Comparison of Different Case-Crossover Variants in Handling Exposure-Time Trend or Persistent-User Bias: Using Dipeptidyl Peptidase-4 Inhibitors and the Risk of Heart Failure as an Example
Comparison of Different Case-Crossover Variants in Handling Exposure-Time Trend or Persistent-User Bias: Using Dipeptidyl Peptidase-4 Inhibitors and the Risk of Heart Failure as an Example
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DOI：
10.1016/j.jval.2019.09.2746
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发表时间：
2020-02-01
期刊：
影响因子：
4.5
通讯作者：
Chang, Chia-Hsuin
中科院分区：
文献类型：
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作者：
Dong, Yaa-Hui;Wang, Shirley, V;Chang, Chia-Hsuin
目的：病例交叉设计对于检查短暂暴露和突然结果之间的关联非常有效，在存在暴露时间趋势或持续用药的情况下评估药物的效果时，如果不恰当地使用病例交叉设计可能会产生虚假关联。我们通过检查与二肽基肽酶 4 (DPP-4) 抑制剂相关的心力衰竭住院 (HFH) 风险，比较了调整这些偏差来源的不同方法。总体而言，现有证据并未表明 HFH 风险较高与 DPP-4 抑制剂相关；然而，这些药物的病例交叉分析可能容易产生偏差。方法：我们进行了病例交叉；年龄、性别、风险组 (ASR) 匹配的病例时间对照；疾病风险评分（DRS）匹配的病例时间对照；病例-病例-时间对照分析，以评估台湾数据库中糖尿病 (DM) 患者中 DPP-4 抑制剂与 HFH 之间的关联。我们还检查了二甲双胍和磺酰脲类药物，两者均假设无效关联。结果：在 362022 名 DM 患者中，确定了 4105 例（病例交叉）、4103 例（ASR 匹配的病例时间对照）、3957 例（DRS 匹配的病例时间对照）和 2812 例（病例时间对照）HFH 病例。在病例交叉分析中，DPP-4 抑制剂和 HFH 的 OR 升高（1.52；95% 置信区间 [95% CI] 0.95-2.42）。 ASR 匹配的病例时间对照、DRS 匹配的病例时间对照和病例时间对照分析产生了接近零的关联（分别为 0.90 [95% CI 0.45-1.83]、0.96 [95% CI 0.46-2.02] 和 0.92 [95% CI 0.39-2.21]）。在病例-病例-时间对照分析中，观察到二甲双胍在不同设计中的无效效应以及磺酰脲类药物的无效效应。结论：我们的病例交叉分析表明 DPP-4 抑制剂可能与 HFH 相关；然而，每种调整曝光时间和持续的用户偏见的方法都会削弱研究结果。案例-案例-时间控制分析的精确度最低。
Objectives: Inappropriate use of the case-crossover design, which is efficient for examining associations between brief exposure and abrupt outcomes, in evaluating the effects of medications in the presence of exposure-time trends or persistent drug use may generate spurious associations. We compared different approaches to adjusting for these sources of bias by examining the risk of heart failure hospitalization (HFH) associated with dipeptidyl peptidase-4 (DPP-4) inhibitors. Overall, existing evidence does not suggest a higher risk of HFH associated with DPP-4 inhibitors; however, case-crossover analyses of these medications may be susceptible to bias.Methods: We conducted case-crossover; age, sex, risk-set (ASR) matched case-time-control; disease risk score (DRS)-matched case-time-control; and case-case-time-control analyses to assess the association between DPP-4 inhibitors and HFH among patients with diabetes mellitus (DM) in a population-based Taiwanese database. We also examined metformin and sulfonylureas, both with assumed null associations.Results: Among 362 022 DM patients, 4105 (case-crossover), 4103 (ASR-matched case-time-control), 3957 (DRS-matched case-time-control), and 2812 (case-case-time-control) HFH cases were identified. The OR for DPP-4 inhibitors and HFH was elevated in the case-crossover analysis (1.52; 95% confidence interval [95% CI] 0.95-2.42). The ASR-matched case-time control, DRS-matched case-time-control, and case-case-time control analyses yielded near-null associations (0.90 [95% CI 0.45-1.83], 0.96 [95% CI 0.46-2.02], and 0.92 [95% CI 0.39-2.21], respectively). Null effects were observed for metformin across designs and for sulfonylureas in the case-case-time control analysis.Conclusions: Our case-crossover analysis suggested DPP-4 inhibitors may be associated with HFH; however, each method for adjusting for exposure-time and persistent user bias attenuated the findings. The case-case-time-control analysis had the least precision.