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10.1007/s40268-016-0158-4 http://scihub22266oqcxt.onion/10.1007/s40268-016-0158-4 C5318326!5318326 !28063023     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28063023 &cmd=llinks): Failed to open stream: HTTP request failed! 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Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease |pdf=|usr=}}{{28063023 }} gab.com Text Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease JO: Drugs R D http://www.kidney.de/pget.php?&tw=1&pmid=28063023 #FOAvip INTRODUCTION: Despite the current standard of care, patients with cardiovascular disease remain at a high risk for recurrent events. Inhibition of thrombin-mediated platelet activation through protease-activated receptor-1 antagonism may provide reductions in atherosclerotic disease beyond those achievable with the current standard of care. OBJECTIVE: Our primary objective is to evaluate the clinical literature regarding the role of vorapaxar (Zontivity?) in the reduction of cardiovascular events in patients with a history of myocardial infarction and peripheral artery disease. In particular, we focus on the potential future directions for protease-activating receptor antagonists in the treatment of a broad range of atherosclerotic diseases. DATA SOURCES: A literature search of PubMed and EBSCO was conducted to identify randomized clinical trials from August 2005 to June 2016 using the search terms: 'vorapaxar', 'SCH 530348', 'protease-activated receptor-1 antagonist', and 'Zontivity?'. Bibliographies were searched and additional resources were obtained. RESULTS: Vorapaxar is a first-in-class, protease-activated receptor-1 antagonist. The Thrombin Receptor Antagonist for Clinical Event Reduction (TRACER) trial did not demonstrate a significant reduction in a broad primary composite endpoint. However, the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P-TIMI 50) trial examined a more traditional composite endpoint and found a significant benefit with vorapaxar. Vorapaxar significantly increased bleeding compared with standard care. Ongoing trials will help define the role of vorapaxar in patients with peripheral arterial disease, patients with diabetes mellitus, and other important subgroups. The use of multivariate modeling may enable the identification of subgroups with maximal benefit and minimal harm from vorapaxar. CONCLUSION: Vorapaxar provides clinicians with a novel mechanism of action to further reduce the burden of ischemic heart disease. Identification of patients with a high ischemic risk and low bleeding risk would enable clinicians to maximize the utility of this unique agent. Twit Text FOAVip Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease ????Drugs R D http://www.kidney.de/pget.php?&tw=1&pmid=28063023 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28063023 #FOAvip English Wikipedia <ref>{{Cite pmid|28063023 }}</ref> Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease #MMPMID28063023 Gryka RJ ; Buckley LF ; Anderson SM Drugs R D 2017[Mar]; 17 (1 ): 65-72 PMID28063023 show ga INTRODUCTION: Despite the current standard of care, patients with cardiovascular disease remain at a high risk for recurrent events. Inhibition of thrombin-mediated platelet activation through protease-activated receptor-1 antagonism may provide reductions in atherosclerotic disease beyond those achievable with the current standard of care. OBJECTIVE: Our primary objective is to evaluate the clinical literature regarding the role of vorapaxar (Zontivity?) in the reduction of cardiovascular events in patients with a history of myocardial infarction and peripheral artery disease. In particular, we focus on the potential future directions for protease-activating receptor antagonists in the treatment of a broad range of atherosclerotic diseases. DATA SOURCES: A literature search of PubMed and EBSCO was conducted to identify randomized clinical trials from August 2005 to June 2016 using the search terms: 'vorapaxar', 'SCH 530348', 'protease-activated receptor-1 antagonist', and 'Zontivity?'. Bibliographies were searched and additional resources were obtained. RESULTS: Vorapaxar is a first-in-class, protease-activated receptor-1 antagonist. The Thrombin Receptor Antagonist for Clinical Event Reduction (TRACER) trial did not demonstrate a significant reduction in a broad primary composite endpoint. However, the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P-TIMI 50) trial examined a more traditional composite endpoint and found a significant benefit with vorapaxar. Vorapaxar significantly increased bleeding compared with standard care. Ongoing trials will help define the role of vorapaxar in patients with peripheral arterial disease, patients with diabetes mellitus, and other important subgroups. The use of multivariate modeling may enable the identification of subgroups with maximal benefit and minimal harm from vorapaxar. CONCLUSION: Vorapaxar provides clinicians with a novel mechanism of action to further reduce the burden of ischemic heart disease. Identification of patients with a high ischemic risk and low bleeding risk would enable clinicians to maximize the utility of this unique agent. |Atherosclerosis/*drug therapy/metabolism [MESH] |Humans [MESH] |Lactones/*pharmacology/*therapeutic use [MESH] |Platelet Aggregation Inhibitors/*pharmacology/*therapeutic use [MESH] |Pyridines/*pharmacology/*therapeutic use [MESH] |Receptors, Proteinase-Activated/*antagonists & inhibitors [MESH]Vorapaxar: The Current Role and Future Directions of a Novel Protease-(epmc).pdf DeepDyve Pubget Overpricing