Angina
Clive Handler, Gerry Coghlan, Nick Brown in Management of Cardiac Problems in Primary Care, 2018
There is an increased risk of in-stent thrombosis occurring several months after implantation of drug-eluting stents (6%)compared with bare metal stents (4%). The risk of thrombosis increases over time from 1% at 30 days to 3% at three years after implantation. In-stent thrombosis may lead to myocardial infarction and death. These concerns do not outweigh the benefits of drug-eluting stents in appropriately selected patients. It is important that antiplatelet drugs are prescribed and that patients take the prescribed medication. These include aspirin 75 mg every morning indefinitely, and clopidogrel 75 mg every morning for one year unless the patient is at high risk of bleeding. It is not yet clear whether clopidogrel should be taken for a longer period of time, particularly in diabetic patients.
The Rational Basis of Thrombosis Models
Josef Hladovec in Antithrombotic Drugs in Thrombosis Models, 2020
Some arterial models deal with coronary arteries. They are often concerned not so much with problems of thrombogenesis but with its consequence, myocardial infarction. Of course, it is possible to stress the differences in the equipment of coronary endothelium in comparison with other arteries, e.g., the strong representation of the adenosine system, in order to justify the much more complicated and cumbersome work with coronaries, particularly in small animals. However, if myocardial infarction is accepted as the end-point indicator, the effectiveness of a drug in similar models may be caused by other mechanisms besides the antithrombotic one, such as antiarrhythmic, metabolic, spasmolytic, etc. It is true that most antiplatelet drugs find their use to be chiefly in the prevention of coronary thrombosis. On the other hand, results of clinical trials do not show any marked tendency to distinguish coronary arteries from those of other regions, e.g., carotid arteries as the main source of TIA.
Rheology of Polycythemias T. C. Pearson
Gordon D. O. Lowe in Clinical Blood Rheology, 2019
There is no doubt that, in these patients, minimizing the risk of vascular occlusive episodes is the major treatment objective. This is achieved by adequate reduction of the PCV and hence the blood viscosity. A PCV value under 0.45 has been suggested. The question of whether the increased platelet count should be reduced to normal levels has been debated. The fact that some of the patients present thrombocythemic symptoms, that they are generally elderly and consequently likely to have vessel disease, and that platelets are undoubtedly involved in the thrombus formation (particularly in the arterial tree), would suggest that reduction of the platelet count to normal levels is indicated. This can be achieved with relatively small doses of chemotherapy.16 Antiplatelet drugs may be used in patients with thrombocythemic symptoms until the platelet count can adequately be reduced with chemotherapy, when symptoms generally resolve. The long-term use of antiplatelet drugs is probably contraindicated on the grounds that they are an ineffective prophylactic measure against thrombosis and increase the risk of hemorrhage.131
Comparison of predictive value of risk scores for gastrointestinal bleeding in antiplatelet therapy
Published in Platelets, 2022
Mei-na Lv, Xiao-chun Zheng, Shao-jun Jiang, Hong-qin Zhang, Fang-Da Xu, Ting-Ting Wu, Wen-Jun Chen, Jin-hua Zhang
With the increased aging of the population, the prevalence of cardiovascular and cerebrovascular diseases is increasing year by year. According to the survey, there are currently about 290 million patients with cardiovascular and cerebrovascular diseases in China, accounting for about 21% of the total population [1,2], and the standardized incidence of stroke among residents aged 40–74 has increased by an average of 8.3% per year [3]. Antiplatelet drugs are one of the important drugs for the prevention and treatment of cardiovascular and cerebrovascular diseases. The use of antiplatelet drugs is also increasing year by year in China. For example, the amount of clopidogrel used in 2018 increased by 1.89 times compared with 2013 [4]. Oral antiplatelet drugs mainly include aspirin, clopidogrel, ticagrelor, cilostazol, and prasugrel. These drugs are widely used to prevent or treat thrombosis and reduce the risk of embolism events, including non-cardiogenic stroke, coronary heart disease, and lower extremity arterial embolism [5–7].
Synthesis and biological evaluation of N-arylpiperazine derivatives of 4,4-dimethylisoquinoline-1,3(2H,4H)-dione as potential antiplatelet agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Monika Marcinkowska, Magdalena Kotańska, Agnieszka Zagórska, Joanna Śniecikowska, Monika Kubacka, Agata Siwek, Adam Bucki, Maciej Pawłowski, Marek Bednarski, Jacek Sapa, Małgorzata Starek, Monika Dąbrowska, Marcin Kołaczkowski
Antiplatelet drugs are the mainstay of the pharmacological treatment for patients with various cardiovascular diseases1. Large clinical trials have revealed that treatment with antiplatelet agents such as clopidogrel and aspirin may reduce the risk of myocardial infraction, stroke or death by almost 22%2. This fact has made them one of the most widely prescribed drugs in the world3. However, despite significant clinical success in preventing the adverse outcome of cardiovascular diseases, many patients experience recurrent atherothrombotic events, despite the treatment with antiplatelet agents. Moreover, many patients are resistant to aspirin and/or clopidogrel, which results in poor prognosis and increased risk of further cardiovascular events2.
Impact of DNA methylation on ADME gene expression, drug disposition, and efficacy
Published in Drug Metabolism Reviews, 2022
Xu Hao, Yuanyuan Li, Jialu Bian, Ying Zhang, Shiyu He, Feng Yu, Yufei Feng, Lin Huang
Antiplatelet drugs such as aspirin and clopidogrel are important drugs for the prevention and treatment of arterial thrombotic diseases. The absorption process of aspirin and clopidogrel in the intestine is affected by ABCB1 (Taubert et al. 2006; Kugai et al. 2013), and CYP2C19 is an important metabolic enzyme of clopidogrel (Hassani Idrissi et al. 2018). Li et al. reported that ABCB1 hypomethylation was associated with lower aspirin absorption, higher platelet reactivity, and an increased risk of ischemic events in patients (Li et al. 2017). Xu et al. also found that the methylation status of the ABCB1 promoter was correlated with arachidonic acid inhibition (AA%) and the reduced efficacy of aspirin treatment in ischemic stroke (Xu and Wang 2021). The above two studies demonstrated a similar correlation between ABCB1 promoter methylation and the effects of aspirin. And hypomethylation of ABCB1 promoter was associated with a decreased response to clopidogrel in ischemic stroke patients via increased ABCB1 mRNA expression (Yang et al. 2015). Sukmawan et al. revealed that the lower DNA methylation level of the CYP2C19 gene increased the risk of clopidogrel resistance and subsequent poorer clinical outcome (Sukmawan et al. 2021).