Comparison of Platelet Aggregation Response and Receptor Occupancy of RPR 109891 Administered Intravenously in Patients With Recent Acute Coronary Syndromes (TIMI15A)

1998 ◽  
Vol 31 (2) ◽  
pp. 353A ◽  
Author(s):  
L Jennings
Keyword(s):  
Platelet Aggregation ◽  
Acute Coronary Syndromes ◽  
Receptor Occupancy ◽  
Aggregation Response ◽  
Coronary Syndromes

Open Multicentre Study of the P 2T Receptor Antagonist AR-C69931MX Assessing Safety, Tolerability and Activity in Patients with Acute Coronary Syndromes

2001 ◽  
Vol 85 (03) ◽  
pp. 401-407 ◽  
Author(s):  
Keith Oldroyd ◽  
Robert Wilcox ◽  
Robert Storey ◽  
Keyword(s):  
Platelet Aggregation ◽  
Receptor Antagonist ◽  
Acute Coronary Syndromes ◽  
Plasma Concentrations ◽  
Antithrombotic Agent ◽  
Serious Adverse Events ◽  
Central Process ◽  
Impedance Aggregometry ◽  
Safety Parameters ◽  
Coronary Syndromes

SummaryPlatelet aggregation is the central process in the pathophysiology of acute coronary syndromes. ADP contributes to thrombosis by activating platelets, and AR-C69931MX is a specific antagonist of this process acting at the P 2T receptor. At 5 hospitals, 39 patients with unstable angina or non-Q wave myocardial infarction, who were receiving aspirin and heparin, were administered intravenous AR-C69931MX with stepped dose increments over 3 h to a plateau of either 2 μg/kg/min for 21 h (Part 1; n = 12) or up to 69 h (Part 2; n = 13) or 4 μg/kg/min for up to 69 h (Part 3: n = 14). Safety parameters, platelet aggregation (PA) induced by ADP 3 μmol/L (impedance aggregometry), bleeding time (BT) and plasma concentrations of AR-C69931XX were assessed. AR-C69931MX was well tolerated. 33 patients completed the study. There were no deaths at 30 days and no serious adverse events attributed to AR-C69931MX. Trivial bleeding (56%) was common. At 24 h, mean inhibition of PA was 96.0 ± 8.6, 94.9 ± 14.4 and 98.7 ± 2.1% and BT was 9.5 ± 8.4, 14.0 ± 9.7 and 16.0 ± 11.1 min for Parts 1, 2 and 3 respectively. At 1 h post-infusion, mean inhibition of PA was 36.2 ± 39.2, 20.7 ± 25.9 and 40.7 ± 36.7% respectively. 90% patients had a plasma half-life for AR-C69931XX of 9 min. In conclusion, AR-C69931MX is a potent, short-acting platelet ADP receptor antagonist suitable for further studies as an antithrombotic agent.

scholarly journals Direct factor IXa inhibition with the RNA-aptamer pegnivacogin reduces platelet reactivity in vitro and residual platelet aggregation in patients with acute coronary syndromes

2017 ◽  
Vol 8 (6) ◽  
pp. 520-526 ◽  
Author(s):  
Dawid L Staudacher ◽  
Vera Putz ◽  
Lukas Heger ◽  
Jochen Reinöhl ◽  
Marcus Hortmann ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Acute Coronary Syndromes ◽  
Platelet Reactivity ◽  
Coagulation Cascade ◽  
Rna Aptamer ◽  
Reversal Agent ◽  
Blood Samples ◽  
Factor Ixa ◽  
Coronary Syndromes

Background:Residual platelet reactivity is a predictor of poor prognosis in patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention. Thrombin is a major platelet activator and upon initiation of the coagulation cascade, it is subsequently produced downstream of factor IXa, which itself is known to be increased in ACS. Pegnivacogin is a novel RNA-aptamer based factor IXa inhibitor featuring a reversal agent, anivamersen. We hypothesized that pegnivacogin could reduce platelet reactivity.Methods:Whole blood samples from healthy volunteers were incubated in vitro in the presence and absence of pegnivacogin and platelet reactivity was analysed. In addition, platelet aggregometry was performed in blood samples from ACS patients in the RADAR trial featuring the intravenous administration of pegnivacogin as well as reversal by anivamersen.Results:In vitro, pegnivacogin significantly reduced adenosine diphosphate-induced CD62P-expression (100% vs. 89.79±4.04%, p=0.027, n=9) and PAC-1 binding (100% vs. 83.02±4.08%, p=0.010, n=11). Platelet aggregation was reduced (97.71±5.30% vs. 66.53±9.92%, p=0.013, n=10) as evaluated by light transmission aggregometry. In the presence of the RNA-aptamer reversal agent anivamersen, neither CD62P-expression nor platelet aggregation was attenuated. In patients with ACS treated with aspirin and clopidogrel, residual platelet aggregation was significantly reduced 20 min after intravenous bolus of 1 mg/kg pegnivacogin (100% versus 43.21±8.23%, p=0.020).Conclusion:Inhibition of factor IXa by pegnivacogin decreases platelet activation and aggregation in vitro. This effect was negated by anivamersen. In ACS patients, platelet aggregation was significantly reduced after intravenous pegnivacogin. An aptamer-based anticoagulant inhibiting factor IXa therefore might be a promising antithrombotic strategy in ACS patients.

scholarly journals Platelet aggregation at discharge: A useful tool in acute coronary syndromes?

2012 ◽  
Vol 31 (9) ◽  
pp. 545-554 ◽  
Author(s):  
Rogério Teixeira ◽  
Pedro Monteiro ◽  
Gilberto Marques ◽  
João Mariano Pego ◽  
Margarida Lourenço ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Acute Coronary Syndromes ◽  
Coronary Syndromes

Response to Dual Antiplatelet Therapy Does Not Impact Bleeding Risks in Patients Undergoing Oral Surgery after Acute Coronary Syndromes

Cardiology ◽  
2015 ◽  
Vol 132 (2) ◽  
pp. 119-123 ◽  
Author(s):  
Damian Dudek ◽  
Wiktor Kuliczkowski ◽  
Jacek Kaczmarski ◽  
Joanna Wiechec ◽  
Edyta Reichman-Warmusz ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Antiplatelet Therapy ◽  
Acute Coronary Syndromes ◽  
Dual Antiplatelet Therapy ◽  
Oral Surgery ◽  
Antiplatelet Agent ◽  
Real Life ◽  
Control Group ◽  
Platelet Activity ◽  
Coronary Syndromes

Introduction: Oral surgery (OS) in patients on antecedent dual antiplatelet therapy (DAPT) may be associated with extra bleeding risks. Monitoring platelet activity in such patients may be beneficial for safety when performing OS. Objectives: The aim of this study was to assess whether platelet function during DAPT impacted the risk of bleeding following OS in patients with acute coronary syndromes (ACS). Patients and Methods: Patients who required OS on top of DAPT with aspirin and clopidogrel (n = 55) for invasively treated ACS were included. The control group (n = 33) consisted of patients who underwent OS with no antiplatelet agent. Platelet aggregation before OS was assessed with a Multiplate® analyzer. Bleeding during OS and at days 1, 3, 7 and 10 after surgery was serially evaluated. Results: All 88 patients completed the study. An incomplete response to aspirin or clopidogrel was observed in 43.6% of the patients. In 11% of the cases, an excessive response to clopidogrel was demonstrated. No excessive bleeding upon OS was exhibited in either group during the entire follow-up. Platelet aggregation values and the use of DAPT did not impact the performance of OS. Conclusion: Therapy with clopidogrel and aspirin after ACS does not seem to increase the risk of real-life bleeding following OS, regardless of the platelet activity response to DAPT.

High post-treatment platelet reactivity is associated with a high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes

2007 ◽  
Vol 97 (02) ◽  
pp. 282-287 ◽  
Author(s):  
Corinne Frere ◽  
Jacques Quilici ◽  
Pierre-Emmanuel Morange ◽  
Lyassine Nait-Saidi ◽  
Christopher Mielot ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Antiplatelet Therapy ◽  
Acute Coronary Syndromes ◽  
Troponin I ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Post Treatment ◽  
Increased Risk ◽  
Coronary Syndromes ◽  
St Elevation

SummaryHigh post-treatment platelet reactivity (HPPR= adenosine diphosphate [ADP] 10 µM-induced platelet aggregation > 70%) identifies low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for non-ST elevation acute coronary syndromes (NSTEACS). This study was designed to compare the incidence of periprocedural myocardial infarction (MI) after stenting for NSTEACS patients between non-responders to dual antiplatelet therapy defined by HPPR and normo-responders. One hundred ninety NSTE-ACS consecutive patients undergoing coronary stenting were included in this prospective study. They received 250 mg aspirin and a 600 mg loading dose of clopidogrel at least 12 hours (h) before percutaneous coronary intervention (PCI). A single post-treatment blood sample was obtained before PCI to analyze maximal intensity of ADP-induced platelet aggregation, and troponin levels were analyzed before PCI, and 12 and 24 h after PCI. Troponin I was considered elevated if > 0.4 ng/ ml. HPPR was present in 22% of patients (n=42). Periprocedural MI occurred significantly more frequently in patients with HPPR than in the normo-responders (43% vs. 24%, p=0.014). After being correlated with recurrent ischemic events after stenting for NSTE-ACS, the HPPR seems to be also a marker of increased risk of periprocedural MI for NSTE-ACS patients.

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