Rottenkolber Marietta, Rottenkolber Dominik, Fischer Rainald, Ibáñez Luisa, Fortuny Joan, Ballarin Elena, Sabaté Monica, Ferrer Pili, Thürmann Petra, Hasford Joerg, Schmiedl Sven
Institute for Medical Information Sciences, Biometry, and Epidemiology, Ludwig-Maximilians Universitaet Muenchen, Marchioninistr. 15, D-81377 Munich, Germany.
Institute of Health Economics and Management and Munich Center of Health Sciences, Ludwig-Maximilians-Universitaet Muenchen, Ludwigstr. 28, D-80539 Munich, Germany; Institute of Health Economics and Management, HelmholtzZentrum München - German Research Centre for Environmental Health, Member of the German Center for Lung Research, Ingolstaedter Landstraße 1, D-85764 Neuherberg, Germany.
Respir Med. 2014 Aug;108(8):1075-90. doi: 10.1016/j.rmed.2014.05.014. Epub 2014 Jun 5.
Empirical results indicate an increased risk for cardiovascular (CV) adverse drug events (ADE) in chronic obstructive pulmonary disease (COPD) patients treated with beta-2-agonists (B2A) and muscarinic antagonists (MA). A systematic review (including a meta-analysis for drug classes with sufficient sample size) was conducted assessing the association between B2A or MA and acute myocardial infarctions (MI) in COPD patients.
Comprehensive literature search in electronic databases (MEDLINE, Cochrane database) was performed (January 1, 1946-April 1, 2013). Results were presented by narrative synthesis including a comprehensive quality assessment. In the meta-analysis, a random effects model was used for estimating relative risk estimates for acute MI.
Eight studies (two systematic reviews, two randomized controlled trials, and four observational studies) were comprised. Most studies comparing tiotropium vs. placebo showed a decreased MI risk for tiotropium, whereas for studies with active control arms no clear tendency was revealed. For short-acting B2A, an increased MI risk was shown after first treatment initiation. For all studies, a good quality was found despite some shortcomings in ADE-specific criteria. A meta-analysis could be conducted for tiotropium vs. placebo only, showing a relative risk reduction of MI (0.74 [0.61-0.90]) with no evidence of statistical heterogeneity among the included trials (I(2) = 0%; p = 0.8090).
An MI-protective effect of tiotropium compared to placebo was found, which might be attributable to an effective COPD treatment leading to a decrease in COPD-related cardiovascular events. Further studies with effective control arms and minimal CV risk are required determining precisely tiotropium's cardiovascular risk.
实证结果表明，在使用β2受体激动剂（B2A）和毒蕈碱拮抗剂（MA）治疗的慢性阻塞性肺疾病（COPD）患者中，发生心血管（CV）不良药物事件（ADE）的风险增加。开展了一项系统评价（包括对样本量充足的药物类别进行荟萃分析），以评估COPD患者中B2A或MA与急性心肌梗死（MI）之间的关联。
在电子数据库（MEDLINE、Cochrane数据库）中进行全面的文献检索（1946年1月1日至2013年4月1日）。结果通过叙述性综合呈现，包括全面的质量评估。在荟萃分析中，采用随机效应模型估计急性心肌梗死的相对风险估计值。
纳入了八项研究（两项系统评价、两项随机对照试验和四项观察性研究）。大多数比较噻托溴铵与安慰剂的研究显示，噻托溴铵可降低心肌梗死风险，而对于有活性对照臂的研究，未发现明确趋势。对于短效B2A，首次开始治疗后显示心肌梗死风险增加。对于所有研究，尽管在ADE特异性标准方面存在一些不足，但质量良好。仅对噻托溴铵与安慰剂进行了荟萃分析，结果显示心肌梗死相对风险降低（0.74[0.61 - 0.90]），纳入试验之间无统计学异质性证据（I² = 0%；p = 0.8090）。
发现与安慰剂相比，噻托溴铵具有心肌梗死保护作用，这可能归因于有效的COPD治疗导致与COPD相关的心血管事件减少。需要进一步开展有有效对照臂且心血管风险最小的研究，以精确确定噻托溴铵的心血管风险。
