Role of Platelets and Antiplatelet Therapy in Cardiovascular Disease

Ueno, Masashi; Kodali, Murali; Tello‐Montoliu, Antonio; Angiolillo, Dominick J.

doi:10.5551/jat.7633

Cited by 43 publications

(31 citation statements)

References 85 publications

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“…Like prasugrel, ticagrelor acts more potent and rapid but does not significantly increase major bleeding events. Drawbacks, however, are increased incidences of dyspnea and ventricular pauses [36]. The PLATO study demonstrated significantly increased reduction rates of cardiovascular syndromes and mortality vs. clopidogrel (-16%), while bleeding events were as frequent as under prasugrel [44].…”

Section: Thienopyridines (Tps)mentioning

confidence: 99%

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Antiplatelet Drugs in Coronary Artery Disease

Picker¹

2012

Perioperative Considerations in Cardiac Surgery

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Section: Thienopyridines (Tps)mentioning

confidence: 99%

“…The CHAMPION trials, however, were stopped early because of lack of efficiency [34,35]. Cangrelor is still being studied as a bridge for clopidogrel prior to surgery [36]. Prasugrel also combines a rapid onset of action (< 30min) with less response variability (0.3%) and a prolonged duration of action (> 3 days).…”

Section: Thienopyridines (Tps)mentioning

confidence: 99%

Antiplatelet Drugs in Coronary Artery Disease

Picker¹

2012

Perioperative Considerations in Cardiac Surgery

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“…The discovery of the ADP receptors, such as the P2Y12, and the possibility to block them pharmacologically, has opened new therapeutic scenario. Currently, clopidogrel, prasugrel, and ticagrelor are used in clinical practice for oral administration in combination with aspirin with a significant reduction in MACE [56,57] after acute coronary syndrome. Substantial differences exist between the oral P2Y12 inhibitors that are responsible of the clinical efficacy.…”

Section: Antiplatelet Agentsmentioning

confidence: 99%

The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target?

Cimmino¹,

Fischetti²,

Golino³

2017

J Thrombo Cir

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Acute thrombus formation is the pathophysiological substrate underlying several clinical conditions, such as acute coronary syndrome (ACS) and stroke. Activation of coagulation cascade is a key step of the thrombotic process: vessel injury results in exposure of the glycoprotein tissue factor (TF) to the flowing blood. Once exposed, TF binds factor VII/VIIa (FVII/FVIIa) and in presence of calcium ions, it forms a tertiary complex able to activate FX to FXa, FIX to FIXa, and FVIIa itself. The final step is thrombin formation at the site of vessel injury with subsequent platelet activation, fibrinogen to fibrin conversion and ultimately thrombus formation.Platelets are the key cells in primary hemostasis. For years they have been considered only as cell fragments participating to primary hemostasis and onto which coagulation factors are assembled in the process of thrombus formation. However, recent advances in platelets pathophysiology have shown that these cells are able to regulate their gene and protein expression, make de novo protein synthesis, and release different mediators with paracrine effects that may interfere with different cell functions.Pharmacological modulation of both side of thrombosis, coagulation cascade and platelet activation, is of great clinical importance. Several clinical trials have clearly shown the efficacy of anticoagulation and/or anti platelet aggregation in different thrombotic disorders. This article aims at reviewing the recent advancements on the two faces of thrombosis focusing on the emerging role of platelets not only as clot-forming components, but highlighting their involvement in the inflammatory-immune system, as well as in modulation of different cell functions.

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“…the cyclo-oxygenase-1 inhibitor aspirin and P2Y 12 receptor antagonists (clopidogrel and prasugrel), even in combination, are not optimal in preventing major atherothrombotic events, and are associated with increased bleeding [1,2]. Concerning this challenge, a recent study, published in this journal, has reported encouraging results showing that 5-HT 2A receptor inhibition by a new antagonist (APD791) improves coronary patency in the in vivo canine model [3].…”

mentioning

confidence: 99%

Effect of 5‐HT2A receptor antagonists on human platelet activation in blood exposed to physiologic stimuli and atherosclerotic plaque

Bampalis

Dwivedi

Shai

et al. 2011

Journal of Thrombosis and Haemostasis

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To cite this article: Bampalis VG, Dwivedi S, Shai E, Brandl R, Varon D, Siess W. Effect of 5-HT 2A receptor antagonists on human platelet activation in blood exposed to physiologic stimuli and atherosclerotic plaque. J Thromb Haemost 2011; 9: 2112-5.New antiplatelet therapies are needed, because the two types of clinically used platelet inhibitors, i.e. the cyclo-oxygenase-1 inhibitor aspirin and P2Y 12 receptor antagonists (clopidogrel and prasugrel), even in combination, are not optimal in preventing major atherothrombotic events, and are associated with increased bleeding [1,2]. Concerning this challenge, a recent study, published in this journal, has reported encouraging results showing that 5-HT 2A receptor inhibition by a new antagonist (APD791) improves coronary patency in the in vivo canine model [3].5-HT 2A receptor antagonists have been long known to inhibit 5-hydroxytryptamine (5-HT)-dependent platelet aggregation [4][5][6][7][8]; however, they have not been successfully introduced as antiplatelet agents in the clinic. 5-HT stored in platelet-dense granules and released from them upon platelet stimulation might serve as a feedback mediator by binding to 5-HT 2A receptors on the platelet surface and support platelet aggregation [9]. Indeed, 5-HT added exogenously to plateletrich plasma (PRP) or blood synergizes with several platelet stimuli in inducing platelet aggregation [5,6,8,10]. A short survey of the literature shows that 5-HT 2A receptor antagonists have unequivocally been shown to inhibit 5-HT-potentiated platelet aggregation of PRP in humans and many other species in vitro and ex vivo [3,6,8,11,12] and 5-HT-stimulated thrombus formation in mice in vivo [13]. There are also animal studies reporting inhibition of aggregation induced by physiologic platelet stimuli (collagen, thrombin, ADP, and epinephrine) by 5-HT 2A receptor antagonists in vitro and ex vivo, and in thrombosis models in vivo, particularly in the Folts model of coronary occlusion in the dog [3,11,12,[14][15][16][17]. However, the results in humans are conflicting [5,[18][19][20].In light of the conflicting results reported in the literature and the recent study in dogs, we decided to perform, for the first time, a comprehensive study of the effects of 5-HT 2A antagonists on platelets in human blood in vitro under static and arterial flow conditions, after stimulation with physiologic agonists and a pathophysiologically relevant platelet agonist, i.e. human atherosclerotic plaque homogenate.We studied three different 5-HT 2A receptor antagonists: ketanserin [21], R-96544 [12], and sarpogrelate [22]. Sarpogrelate is a drug introduced clinically as a therapeutic agent for the treatment of peripheral artery occlusive disease [23]. It has been shown recently that sarpogrelate treatment inhibits 5-HTpotentiated platelet aggregation in patients with ischemic stroke [24].Hirudin-anticoagulated blood from healthy volunteers was used in all experiments. Multiple electrode aggregometry was used to measure platelet aggregation in blood (Dyn...

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Role of Platelets and Antiplatelet Therapy in Cardiovascular Disease

Cited by 43 publications

References 85 publications

Antiplatelet Drugs in Coronary Artery Disease

Antiplatelet Drugs in Coronary Artery Disease

The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target?

Effect of 5‐HT2A receptor antagonists on human platelet activation in blood exposed to physiologic stimuli and atherosclerotic plaque

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