Chan Andrew T, Manson JoAnn E, Albert Christine M, Chae Claudia U, Rexrode Kathryn M, Curhan Gary C, Rimm Eric B, Willett Walter C, Fuchs Charles S
Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Circulation. 2006 Mar 28;113(12):1578-87. doi: 10.1161/CIRCULATIONAHA.105.595793. Epub 2006 Mar 13.
Although randomized trials of cyclooxygenase-2 (COX-2) inhibitors have shown increased cardiovascular risk, studies of nonselective, nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen have been inconsistent.
We examined the influence of NSAIDs and acetaminophen on the risk of major cardiovascular events (nonfatal myocardial infarction, fatal coronary heart disease, nonfatal and fatal stroke) in a prospective cohort of 70,971 women, aged 44 to 69 years at baseline, free of known cardiovascular disease or cancer, who provided medication data biennially since 1990. During 12 years of follow-up, we confirmed 2041 major cardiovascular events. Women who reported occasional (1 to 21 d/mo) use of NSAIDs or acetaminophen did not experience a significant increase in the risk of cardiovascular events. However, after adjustment for cardiovascular risk factors, women who frequently (> or =22 d/mo) used NSAIDs had a relative risk (RR) for a cardiovascular event of 1.44 (95% CI, 1.27 to 1.65) compared with nonusers, whereas those who frequently consumed acetaminophen had a RR of 1.35 (95% CI, 1.14 to 1.59). The elevated risk associated with frequent NSAID use was particularly evident among current smokers (RR=1.82; 95% CI, 1.38 to 2.42) and was absent among never smokers (Pinteraction=0.02). Moreover, we observed significant dose-response relations: Compared with nonusers, the RRs for a cardiovascular event among women who used > or =15 tablets per week were 1.86 (95% CI, 1.27 to 2.73) for NSAIDs and 1.68 (95% CI, 1.10 to 2.58) for acetaminophen.
Use of NSAIDs or acetaminophen at high frequency or dose is associated with a significantly increased risk for major cardiovascular events, although more moderate use did not confer substantial risk.
尽管环氧化酶-2（COX-2）抑制剂的随机试验显示心血管风险增加，但关于非选择性非甾体抗炎药（NSAIDs）和对乙酰氨基酚的研究结果并不一致。
我们在一个前瞻性队列中研究了NSAIDs和对乙酰氨基酚对主要心血管事件（非致命性心肌梗死、致命性冠心病、非致命性和致命性中风）风险的影响，该队列包括70971名年龄在44至69岁之间、基线时无已知心血管疾病或癌症的女性，她们自1990年起每两年提供一次用药数据。在12年的随访期间，我们确认了2041例主要心血管事件。报告偶尔（每月1至21天）使用NSAIDs或对乙酰氨基酚的女性，心血管事件风险未显著增加。然而，在对心血管危险因素进行调整后，频繁（每月≥22天）使用NSAIDs的女性发生心血管事件的相对风险（RR）为1.44（95%CI，1.27至1.65），而频繁服用对乙酰氨基酚的女性RR为1.35（95%CI，1.14至1.59）。频繁使用NSAIDs相关的风险升高在当前吸烟者中尤为明显（RR = 1.82；95%CI，1.38至2.42），而从不吸烟者中则不存在（P相互作用 = 0.02）。此外，我们观察到显著的剂量反应关系：与未使用者相比，每周使用≥15片NSAIDs的女性发生心血管事件的RR为1.86（95%CI，1.27至2.73），使用对乙酰氨基酚的女性RR为1.68（95%CI，1.10至2.58）。
高频率或高剂量使用NSAIDs或对乙酰氨基酚与主要心血管事件风险显著增加相关，尽管使用频率较低时风险不大。
