Clinical Significance of Platelet Reactivity on Clopidogrel During Off-pump Coronary Artery Bypass

Objective: To evaluate the early and late prognoses of patients according to platelet reactivity after clopidogrel administration and determine whether the measurement of platelet inhibition predicted 1-year clinical outcomes after off-pump coronary bypass (OPCAB) Study design

• Prospective, observational, single-center study
• Subjects with OPCAB surgery who meet all inclusion and exclusion criteria will be enrolled.
• Platelet reactivity after 7-days clopidogrel treatment from the day of surgery will be measured by VerifyNow system.
• Dual antiplatelet therapy including aspirin and clopidogrel will be administered for 1 year after surgery and subjects will be followed-up for 1 year about primary endpoint.
• Cutoff value of P2Y12 reactivity units (PRUs) for primary endpoint will be assessed and the cohort will be divided by the PRU cutoff value (low/high platelet reactivity groups).
• The primary and secondary endpoints will be compared between two groups

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Dual antiplatelet therapy including aspirin and clopidogrel after off-pump coronary bypass surgery

• Study Type: Observational
• Enrollment (Actual): 859

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Division of Cardiovascular Surgery, Severance Cardiovascular Hospital , Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients with indications for surgical myocardial revascularization

Description

Inclusion Criteria:

• Patients with indications for surgical myocardial revascularization
• Patients who undergo off-pump coronary artery bypass
• Age between 19~80 years
• Patients with signed informed consent

Exclusion Criteria:

• Patients with combined surgery with coronary bypass grafting
• On-pump conversion
• Patients with moderate renal dysfunction (creatinine>2.0mg/dl) or need for dialysis
• Patients with chronic treatment with proton pump inhibitors
• Patients with preoperative bleeding
• Thrombocytopenia (Platelet count 70,000/ml)
• Re-do surgery
• Early death before the measurement of platelet reactivity

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Low platelet reactivity group; Platelet reactivity will be measured after 7-days treatment of clopidogrel by VerifyNow system and the cohort will be divided by two group according to P2Y12 reactivity unit (PRU) cutoff value. Receiver operating characteristic (ROC) curves will be plotted to assess the optimal PRU cutoff value for differentiating between patients with and without subsequent MACEs after 1 year of follow-up. Low platelet reactivity indicates good response to clopidogrel and high platelet reactivity, resistance to clopidogrel. Groups will be "Low platelet reactivity group" and "High platelet reactivity group"	Drug: Dual antiplatelet therapy including aspirin and clopidogrel after off-pump coronary bypass surgery; aspirin 100mg/day and clopidogrel 75mg/day, PO, from the day of surgery for 1 year
high platelet reactivity group; Platelet reactivity will be measured after 7-days treatment of clopidogrel by VerifyNow system and the cohort will be divided by two group according to P2Y12 reactivity unit (PRU) cutoff value. Receiver operating characteristic (ROC) curves will be plotted to assess the optimal PRU cutoff value for differentiating between patients with and without subsequent MACEs after 1 year of follow-up. Low platelet reactivity indicates good response to clopidogrel and high platelet reactivity, resistance to clopidogrel. Groups will be "Low platelet reactivity group" and "High platelet reactivity group"	Drug: Dual antiplatelet therapy including aspirin and clopidogrel after off-pump coronary bypass surgery; aspirin 100mg/day and clopidogrel 75mg/day, PO, from the day of surgery for 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular events (MACEs)	The primary endpoint of the study was the 1-year incidence of MACEs, which included the following: (1) cardiac death, defined as death in the presence of acute coronary syndrome, sudden cardiac arrest with documented cardiac arrhythmia, or refractory congestive heart failure; 2) nonfatal MI; and (3) target vessel revascularization in relation to platelet reactivity as measured by the VerifyNow system.	1 year after off-pump coronary bypass surgery

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Patti G, Nusca A, Mangiacapra F, Gatto L, D'Ambrosio A, Di Sciascio G. Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study. J Am Coll Cardiol. 2008 Sep 30;52(14):1128-33. doi: 10.1016/j.jacc.2008.06.038.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: October 7, 2013
• First Submitted That Met QC Criteria: October 7, 2013
• First Posted (Estimate): October 9, 2013

Study Record Updates

• Last Update Posted (Estimate): October 9, 2013
• Last Update Submitted That Met QC Criteria: October 7, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Platelet activity, CABG, off-pump surgery
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: 4-2011-0309

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No