Bavry Anthony A, Thomas Fridtjof, Allison Matthew, Johnson Karen C, Howard Barbara V, Hlatky Mark, Manson JoAnn E, Limacher Marian C
From the North Florida/South Georgia Veterans Health System, Gainesville, FL (A.A.B); Division of Cardiovascular Medicine, University of Florida, Gainesville (A.A.B., M.C.L.); Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis (F.T., K.C.J.); Division of Preventive Medicine, University of California, San Diego, La Jolla (M.A.); MedStar Health Research Institute, Hyattsville, MD (B.V.H.); Health Research and Policy/Cardiovascular Medicine, Stanford University, CA (M.H.); and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.E.M.).
Circ Cardiovasc Qual Outcomes. 2014 Jul;7(4):603-10. doi: 10.1161/CIRCOUTCOMES.113.000800. Epub 2014 Jul 8.
Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 when compared with cox-1 inhibition.
Postmenopausal women enrolled in the Women's Health Initiative were classified as regular users or nonusers of nonaspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total cardiovascular disease defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (eg, celecoxib), nonselective agents with cox-2>cox-1 inhibition (eg, naproxen), and nonselective agents with cox-1>cox-2 inhibition (eg, ibuprofen) with the primary outcome. Overall, 160 801 participants were available for analysis (mean follow-up, 11.2 years). Regular NSAID use at some point in time was reported by 53 142 participants. Regular NSAID use was associated with an increased hazard for cardiovascular events versus no NSAID use (hazard ratio [HR], 1.10; 95% confidence interval, 1.06-1.15; P<0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for cardiovascular events (hazard ratio, 1.13; 1.04-1.23; P=0.004 and celecoxib only: HR, 1.13; 1.01-1.27; P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for cardiovascular events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR, 1.17; 1.10-1.24; P<0.001 and naproxen only: HR, 1.22; 1.12-1.34; P<0.001). This harmful association remained among concomitant aspirin users. We did not observe a risk elevation for agents with cox-1>cox-2 inhibition (HR, 1.01; 0.95-1.07; P=0.884 and ibuprofen only: HR, 1.00; 0.93-1.07; P=0.996).
Regular use of selective cox-2 inhibitors and nonselective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for cardiovascular events. Nonselective agents with cox-1>cox-2 inhibition were not associated with increased cardiovascular risk.
www.clinicaltrials.gov. Unique identifier: NCT00000611.
关于非甾体抗炎药（NSAIDs）心血管毒性的确凿数据稀少。我们假设，绝经后女性经常使用NSAIDs会增加心血管事件风险，且与环氧化酶（COX）-2抑制作用相比，COX-1抑制作用下这种关联更强。
参加女性健康倡议的绝经后女性被分为阿司匹林以外NSAIDs的经常使用者或非使用者。Cox回归将NSAIDs使用作为随时间变化的协变量，研究其与定义为心血管死亡、非致命性心肌梗死或非致命性中风的总体心血管疾病主要结局的关联。二次分析考虑了选择性COX-2抑制剂（如塞来昔布）、COX-2>COX-1抑制作用的非选择性药物（如萘普生）以及COX-1>COX-2抑制作用的非选择性药物（如布洛芬）与主要结局的关联。总体而言，160801名参与者可供分析（平均随访11.2年）。53142名参与者报告在某个时间点经常使用NSAIDs。与不使用NSAIDs相比，经常使用NSAIDs与心血管事件风险增加相关（风险比[HR]，1.10；95%置信区间，1.06 - 1.15；P<0.001）。选择性COX-2抑制剂与心血管事件风险适度增加相关（风险比，1.13；1.04 - 1.23；P = 0.004，仅塞来昔布：HR，1.13；1.01 - 1.27；P = 0.031）。在阿司匹林使用者中，同时使用选择性COX-2抑制剂与心血管事件风险增加不再相关。COX-2>COX-1抑制作用的药物风险增加（HR，1.17；1.10 - 1.24；P<0.001，仅萘普生：HR，1.22；1.12 - 1.34；P<0.001）。这种有害关联在同时使用阿司匹林的使用者中仍然存在。我们未观察到COX-1>COX-2抑制作用的药物风险升高（HR，1.01；0.95 - 1.07；P = 0.884，仅布洛芬：HR，1.00；0.93 - 1.07；P = 0.996）。
经常使用选择性COX-2抑制剂和COX-2>COX-1抑制作用的非选择性NSAIDs显示心血管事件风险适度增加。COX-1>COX-2抑制作用的非选择性药物与心血管风险增加无关。
