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

Q: What are the key findings of this study?

Higher-dose aspirin (300-325 mg/day) modestly lowered urinary 11-dTXB2 (153.0 vs 164.3 ng/mmol creatinine; p=0.03) without suppressing prostacyclin, while Q4 vs Q1 11-dTXB2 predicted MACE (OR 3.44).

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Acute coronary syndrome undergoing an intended invasive strategy (n=1426). Intervention: Urinary 11-dehydro thromboxane B2 (11-dTXB2, highest quartile Q4 vs Q1) and higher-dose aspirin (300-325 mg/day) vs. Lowest quartile (Q1) of urinary 11-dTXB2 and lower-dose aspirin (75-100 mg/day). Primary outcome: Major adverse cardiovascular events (composite of myocardial infarction, ischemic stroke, or non-hemorrhagic cardiovascular death) (OR 3.44, 95% CI 2.24-5.30, p=<0.0001).

Q: What does this research mean for the field?

Higher-dose aspirin modestly reduces urinary thromboxane without suppressing urinary prostacyclin, refuting the hypothesis that systemic prostacyclin suppression accounts for the lack of clinical benefit of higher-dose aspirin in acute coronary syndrome. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine relationships between aspirin dose, urinary thromboxane and prostacyclin metabolites, and ischemic and bleeding outcomes in acute coronary syndrome.

John W. Eikelboom; S R Mehta; 易企龙; J Weitz

doi:10.1016/j.thromres.2026.109788

July 21, 2026Thrombosis ResearchOpen Access

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

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Key result

Highest urinary 11-dTXB2 levels linked to ~3.4-fold higher odds of MACE.

OR 3.44
95% CI 2.24-5.30
P<0.0001
n=1,426

Why the study?

In CURRENT-OASIS 7, higher-dose aspirin did not improve outcomes compared with lower-dose aspirin, prompting evaluation of whether greater prostacyclin suppression explains the absence of clinical benefit.

Does higher-dose aspirin (300-325 mg/day) compared with lower-dose aspirin (75-100 mg/day) suppress systemic urinary prostacyclin metabolites and explain the absence of clinical benefit on major adverse cardiovascular events in patients with acute coronary syndromes?

Key Points

To determine relationships between aspirin dose, urinary thromboxane and prostacyclin metabolites, and ischemic and bleeding outcomes in acute coronary syndrome.
Conducted a nested case-control study within the randomized CURRENT-OASIS 7 trial (NCT00335452) evaluating patients receiving aspirin 75-100 mg/day versus 300-325 mg/day who were not taking nonsteroidal anti-inflammatory drugs.
Measured creatinine-corrected urinary 11-dehydro thromboxane B2 (11-dTXB2) and 2,3-dinor-6-keto-prostaglandin F1α in cases with myocardial infarction, ischemic stroke, or non-hemorrhagic cardiovascular death (n = 275), or major bleeding (n = 137), and controls without ischemic or bleeding events (n = 1014).
Evaluated associations using multivariable logistic regression across quartiles and restricted cubic splines.
Aspirin 300-325 mg/day modestly reduced urinary 11-dTXB2 compared with 75-100 mg/day (geometric mean 153.0 vs 164.3 ng/mmol creatinine; p = 0.03) and the 11-dTXB2/prostacyclin ratio (0.09 vs 0.10; p = 0.02), but did not lower the prostacyclin metabolite (1767.1 vs 1694.5 ng/mmol creatinine; p = 0.25).
Higher quartiles of 11-dTXB2 strongly predicted MACE, with adjusted odds ratios of 1.01 (95% CI 0.63–1.62) for Q2, 2.38 (95% CI 1.54–3.66) for Q3, and 3.44 (95% CI 2.24–5.30) for Q4 compared with Q1 (p for trend < 0.0001).

Study Design

Type

Case-Control (n=1,426)

Blinding

Open-label aspirin dose assignment with blinded adjudication of outcomes

Randomization

2 x 2 factorial randomization in parent trial (CURRENT-OASIS 7)

Structured PICO

Does higher-dose aspirin (300-325 mg/day) compared with lower-dose aspirin (75-100 mg/day) suppress systemic urinary prostacyclin metabolites and explain the absence of clinical benefit on major adverse cardiovascular events in patients with acute coronary syndromes?

P

Population

1,426 patients with acute coronary syndromes referred for an invasive strategy and not taking NSAIDs (275 MACE cases, 137 major bleeding cases, and 1,014 event-free controls) followed for 30 days in a nested case-control substudy of CURRENT-OASIS 7.

E

Exposure

Higher-dose aspirin (300-325 mg/day for 30 days after an initial loading dose, combined with either standard-dose clopidogrel [300-mg loading dose then 75 mg/day] or double-dose clopidogrel [600-mg loading dose then 150 mg/day for 6 days, followed by 75 mg/day]).

C

Comparator

Lower-dose aspirin (75-100 mg/day for 30 days after an initial loading dose, combined with either standard-dose or double-dose clopidogrel).

O

Outcome

Urinary 11-dehydro thromboxane B2 (11-dTXB2) and 2,3-dinor-6-keto-prostaglandin F1α (prostacyclin metabolite) levels (corrected for creatinine, at a median of 4 days after randomization), and their association with major adverse cardiovascular events (MACE: composite of myocardial infarction, ischemic stroke, or non-hemorrhagic cardiovascular death) over 30 days, with blinded adjudication.composite

Main Result

Odds Ratio: 3.44 (95% CI 2.24–5.3)

p-value: p=<0.0001

In acute coronary syndrome, higher-dose aspirin (300-325 mg/day) modestly reduces urinary thromboxane without suppressing systemic urinary prostacyclin metabolites, refuting the hypothesis that systemic prostacyclin inhibition offsets the benefits of higher-dose aspirin.

Limitations

All patients received an initial loading dose of aspirin, and only a single urine sample was collected at a median of 4 days after randomization, so residual loading-dose effects may have attenuated between-group differences
Unable to collect urine at a later time point because there were no in-person follow-up visits after hospital discharge
Case-control design depended on urinary metabolites without measuring serum thromboxane or local vascular prostacyclin production
Possible confounding effect of non-adherence or unrecorded use of non-steroidal anti-inflammatory drugs cannot be excluded
The magnitude of association between 11-dTXB2 and MACE risk was greater than the benefit of aspirin and may reflect underlying inflammation, vascular disease burden, and other risk determinants
All patients received an initial loading dose of aspirin and only a single urine sample was collected at a median of 4 days after randomization, so residual effects of the loading dose may have attenuated group differences.
Unable to collect urine at a later time point because there were no in-person follow-up visits after hospital discharge.
Employed a case-control design and depended on urinary metabolites without measuring serum thromboxane or local vascular prostacyclin production.
Cannot exclude possible confounding effects of non-adherence or unrecorded use of non-steroidal anti-inflammatory drugs.
The magnitude of the association between 11-dTXB2 and MACE risk was greater than the benefit of aspirin and may reflect underlying inflammation, vascular disease burden, and other risk determinants.

Implication

Higher-dose aspirin modestly lowers thromboxane without prostacyclin suppression; leaves open 11-dTXB2 as MACE predictor on aspirin.

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.

Discussion

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Cite This Study

Eikelboom et al. (2026) conducted a case-control in Acute coronary syndrome undergoing an intended invasive strategy (n=1,426). Urinary 11-dehydro thromboxane B2 (11-dTXB2, highest quartile Q4 vs Q1) and higher-dose aspirin (300-325 mg/day) vs. Lowest quartile (Q1) of urinary 11-dTXB2 and lower-dose aspirin (75-100 mg/day) was evaluated on Major adverse cardiovascular events (composite of myocardial infarction, ischemic stroke, or non-hemorrhagic cardiovascular death) (OR 3.44, 95% CI 2.24-5.30, p=<0.0001). Higher-dose aspirin (300-325 mg/day) modestly lowered urinary 11-dTXB2 (153.0 vs 164.3 ng/mmol creatinine; p=0.03) without suppressing prostacyclin, while Q4 vs Q1 11-dTXB2 predicted MACE (OR 3.44).

synapsesocial.com/papers/6a7094fb35aa2c282ce1e6e6 https://doi.org/10.1016/j.thromres.2026.109788

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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