Medical Research Council Centre for Causal Analyses and Translational Epidemiology, School of Social and Community Medicine, Faculty of Medicine and Dentistry, University of Bristol, Barley House, Oakfield Grove, Bristol, United Kingdom.
Epidemiology. 2013 May;24(3):352-62. doi: 10.1097/EDE.0b013e318289e024.
Instrumental variable analysis can estimate treatment effects in the presence of residual or unmeasured confounding. We compared ordinary least squares regression versus instrumental variable estimates of the effects of selective cyclooxygenase-2 inhibitors (COX-2s) relative to nonselective nonsteroidal anti-inflammatory drug (NSAID) prescriptions on incidence of upper gastrointestinal complications and myocardial infarction (MI).
We sampled a cohort of 62,933 first-time users of COX-2s or nonselective NSAIDs older than 60 years in the Clinical Practice Research Datalink. The instruments were physicians' previous prescriptions of COX-2s or nonselective NSAIDs, which are surrogates for physician preferences. We estimated risk differences of incident upper gastrointestinal complications and MI within 180 days of first COX-2 versus nonselective NSAID prescription.
Using ordinary least squares regression, adjusted for baseline confounders, we observed little association of COX-2 prescriptions with incident upper gastrointestinal complications (risk difference = -0.08 [95% confidence interval = -0.20 to 0.04]) or MI (0.06 [-0.06 to 0.17]) per 100 patients treated. Our adjusted instrumental variable results suggested 0.46 per 100 (-0.15 to 1.07) fewer upper gastrointestinal complications and little difference in acute MIs (0.08 per 100 [-0.61 to 0.76]), within 180 days of being prescribed COX-2s. Estimates were more precise when we used 20 previous prescriptions; the instrumental variable analysis implied 0.74 (0.28 to 1.19) fewer MIs per 100 patients prescribed COX-2s.
Using instrumental variable analysis, we found some evidence that COX-2 prescriptions reduced the risk of upper gastrointestinal complications, consistent with randomized controlled trials. Our results using multiple instruments suggest that COX-2s may have heterogeneous within-class effects on MI.
工具变量分析可以在存在残余或未测量混杂的情况下估计治疗效果。我们比较了普通最小二乘法回归与工具变量估计选择性环氧化酶-2 抑制剂 (COX-2s) 相对于非选择性非甾体抗炎药 (NSAID) 处方对上消化道并发症和心肌梗死 (MI) 发生率的影响。
我们在临床实践研究数据库中抽取了 62933 例年龄大于 60 岁的首次使用 COX-2s 或非选择性 NSAID 的患者队列。该工具是医生之前开具 COX-2s 或非选择性 NSAID 的处方，这是医生偏好的替代指标。我们估计了首次 COX-2 与非选择性 NSAID 处方后 180 天内上消化道并发症和 MI 的发生率差异。
使用普通最小二乘法回归，调整基线混杂因素后，我们观察到 COX-2 处方与上消化道并发症发生率（风险差异 = -0.08 [95%置信区间 = -0.20 至 0.04]）或 MI（0.06 [-0.06 至 0.17]）之间的关联很小。我们调整后的工具变量结果表明，每 100 例治疗患者中，使用 COX-2 治疗的上消化道并发症减少 0.46（-0.15 至 1.07），急性 MI 差异不大（每 100 例增加 0.08 [ -0.61 至 0.76]），在 180 天内使用 COX-2。当我们使用 20 个之前的处方时，估计值更准确；工具变量分析意味着每 100 例服用 COX-2 的患者中，MI 减少 0.74（0.28 至 1.19）。
使用工具变量分析，我们发现一些证据表明 COX-2 处方降低了上消化道并发症的风险，与随机对照试验一致。我们使用多种工具的结果表明，COX-2 可能对 MI 具有类内异质性影响。
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