Preventing Gastroduodenal Bleeding in Oral Anticoagulant Users

预防口服抗凝剂使用者的胃十二指肠出血

• 批准号: 8666807
• 负责人: WAYNE A RAY
• 金额: $ 45.56万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8666807
• 关键词: Accounting; Adverse drug effect; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Anticoagulants; Cardiovascular system; Comorbidity; Complication; Data; Databases; Drug usage; Functional disorder; Gastric Acid; Gastrointestinal tract structure; Guidelines; Healed; Hemorrhage; Histamine-2 Receptor Antagonist; Historical Cohort Studies; Hospitalization; Lead; Medicaid; Medicare; Non-Steroidal Anti-Inflammatory Agents; Oral; Patients; Pharmaceutical Preparations; Pharmacotherapy; Population; Production; Proton Pump Inhibitors; Randomized Controlled Trials; Recommendation; Recording of previous events; Recurrence; Risk; Risk Factors; Safety; Sampling; Site; Techniques; Tennessee; Testing; Ulcer; Warfarin; clinical practice; clopidogrel; design; gastrointestinal; healing; high risk; improved; novel; patient population; prevent; protective effect; public health relevance

DESCRIPTION (provided by applicant): Warfarin is a mainstay of cardiovascular pharmacotherapy and one of the most frequently prescribed medications in the U.S. However, major bleeding is a frequent and potentially devastating complication of its use, affecting approximately 3% of patients annually. Serious warfarin-related bleeding most commonly occurs in the gastrointestinal (GI) tract, accounting for about 1/3 of major bleeds. This suggests proton-pump inhibitors (PPIs) might improve warfarin safety. This hypothesis is supported by our understanding of the pathophysiology of warfarin-related bleeding as well as by studies of other pro-hemorrhagic drugs. A benefit for PPI cotherapy would be greatest for the many warfarin users with other risk factors for GI bleeding. However, the hypothesis that PPIs prevent serious warfarin-related GI bleeding, although plausible, has not been tested. The available evidence is largely indirect and cannot, by itself, support recommending PPI cotherapy to warfarin patients. Indeed, contemporary anticoagulant guidelines do not mention PPIs. Histamine-2 receptor antagonists (H2RAs) also might be considered to prevent serious warfarin-related GI bleeding, although they may be less effective than PPIs. Novel oral anticoagulants, more convenient to use than warfarin, will account for a growing proportion of oral anticoagulant use. However, these also cause serious GI bleeding; some have risk greater than that of warfarin. Thus, PPIs may have the potential to markedly improve the safety of novel anticoagulants. We will conduct a large historical cohort study in Tennessee Medicaid and the national 5% Medicare sample assessing whether concurrent PPI/H2RA in oral anticoagulant users reduces risk of serious GI bleeding, critical data to improve the safety of these widely used medications. We will test two hypotheses: Aim 1: In Tennessee Medicaid warfarin users, concurrent PPI or H2RA use decreases risk of hospitalizations for gastroduodenal bleeding. Aim 2: In novel oral anticoagulant users in the Medicare sample, concurrent PPI or H2RA use decreases risk of hospitalizations for gastroduodenal bleeding. For each of these aims, we also will test whether the protective effect is greater for PPIs than for H2RAs as well as whether the absolute benefit varies according to number of GI bleeding risk factors.

描述（由申请人提供）：华法林是心血管药物治疗的支柱，也是美国最常用的处方药之一。然而，大出血是其使用的常见和潜在破坏性并发症，每年影响约3%的患者。 华法林相关的严重出血最常发生在胃肠道（GI），约占大出血的1/3。这表明质子泵抑制剂（PPI）可能会改善华法林的安全性。我们对华法林相关出血的病理生理学的理解以及对其他促出血药物的研究支持了这一假设。PPI联合治疗对许多有其他GI出血风险因素的华法林使用者的获益最大。 然而，PPI预防华法林相关严重GI出血的假设虽然合理，但尚未得到检验。现有的证据大多是间接的，本身不能支持向华法林患者推荐PPI联合治疗。事实上，当代抗凝指南并未提及PPI。 组胺-2受体拮抗剂（H2 RAs）也可用于预防华法林相关的严重GI出血，尽管其效果可能不如PPI。 新型口服抗凝剂比华法林更方便使用，将占口服抗凝剂使用的比例越来越大。然而，这些药物也会导致严重的胃肠道出血;有些药物的风险大于华法林。因此，PPI可能具有显著改善新型抗凝剂安全性的潜力。 我们将在田纳西州医疗补助计划和全国5%医疗保险样本中进行一项大型历史队列研究，评估口服抗凝剂使用者同时使用PPI/H2 RA是否会降低严重胃肠道出血的风险，这是提高这些广泛使用的药物安全性的关键数据。我们将测试两个假设：目标1：在田纳西州医疗补助华法林使用者中，同时使用PPI或H2 RA可降低因胃十二指肠出血住院的风险。目标二：在Medicare样本中的新口服抗凝剂使用者中，同时使用PPI或H2 RA可降低因胃十二指肠出血住院的风险。对于这些目标中的每一个，我们还将测试PPI的保护作用是否大于H2 RA，以及绝对获益是否根据GI出血风险因素的数量而变化。