未经批准:非甾体抗炎药(NSAIDs)是最常用的药物之一,处方和柜台。NSAIDs在关节炎患者中的长期心血管安全性引起了争议。人们仍然对不良心肾作用的相对发生率和严重程度感到担忧,特别是在患有心血管(CV)疾病或疾病危险因素的关节炎患者中,如PRECISION(塞来昔布综合安全性与布洛芬或萘普生)试验参与者(NCT00346216)。我们进一步研究了在PRECISION人群中,选择性COX-2抑制剂塞来昔布是否具有优于布洛芬或萘普生的心肾安全性。
结果:2.48万需要NSAIDs治疗骨关节炎或类风湿性关节炎(RA)且CV风险增加的患者随机接受塞来昔布治疗,布洛芬,或者萘普生.当前预先指定的二次分析评估了发病率,严重程度,和预先指定的复合心肾结局的NSAID相关风险(裁定的肾脏事件,充血性心力衰竭住院治疗,或因高血压住院)在意向治疗(ITT)人群中。治疗中的分析评估了服用研究药物的患者的安全性。平均治疗时间为20.3±16.0个月,平均随访时间为34.1±13.4个月,在ITT人群中,主要心肾复合结局发生在423例患者(1.76%).在这423名患者中,118人(28%)在塞来昔布,166(39%)布洛芬,萘普生组139例(33%)。在调整了独立临床变量的多变量Cox回归模型中,与布洛芬相比,塞来昔布的风险显著降低[风险比(HR)0.67,置信区间(CI)0.53-0.85,P=0.001),与萘普生相比,风险有降低趋势(HR0.79,CI0.61-1.00,P=0.058).在ITT分析中,220例患者发生了有临床意义的肾脏事件,事件发生率为0.71%,1.14%,塞来昔布为0.89%,布洛芬,和萘普生,分别为(P=0.052),而在治疗分析中,这一比例为0.52%,0.91%,0.78%(P<0.001)。
结论:在当前时代,在关节炎患者中,长期使用NSAID与少数心肾事件相关.在研究的剂量下,与布洛芬或萘普生相比,塞来昔布的肾脏事件更少,因此心血管安全性更高.这些结果对于管理患有慢性关节炎疼痛和肾功能受损和/或心力衰竭的高风险的个体的从业者具有相当大的临床意义。临床试验注册:NCT00346216。
UNASSIGNED: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs, both prescribed and over the counter. The long-term cardiovascular safety of NSAIDs in patients with arthritis has engendered controversy. Concerns remain regarding the relative incidence and severity of adverse cardiorenal effects, particularly in arthritis patients with established cardiovascular (CV) disease or risk factors for disease as illustrated by the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen)
trial participants (NCT00346216).We further investigated whether the selective COX-2 Inhibitor celecoxib has a superior cardiorenal safety profile compared with ibuprofen or naproxen in the PRECISION population.
RESULTS: Twenty-four thousand eighty-one patients who required NSAIDs for osteoarthritis or rheumatoid arthritis (RA) and had increased CV risk randomly received celecoxib, ibuprofen, or naproxen. The current pre-specified secondary analysis assessed the incidence, severity, and NSAID-related risk of the pre-specified composite cardiorenal outcome (adjudicated renal event, hospitalization for congestive heart failure, or hospitalization for hypertension) in the intention-to-treat (ITT) population. An on-treatment analysis assessed safety in those taking the
study medication. Following a mean treatment duration of 20.3 ± 16.0 months and a mean follow-up of 34.1 ± 13.4 months, the primary cardiorenal composite outcome occurred in 423 patients (1.76%) in the ITT population. Of these 423 patients, 118 (28%) were in the celecoxib, 166 (39%) in the ibuprofen, and 139 (33%) in the naproxen group. In a multivariable Cox regression model adjusted for independent clinical variables, celecoxib showed a significantly lower risk compared with ibuprofen [hazard ratio (HR) 0.67, confidence interval (CI) 0.53-0.85, P = 0.001) and a trend to lower risk compared with naproxen (HR 0.79, CI 0.61-1.00, P = 0.058). In the ITT analysis, clinically significant renal events occurred in 220 patients with events rates of 0.71%, 1.14%, and 0.89% for celecoxib, ibuprofen, and naproxen, respectively (P = 0.052), while in the on-treatment analysis the rates were 0.52%, 0.91%, and 0.78% (P < 0.001).
CONCLUSIONS: In the current era, long-term NSAID use was associated with few cardiorenal events in arthritis patients. At the doses studied, celecoxib displayed fewer renal events and hence more favourable cardiovascular safety compared with ibuprofen or naproxen. These results have considerable clinical implications for practitioners managing individuals with chronic arthritis pain and high risk of impaired renal function and/or heart failure.Clinical
Trial Registration: NCT00346216.