Pharmacodynamic Effects of Low-dose Rivaroxaban With Antiplatelet Therapies
- Conditions
- Coronary Artery DiseasePeripheral Arterial DiseaseAtrial Fibrillation
- Interventions
- Registration Number
- NCT03718429
- Lead Sponsor
- University of Florida
- Brief Summary
Recent studies indicate that anti-factor-Xa inhibition with low-dose rivaroxaban may have a role in the reduction of ischemic recurrences in patients with atherosclerotic disease manifestations.
To date there is very little data, and not conducted in human subjects, on the interplay between anti-Xa blockade with low-dose rivaroxaban and antiplatelet therapies, and in particular how this affects profiles of platelet reactivity and thrombin generation. Given the potential role for the use of low-dose rivaroxaban for the prevention of ischemic recurrences in patients with atherothrombotic disease manifestations, including coronary artery disease (CAD) and peripheral arterial disease (PAD), the study team proposes a prospective pharmacodynamic (PD) investigation assessing the impact of low-dose rivaroxaban when used in combination with antiplatelet treatment regimens commonly used in clinical practice.
- Detailed Description
Recent studies indicate that anti-factor-Xa inhibition with low-dose rivaroxaban may have a role in the reduction of ischemic recurrences in patients with atherosclerotic disease manifestations.
However, although the introduction of newer antithrombotic strategies has been associated with a reduction in ischemic recurrences in high-risk patients, these have been consistently associated with an increase in bleeding complications. These have been observed particularly with the combination of an oral anticoagulant agent, including low-dose rivaroxaban, with standard DAPT, also known as "triple therapy". Observations from laboratory and clinical studies suggest that in the presence of effective blockade of other pathways triggering thrombotic complications aspirin may not offer added antithrombotic effects but contribute to the increased bleeding. These observations have set the basis for a large number of clinical outcomes studies evaluating whether dropping aspirin in the presence of more potent and effective blockade of other pathways triggering thrombosis has a better safety profile without a tradeoff in efficacy. Amongst these strategies, the use of low-dose rivaroxaban in adjunct to a P2Y12 inhibitor, also known as dual therapy, has been proposed. This approach may be of potential benefit to reduce atherothrombotic complications in high-risk patients following an acute coronary event. On the other hand, regimens with more modest antithrombotic effects compared with a combination of low-dose rivaroxaban and a P2Y12 receptor inhibitor such as low-dose rivaroxaban alone or in combination with aspirin may be more suitable in more stabilized patients.
To date there is very little data, and not conducted in human subjects, on the interplay between anti-Xa blockade with low-dose rivaroxaban and antiplatelet therapies, and in particular how this affects profiles of platelet reactivity and thrombin generation. Given the potential role for the use of low-dose rivaroxaban for the prevention of ischemic recurrences in patients with atherothrombotic disease manifestations, including coronary artery disease (CAD) and peripheral arterial disease (PAD), the study team proposes a prospective pharmacodynamic (PD) investigation assessing the impact of low-dose rivaroxaban when used in combination with antiplatelet treatment regimens commonly used in clinical practice.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 86
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description aspirin Rivaroxaban 2.5 mg Tablet Patients on aspirin 81 mg daily will be treated with adjunctive low-dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy will be suspended for 7-10 days. aspirin and clopidogrel Rivaroxaban 2.5 mg Tablet Patients on aspirin (81 mg daily) plus clopidogrel (75 mg daily) will be treated with adjunctive low-dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy will be suspended for 7-10 days. aspirin and ticagrelor Rivaroxaban 2.5 mg Tablet Patients on aspirin (81 mg daily) and ticagrelor (90 mg bid) will be treated with adjunctive low-dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy will be suspended for 7-10 days.
- Primary Outcome Measures
Name Time Method Platelet-Mediated Global Thrombogenicity 20 days Comparison of platelet-mediated global thrombogenicity measured by light transmittance aggregometry following collagen-related peptide+adenosine diphosphate+ tissue factor (CATF) stimuli between aspirin plus clopidogrel vs. aspirin plus clopidogrel plus rivaroxaban. This was reported as maximal aggregation %. The combination of agonists included in the CATF cocktail leads to activation of multiple platelet pathways including thrombin generation and is therefore a marker of thrombus formation mediated by platelets.
Platelet Aggregation Measured by VerifyNow PRU 20 days P2Y12 reaction units (PRU) by VerifyNow of dual antiplatelet therapy vs. dual antiplatelet therapy plus rivaroxaban. VerifyNow is a turbidimetric based optical detection system which measures platelet aggregation induced by ADP as an increase in light transmittance.
Thrombin Generation 20 days Comparison of thrombin generation, reported as peak thrombin level measured by a thrombin generation assay, between aspirin plus clopidogrel vs. aspirin plus clopidogrel plus rivaroxaban. This is reflective of the amount of thrombin that is generated following stimuli with tissue factor. The theombin generation assay will be carried out using Technothrombin® fluorogenic assay kit.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
Cardiovascular Research Center,
🇺🇸Jacksonville, Florida, United States
UF Health Jacksonville
🇺🇸Jacksonville, Florida, United States