Advances in Antiplatelet Therapy: Agents in Clinical Development
ABSTRACT Antiplatelet agents are the cornerstone of treatment for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. The current "gold standard" consists of a combination of aspirin and clopidogrel administered orally shortly before invasive procedures and then continued in the form of maintenance doses. Not all patients respond optimally to standard therapy. Resistance to the antiplatelet activity of both drugs when used either singly or in combination has been observed and may lead to treatment failure, including further atherothrombotic events. Potential limitations associated with the combined use of aspirin and clopidogrel have inspired clinical investigation into several promising new antiplatelet agents as potential additions or alternatives to standard therapy. The candidates include prasugrel, which has a mechanism similar to that of clopidogrel but with superior pharmacokinetics; ticagrelor, a nonthienopyridine that binds reversibly to the platelet P2Y(12) receptor; cangrelor, an intravenously administered analogue of ticagrelor; and various thrombin receptor antagonists.
SourceAvailable from: Joakim Alfredsson
[Show abstract] [Hide abstract]
ABSTRACT: In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin) and anticoagulation (ie, warfarin) medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor) and anticoagulant (dabigatran) agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and anticoagulation therapy. However, several factors may limit its usefulness and should be considered.Pharmacogenomics and Personalized Medicine 01/2015; 8:43. DOI:10.2147/PGPM.S52900
[Show abstract] [Hide abstract]
ABSTRACT: Vorapaxar is a novel platelet inhibitor that potently and selectively inhibits thrombin-mediated platelet activation without interfering with thrombin-mediated cleavage of fibrinogen via antagonism of the platelet proteinase-activated receptor PAR1. Vorapaxar is a non-peptide himbacine analogue that has been developed for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or peripheral arterial disease. Copyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.Drugs of today (Barcelona, Spain: 1998) 11/2014; 50(11):747-756. DOI:10.1358/dot.2014.50.11.2225852 · 1.00 Impact Factor