哮喘患者使用长效支气管扩张剂的心血管风险：22项随机对照试验的荟萃分析
2025/04/06
摘要
背景：长效支气管扩张剂与吸入性糖皮质激素（ICS）联合使用可以改善哮喘的控制。然而，这些药物对哮喘患者的心血管安全性从未得到全面评估。值得注意的是，越来越多的证据表明哮喘与心血管疾病之间存在正相关关系。
目的：评价哮喘患者加用长效支气管扩张剂的心血管安全性。
方法：在PubMed、Embase、Cochrane Library和Web of Science上进行全面检索后，我们纳入了评估长效支气管扩张剂对哮喘患者心血管安全性的随机对照试验。主要结局是总心血管不良事件发生率的比较。次要结局包括药物相关不良事件、导致停药的不良事件、严重不良事件和致命不良事件。
结果：共纳入22项试验，62915名患者。使用长效支气管扩张剂显著增加了导致停药的心血管不良事件的发生率（IRR:3.05，95%CI:1.07-8.48）。在接受长效支气管扩张剂治疗的患者中，总心血管不良事件、药物相关不良事件、严重不良事件和致命不良事件的发生率较高，但差异不显著。对于总心血管不良事件和致命不良事件的比较，证据的确定性较低。对于药物相关不良事件、导致停药的不良事件和严重不良事件的比较，证据的确定性非常低。
结论：哮喘患者心血管不良事件的发生率相当低，与未接触长效支气管扩张剂的患者相比，只有导致停药的不良事件风险显著增加。考虑到潜在的报告偏差，需要更多的研究来证实目前的发现。
Cardiovascular Risk of the Use of Long-acting Bronchodilators in Patients with Asthma: A Meta-analysis of 22 Randomized Controlled Trials
Le Bai, Tingyuan Li, Dongwei Zhu, Qi Zhao, Yong Xu, Xianmei Zhou
Abstract
Background: Long-acting bronchodilators can improve the control of asthma when added to inhaled corticosteroids (ICS). However, the cardiovascular safety of these drugs in patients with asthma has never been comprehensively evaluated. Notably, growing evidence have indicated a positive association between asthma and cardiovascular diseases.
Objective: To evaluate the cardiovascular safety of addition of long-acting bronchodilators in patients with asthma.
Methods: After a comprehensive retrieval in PubMed, Embase, Cochrane Library and Web of Science, we included randomized controlled trials that assessed the cardiovascular safety of long-acting bronchodilators in patients with asthma. The primary outcome was the comparation of incidence of total cardiovascular AEs. Secondary outcomes included drug-related AEs, AEs leading to discontinuation, serious AEs and fatal AEs.
Results: A total of 22 trials with 62,915 patients were included. The use of long-acting bronchodilators significantly increased the incidence of cardiovascular AEs leading to discontinuation (IRR: 3.05, 95% CI: 1.07-8.48). The incidences of total cardiovascular AEs, drug-related AEs, serious AEs and fatal AEs were higher in patients treated with long-acting bronchodilators, but the differences were not significant. The certainty of evidence was low for comparations of total cardiovascular AEs and fatal AEs. The certainty of evidence was very low for comparations of drug-related AEs, AEs leading to discontinuation and serious AEs.
Conclusion: The incidence of cardiovascular AEs was quite low in patients with asthma, and only the risk of AEs leading to discontinuation significantly increased compared with those not exposure to long-acting bronchodilators. More studies are required to confirm the present findings in consideration of the potential reporting bias.
背景：长效支气管扩张剂与吸入性糖皮质激素（ICS）联合使用可以改善哮喘的控制。然而，这些药物对哮喘患者的心血管安全性从未得到全面评估。值得注意的是，越来越多的证据表明哮喘与心血管疾病之间存在正相关关系。
目的：评价哮喘患者加用长效支气管扩张剂的心血管安全性。
方法：在PubMed、Embase、Cochrane Library和Web of Science上进行全面检索后，我们纳入了评估长效支气管扩张剂对哮喘患者心血管安全性的随机对照试验。主要结局是总心血管不良事件发生率的比较。次要结局包括药物相关不良事件、导致停药的不良事件、严重不良事件和致命不良事件。
结果：共纳入22项试验，62915名患者。使用长效支气管扩张剂显著增加了导致停药的心血管不良事件的发生率（IRR:3.05，95%CI:1.07-8.48）。在接受长效支气管扩张剂治疗的患者中，总心血管不良事件、药物相关不良事件、严重不良事件和致命不良事件的发生率较高，但差异不显著。对于总心血管不良事件和致命不良事件的比较，证据的确定性较低。对于药物相关不良事件、导致停药的不良事件和严重不良事件的比较，证据的确定性非常低。
结论：哮喘患者心血管不良事件的发生率相当低，与未接触长效支气管扩张剂的患者相比，只有导致停药的不良事件风险显著增加。考虑到潜在的报告偏差，需要更多的研究来证实目前的发现。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（J Allergy Clin Immunol Pract. 2025 Mar 6:S2213-2198(25)00208-9. doi: 10.1016/j.jaip.2025.02.035.）
Cardiovascular Risk of the Use of Long-acting Bronchodilators in Patients with Asthma: A Meta-analysis of 22 Randomized Controlled Trials
Le Bai, Tingyuan Li, Dongwei Zhu, Qi Zhao, Yong Xu, Xianmei Zhou
Abstract
Background: Long-acting bronchodilators can improve the control of asthma when added to inhaled corticosteroids (ICS). However, the cardiovascular safety of these drugs in patients with asthma has never been comprehensively evaluated. Notably, growing evidence have indicated a positive association between asthma and cardiovascular diseases.
Objective: To evaluate the cardiovascular safety of addition of long-acting bronchodilators in patients with asthma.
Methods: After a comprehensive retrieval in PubMed, Embase, Cochrane Library and Web of Science, we included randomized controlled trials that assessed the cardiovascular safety of long-acting bronchodilators in patients with asthma. The primary outcome was the comparation of incidence of total cardiovascular AEs. Secondary outcomes included drug-related AEs, AEs leading to discontinuation, serious AEs and fatal AEs.
Results: A total of 22 trials with 62,915 patients were included. The use of long-acting bronchodilators significantly increased the incidence of cardiovascular AEs leading to discontinuation (IRR: 3.05, 95% CI: 1.07-8.48). The incidences of total cardiovascular AEs, drug-related AEs, serious AEs and fatal AEs were higher in patients treated with long-acting bronchodilators, but the differences were not significant. The certainty of evidence was low for comparations of total cardiovascular AEs and fatal AEs. The certainty of evidence was very low for comparations of drug-related AEs, AEs leading to discontinuation and serious AEs.
Conclusion: The incidence of cardiovascular AEs was quite low in patients with asthma, and only the risk of AEs leading to discontinuation significantly increased compared with those not exposure to long-acting bronchodilators. More studies are required to confirm the present findings in consideration of the potential reporting bias.
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韩国成年哮喘患者的早期临床缓解及其在肺功能下降和恶化中的作用
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Dupilumab 诱导 2 型哮喘患者的长期治疗临床缓解
