Vanderbilt Center for Education/Research on Therapeutics

描述（由申请人提供）：慢性肌肉骨骼问题和相关疼痛在临床实践中很常见，对医疗保险参保者的影响不成比例。最有效的治疗方法，非甾体抗炎药（NSAIDs）大大增加了严重消化性溃疡疾病的风险。coxib是一种新型抗炎药物，旨在避免胃肠道并发症，但会增加心血管事件的风险。剩下的替代方案是使用非甾体抗炎药来预防胃肠道并发症，这是很有吸引力的，尽管在循证指南中推荐使用，但并未被广泛使用。内窥镜研究表明，质子泵抑制剂（PPI）和双剂量H2受体拮抗剂（H2RA）等耐受性良好的药物可减少非甾体抗炎药引起的侵蚀。然而，没有临床试验表明非甾体抗炎药联合PPI或H2RA可降低临床重要的非甾体抗炎药引起的胃肠道并发症的风险；也没有足够有力的试验将这种联合治疗与coxib进行比较。这种试验现在不太可能进行，因为许多药物已经过了专利期，而且非甾体抗炎药和coxib治疗的危害是众所周知的。因此，缺乏可靠的临床数据来评估非甾体抗炎药与胃保护治疗的相对安全性。这些比较有效性数据的缺乏也将阻碍医疗保险政策的发展，该政策旨在促进关节炎和非创伤性关节疾病患者的最佳药物治疗，同时将消化性溃疡疾病、缺血性心脏病和中风的风险降至最低。我们建议通过TennCare数据库中的药物流行病学研究来解决这些问题，TennCare数据库是我们广泛使用的资源。我们将进行一项方法新颖的“新使用者”设计队列研究，以减少通道偏差，以解决两个主要假设：H1：目前使用胃保护治疗的非甾体抗炎药的严重胃病发生率低于未使用胃保护治疗的非甾体抗炎药。H2：目前使用coxibs的患者中严重胃病的发生率低于使用非甾体抗炎药并进行胃保护治疗的患者。该队列将包括109,290名新的NSAID/coxib使用者，并将具有检测保护性比率的能力（= 0.05,1 -= 0.80）。H1和H2都是74。

DESCRIPTION (PROVIDED BY APPLICANT): Chronic musculoskeletal problems and associated pain are common in clinical practice and affect Medicare enrollees disproportionately. The most effective treatment, non-steroidal anti-inflammatory drugs (NSAIDs) substantially increase the risk of serious peptic ulcer disease. The coxibs, a new class of anti inflammatory agents designed to avoid gastrointestinal complications, increase the risk of cardiovascular events. The remaining alternative, an NSAID with therapy to prevent gastrointestinal complications, is attractive, and although recommended in evidence-based guidelines, is not widely used. Endoscopic studies have shown that NSAID-induced erosions are decreased by proton pump inhibitors (PPI) and double-dose H2 receptor antagonist (H2RA), well tolerated drugs. However, there is no clinical trial showing that an NSAID with a PPI or H2RA decreases the risk of clinically important NSAID-induced gastrointestinal complications; nor is there an adequately powered trial comparing this combination therapy with a coxib. Such trials now are unlikely to be performed since many of the drugs are off patent and the hazards of both NSAID and coxib therapy are well known. Thus, robust clinical data to evaluate the comparative safety of NSAIDs with gastroprotective therapy is lacking. The absence of these comparative effectiveness data also will impede the development of Medicare policies that promote optimal pharmacotherapy for patients with arthritis and non-traumatic joint disorders while minimizing the risks of peptic ulcer disease, ischemic heart disease, and stroke. We propose to address these questions with pharmacoepidemiologic studies in the TennCare database, a resource we have used extensively. We will conduct a methodologically novel "new-user" design cohort study that will decrease channeling bias, to address two primary hypotheses: H1: The incidence of serious gastropathy in current users of NSAIDs with gastroprotective therapy is lower than that for NSAIDs absent gastroprotective therapy. H2: The incidence of serious gastropathy in current users of coxibs is lower than that for NSAIDs with gastroprotective therapy. The cohort will include 109,290 new NSAID/coxib users and will have a power (=.05, 1.-=.80) to detect protective rate-ratio of .74 for both H1 and H2.