Relevance of Platelet-independent Effects of Aspirin to Its Salutary Effect in Atherosclerosis-related Events

Khan, Qaisar; Mehta, Jawahar L.

doi:10.5551/jat.12.185

Cited by 32 publications

(21 citation statements)

References 39 publications

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“…Acetylsalicylic acid (ASS) inhibits both COX isoenzymes. 119 The direct antithrombotic effect of ASS is mediated by inhibition of COX-1 in platelets resulting in a decreased production of thromboxane A2. Although most of the benefits of ASS in the prevention of cardio-and cerebrovascular events have been attributed to this mechanism, ASS probably in addition exerts platelet-independent effects by inhibition of COX-2.…”

Section: Cox Inhibitionmentioning

confidence: 99%

Inflammation and Atherosclerosis

Stoll

Bendszus

2006

Stroke

420

157

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Background and Purpose-The simplistic view of atherosclerosis as a disorder of pathological lipid deposition has been redefined by the more complex concept of an ongoing inflammatory response. Summary of Review-Apolipoprotein E and low-density lipoprotein (LDL)-receptor-deficient mice develop accelerated atherosclerosis allowing in-depth pathophysiological investigations. Atherosclerotic plaques in these mice contain large numbers of T cells and macrophages. Crossbreading apolipoprotein E-deficient mice with T-cell-deficient mice and mice with impaired macrophage function (osteopetrotic op/op mice) disclosed the important impact of immune cells on atherosclerotic lesion development. In contrast to the detrimental role of T cells and macrophages, B cells appear to be atheroprotective. These basic experimental findings have partly been confirmed in studies of the human carotid artery system. Inflammation is not only instrumental in the development of human atheromatous plaques, but, importantly, plays a crucial role in the destabilization of internal carotid artery plaques, thus converting chronic atherosclerosis into an acute thrombo-embolic disorder. Humoral factors involved in internal carotid artery destabilization include cytokines, cyclooxygenase-2, matrix metalloproteinases, and tissue factor. Antibodies to oxidized LDL can reflect disease activity on one hand, but can also confer atheroprotection. Novel MRI techniques may aid in the in vivo assessment of acute plaque inflammation in humans. Conclusions-The

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Section: Cox Inhibitionmentioning

confidence: 99%

Inflammation and Atherosclerosis

Stoll

Bendszus

2006

Stroke

420

157

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“…Written informed consent was obtained from all subjects before study enrollment. Major exclusion criteria included: pregnancy, serious illness, use of any investigational drug within 30 days, history of a bleeding diathesis, severe hypertension, major surgery within 2 weeks, platelet count 100,000/mm 3 , and impaired renal and/or hepatic function.…”

Section: Subjectsmentioning

confidence: 99%

Safety and Exploratory Efficacy of the Novel Thrombin Receptor (PAR-1) Antagonist SCH530348 for Non-ST-Segment Elevation Acute Coronary Syndrome

Goto

Yamaguchi

Ikeda

et al. 2010

JAT

103

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Aim: A previous phase 2 study of patients undergoing non-urgent PCI treated with SCH530348 plus aspirin and clopidogrel tended to reduce MACE without increased bleeding. This study evaluated the safety of SCH530348 in Japanese patients with NSTE ACS. Methods: Subjects (117), in whom PCI was planned, received standard-of-care (aspirin, ticlopidine, and heparin) and were randomized 4:1 to receive either SCH530348 (20 or 40 mg loading dose followed by 1 mg/d or 2.5 mg/d for 60 days) or placebo. The key safety endpoint was TIMI major and minor bleeding in the PCI cohort (n 92). The key exploratory efficacy endpoint was MACE and death within 60 days. Addition of SCH530348 to standard-of-care did not significantly increase the rate of TIMI major and minor bleeding (or non-TIMI bleeding) in the primary cohort. Results: Incidence (non-MACE) and discontinuation of AEs were similar across groups. PCI subjects treated with SCH530348 plus standard-of-care experienced a significant reduction in periprocedural MI compared with standard-of-care alone (16.9% vs 42.9%, respectively; p 0.013). There were no deaths or any other MACE. Conclusion: SCH530348 added to standard-of-care did not result in excess bleeding in Japanese subjects with NSTE ACS but significantly reduced the incidence of periprocedural MI in subjects undergoing urgent PCI. J Atheroscler Thromb, 2010; 17:156-164.

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“…COX-1 inhibition results in decreased platelet adhesion and aggregation, whereas COX-2 inhibition decreases inflammation. 12,13 Both of these actions would be expected to limit neointimal formation and to have a favorable impact on shunt patency and durability. Aspirin use was associated with a Ͼ7-fold reduction in the risk of shunt thrombosis and a decreased risk of death among patients undergoing a systemic-to-pulmonary shunt, including the Norwood procedure.…”

Section: Article P 293mentioning

confidence: 99%

Aspirin

Tweddell

2007

Circulation

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ependence on an expanded polytetrafluoroethylene graft for provision of pulmonary blood flow is a common yet precarious interval through which a population of patients with congenital heart disease must pass. The goals of the systemic-to-pulmonary artery shunt are to relieve cyanosis and to provide time before establishing in-series circulation by either complete repair of 2-ventricle lesions or, in the case of the single-ventricle patient, a bidirectional Glenn shunt. In the case of patients with single-ventricle anatomy, this period of parallel circulation is necessary to permit the lung maturation and the reduction in pulmonary vascular resistance that are necessary for subsequent palliation. For patients who will ultimately achieve a 2-ventricle repair, the goals of a preliminary shunt may include increasing the size of the pulmonary artery size or having a larger, older patient at the time of repair. This period of parallel circulation is tenuous, and the patient remains at increased risk during this period of altered circulation. Article p 293With parallel circulation, cardiac output from the heart is partitioned to the lungs and body based on the relative resistances of the pulmonary and systemic circulations. If the shunt is large, the patient will experience excessive pulmonary blood flow and congestive heart failure. Furthermore, with a large shunt, diastolic pressure is low and coronary circulation may be impaired. With stress, autonomic reflexes will result in an acute increase in sympathetic tone. The elevation of systemic vascular resistance leads to acute increase in the ratio of pulmonary to systemic flow. In the face of limited cardiac output, this acute increase in the ratio of pulmonary to systemic flow can result in a critical reduction in systemic oxygen delivery. Therefore, autonomic reflexes aimed at maintaining vital organ perfusion with in-series circulation have an adverse effect in patients with parallel circulation and can result in a critical reduction in oxygen delivery. This is likely to be one mechanism of death for patients with parallel circulation. 1,2 Alternatively, if the shunt is sufficiently limiting, then increasing pulmonary blood flow in response to increased metabolic demands such as may occur with fever or exercise will not be possible, increased cyanosis results, and again a critical reduction in oxygen delivery will occur. Additional limitations of parallel circulation include the potential for parenchymal lung disease, anemia, and decreased cardiac output to result in worsening cyanosis. Decreased cardiac output from the single ventricle may be the result of myocardial dysfunction, atrioventricular valve regurgitation, or arrhythmias. In addition, dehydration will result in decreased preload with decreased cardiac output and may occur in the course of an acute illness resulting from decreased fluid intake, gastrointestinal loss, and/or fever. Diuretic use is common in this patient population and will limit the ability of the patient to autoregulate fluid status in t...

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Relevance of Platelet-independent Effects of Aspirin to Its Salutary Effect in Atherosclerosis-related Events

Cited by 32 publications

References 39 publications

Inflammation and Atherosclerosis

Inflammation and Atherosclerosis

Safety and Exploratory Efficacy of the Novel Thrombin Receptor (PAR-1) Antagonist SCH530348 for Non-ST-Segment Elevation Acute Coronary Syndrome

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