Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Drug Saf. 2010 Nov 1;33(11):1003-14. doi: 10.2165/11536840-000000000-00000.
Recently, a 4-fold increase in risk of sudden cardiac death (SCD) was reported for domperidone in a study that focused on corrected QT interval (QTc)-prolonging drugs as a class and their association with SCD.
To evaluate the association between the use of domperidone and serious non-fatal ventricular arrhythmia (VA) and SCD in the general population.
We performed a population-based, case-control study during 1996-2007 in the Integrated Primary Care Information (IPCI) database, a longitudinal general practice research database in the Netherlands. We included all patients aged ≥18 years without cancer in the source population. We studied the association between the use of domperidone by recency of use (current, past and none) and daily dose, and the risk of serious non-fatal VA or SCD. Cases were defined as a natural death due to cardiac causes heralded by abrupt loss of consciousness within 1 hour after the onset of acute symptoms or an unwitnessed, unexpected death of someone seen in a stable medical condition <24 hours previously with no evidence of a non-cardiac cause. Controls were randomly drawn from the source population and matched to cases on age, sex, practice and index date. We compared the exposure odds for SCD alone and VA plus SCD by means of conditional logistic regression while adjusting for all available confounders. In addition, we stratified by insurance type.
The study population comprised 1366 cases (62 VA and 1304 SCD) and 14114 matched controls. Of all cases, ten patients were current domperidone users at the index date, all with SCD. The matched unadjusted odds ratio of domperidone and SCD was 3.72 (95% CI 1.72, 8.08). Daily doses >30 mg were associated with a significant increased risk of SCD (adjusted odds ratio [OR(adj)] 11.4 [95% CI 1.99, 65.2]). Since there was a near interaction with health insurance (p = 0.050), all analyses were stratified by insurance. In publicly insured patients, seven cases were current users at the index date. Current use was associated with a significant increased risk of SCD (OR(adj) 4.17 [95% CI 1.33, 13.1]). Amongst privately insured patients there was one domperidone-exposed case, and amongst non-insured there were two.
Current use of domperidone, especially high doses, is associated with an increased risk of SCD. We could not demonstrate an effect of domperidone on non-fatal VA due to absence of exposed cases.
最近，一项研究报告称，多潘立酮的风险增加了 4 倍，可能导致心脏性猝死（SCD），该研究主要关注的是延长校正 QT 间期（QTc）的药物作为一类药物及其与 SCD 的关联。
评估多潘立酮的使用与一般人群中严重非致命性室性心律失常（VA）和 SCD 之间的关系。
我们在 1996 年至 2007 年期间在综合初级保健信息（IPCI）数据库中进行了一项基于人群的病例对照研究，该数据库是荷兰的一个纵向一般实践研究数据库。我们纳入了源人群中年龄≥18 岁且无癌症的所有患者。我们研究了最近使用（当前、过去和无）和日剂量的多潘立酮使用与严重非致命性 VA 或 SCD 风险之间的关系。病例定义为急性症状发作后 1 小时内突然意识丧失而导致的自然死亡，或 24 小时前病情稳定的无人见证的意外死亡，且无非心脏原因的证据。对照组从源人群中随机抽取，并按年龄、性别、实践和索引日期与病例匹配。我们通过条件逻辑回归比较了 SCD 单独和 VA 加 SCD 的暴露几率，同时调整了所有可用的混杂因素。此外，我们还按保险类型进行了分层。
研究人群包括 1366 例病例（62 例 VA 和 1304 例 SCD）和 14114 例匹配的对照。在所有病例中，有 10 名患者在索引日期时是当前多潘立酮使用者，均为 SCD。未调整的多潘立酮和 SCD 的匹配比值比（OR）为 3.72（95%CI 1.72，8.08）。日剂量>30mg 与 SCD 风险显著增加相关（调整后的比值比[OR（adj）]为 11.4[95%CI 1.99，65.2]）。由于与健康保险存在接近的交互作用（p=0.050），因此所有分析均按保险类型进行分层。在公共保险患者中，有 7 例病例在索引日期时是当前使用者。当前使用与 SCD 风险显著增加相关（OR（adj）为 4.17[95%CI 1.33，13.1]）。在私人保险患者中，有 1 例多潘立酮暴露病例，而非保险患者中有 2 例。
当前使用多潘立酮，尤其是高剂量，与 SCD 风险增加有关。由于暴露病例的缺乏，我们无法证明多潘立酮对非致命性 VA 的影响。
