Coronary Stent Thrombosis Related to Aspirin Resistance: What are the Underlying Mechanisms?

Acute coronary stent thrombosis represents a serious complication for which aspirin resistance could be a potential cause. The actual case is a myocardial infarction treated with immediate stenting of the right coronary artery followed by elective stenting of the left anterior descending artery 4 days later. Despite standard antiplatelet therapy, stents in both arteries occluded 2 days after the last procedure. The patient's blood samples were analyzed and revealed the presence of aspirin resistance as well as elevated thromboxane B(2) plasma levels. No thrombophilic disorder was detected. Today the mechanism of aspirin resistance is mostly unknown. Further research as well as recommendations for laboratory screening and for alternative pharmacological treatment options are required.     

Aspirin resistance: fact or fiction?

A meta-analysis of clinical studies of patients with cardiovascular disease demonstrated that the use of aspirin was associated with a 22% decrease in death rates and relevant ischemic vascular events. However, clinical studies demonstrated that patients that regularly took aspirin presented recurrence of cardiovascular events. Such observation led to the question whether, in some patients, the aspirin was not effective in blocking platelet aggregation and these patients were called unresponsive to aspirin or aspirin-resistant. The clinical aspirin resistance is characterized as the occurrence of cardiovascular events in patients during treatment with aspirin, whereas the laboratory resistance is defined as the persistence of platelet aggregation, documented by laboratory test, in patients regularly taking aspirin. Patients that are aspirin-resistant presented, according to laboratory tests, on average 3.8 times more cardiovascular events when compared to non-resistant ones.     

Aspirin resistance: does it exist?

Aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1). Aspirin sensitivity can be measured easily by its inhibition of arachidonic acid (AA) -induced platelet aggregation. Aspirin resistance has to be defined by its inability to inhibit COX-1. By using this definition, aspirin resistance very likely does not exist. A specific rapid laboratory test using either AA-induced platelet aggregation or AA-induced malondialdehyde production in platelet-rich plasma is needed to test aspirin sensitivity. The reports on so-called aspirin resistance are usually due to noncompliance of aspirin intake or consumption of inadequate doses of aspirin. In addition, data generated from using nonspecific platelet function tests have added confusion to this observed phenomenon of aspirin resistance.     

Aspirin resistance: is this term meaningful?

PURPOSE OF REVIEW: To review data for and against the existence of 'aspirin resistance', a term coined to indicate aspirin-treated patients having ex-vivo tests of platelet activation insensitive to aspirin treatment and recurrence of cardiovascular disease. RECENT FINDINGS: 'Aspirin resistance' defined by ex-vivo tests of platelet activation yielded values ranging from 21 to 78%, indicating that such tests do not provide a useful measurement. In long-term aspirin-treated patients, studies demonstrated small but functionally relevant platelet thromboxane A2 formation that was responsible for an enhanced platelet activation in response to platelet agonist. These studies, however, did not fully exclude that aspirin compliance may be implicated in such phenomena. Two trials performed in patients with coronary artery disease demonstrated that laboratory evidence of aspirin resistance was no longer detectable when aspirin compliance was accurately monitored. SUMMARY: Given the multifactorial nature of atherothrombosis, recurrence of cardiovascular events in aspirin-treated patients does not necessarily suggest 'drug failure'. A cause-effect relationship between platelet insensitivity to aspirin and cardiovascular recurrence has not been defined overall because aspirin compliance has been scarcely considered. Until this information is taken into account, the existence of 'clinical resistance' to aspirin should be reconsidered.     

High Pressure Coronary Stenting: Efficacy and Safety of Aspirin Versus Coumadin Plus Aspirin Ñ Preliminary Results of a Randomized Study

The efficacy and safety of treatment after coronary stenting was examined with aspirin alone, 100 mg daily, as compared to coumadin plus aspirin. Data from the first 101 patients, 73 men and 28 women, aged 59.2 +/- 9.3 years, of a prospective randomized study are presented in this preliminary report. Forty-eight patients suffered from one-vessel disease, 32 had two- and 21 three-vessel disease. Indications for stenting were stable angina in 65 patients, unstable angina in 16, threatening myocardial infarction in 4 and restenosis in 16 patients. The stents were implanted by high pressure balloon inflation (14.5 +/- 2.2 atm), 55 of them were Palmaz-Schatz, 31 Micro, 10 Gianturco-Roubin, 2 Wiktor and 3 combined stents. Intravascular ultrasonographic guidance was not performed. The primary end point was defined as the absence of the following events: death, subacute coronary artery closure, acute myocardial infarction, emergency coronary bypass surgery, repeated PTCA, major bleeding or arterio-venous aneurysms needing transfusion or surgery. Eighty out of 101 patients (79.2%), 41 out of 47 (87.2%) in the aspirin group and 39 out of 54 (72.2%) in the coumadin plus aspirin group (p = 0.06) were free of events during hospitalization (9.5 +/- 5.7 days, median: 8 days). Forty-five out of 47 patients (95.7%) in the aspirin and 51 out of 54 (94.4%) in the coumadin plus aspirin group (p = 0.8) were without subacute closure. One death occurred in the aspirin group due to stent abscess two weeks after an angiographically successful stent recanalization. All 7 arterio-venous aneurysms with surgical interventions occurred in the coumadin group (p = 0.01). No emergency bypass surgery had to be performed. If these preliminary results will be confirmed by the final analysis, the combination of coumadin with aspirin does not show more efficacy or safety as compared with aspirin alone in the treatment after high-pressure coronary stenting during the hospital stay.     

Aspirin and ACE-inhibitors: for Wedding or Funeral?

Journal of Thrombosis and Thrombolysis -     

Aspirin,Ticlopidine,Clopidogrel三药临床应用比较

Aspirin,Ticlopidine(Ticlid),Clopidogrel(Plavix)三药都是抗血小板凝集的药物,临床常应用于血栓形成的预防及治疗。 Aspirin应用于临床已有百年历史,被誉为廿世纪的奇迹药物(wonder drug of the 20 th centruy)。自从1971年被证实它有抗血小板凝集作用后,在脑血管意外疾病,心血管疾病,以及某些外周血管疾病治疗中,Aspirin一直作为传统药物用来预防血栓形成。它是非处方药物,价格便宜。 自从药物Ticlopidine和Clopidogrel出现后,     

Aspirin in peripheral arterial disease: breakthrough or pitfall?

BACKGROUND: This paper introduces a proof-of-concept trial in progress, supposedly providing new important information on anti-platelet drugs used in patients with peripheral arterial disease (PAD). The Arteriogenesis Competence Network (Art.Net.) of the Universities of Basel, Berlin, and Freiburg could show in animal models that Aspirin (ASA), in contrast to Clopidogrel, inhibits the formation of an appropriate collateral network (arteriogenesis). This trial is supposed to reproduce the animal data in man. MATERIALS AND METHODS: In a prospective, double-blind, parallel-group, bi-national (D, CH), multicentre trial, 250 patients will be randomised to either 100 mg ASA or 75 mg Clopidogrel once daily. Patients will then enter a three months structured rehabilitation programme with daily physical training supposed to induce arteriogenesis. The claudication distances will be tested as the primary endpoint at baseline, 6 weeks, and at 3 months. Also, the 24h physical activity profile of all patients will be electronically documented. CONCLUSIONS: This trial will provide information on potential disadvantages when using ASA in PAD patients. If data emerging from animal pharmacology can be reproduced in man, the present standard scheme of anti-aggregant treatment in PAD patients has to be reconsidered.