Vaduganathan Muthiah, Cannon Christopher P, Cryer Byron L, Liu Yuyin, Hsieh Wen-Hua, Doros Gheorghe, Cohen Marc, Lanas Angel, Schnitzer Thomas J, Shook Thomas L, Lapuerta Pablo, Goldsmith Mark A, Laine Loren, Bhatt Deepak L
Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Mass.
Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Mass; Harvard Clinical Research Institute, Boston, Mass.
Am J Med. 2016 Sep;129(9):1002-5. doi: 10.1016/j.amjmed.2016.03.042. Epub 2016 Apr 30.
Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention.
All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up.
Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio [HR] 0.43; 95% confidence interval [CI], 0.22-0.85; P = .02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P = .05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P = .27).
PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.
质子泵抑制剂（PPIs）已被证明可降低需要双重抗血小板治疗（DAPT）的患者发生胃肠道事件的几率。关于PPIs在急性冠状动脉综合征或经皮冠状动脉介入治疗后高危心血管亚组中的疗效和安全性的数据有限。
所有纳入COGENT（氯吡格雷与胃肠道事件优化试验）的患者在之前21天内开始接受DAPT（联合阿司匹林和氯吡格雷）用于各种适应症。这些对COGENT试验的事后分析评估了在因两种最常见适应症而需要DAPT的患者亚组中，奥美拉唑与安慰剂相比的疗效和安全性：1）在随机分组后14天内接受经皮冠状动脉介入治疗（无论何种适应症）的患者（n = 2676；71.2%）；2）患有急性冠状动脉综合征且接受或未接受经皮冠状动脉介入治疗的患者（n = 1573；41.8%）。使用未调整的Cox比例风险模型来估计直至最终随访时的效应量。
中位随访时间为110天（四分位间距55 - 167天）。在接受经皮冠状动脉介入治疗的患者中，奥美拉唑在180天时显著降低了复合胃肠道事件的发生率（1.2%对2.7%；风险比[HR] 0.43；95%置信区间[CI]，0.22 - 0.85；P = 0.02），且未增加复合心血管事件的发生率（5.4%对6.3%；HR 1.00；95% CI，0.67 - 1.50；P = 1.00）。同样，奥美拉唑降低了患有急性冠状动脉综合征患者在180天时主要胃肠道终点事件的风险（1.1%对2.7%；HR 0.37；95% CI，0.13 - 1.01；P = 0.05），心血管事件无显著增加（5.6%对4.5%；HR 1.40；95% CI, 0.77 - 2.53；P = 0.27）。
PPI治疗可降低胃肠道出血风险，在高危心血管亚组中不会显著增加主要心血管事件的发生，无论DAPT的适应症如何。未来需要开展研究以明确针对更高强度和更长疗程DAPT的最佳胃保护策略。
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