PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization
| العنوان: | PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization |
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| المؤلفون: | Kevin P. Bliden, Paul A. Gurbel, Lidija Covic, Athan Kuliopulos, Elizabeth K. Fletcher, Susan E. Turner, Jeffrey J. Rade, Daniel H. Cox, Carey Kimmelstiel |
| المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Cardiac Catheterization, Time Factors, medicine.medical_treatment, Cell-Penetrating Peptides, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, Recurrence, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Infusions, Intravenous, Cardiac catheterization, biology, troponin, Middle Aged, Thrombosis, Treatment Outcome, myocardial infarction, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiology, Female, Stents, Cardiology and Cardiovascular Medicine, Blood Platelets, medicine.medical_specialty, Acute coronary syndrome, Proof of Concept Study, acute coronary syndrome, Lipopeptides, Necrosis, 03 medical and health sciences, Percutaneous Coronary Intervention, Double-Blind Method, Internal medicine, medicine, Humans, Receptor, PAR-1, Pepducin, Aged, business.industry, Myocardium, Percutaneous coronary intervention, medicine.disease, Troponin, United States, biology.protein, business, Platelet Aggregation Inhibitors, Clinical and Population Studies |
| الوصف: | Supplemental Digital Content is available in the text. Objective: Arterial thrombosis leading to ischemic injury worsens the prognosis of many patients with cardiovascular disease. PZ-128 is a first-in-class pepducin that reversibly inhibits PAR1 (protease-activated receptor 1) on platelets and other vascular cells by targeting the intracellular surface of the receptor. The TRIP-PCI (Thrombin Receptor Inhibitory Pepducin in Percutaneous Coronary Intervention) trial was conducted to assess the safety and efficacy of PZ-128 in patients undergoing cardiac catheterization with intent to perform percutaneous coronary intervention. Approach and Results: In this randomized, double-blind, placebo-controlled, phase 2 trial, 100 patients were randomly assigned (2:1) to receive PZ-128 (0.3 or 0.5 mg/kg), or placebo in a 2-hour infusion initiated just before the start of cardiac catheterization, on top of standard oral antiplatelet therapy. Rates of the primary end point of bleeding were not different between the combined PZ-128 doses (1.6%, 1/62) and placebo group (0%, 0/35). The secondary end points of major adverse coronary events at 30 and 90 days did not significantly differ but were numerically lower in the PZ-128 groups (0% and 2% in the PZ-128 groups, 6% and 6% with placebo, p=0.13, p=0.29, respectively). In the subgroup of patients with elevated baseline cardiac troponin I, the exploratory end point of 30-day major adverse coronary events + myocardial injury showed 83% events in the placebo group versus 31% events in the combined PZ-128 drug groups, an adjusted relative risk of 0.14 (95% CI, 0.02–0.75); P=0.02. Conclusions: In this first-in-patient experience, PZ-128 added to standard antiplatelet therapy appeared to be safe, well tolerated, and potentially reduced periprocedural myonecrosis, thus providing the basis for further clinical trials. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02561000. |
| تدمد: | 1524-4636 1079-5642 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5052005b268ffa6d4cd4b7e56b0e6f33 https://doi.org/10.1161/atvbaha.120.315168 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5052005b268ffa6d4cd4b7e56b0e6f33 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 10795642 |
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