Low-Dose Aspirin for the Prevention of Atherothrombosis

Patrono, Carlo; Rodrı́guez, Luis A. Garcı́a; Landolfi, Raffaele; Baigent, Colin

doi:10.1056/nejmra052717

Cited by 1,074 publications

(829 citation statements)

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“…First, during the acute phase of AMI, more platelets are released and overactivated 1, 19. Newly formed platelets beside their constitutive cyclooxygenase (COX)‐1 expression, retain COX‐2 activity contributing to additional TX synthesis 1, 2, 11, 20, 21. Further, intense thrombotic and concomitant acute inflammatory processes present in AMI induce TX synthesis from sources other than platelets, mostly inflammatory (monocytes and macrophages) and endothelial cells 22.…”

Section: Discussionmentioning

confidence: 99%

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Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Szczeklik

Stodółkiewicz

Rzeszutko

et al. 2016

JAHA

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BackgroundUrinary 11‐dehydro‐thromboxane (TX)B2 has been described as a potential predictive biomarker of major adverse cardiovascular events (MACEs) in high cardiac risk patients. This part of LTIMI (Leukotrienes and Thromboxane In Myocardial Infarction) study aimed to evaluate the relationship between 11‐dehydro‐TXB 2 and MACEs in patients with acute myocardial infarction (AMI).Methods and Results LTIMI was an observational, prospective study in 180 consecutive patients with AMI type 1 referred for primary percutaneous coronary intervention. On admission and at follow‐up visits (1 month, 1 year), 11‐dehydro‐TXB 2 was measured in urinary samples by using high‐performance liquid chromatography–tandem mass spectrometry. The primary outcome was occurrence of composite MACEs during 1‐year after AMI. Left ventricular ejection fraction was assessed in echocardiography on admission and at 1‐year follow‐up. Analyses of 11‐dehydro‐TXB 2 (pg/mg creatinine) were performed on log‐transformed data and expressed as median with IQR (Q1–Q3). 11‐Dehydro‐TXB 2 level on admission was 7.39 (6.85–8.01) and decreased at 1 month (6.73, 6.27–7.12; P<0.001) and 1‐year follow‐up (6.37, 5.91–6.94; P<0.001). In univariate analysis, baseline 11‐dehydro‐TXB 2 was higher in patients with MACEs (n=60; 7.73, 7.07–8.60) compared with those without MACEs (n=119; 7.28, 6.68–7.79; P=0.002). In multivariate regression model, 11‐dehydro‐TXB 2 and 3 other variables (diabetes, multivessel disease, and left ventricular ejection fraction) were found to be best 1‐year cumulative MACE predictors with odds ratio for 11‐dehydro‐TXB 2 of 1.58 (95% CI 1.095–2.33; P=0.017) and area under the curve (in receiver operating characteristic analysis of 0.8). Baseline 11‐dehydro‐TXB 2 negatively correlated with both left ventricular ejection fraction on admission (R=−0.21; P=0.006) and after 1 year (R=−0.346; P<0.001).Conclusions11‐Dehydro‐TXB 2 predicts 1‐year cumulative MACEs in AMI patients and provides prognostic information on the left ventricular performance.

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Section: Discussionmentioning

confidence: 99%

“…Thromboxane (TX)A 2 is a potent platelet agonist and vasoconstrictor1 produced mostly by platelets, which play a pivotal role in thrombogenesis at sites of vulnerable plaque and provide a strong rationale for blocking their function in the setting of acute myocardial infarction (AMI) 1, 2…”

Section: Introductionmentioning

confidence: 99%

Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Szczeklik

Stodółkiewicz

Rzeszutko

et al. 2016

JAHA

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“…The benefits of low-dose aspirin are well established in secondary prevention (1,39,42). In primary prevention, a recent meta-analysis of more than 50,000 women and 40,000 men taking part in six randomized trials has indicated that low-dose aspirin therapy is associated with a significant reduction in cardiovascular events in both men and women (3).…”

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confidence: 99%

Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

Bulckaen¹,

Prévost²,

Boulanger³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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The age-related impairment of endothelium-dependent vasodilatation contributes to increased cardiovascular risk in the elderly. For primary and secondary prevention, aspirin can reduce the incidence of cardiovascular events in this patient population. The present work evaluated the effect of low-dose aspirin on age-related endothelial dysfunction in C57B/J6 aging mice and investigated its protective antioxidative effect. Agerelated endothelial dysfunction was assessed by the response to acetylcholine of phenylephrine-induced precontracted aortic segments isolated from 12-, 36-, 60-, and 84-wk-old mice. The effect of low-dose aspirin was examined in mice presenting a decrease in endothelial-dependent relaxation (EDR). The effects of age and aspirin treatment on structural changes were determined in mouse aortic sections. The effect of aspirin on the oxidative stress markers malondialdehyde and 8-hydroxy-2Ј-deoxyguanosine (8-OhdG) was also quantified. Compared with that of 12-wk-old mice, the EDR was significantly reduced in 60-and 84-wk-old mice (P Ͻ 0.05); 68-wkold mice treated with aspirin displayed a higher EDR compared with control mice of the same age (83.9 Ϯ 4 vs. 66.3 Ϯ 5%; P Ͻ 0.05). Aspirin treatment decreased 8-OHdG levels (P Ͻ 0.05), but no significant effect on intima/media thickness ratio was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 wk of age). It was found that low-dose aspirin is able to prevent age-related endothelial dysfunction in aging mice. However, the absence of this effect in the older age groups demonstrates that treatment should be initiated early on. The underlying mechanism may involve the protective effect of aspirin against oxidative stress. endothelium; intima/media; vasodilatation; oxidative stress AGE-ASSOCIATED CHANGES SUCH as endothelial dysfunction are involved in the significantly increased risk of cardiovascular complications and microthrombus formation in the elderly patient population (44). The presence of endothelial dysfunction in the coronary or peripheral circulation has been shown to constitute a risk factor for cardiovascular events independent of the development of atherosclerosis or other vascular risk factors (22,(43)(44)(45). There is emerging evidence that age-associated endothelial dysfunction is related to the local formation of reactive oxygen and nitrogen species within and in the vicinity of the vascular wall (13,25,36,43,49). Therapeutic approaches capable of preventing or reversing age-related endothelial dysfunction may thus help to reduce cardiovascular risk in the elderly.Age-related endothelial-dependent relaxation (EDR) decreases in the large vessels of different animal species including humans (36). EDR in response to acetylcholine (ACh) decreases with age in the rat aorta: the maximal relaxation effect of ACh is 100% in 4-to 6-wk-old, 50% in 3-to 6-mo-old, and 25% in 12-to 25-mo-old rats (29). The agerelated decrease in EDR varies from one vessel to another and from one species to anot...

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“…This is partly due to recommendations by various neurological and cardiovascular societies that antiplatelet agents should be used for the prevention of ischemic stroke or ischemic heart disease (1,2). In Japan, the use of low-dose aspirin for these conditions has been progressively increasing since antiplatelet therapy with lowdose aspirin was first covered by the National Health Insurance Scheme in 2000.…”

Section: Introductionmentioning

confidence: 99%

Role of Antithrombotic Therapy and Nonsteroidal Anti-inflammatory Drug Use in Bleeding Gastroduodenal Ulcers

et al. 2009

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Low-Dose Aspirin for the Prevention of Atherothrombosis

Cited by 1,074 publications

References 90 publications

Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

Role of Antithrombotic Therapy and Nonsteroidal Anti-inflammatory Drug Use in Bleeding Gastroduodenal Ulcers

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Low-Dose Aspirin for the Prevention of Atherothrombosis

Cited by 1,074 publications

References 90 publications

Urinary 11‐Dehydro‐Thromboxane B 2 as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Urinary 11‐Dehydro‐Thromboxane B 2 as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

Role of Antithrombotic Therapy and Nonsteroidal Anti-inflammatory Drug Use in Bleeding Gastroduodenal Ulcers

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Product

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Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

Urinary 11‐Dehydro‐Thromboxane B ₂ as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study