Impact of Hybrid Coronary Revascularization on Antiplatelet Therapy

NCT ID: NCT02293928

Last Updated: 2014-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-10-31

Study Completion Date

2013-04-30

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Coronary Artery Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Elective hybrid coronary revascularization

All patients are treated with non-enteric coated aspirin 75 mg once daily prior to study participation. Aspirin treatment is discontinued 8-10 days prior to surgery and resumed 6-9 hours after surgery. Left internal mammary grafting of the left descendent coronary artery is performed off-pump through an inferior J-hemisternotomy (JOPCAB). All patients receive an oral loading dose of aspirin 300 mg 6-9 hours after surgery followed by daily maintenance doses of 75 mg aspirin. An oral loading dose of clopidogrel 300 mg 12 hours prior to PCI is followed by daily maintenance doses of 75 mg for 12 months. Patients are followed for 1 year.

Hybrid coronary revascularization

Intervention Type PROCEDURE

Hybrid coronary revascularization with standard double antiplatelet therapy

Interventions

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Hybrid coronary revascularization

Hybrid coronary revascularization with standard double antiplatelet therapy

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Danish Heart Foundation

OTHER

Sponsor Role collaborator

Aase and Ejnar Danielsens Foundation

OTHER

Sponsor Role collaborator

Aarhus University Hospital Skejby

OTHER

Sponsor Role lead

Responsible Party

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Ivy Modrau

Junior Consultant

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ivy S Modrau, MD, DMSc

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospitak Skejby

Locations

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Aarhus University Hospital

Aarhus, , Denmark

Site Status

Countries

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Denmark

References

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Modrau IS, Wurtz M, Kristensen SD, Hvas AM. Reduced Effect of Aspirin and Clopidogrel Following Hybrid Coronary Revascularization. Clin Appl Thromb Hemost. 2015 Oct;21(7):603-11. doi: 10.1177/1076029615573304. Epub 2015 Mar 9.

Reference Type DERIVED
PMID: 25753965 (View on PubMed)

Other Identifiers

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10-000439

Identifier Type: -

Identifier Source: org_study_id