一項(xiàng)HORIZONS-AMI(血管成形術(shù)和支架治療急性心肌梗死一致性結(jié)果)臨床試驗(yàn)表明，行直接冠狀動(dòng)脈介入術(shù)的ST段抬高心梗病人，出院服用大劑量阿司匹林出現(xiàn)大出血并發(fā)癥的幾率比給予小劑量的阿司匹林患者高，并且大劑量的阿司匹林并沒(méi)有額外的防止缺血性事件發(fā)生的保護(hù)作用。

　　在臨床指南中，阿司匹林的推薦劑量從82mg到325mg不等，那是因?yàn)橹斑€沒(méi)有任何一項(xiàng)前瞻性的隨機(jī)對(duì)照研究來(lái)證實(shí)究竟哪一種劑量對(duì)這些病人最有益處。臨床醫(yī)生重視阿司匹林導(dǎo)致的出血并發(fā)癥，但卻沒(méi)做阿司匹林最有益劑量的相關(guān)實(shí)驗(yàn)。這項(xiàng)研究的作者，紐約西奈山醫(yī)學(xué)院RoxanaMehran博士，在接受記者的采訪時(shí)說(shuō)，“我認(rèn)為藥物不僅要能夠防止缺血性事件發(fā)生，同時(shí)也不該將病人置于出血并發(fā)癥的危險(xiǎn)中。”

　　這項(xiàng)HORIZONS-AMI研究發(fā)表在2012年12月的《美國(guó)心臟病學(xué)學(xué)院心血管介入雜志》[JACC Cardiovasc Interv 2012 Dec]的《心臟介入》板塊上：關(guān)于2289名術(shù)后出院病人服用低劑量阿司匹林（<200mg/天）和562名服用低劑量阿司匹林（>200mg/天）三年預(yù)后對(duì)比分析。但是這畢竟是一項(xiàng)回顧性分析，可能受制于此類研究具有的混雜因素，比如，高劑量阿司匹林組更可能是行了經(jīng)股動(dòng)脈心臟介入術(shù)而不是經(jīng)橈動(dòng)脈心臟介入術(shù)，會(huì)置入更長(zhǎng)的支架，有更長(zhǎng)的X線透視檢查時(shí)間，相對(duì)更大的容積，同時(shí)縮短了的發(fā)作后入院急診室到首次球囊擴(kuò)張時(shí)間。

　　研究中有個(gè)發(fā)現(xiàn)比較有趣：高劑量的阿司匹林并沒(méi)有帶來(lái)任何形式的缺血保護(hù)作用，相反卻將病人暴露于更多的風(fēng)險(xiǎn)中。Mehran博士指出，這次發(fā)現(xiàn)結(jié)果雖然可喜，但這項(xiàng)研究還有一些限制因素，它并不是一項(xiàng)前瞻性的臨床隨機(jī)對(duì)照研究。確定阿司匹林的劑量并不是這項(xiàng)研究的主要目的。所以它受限于一些無(wú)法預(yù)測(cè)的混雜因素，而且臨床醫(yī)生們已經(jīng)知道給患者予高劑量阿司匹林和低劑量阿司匹林存在很大的差異。

　　所以研究人員在一項(xiàng)傾向評(píng)分多元分析中調(diào)整了患者基線特征，研究顯示：出院病人給予高劑量阿司匹林會(huì)帶來(lái)接近三倍的大出血發(fā)生率（風(fēng)險(xiǎn)比2.80,95%置信區(qū)間為1.31-5.99）。大出血發(fā)生率的提高在出院后兩個(gè)月就以顯現(xiàn)，在整個(gè)三年的隨訪期中持續(xù)增長(zhǎng)，但是高劑量阿司匹林并沒(méi)有減少缺血性事件的發(fā)生。

　　這項(xiàng)研究又一次表明，我們應(yīng)該多多關(guān)注急性心?；颊叩娘L(fēng)險(xiǎn)水平，因?yàn)槲覀円呀?jīng)知道這些患者不僅有缺血性風(fēng)險(xiǎn)還有出血性風(fēng)險(xiǎn)。必須根據(jù)出血風(fēng)險(xiǎn)去平衡，以確保我們選擇了合適劑量的阿司匹林。

　　HORIZONS-AMI研究沒(méi)有使用具有更強(qiáng)抗血小板作用的藥物，如替卡格雷（商品名Brilinta，阿斯利康制藥）及普拉格雷（商品名Effient禮來(lái)制藥），但是這些藥物對(duì)臨床醫(yī)生觸手可及，所以很有必要把注意力放在低劑量的阿司匹林上，那么就需要前瞻性的隨機(jī)對(duì)照臨床試驗(yàn)來(lái)證實(shí)出院帶藥時(shí)究竟哪種劑量的阿司匹林對(duì)ST抬高的急性心梗患者、非ST抬高急性心梗患者以及不穩(wěn)定心絞痛患者合適。

　　More bleeding, no extra ischemic protection with high-dose aspirin in HORIZONS-AMI

　　Ann Arbor, MI - An analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial has shown that patients with ST-segment-elevation MI (STEMI) undergoing primary PCI discharged on high-dose aspirin have higher rates of major bleeding than those discharged on low-dose aspirin. The high-dose aspirin also failed to provide any additional protection against ischemic events .

　　"In the clinical guidelines, the recommended dose of aspirin ranges anywhere from 82 mg to 325 mg because we don't really have any prospective, randomized study showing which dose is actually best for these patients, which is kind of interesting given that we are now putting so much of our attention on the bleeding complications," Dr Roxana Mehran (Mount Sinai School of Medicine, New York), one of the study authors, told heartwire. "I think it's important that agents not only protect you against ischemia but also don't expose you to the harm of bleeding complications."

　　The HORIZONS-AMI analysis, published in the December 2012 issue of JACC: Cardiovascular Interventions, compared three-year outcomes among 2289 patients discharged on low-dose aspirin (<200 mg/day) and 562 patients treated with high-dose aspirin (>200 mg/day). The analysis is a post hoc one, however, and subject to the possibility of confounding associated with such reports. For example, patients discharged on high-dose aspirin were more likely to undergo femoral PCI (vs radial) and had longer stents implanted, longer fluoroscopy times, and more contrast volume, as well as shorter symptom onset and door-to-balloon inflation times.

　　"The intriguing finding we found in this study was that the high-dose aspirin did not provide any benefit in terms of ischemic protection and exposed the patient to more risk," said Mehran. "Now, having said that, there are some limitations attached to this, as this was not a randomized, prospective clinical trial. The dosing of aspirin was the not the intent of the HORIZONS-AMI study. Therefore, it is subject to unmeasured confounders, and we already know there was a big difference in the patients prescribed high-dose aspirin and those given low-dose aspirin."

　　That said, the researchers adjusted for these baseline patient characteristics and showed in a propensity-score-adjusted multivariate analysis that discharge on high-dose aspirin was associated with a nearly threefold increased risk of major bleeding (hazard ratio 2.80; 95% CI 1.31-5.99). The increase in major bleeding occurred within the first two months following hospital discharge but continued to increase over the entire three-year follow-up period. High-dose aspirin was not associated with a reduction in any ischemic events.

　　"Once again, the moral of the story is that we really need to pay a lot of attention to the level of risk of our STEMI patients, understanding that these patients are at risk of bleeding and ischemic complications," said Mehran. "We have to balance that, and that balance may very well include making sure we choose the right dose of aspirin depending on their risk of bleeding."

　　Mehran noted that the HORIZONS-AMI study did not use the more potent antiplatelet agents, such as ticagrelor (Brilinta, AstraZeneca) or prasugrel (Effient, Lilly), but with these agents available to clinicians there is an increased need to focus on using lower-dose aspirin. There is also a need for randomized, prospective trials evaluating different doses of aspirin on discharge in patients with STEMI, non-STEMI, and unstable angina, she added.