ICS/long-acting β-agonist (LABA) designed to evaluate all-cause mortality as the primary endpoint, were not able to show a mortality benefit for these combinations vs. placebo: the TORCH trial showed a 17.5% reduction in mortality with salmeterol/fluticasone propionate that did not reach statistical significance with the notorious p-value of 0.052 [3], whereas the SUMMIT trial did not show any survival benefit for vilanterol/fluticasone furoate in COPD patients with history of cardiovascular disease or with cardiovascular risk factors [4]. Other trials that were not powered to evaluate mortality have provided con-tradicting results, with the 2-year INSPIRE trial in exacer-bating COPD patients showing a mortality benefit for salmeterol/fluticasone vs. tiotropium [5], whereas that was not the case for the FLAME trial in the comparison of salmeterol/fluticasone and the LABA/long-acting muscarinic antagonist (LAMA) combination of indacaterol/glycopyrro-nium [6], not allowing for firm conclusions. Recently the topic was revisited in the large IMPACT [7] and ETHOS [8] trials, that showed a 28% and 49% reduction in mortality with