scholarly journals PHARMACODYNAMIC EFFECTS OF ADJUNCTIVE CLOPIDOGREL THERAPY IN PATIENTS WITH ATHEROSCLEROTIC DISEASE ON DUAL PATHWAY INHIBITION WITH ASPIRIN AND LOW-DOSE RIVAROXABAN

2021 ◽  
Vol 77 (18) ◽  
pp. 1187
Author(s):  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Latonya Been ◽  
Patrick Abou Jaoude ◽  
Andrea Rivas ◽  
...  
2018 ◽  
Vol 118 (09) ◽  
pp. 1528-1534 ◽  
Author(s):  
Uwe Zeymer ◽  
Benedikt Schrage ◽  
Dirk Westermann

AbstractThe optimal anti-thrombotic therapy for secondary prevention after an acute coronary syndrome is still a matter of debate. While current guidelines recommend dual anti-platelet therapy with aspirin and a P2Y12 inhibitor over 12 months especially in patients with stent implantation, the value of prolonged anticoagulation is still controversial. In the ATLAS-TIMI 52 trial, a low-dose direct factor Xa inhibition with rivaroxaban compared with placebo reduced the combined primary endpoint of cardiovascular mortality, myocardial infraction and stroke with an increase in major bleeding complications. This article discusses the value and problems of adding low-dose rivaroxaban to anti-platelet therapy as secondary prevention measure after an acute myocardial infarction. It will describe the pros and cons of intensified anti-platelet therapy versus dual pathway inhibition and give recommendations for different patient groups in clinical practice.


2020 ◽  
Vol 120 (08) ◽  
pp. 1147-1158 ◽  
Author(s):  
Jeffrey Ian Weitz ◽  
Dominick J. Angiolillo ◽  
Tobias Geisler ◽  
Stefan Heitmeier

AbstractDespite advances in secondary prevention strategies in patients with cardiovascular disease, the residual risk of recurrent atherothrombotic events remains high. Dual-antiplatelet therapy is the standard of care for secondary prevention in patients with acute coronary syndrome (ACS), whereas single antiplatelet therapy, generally with aspirin, is the standard of care for secondary prevention in stable patients with coronary artery disease (CAD), peripheral artery disease (PAD), or cerebrovascular disease. However, atherosclerotic plaque disruption not only triggers platelet activation but also results in thrombin generation because of tissue factor exposure. Therefore, blocking both pathways by combining antiplatelet therapy with an anticoagulant, or dual pathway inhibition (DPI), has the potential to be more effective than inhibiting either pathway alone. The benefit of DPI has been demonstrated in the ATLAS ACS 2-TIMI 51, COMPASS, and VOYAGER PAD trials, where the combination of rivaroxaban vascular dose (2.5 mg twice daily) plus aspirin significantly reduced the risk of atherothrombotic events compared with aspirin across a broad range of patients, including those with recent ACS, those with chronic CAD and/or PAD, and patients with PAD who have undergone peripheral revascularization. This article provides the rationale for this regimen in more detail, including why the DPI regimen with the rivaroxaban vascular dose was developed for vascular protection in a broad spectrum of patients with atherosclerotic disease.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Mattia Galli ◽  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Latonya Been ◽  
Patrick Jaoude ◽  
...  

Abstract Aims Inhibition of thrombin-mediated signalling processes using a vascular dose of rivaroxaban in adjunct to single antiplatelet therapy, known as dual-pathway inhibition (DPI), reduces atherothrombotic events in patients with stable atherosclerotic disease. However, there is limited data on the pharmacodynamic (PD) effects of this strategy. Methods This investigation was conducted in selected cohorts of patients (n = 40) with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group PD study who were treated with either aspirin, aspirin plus rivaroxaban 2.5 mg/bid or clopidogrel plus rivaroxaban 2.5 mg/bid. Multiple PD assays providing a comprehensive assessment of markers of thrombosis were used. The primary endpoint was the comparison between groups of platelet-mediated global thrombogenicity by light transmittance aggregometry (LTA) following stimuli with collagen-related peptide + adenosine diphosphate + tissue factor (CATF). Results There were no differences in the primary endpoint between aspirin vs. aspirin plus rivaroxaban 2.5 mg/bid (P = 0.110), aspirin vs. clopidogrel plus rivaroxaban 2.5 mg/bid (P = 0.611) or aspirin plus rivaroxaban 2.5 mg/bid vs. clopidogrel plus rivaroxaban 2.5 mg/bid (P = 0.315). Rivaroxaban-based treatments significantly reduced markers of thrombin generation (peak thrombin and thrombin velocity index). Clopidogrel-based treatments reduced markers of P2Y12 signalling (LTA ADP 20 max and VerifyNow). Aspirin-based treatments reduced markers of markers of cyclooxygenase-1 activity (LTA collagen). Conclusions Compared with aspirin alone, DPI with either aspirin or clopidogrel might provide superior ischaemic protection by targeting pathways alternative to those affected by antiplatelet agents with only a moderate trade-off in bleeding as supported by similar platelet-mediated global thrombogenicity between treatments.


Author(s):  
Mattia Galli ◽  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Latonya Been ◽  
Patrick Abou Jaoude ◽  
...  

Aim: Inhibition of thrombin-mediated signaling processes using a vascular dose of rivaroxaban in adjunct to antiplatelet therapy, known as dual-pathway inhibition (DPI), reduces atherothrombotic events in patients with stable atherosclerotic disease. However, there are limited data on the pharmacodynamic (PD) effects of this strategy. Methods and Results: This investigation was conducted in selected cohorts of patients (n=40) with stable atherosclerotic disease enrolled within a larger prospective PD study who were treated with either aspirin plus clopidogrel (DAPT), aspirin plus rivaroxaban 2.5 mg/bid (DPI) or DAPT plus rivaroxaban 2.5 mg/bid. Multiple PD assays assessing of markers of thrombosis were used. PD endpoints included platelet-mediated global thrombogenicity measured by light transmittance aggregometry (LTA) following stimuli with CATF [collagen‐related peptide +adenosine diphosphate (ADP) +tissue factor (TF)], markers of P2Y12 reactivity, markers of platelet aggregation using LTA following several stimuli (arachidonic acid, ADP, collagen, TF, and TRAP), thrombin generation and thrombus formation. There was no difference in platelet-mediated global thrombogenicity between groups. Rivaroxaban significantly reduced thrombin generation and was associated with a trend towards reduced TF-induced platelet aggregation. Clopidogrel-based treatments reduced markers of P2Y12 signaling and TRAP‐induced platelet aggregation. There were no differences between groups on markers of cyclooxygenase‐1 mediated activity. Conclusions: Compared with DAPT, DPI does not result in any differences in platelet-mediated global thrombogenicity, but reduces thrombin generation. These PD observations support that modulating thrombin generation by means of factor Xa inhibition in adjunct to antiplatelet therapy provides effective antithrombotic effects, supporting the efficacy and safety findings of DPI observed in clinical


Author(s):  
Francesco SUMMARIA ◽  
Giuseppe BIONDI-ZOCCAI ◽  
Enrico ROMAGNOLI ◽  
Mamas A. MAMAS ◽  
Francesco FRANCHI ◽  
...  

2006 ◽  
Vol 8 (suppl_G) ◽  
pp. G3-G9 ◽  
Author(s):  
Borja Ibanez ◽  
Gemma Vilahur ◽  
Juan J. Badimon

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