Department of Medicine, Section of Internal and Cardiovascular Medicine, University Perugia, Italy.
Division of Infectious Diseases, Department of Experimental Medicine, University of Perugia, Perugia, Italy.
Int J Cardiol. 2018 Jul 15;263:118-124. doi: 10.1016/j.ijcard.2018.04.052. Epub 2018 Apr 12.
Ischemic cardiovascular events are a relevant cause of morbidity and mortality in HIV-infected patients. Use of abacavir (ABC), a nucleoside analog reverse transcriptase inhibitor, has been associated with increased risk of myocardial infarction (MI) and with platelet hyperreactivity. We explored whether low-dose aspirin reduces in vivo platelet activation and platelet hyperreactivity induced by ABC in HIV-infected subjects.
In a randomized, placebo-controlled, cross-over study forty HIV-infected patients with ABC-associated platelet hyperreactivity, defined by a score based on laboratory variables reflecting in vivo platelet activation and ex vivo platelet hyperresponsiveness, were randomized to aspirin 100 mg daily for 15 days with subsequent cross-over to placebo for additional 15 days or placebo for 15 days with subsequent cross-over to aspirin for further 15 days. In vivo and ex vivo platelet activation markers were measured at day 15 and 30. One group of healthy subjects, one of untreated HIV infected-patients and one treated without ABC, were studied concomitantly. Serum TxB and urinary 11-dehydro-TxB were decreased by aspirin in ABC-treated patients, but not as much as in healthy controls. Aspirin therapy reduced significantly platelet hyperreactivity (score: from 9.3, 95% CIs 8.7 to 10.0, to 7.5, 6.9 to 8.0), however without bringing it back to the levels of healthy controls (score: 4.6, 95% CIs 3.6 to 5.6).
Aspirin reduces ABC-induced in vivo platelet activation and platelet hyperreactivity in HIV-infected patients, however without normalizing them. Whether the observed reduction of platelet activation is sufficient to prevent cardiovascular events requires a prospective trial.
缺血性心血管事件是 HIV 感染患者发病率和死亡率的一个重要原因。核苷类似物逆转录酶抑制剂阿巴卡韦（ABC）的使用与心肌梗死（MI）风险增加和血小板高反应性相关。我们探讨了低剂量阿司匹林是否能降低 HIV 感染患者中 ABC 诱导的体内血小板激活和血小板高反应性。
在一项随机、安慰剂对照、交叉研究中，40 名因 ABC 引起血小板高反应性的 HIV 感染患者（定义为基于反映体内血小板激活和体外血小板高反应性的实验室变量的评分）被随机分为每日服用阿司匹林 100mg 组（连续 15 天），随后交叉至安慰剂组（连续 15 天），或安慰剂组（连续 15 天），随后交叉至阿司匹林组（连续 15 天）。在第 15 天和第 30 天测量体内和体外血小板激活标志物。同时研究了一组健康受试者、一组未经治疗的 HIV 感染患者和一组未用 ABC 治疗的患者。阿司匹林治疗可降低 ABC 治疗患者的血清 TxB 和尿 11-脱氢-TxB，但不如健康对照组明显。阿司匹林治疗可显著降低血小板高反应性（评分：从 9.3，95%CI 8.7 至 10.0，降至 7.5，6.9 至 8.0），但未恢复至健康对照组水平（评分：4.6，95%CI 3.6 至 5.6）。
阿司匹林可降低 HIV 感染患者中 ABC 诱导的体内血小板激活和血小板高反应性，但不能使其恢复正常。观察到的血小板激活减少是否足以预防心血管事件需要前瞻性试验。
