Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin
Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin
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DOI：
10.1053/j.gastro.2019.05.056
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发表时间：
2019-09-01
期刊：
影响因子：
29.4
通讯作者：
Yusuf, Salim
中科院分区：
文献类型：
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作者：
Moayyedi, Paul;Eikelboom, John W.;Yusuf, Salim
背景与目的:质子泵抑制剂(PPIs)是治疗酸相关疾病的有效药物。这些药物在短期内耐受性良好，但在观察性研究中，长期治疗与不良事件相关。我们的目的是通过一项足够有力的随机试验来证实这些发现。方法：我们对17598名稳定型心血管疾病和外周动脉疾病患者进行了一项3 × 2的部分因子双盲试验，随机分为泮托拉唑（40mg /天，n = 8791）和安慰剂（n = 8807）两组。参与者也被随机分配到接受利伐沙班（2.5毫克，每日两次）和阿司匹林（100毫克，每日一次），利伐沙班（5毫克，每日两次），或阿司匹林（100毫克）单独的组。我们每6个月收集有关肺炎、艰难梭菌感染、其他肠道感染、骨折、胃萎缩、慢性肾病、糖尿病、慢性阻塞性肺病、痴呆、心血管疾病、癌症、住院和全因死亡率的数据。患者的中位随访时间为3.01年，随访时间为53152例患者年。结果：泮托拉唑组与安慰剂组在除肠道感染外的安全事件方面无统计学差异（安慰剂组为1.4% vs 1.0%；优势比为1.33；95%可信区间为1.01-1.75）。对于所有其他安全性结果，除了艰难梭菌感染外，各组之间的比例相似，艰难梭菌感染在泮托拉唑组中大约是安慰剂组的两倍，尽管只有13个事件，因此这种差异没有统计学意义。结论：在一项大型安慰剂对照随机试验中，我们发现泮托拉唑在使用3年期间与任何不良事件无关，除了可能增加肠道感染的风险。ClinicalTrials.gov编号：NCT01776424。
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 x 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.