What initial dose of aspirin is right for STEMI patients? 

　　2007年12月17日的循环杂志的研究显示对于ST段抬高急性心肌梗死患者162mg阿司匹林有效性和325mg相似，安全性更好。该研究由Duke研究所的Jeffrey Berger等完成，作者解释阿司匹林是STEMI治疗的基石，证据主要是ISIS-2试验，该试验显示162.5mg阿司匹林降低死亡率23%，ACC/AHA指南中该剂量是1类推荐，证据级别A，相反325mg阿司匹林为1C类推荐。

　　Berger等指出尽管有这些建议，在美国最常见的初始剂量是325mg，作者指出只有一个随机试验比较溶栓治疗患者初始阿司匹林剂量，但该试验仅入选162例患者，作者对两个STEMI溶栓试验GUSTO I和GUSTO III开展了回顾性分析，共分析了56080例患者，比较162mg和325mg的短期临床预后。

　　结果显示24.4%的患者初始剂量为325mg，75.6%患者为162mg，24小时和30天两组死亡率和心脏事件无显著性差异。但325mg显著增加了轻度和严重出血发生率(OR 1.14; 95% CI 1.05-1.24; p<0.003)。

24小时心脏事件

心脏事件 　　 阿司匹林 162 mg  　　　阿司匹林 325 mg 　　 p  　　　纠正的 OR (95% CI)

－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－
死亡  　　　　　　2.8 　　　　　　　　　2.9 　　　　　　　0.894 　　　1.01 (0.82-1.25)
MI  　　　　　　　0.5 　　　　　　　　　0.7 　　　　　　　0.057 　　　　1.22 (0.89-1.67)
卒中 　　　　　　 0.7 　　　　　　　　　0.9 　　　　　　　0.017 　　　1.16 (0.87-1.53)
出血  　　　　　　0.5 　　　　　　　　　0.6 　　　　　　　0.067 　　　1.04 (0.75-1.45)
无出血  　　　　　0.1 　　　　　　　　　0.2 　　　　　　　0.034 　　　1.68 (0.94-2.99)
死亡、心肌梗死和卒中 3.9 　　　　　　　　4.2 　　　　　　　0.111 　　　1.05 (0.91-1.21)
死亡和心肌梗死 　　3.4 　　　　　　　　　3.6 　　　　　　　0.362 　　　　1.04 (0.89-1.21)

－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－

　　Berger等说，“我们的结果和以前阿司匹林研究一致，即大剂量阿司匹林有相似的有效性，但会增加出血发生率。本研究再次扩展了该结果，即使最初阿司匹林剂量有临床价值，但不应被过分强调。我们的研究结论支持最初阿司匹林剂量从325mg降低到162mg能显著降低出血危险，而不丧失有效性。”

　　作者还指出该研究也有多个局限性，包括该研究为回顾性研究的特点，并不是阿司匹林不同剂量的随机试验。尽管如此作者建议STEMI患者中最初阿司匹林剂量162mg和325mg有效性相似，但更为安全。

　　（武警总医院　韩玮　编译）

　　（来源：www.theheart.org）

What initial dose of aspirin is right for STEMI patients? 
 
December 20, 2007  
Sue Hughes

Durham, NC - An initial dose of 162-mg aspirin may be as effective as and perhaps safer than 325 mg for the acute treatment of ST-elevation MI (STEMI), a new study suggests

The study, published online in Circulation on December 17, 2007, was conducted by a group led by Dr Jeffrey Berger (Duke Clinical Research Institute, Durham, NC). They explain that aspirin therapy is a cornerstone in the immediate treatment of STEMI and that much of the data supporting its use comes from the ISIS-2 trial, which showed that a 162.5-mg dose reduced five-week vascular mortality by 23%, which led to an ACC/AHA class 1, level of evidence A, recommendation for this dose. In contrast, use of a 325-mg dose of aspirin has a class 1, level of evidence C, recommendation, due to a paucity of data on this dose.

Berger et al point out that despite these recommendations, the most common initial dose of aspirin in the US has been 325 mg. They note that there has been only a single randomized trial that compared initial aspirin doses among those receiving fibrinolytic therapy, but that trial stopped early after enrolling only 162 patients. They therefore conducted a retrospective analysis of two large STEMI fibrinolytic trials, GUSTO I and GUSTO III, with a combined database of 56 080 STEMI patients, to assess immediate aspirin dose (162 vs 325 mg) and short-term outcomes after STEMI.

Results showed that 24.4% of patients (11 828) received an initial aspirin dose of 325 mg, and 75.6% (36 594) received 162 mg. There was no significant difference between the two doses in terms of mortality or other cardiac events at 24 hours or at seven and 30 days.

Cardiac events at 24 hours

Event                          　Aspirin 162 mg 　　　 Aspirin 325 mg  　　　　　p  　　　　　　Adjusted OR (95% CI)
－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－
Death  　　　　　　　　　　2.8 　　　　　　　　　　2.9 　　　　　　　0.894 　　　　1.01 (0.82-1.25)
MI  　　　　　　　　　　　　0.5　　　　　　　　　　 0.7 　　　　　　　0.057 　　　　1.22 (0.89-1.67)
Stroke  　　　　　　　　　　0.7 　　　　　　　　　　0.9　　　　　　　 0.017 　　　　1.16 (0.87-1.53)
Hemorrhagic 　　　　　　　 0.5　　　　　　　　　　 0.6 　　　　　　　0.067 　　　　1.04 (0.75-1.45)
Nonhemorrhagic  　　　　　0.1　　　　　　　　　　 0.2 　　　　　　　0.034 　　　　1.68 (0.94-2.99)
Death/MI/stroke  　　　　　　3.9 　　　　　　　　　4.2 　　　　　　　　0.111 　　　1.05 (0.91-1.21)
Death/MI  　　　　　　　　　3.4 　　　　　　　　　3.6 　　　　　　　　0.362 　　　　1.04 (0.89-1.21)

－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－－

 But the 325-mg dose was associated with a significant increase in the risk of moderate or severe bleeding compared with the 162-mg dose (OR 1.14; 95% CI 1.05-1.24; p<0.003).

Berger et al write: "Our data are consistent with prior aspirin studies that have shown similar efficacy and increased bleeding risk with a higher aspirin dose. The present study extends these findings and demonstrates that even the initial dose of aspirin may have clinical implications and therefore should not be overlooked. Our study raises the hypothesis that lowering the initial dose of aspirin from 325 to 162 mg may substantially lower the risk of bleeding without loss of efficacy."

The authors acknowledge that there are several limitations to this study, including the fact that it was a post hoc analysis of prospectively collected data from two clinical trials in which the dose of aspirin was not randomized or stipulated in the study protocol. Despite this, they say that the data do suggest that for the first dose of aspirin, 162 mg may be as effective as and safer than 325 mg for the acute treatment of STEMI. "This higher associated bleeding risk reinforces the importance of finding the lowest effective aspirin dose as an important goal in each clinical setting," they conclude.

责任编辑　刘瑞琦