Aspirin dose, urinary thromboxane and prostacyclin metabolites, and clinical outcome in acute coronary syndrome: A nested case-control study from CURRENT-OASIS 7

IF 3.4 3区医学 Q1 HEMATOLOGY

Thrombosis research Pub Date : 2026-08-01 Epub Date: 2026-07-21 DOI:10.1016/j.thromres.2026.109788

John W. Eikelboom, Shamir R. Mehta, Qilong Yi, Jeffrey I. Weitz

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Abstract

Background

Aspirin reduces urinary thromboxane, which predicts major adverse cardiovascular events (MACE) during aspirin therapy. However, in CURRENT-OASIS 7, higher-dose aspirin did not improve outcomes compared with lower-dose aspirin.

Objectives

To assess relationships between aspirin dose, urinary thromboxane and prostacyclin metabolites, and ischemic and bleeding outcomes, and to determine whether greater prostacyclin suppression with higher-dose aspirin explains the absence of clinical benefit.

Methods

In a nested case-control study within CURRENT-OASIS 7, urinary 11-dehydro thromboxane B2 (11-dTXB2) and 2,3-dinor-6-keto-prostaglandin F1α, corrected for creatinine and expressed as ng/mmol creatinine, were measured in patients not taking nonsteroidal anti-inflammatory drugs. Cases had myocardial infarction, ischemic stroke, or non-hemorrhagic cardiovascular death (n = 275), or major bleeding (n = 137); controls had neither ischemic nor bleeding events (n = 1014). Associations were assessed with multivariable logistic regression by quartiles and restricted cubic splines.

Results

Compared with aspirin 75–100 mg/day, aspirin 300–325 mg/day modestly lowered 11-dTXB2 (153.0 vs 164.3 ng/mmol creatinine; p = 0.03) and the 11-dTXB2/prostacyclin metabolite ratio (0.09 vs 0.10; p = 0.02) but not the prostacyclin metabolite (1767.1 vs 1694.5 ng/mmol creatinine; p = 0.25). Higher 11-dTXB2 quartiles predicted MACE, with adjusted odds ratios of 1.01, 2.38, and 3.44 for quartiles 2–4 versus quartile 1, whereas prostacyclin-metabolite quartiles did not. In spline analyses, 11-dTXB2 remained associated with MACE (p < 0.0001), whereas the prostacyclin metabolite did not (p = 0.67).

Conclusions

In acute coronary syndrome, higher-dose aspirin modestly reduced urinary thromboxane without lowering the urinary prostacyclin metabolite. These findings do not support the hypothesis that systemic prostacyclin suppression by higher dose aspirin offsets any benefits of greater thromboxane suppression. Trial registration: ClinicalTrials.gov, NCT00335452.

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阿司匹林剂量、尿血栓素和前列环素代谢物与急性冠脉综合征的临床结局：CURRENT-OASIS的巢式病例对照研究

背景：阿司匹林降低尿血栓素，预测阿司匹林治疗期间的主要不良心血管事件（MACE）。然而，在CURRENT-OASIS 7中，与低剂量阿司匹林相比，高剂量阿司匹林并没有改善预后。目的：评估阿司匹林剂量、尿血栓素和前列环素代谢物与缺血性和出血结局之间的关系，并确定高剂量阿司匹林是否能更好地抑制前列环素，从而解释临床获益缺失的原因。方法：在CURRENT-OASIS 7的一项嵌套病例对照研究中，在未服用非甾体类抗炎药的患者中测量尿11-脱氢血栓素B2 （11-dTXB2）和2,3-二-6-酮前列腺素F1α，校正肌酐并以ng/mmol肌酐表示。心肌梗死、缺血性卒中或非出血性心血管死亡（n = 275）或大出血（n = 137）；对照组无缺血性和出血事件（n = 1014）。通过四分位数和限制三次样条的多变量logistic回归评估相关性。结果：与阿司匹林75 ~ 100 mg/d相比，阿司匹林300 ~ 325 mg/d可适度降低11-dTXB2 （153.0 vs 164.3 ng/mmol肌酐，p = 0.03）和11-dTXB2/ prostcycloin代谢物比值（0.09 vs 0.10, p = 0.02），但对prostcycloin代谢物比值（1767.1 vs 1694.5 ng/mmol肌酐，p = 0.25）无显著影响。较高的11-dTXB2四分位数预测MACE， 2-4四分位数与1四分位数的调整比值比分别为1.01、2.38和3.44，而前列环素代谢物四分位数则没有。在样条分析中，11-dTXB2仍与MACE相关(p)。结论：在急性冠脉综合征中，高剂量阿司匹林可适度降低尿血栓素，但不降低尿前列环素代谢物。这些发现不支持高剂量阿司匹林对全身前列环素的抑制会抵消大剂量血栓素抑制的任何益处的假设。试验注册：ClinicalTrials.gov, NCT00335452。

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来源期刊

Thrombosis research 医学-外周血管病

CiteScore

14.60

自引率

4.00%

发文量

364

审稿时长

31 days

期刊介绍： Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.