Shin Sun Mi, Jeong Han Eol, Lee Hyesung, Shin Ju-Young
School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Pharmacoepidemiol Drug Saf. 2020 Dec;29(12):1636-1649. doi: 10.1002/pds.5106. Epub 2020 Sep 1.
To assess the association between domperidone and adverse cardiovascular events.
We conducted nested case-control and case-time-control studies using Korea's healthcare database (2002-2015). We identified patients without history of hospitalization, cancer, or cardiovascular diseases in 2002. From our cohort, those diagnosed with an adverse cardiovascular event (case), composite of arrhythmia, hypertension, or acute myocardial infarction were matched to two controls using risk-set sampling on various sociodemographic variables. Exposure was assessed in the 1 to 7 days, or in the 1 to 7 days (hazard period) and 91 to 97 days (control period) prior to index date, in nested case-control and case-time control studies, respectively. We compared domperidone to metoclopramide or non-use and estimated odds ratios (OR) with 95% confidence intervals (CI) using conditional logistic regression.
From 627 799 patients, we identified 71 555 cases and 141 833 controls. In the nested case-control study, while the risk of cardiovascular events was increased with domperidone (OR 1.38, 95% CI 1.28-1.47) compared to non-use, the risk was reduced (0.64, 0.57-0.72) compared to metoclopramide. In the case-time-control study, similar increased risk was found when compared to non-use (1.40, 1.29-1.52) but a reduced risk as compared with metoclopramide (0.63, 0.54-0.72). Risk of myocardial infarction associated with domperidone was highest (nested case-control: 1.94, 1.33-2.83; case-time-control: 1.91, 1.01-3.62) when compared to non-use but did not indicate an increased risk when compared to metoclopramide (nested case-control: 0.60, 0.32-1.13; case-time-control: 0.70, 0.25-1.98).
Our findings support a positive association between domperidone and adverse cardiovascular events. However, domperidone may have a safer cardiovascular profile than metoclopramide.
评估多潘立酮与不良心血管事件之间的关联。
我们利用韩国医疗数据库（2002 - 2015年）进行了巢式病例对照研究和病例时间对照研究。我们确定了2002年没有住院史、癌症或心血管疾病史的患者。在我们的队列中，那些被诊断为发生不良心血管事件（病例组）的患者，即心律失常、高血压或急性心肌梗死的综合病例，通过对各种社会人口统计学变量进行风险集抽样，与两名对照进行匹配。在巢式病例对照研究和病例时间对照研究中，分别在索引日期前1至7天，或在索引日期前1至7天（危险期）和91至97天（对照期）评估暴露情况。我们将多潘立酮与甲氧氯普胺或未用药情况进行比较，并使用条件逻辑回归估计比值比（OR）及其95%置信区间（CI）。
从627799名患者中，我们确定了71555例病例和141833名对照。在巢式病例对照研究中，与未用药相比，使用多潘立酮时心血管事件风险增加（OR 1.38，95%CI 1.28 - 1.47），但与甲氧氯普胺相比风险降低（0.64，0.57 - 0.72）。在病例时间对照研究中，与未用药相比也发现了类似的风险增加（1.40，1.29 - 1.52），但与甲氧氯普胺相比风险降低（0.63，0.54 - 0.72）。与未用药相比，多潘立酮相关的心肌梗死风险最高（巢式病例对照研究：1.94，1.33 - 2.83；病例时间对照研究：1.91，1.01 - 3.62），但与甲氧氯普胺相比未显示风险增加（巢式病例对照研究：0.60，0.32 - 1.13；病例时间对照研究：0.70，0.25 - 1.98）。
我们的研究结果支持多潘立酮与不良心血管事件之间存在正相关。然而，多潘立酮的心血管安全性可能比甲氧氯普胺更高。
