INTRODUCTION Some observational studies suggest a cardiovascular risk from proton-pump inhibitor (PPI) treatment, but observational data may be subject to bias. We conducted a meta-analysis of randomized controlled trial data on cardiovascular events during PPI treatment. METHODS Manufacturers of PPIs provided data from their PPI clinical trial programs. We included randomized trials with at least 100 subjects, treatment duration >30 days, and a non-PPI comparator (active or placebo). We obtained person-time of exposure per trial, to calculate summary incidence rate ratios (primary analysis) and incident rate differences (secondary analysis). Our primary composite outcome was major adverse cardiovascular events-plus (MACE+), which included nonfatal myocardial infarction, nonfatal stroke, fatal cardiovascular adverse events, hospitalization for unstable angina, or coronary revascularization; events were adjudicated blindly. RESULTS Cardiovascular outcomes were infrequent in randomized trials of PPIs, and our primary analysis found no overall association (summary incident rate ratio, MACE+ events, PPI:placebo, 0.72) (95% confidence interval 0.42-1.26). There was some heterogeneity by indication category, and by the incidence rate difference metric, gastroesophageal reflux disorder trials had 1.04 (95% confidence interval 0.58-1.50) excess MACE+ events per 100 person-years of treatment vs placebo. Comparisons with active controls generally showed positive incidence rate differences with PPI treatment. DISCUSSION Overall, we found no association of cardiovascular events with PPI treatment. Cardiovascular events appeared more frequent with PPI treatment in gastroesophageal reflux disorder trials, but results from this subgroup should be interpreted with the limitations of the analysis in mind, including sparse outcome counts and lack of individual patient data.

中文翻译：

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质子泵抑制剂和心血管不良事件：随机对照试验的荟萃分析。


引言 一些观察性研究表明质子泵抑制剂（PPI）治疗存在心血管风险，但观察性数据可能存在偏差。我们对 PPI 治疗期间心血管事件的随机对照试验数据进行了荟萃分析。方法 PPI 制造商提供了其 PPI 临床试验项目的数据。我们纳入了至少 100 名受试者、治疗持续时间 >30 天和非 PPI 比较剂（活性药物或安慰剂）的随机试验。我们获得了每次试验的人次暴露量，以计算总结发病率比率（主要分析）和发病率差异（二次分析）。我们的主要复合结局是主要不良心血管事件+（MACE+），其中包括非致命性心肌梗塞、非致命性中风、致命性心血管不良事件、不稳定心绞痛住院或冠状动脉血运重建；事件的裁决是盲目的。结果 在 PPI 随机试验中，心血管结局并不常见，我们的初步分析发现没有总体关联（总体发生率比、MACE+ 事件、PPI：安慰剂，0.72）（95% 置信区间 0.42-1.26）。根据适应症类别和发病率差异指标，胃食管反流病试验与安慰剂相比，每 100 人年治疗中有 1.04 例（95% 置信区间 0.58-1.50）过量 MACE+ 事件。与主动对照的比较通常显示出 PPI 治疗的阳性发病率差异。讨论 总体而言，我们发现心血管事件与 PPI 治疗没有关联。 在胃食管反流病试验中，使用 PPI 治疗后，心血管事件似乎更频繁，但解释该亚组结果时应考虑到分析的局限性，包括结果计数稀疏和缺乏个体患者数据。