PAR-1 Inhibitors: A Novel Class of Antiplatelet Agents for the Treatment of Patients with Atherothrombosis

Author(s):  
Sergio Leonardi ◽  
Richard C. Becker
Keyword(s):  
2009 ◽  
Vol 29 (03) ◽  
pp. 285-290 ◽  
Author(s):  
K. E. Guyer

SummaryAntiplatelet therapy has demonstrated significant clinical benefit in the treatment of acute coronary syndrome. However, as with any treatment strategy it has been unable to prevent all cardiovascular events. This is far from surprising when considering the complexity of arterial thrombosis and more specifically platelet physiology. This lack of treatment success has provoked the introduction of various diagnostic tests and testing platforms with the intent of guiding and optimizing clinical treatment. Such tests have resulted in the generation of clinical data that suggest suboptimal response to antiplatelet agents such as aspirin and clopidogrel.In the case of both aspirin and clopidogrel, this suboptimal response has been termed resistance. Drug resistance would imply a lack of pharmacological response that has not been specifically investigated in many of the clinical studies performed to date. Rather, the term resistance has been used to describe various facets of platelet activation and aggregation relative to the testing method. Many of these measured parameters are not addressed in the therapeutic intent of the antiplatelet drug in question.


2009 ◽  
Vol 29 (03) ◽  
pp. 274-278 ◽  
Author(s):  
U. Steigerwald ◽  
U. Walter ◽  
J. Kössler

SummaryInhibition of platelet function plays an important role in the treatment and secondary prevention of cardiovascular or cerebrovascular ischemic diseases. Established antiplatelet agents use different pharmacological targets for this role. Acetylic salicylic acid achieves a reduction of thromboxane A2 formation by inhibition of COX-1. Ticlopidin or clopidogrel are ADP-P2Y12 receptor antagonists. Tirofiban, abciximab or eptifibatid are used for the inhibition of the glycoprotein IIb/IIIa receptor which is activated at the surface of platelets preceding the final step of their aggregation. The mechanism of dipyridamole is based on the inhibition of adenosine uptake and of phosphodiesterase-5.Efforts are made to improve antiplatetelet therapy with the aim to find agents with favorable clinical outcome and lower bleeding risk. Current clinical studies focus on a new generation of ADP receptor antagonists (prasugrel, cangrelor and ticagrelor) as successors of ticlopidin and clopidogrel after coronary arterial interventions. Developments using platelet targets different from established drugs are thrombin receptor antagonists (like SCH530348) or thromboxane receptor antagonists (like S18886/terutroban) in patients with cerebrovascular events. Results from recent experimental studies could lead to new strategies for antiplatetelet therapy (like inhibition of GP Ib receptor, GP VI receptor, platelet-leukocyte interaction, factor XII and others) in the future.


1995 ◽  
Vol 74 (01) ◽  
pp. 302-308 ◽  
Author(s):  
Barry S Coller ◽  
Keaven Anderson ◽  
Harlan F Weisman
Keyword(s):  

2017 ◽  
Vol 23 (9) ◽  
pp. 1279-1293 ◽  
Author(s):  
Maria E. Tsoumani ◽  
Alexandros D. Tselepis

2016 ◽  
Vol 22 (13) ◽  
pp. 1857-1861 ◽  
Author(s):  
Gregory Tsoucalas ◽  
Jacques Chevallier ◽  
Marianna Karamanou ◽  
Theodoros Papaioannou ◽  
Markos Sgantzos ◽  
...  
Keyword(s):  

2021 ◽  
Vol 11 (6) ◽  
pp. 497
Author(s):  
Yoonsuk Jung ◽  
Eui Im ◽  
Jinhee Lee ◽  
Hyeah Lee ◽  
Changmo Moon

Previous studies have evaluated the effects of antithrombotic agents on the performance of fecal immunochemical tests (FITs) for the detection of colorectal cancer (CRC), but the results were inconsistent and based on small sample sizes. We studied this topic using a large-scale population-based database. Using the Korean National Cancer Screening Program Database, we compared the performance of FITs for CRC detection between users and non-users of antiplatelet agents and warfarin. Non-users were matched according to age and sex. Among 5,426,469 eligible participants, 768,733 used antiplatelet agents (mono/dual/triple therapy, n = 701,683/63,211/3839), and 19,569 used warfarin, while 4,638,167 were non-users. Among antiplatelet agents, aspirin, clopidogrel, and cilostazol ranked first, second, and third, respectively, in terms of prescription rates. Users of antiplatelet agents (3.62% vs. 4.45%; relative risk (RR): 0.83; 95% confidence interval (CI): 0.78–0.88), aspirin (3.66% vs. 4.13%; RR: 0.90; 95% CI: 0.83–0.97), and clopidogrel (3.48% vs. 4.88%; RR: 0.72; 95% CI: 0.61–0.86) had lower positive predictive values (PPVs) for CRC detection than non-users. However, there were no significant differences in PPV between cilostazol vs. non-users and warfarin users vs. non-users. For PPV, the RR (users vs. non-users) for antiplatelet monotherapy was 0.86, while the RRs for dual and triple antiplatelet therapies (excluding cilostazol) were 0.67 and 0.22, respectively. For all antithrombotic agents, the sensitivity for CRC detection was not different between users and non-users. Use of antiplatelet agents, except cilostazol, may increase the false positives without improving the sensitivity of FITs for CRC detection.


2021 ◽  
Vol 203 ◽  
pp. 46-56
Author(s):  
Linda Herfs ◽  
Frauke Swieringa ◽  
Natalie Jooss ◽  
Mike Kozlowski ◽  
Floor C.J. Heubel-Moenen ◽  
...  

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001628
Author(s):  
Kamal Matli ◽  
Raymond Farah ◽  
Mario Maalouf ◽  
Nibal Chamoun ◽  
Christy Costanian ◽  
...  

Although primarily affecting the respiratory system, COVID-19 causes multiple organ damage. One of its grave consequences is a prothrombotic state that manifests as thrombotic, microthrombotic and thromboembolic events. Therefore, understanding the effect of antiplatelet and anticoagulation therapy in the context of COVID-19 treatment is important. The aim of this rapid review was to highlight the role of thrombosis in COVID-19 and to provide new insights on the use of antithrombotic therapy in its management. A rapid systematic review was performed using preferred reporting items for systematic reviews. Papers published in English on antithrombotic agent use and COVID-19 complications were eligible. Results showed that the use of anticoagulants increased survival and reduced thromboembolic events in patients. However, despite the use of anticoagulants, patients still suffered thrombotic events likely due to heparin resistance. Data on antiplatelet use in combination with anticoagulants in the setting of COVID-19 are quite scarce. Current side effects of anticoagulation therapy emphasise the need to update treatment guidelines. In this rapid review, we address a possible modulatory role of antiplatelet and anticoagulant combination against COVID-19 pathogenesis. This combination may be an effective form of adjuvant therapy against COVID-19 infection. However, further studies are needed to elucidate potential risks and benefits associated with this combination.


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