Department of Neurology, Cerebrovascular Division, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA,
Department of Neurology, Cerebrovascular Division, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
Cerebrovasc Dis. 2020;49(3):237-243. doi: 10.1159/000508026. Epub 2020 May 5.
Two recent cerebrovascular studies, Clopidogrel (Clo) in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and minor ischemic stroke (POINT), have purportedly demonstrated the superiority of early dual antiplatelet therapy (DAPT), using aspirin (ASA) plus Clo, in comparison to ASA alone following the occurrence of acute minor cerebral infarction or transient ischemic attack. However, limitations to these trials exist that may not have been adequately explored and presented in the literature, and which may impact the overall efficacy and benefit of DAPT in these situations. Herein we provide a detailed and extensive critique of these 2 trials and of a combined analysis, with particular attention to study data and analyses pertaining to hemorrhagic complications.
DAPT may be superior to ASA alone in preventing recurrent cerebral ischemic events, but exclusively during the first 7-10 days of treatment, and probably only in the presence of acute infarction on cerebral imaging. The impact of minor hemorrhages, which are often clinically consequential and which frequently lead to permanent DAPT discontinuation, has not been adequately considered in the available analyses. Based on data from the trials, DAPT use causes more major and minor hemorrhages than ASA use alone or Clo alone, and Clo use results in fewer hemorrhages than the use of ASA alone. Analyses that include hemorrhage data from the period of Clo alone use as part of the DAPT data may provide inaccurate and erroneous conclusions regarding the relative safety and overall net benefit of DAPT use over ASA alone.
两项最近的脑血管研究，即氯吡格雷（Clo）在急性非致残性脑血管事件高风险患者中的应用（CHANCE）和短暂性脑缺血发作和小缺血性卒中的血小板导向抑制（POINT），据称表明了早期双联抗血小板治疗（DAPT）的优越性，即在急性小面积脑梗死或短暂性脑缺血发作后，使用阿司匹林（ASA）加 Clo 比单用 ASA 更有效。然而，这些试验存在一些局限性，可能没有在文献中得到充分探讨和阐述，这些局限性可能会影响这些情况下 DAPT 的整体疗效和获益。在此，我们详细而广泛地评价了这两项试验以及一项联合分析，特别关注与出血并发症相关的研究数据和分析。
DAPT 可能优于单用 ASA，预防复发性脑缺血事件，但仅在治疗的前 7-10 天有效，而且可能仅在脑影像学显示急性梗死时有效。轻微出血的影响在现有分析中没有得到充分考虑，轻微出血通常具有临床意义，并且常常导致永久性停止 DAPT。与单用 ASA 或 Clo 相比，DAPT 治疗导致更多的大出血和小出血，而 Clo 治疗导致的出血比单用 ASA 更少。分析中如果将 Clo 单独使用期间的数据纳入 DAPT 数据中，可能会对 DAPT 与单用 ASA 相比的相对安全性和总体净获益产生不准确和错误的结论。
