Valkhoff Vera E, van Soest Eva M, Mazzaglia Giampiero, Molokhia Mariam, Schade René, Trifiro Gianluca, Goldstein Jay L, Hernandez-Diaz Sonia, Kuipers Ernst J, Sturkenboom Miriam C J M
Erasmus University Medical Centre, Rotterdam, The Netherlands.
Arthritis Rheum. 2012 Aug;64(8):2792-802. doi: 10.1002/art.34433.
Guidelines recommend coprescription of gastroprotective agents (GPAs) in patients receiving cyclooxygenase 2 inhibitors (coxibs) who are at high risk of upper gastrointestinal (UGI) tract complications (i.e., patients with a previous complicated ulcer or with multiple risk factors). Suboptimal GPA adherence has been shown to diminish the gastroprotective effect during use of nonselective nonsteroidal antiinflammatory drugs, but little is known about the effect of GPA adherence during coxib treatment. We undertook this study to determine the association between GPA adherence and UGI tract events among patients receiving coxibs.
Using primary care data from 3 databases, we conducted a case-control study in a cohort of patients age ≥50 years who were newly starting treatment with coxibs and concomitantly taking GPAs. Patients who had a UGI tract event (bleeding or symptomatic ulcer) were matched to event-free controls for age, sex, database, and calendar date. Coxib treatment intervals were defined as consecutive coxib prescriptions with intervening gaps not exceeding the duration of the previous coxib prescription. Adherence to GPAs was calculated as the proportion of days of coxib treatment covered by a GPA prescription. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using conditional logistic regression analysis.
The coxib plus GPA-treated cohort consisted of 14,416 coxib-treated patients who received GPAs for at least 1 day, yielding 16,442 coxib treatment intervals in which a GPA was coprescribed. Most patients were treated with coxibs for <30 days. Seventy-four patients had a UGI tract event during or shortly after a coxib treatment interval in which a GPA was coprescribed, with an incidence rate of 11.9 (95% CI 9.4-14.8) per 1,000 years of coxib treatment. The risk of UGI tract events was 1.97 (95% CI 0.84-4.60) for patients with <20% adherence to GPAs compared to patients with >80% adherence to GPAs. For every 10% decrease in GPA adherence, the risk of UGI tract events increased by 9% (OR 1.09 [95% CI 1.00-1.18]).
Decreasing GPA adherence among coxib-treated patients is associated with an increased risk of UGI tract events.
指南建议，对于有上消化道（UGI）并发症高风险的患者（即有既往复杂性溃疡或有多种风险因素的患者），在接受环氧化酶2抑制剂（coxibs）治疗时应联合开具胃保护剂（GPA）。在使用非选择性非甾体抗炎药期间，已证实GPA依从性欠佳会降低胃保护作用，但对于coxib治疗期间GPA依从性的影响知之甚少。我们开展这项研究以确定接受coxibs治疗的患者中GPA依从性与UGI事件之间的关联。
利用来自3个数据库的初级保健数据，我们对年龄≥50岁、新开始coxibs治疗并同时服用GPA的患者队列进行了一项病例对照研究。发生UGI事件（出血或有症状性溃疡）的患者与无事件的对照者按年龄、性别、数据库和日历日期进行匹配。Coxib治疗间隔定义为连续的coxib处方，其间的间隔不超过前一个coxib处方的持续时间。GPA依从性按GPA处方覆盖的coxib治疗天数比例计算。使用条件逻辑回归分析计算比值比（OR）及95%置信区间（95%CI）。
接受coxib加GPA治疗的队列包括14416例接受coxib治疗且至少服用GPA 1天的患者，产生了16442个联合开具GPA的coxib治疗间隔。大多数患者接受coxibs治疗的时间<30天。74例患者在联合开具GPA的coxib治疗间隔期间或之后不久发生了UGI事件，每1000年coxib治疗的发生率为11.9（95%CI 9.4-14.8）。与GPA依从性>80%的患者相比，GPA依从性<20%的患者发生UGI事件的风险为1.97（95%CI 0.84-4.60）。GPA依从性每降低10%，UGI事件的风险增加9%（OR 1.09 [95%CI 1.00-1.18]）。
coxib治疗患者中GPA依从性降低与UGI事件风险增加有关。
