Impact of Hybrid Coronary Revascularization on Antiplatelet Therapy

Coronary Artery Disease Clinical Trial

Official title:

Impact of Hybrid Coronary Revascularization on Antiplatelet Effect of Aspirin and Clopidogrel

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02293928
• Other study ID #: 10-000439
• Status: Completed
• Phase: N/A
• First received: November 13, 2014
• Last updated: November 13, 2014
• Start date: October 2010
• Est. completion date: April 2013

Study information

• Verified date: November 2014
• Source: Aarhus University Hospital Skejby
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: National Board of Health
• Study type: Observational

Clinical Trial Summary

The effect of antiplatelet therapy is impaired among patients, who recently underwent on-pump coronary artery bypass grafting. The impact of hybrid coronary revascularization using minimal invasive surgical techniques on the antiplatelet effect of aspirin and clopidogrel remains unclear.

The aim of the study is to describe the impact of hybrid coronary revascularization on the effect of aspirin and clopidogrel. Furthermore, we will investigate whether high baseline platelet aggregation, high postoperative levels of platelet turnover and acute-phase response may contribute to the effect.

Description:

Objective:

The effect of antiplatelet therapy is impaired among patients, who recently underwent on-pump coronary artery bypass grafting. The impact of hybrid coronary revascularization using minimal invasive surgical techniques on the antiplatelet effect of aspirin and clopidogrel remains unclear.

We hypothesize that hybrid coronary revascularization is associated with a transiently reduced antiplatelet effect of aspirin and clopidogrel. We hypothesize that the reduced antiplatelet effect of aspirin and clopidogrel could be explained by increased platelet turnover with an increased fraction of immature platelets in the peripheral blood. Furthermore, we hypothesize that the reduced antiplatelet effect is associated with increased inflammatory markers in the early postoperative phase. We hypothesize, that high platelet aggregation prior to the intervention is associated with reduced effect of antiplatelet therapy following hybrid coronary revascularization.

Methods:

40 patients with coronary artery disease will be enrolled in this prospective cohort study (recruited from a prospective pilot study conducted to assess feasibility and safety of hybrid coronary revascularization combining minimally invasive off-pump coronary artery bypass grafting through an inferior J-hemisternotomy (JOPCAB) with percutaneous coronary intervention - Clinicaltrials.gov identifier: NCT01496664). Demographics and medical history are documented preoperatively. The predicted mortality is assessed by means of the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) I. Adverse cardiovascular events are recorded prospectively, including graft dysfunction, myocardial infarction, stroke, and pulmonary embolism.

Six blood samples are obtained from each patient:

• Pre-OP: in the outpatient setting while patients were on aspirin 75 mg daily

• Baseline: in the morning prior to surgery after eight to ten days of aspirin discontinuation (off-aspirin)

• Post-OP: on the first postoperative day when aspirin had been resumed

• Pre-PCI: on the day prior to PCI

• Post-PCI: on the first day after PCI following initiation of dual antiplatelet therapy

• 1-year follow-up: when patients were still on maintenance aspirin 75 mg and clopidogrel 75 mg Platelet function analyses are performed using Multiplate® Analyzer (Roche, Roche Diagnostics, Mannheim, Germany), VerifyNow® Aspirin, and VerifyNow® P2Y12 (Accumetrics Inc., San Diego, CA, USA). For Multiplate® Analyzer, arachidonic acid (1.0 mM) and adenosine diphosphate (6.4 and 20 uM) are used as agonists.

Complete blood counts, including immature platelet fraction (IPF), immature platelet count (IPC), and mean platelet volume (MPV), are performed using a Sysmex XE-5000 haematology analyzer (Sysmex, Kobe, Japan) with upgraded software (XE IPF Master, Sysmex) enabling flow cytometric detection of the IPF. Enzyme-linked immunosorbent assays are used according to the manufacturers' instructions to measure serum thromboxane B2 (Cayman Chemical, Ann Arbor, MI, USA) and thrombopoietin (R&D Systems Europe, Abingdon, UK). Plasma C-reactive protein was measured by immunoprecipitation using the Cobas® 6000 (Roche, Basel, Switzerland). Von Willebrand factor (antigen) and coagulation factor VIII (functional) are measured using the ACL TOP (ILS Laboratories, Bedford, MA, USA).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• symptomatic multivessel coronary artery disease

• treatment with non-enteric coated aspirin 75 mg once daily

Exclusion Criteria:

• aspirin or clopidogrel intolerance

• conditions prohibitive of aspirin discontinuation prior to surgery

• use of anticoagulants or any drugs other than aspirin known to affect platelet function

• use of immunosuppressive drugs

• platelet count <100 or >450 x 109/l

• inability to give informed consent

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Procedure:
• Hybrid coronary revascularization
Hybrid coronary revascularization with standard double antiplatelet therapy

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (3)

Lead Sponsor	Collaborator
Aarhus University Hospital Skejby	Aase and Ejnar Danielsens Foundation, Danish Heart Foundation

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Compliance to aspirin treatment at enrollment	measured by levels of serum thromboxane B2 below 30 ng/ml	8-10 days preoperative	No
Other	Compliance to aspirin treatment at 1 year follow-up	measured by levels of serum thromboxane B2 below 30 ng/ml	1 year	No
Primary	Change in aspirin antiplatelet effect from preoperative to three days postoperative	Platelet aggregation measured by VerifyNow® Aspirin and Multiplate® Analyzer	12-14 days	No
Secondary	Change on aspirin antiplatelet effect from 3 days postoperative to 1 year follow-up	Platelet aggregation measured by VerifyNow® Aspirin and Multiplate® Analyzer	1 year	No
Secondary	Change on clopidogrel antiplatelet effect from first day after PCI to 1 year follow-up	Platelet aggregation measured by VerifyNow®P2Y12 and Multiplate® Analyzer	1 year	No
Secondary	Association between baseline platelet aggregation (off-aspirin) and aspirin antiplatelet effect	Platelet aggregation measured by VerifyNow® Aspirin and Multiplate® Analyzer Baseline aggregation is compared to aggragation preoperatively (on maintenance aspirin treatment) and postoperatively (when aspirin is resumed).	12-14 days	No
Secondary	Correlation between acute phase reactants and platelet aggregation	C-reactive protein, von Willebrand factor (antigen), and coagulation factor VIII (functional)	8-10 days preoperative until 1 year postoperative	No
Secondary	Correlation between platelet turnover and platelet aggregation	Platelet turnover assessed by Complete blood counts, including immature platelet fraction, immature platelet count, mean platelet volume and thrombopoietin.	8-10 days preoperative until 1 year postoperative	No