Newer agents in antiplatelet therapy: a review

Abstract

Antiplatelet therapy remains the mainstay in preventing aberrant platelet activation in pathophysiological conditions such as myocardial infarction, ischemia, and stroke. Although there has been significant advancement in antiplatelet therapeutic approaches, aspirin still remains the gold standard treatment in the clinical setting. Limitations in safety, efficacy, and tolerability have precluded many of the antiplatelet inhibitors from use in patients. Unforeseen incidences of increased bleeding risk and recurrent arterial thrombosis observed in patients have hampered the development of superior next generation antiplatelet therapies. The pharmacokinetic and pharmacodynamic profiles have also limited the effectiveness of a number of antiplatelet inhibitors currently in use due to variability in metabolism, time to onset, and reversibility. A focused effort in the development of newer antiplatelet therapies to address some of these shortcomings has resulted in a significant number of potential antiplatelet drugs which target enzymes (phosphodiesterase, cyclooxygenase), receptors (purinergic, prostaglandins, protease-activated receptors, thromboxane), and glycoproteins (αIIbβ3, GPVI, vWF, GPIb) in the platelet. The validation and search for newer antiplatelet therapeutic approaches proven to be superior to aspirin is still ongoing and should yield a better pharmacodynamic profile with fewer untoward side-effects to what is currently in use today.

Vipegitide: a folded peptidomimetic partial antagonist of α2β1 integrin with antiplatelet aggregation activity

“…The blood of mice injected with Vipegitide and Vipegitide-PEG2 after 10 hours was submitted for hematological and biochemical analysis. The values for white blood cells, red blood cells, and platelet counts were in the normal range of 6–15×10 3 /μL, 7–12×10 6 /μL, and 200–450×10 3 /μL, respectively, for mice injected with Vipegitide and Vipegitide-PEG2, similar to the values obtained for control mice. Additional evidence of the lack of hemorrhage or anemic conditions was indicated by similar values for hematocrit, in the range of 35%–45%, and mean corpuscular hemoglobin, 11.1–12.7 pg/mouse, between Vipegitide- and Vipegitide-PEG2-injected mice compared to control mice.…”

“… 4 Food and Drug Administration (FDA)-approved drugs such as ticlopidine, clopidogrel, prasugrel, and ticagrelor are antagonists of purinergic P2Y12 receptor, through which ADP elicits platelet aggregation. 5 , 6 Fibrinogen receptor αΙΙbβ3 integrin plays a significant role in platelet adhesion and aggregation. The studies of this receptor resulted in development of three antagonists, which were approved by the FDA for the therapy of ACS.…”

Cilostazol enhances endothelium-dependent vasodilatation of intact endothelium in isolated rat aortic rings

“…Cilostazol (CIL) is a quinolone derivative and a cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase type III (PDE III) inhibitor. [3][4][5] It has an antiplatelet and antithrombotic activity and is commonly used in the medical treatment of peripheral vascular disease. [6] Cilostazol induces vasodilatation by increasing the cAMP in the vascular smooth muscle cells and decreasing the intracellular calcium concentration.…”

Zastosowanie prasugrelu w ostrych zespołach wieńcowych

“…Przewidywany średni czas powrotu funkcji płytek w przypadku stosowania prasugrelu jest najdłuższy w porównaniu z pozostałymi inhibitorami receptorów P2Y 12 i wynosi co najmniej 7 dni [7]. Głównymi działaniami niepożądanymi prasugrelu są krwawienia, występujące częściej niż w przypadku klopidogrelu [6,8]. Zarówno leki zwiększające, jak i hamujące aktywność izoenzymu CYP3A nie wpływają na działanie prasugrelu [6].…”