Aggressive Cholesterol Therapy to Inhibit Vein Graft Events After CABG (ACTIVE Trial) (ACTIVE)

Aggressive Cholesterol Therapy to Inhibit Vein Graft Events (ACTIVE Trial): Does High-Dose Postoperative Statin Therapy Improve Graft Patency After Coronary Bypass?

During coronary artery bypass graft surgery (CABG), saphenous vein from the leg is used to bypass the atherosclerotic blockages in the arteries of the heart. Unfortunately, vein bypasses themselves develop blockages over time, a process termed saphenous vein graft disease. By lowering cholesterol levels in the blood, statin medications are used after surgery to prevent the development of atherosclerotic blockages in the vein bypasses. Recently, higher doses of statin medications have been introduced, with some studies showing that they are more effective than traditional doses when used in heart attack patients. Furthermore, laboratory tests have shown that higher doses of statin medications can slow the development of atherosclerosis. Despite these benefits, very little is known regarding the use of high-dose statin therapy after bypass surgery in humans.

The goal of this study will be to see if high-dose statin therapy will prevent the development of vein graft occlusion during the first year after bypass surgery. Patients will be randomized to receive either high-dose statin therapy or conventional moderate-dose statin therapy starting within 4 days of surgery and continuing for the duration of one year after the operation. The statin medication will be given in capsule form. During the course of this study, neither the patient nor the health care team will know which treatment each patient is receiving. One year after bypass surgery, a computed tomography (CT) coronary angiogram will be performed to evaluate the patency of the vein bypasses.

Study Overview

• Status: Completed
• Conditions: Saphenous Vein Graft Disease
• Intervention / Treatment: Drug: Atorvastatin 80 mg daily; Drug: Atorvastatin 10 mg daily

Detailed Description

The current clinical guidelines recommend treatment to achieve LDL levels <100 mg/dL after surgical coronary revascularization. However, recent studies have illustrated that even more intensive lipid reduction with high-dose statins can further improve cardiovascular outcomes. Targeting LDL levels to 70 mg/dL after CABG with intensive statin therapy may prevent the process of postoperative saphenous vein graft disease and lead to improved graft patency. Therefore, in the ACTIVE Trial, we will conduct a randomized controlled trial comparing high-dose (80 mg atorvastatin) to moderate-dose (10 mg atorvastatin)statin therapy in patients undergoing CABG with saphenous vein grafts. The effect of aggressive cholesterol therapy on the process of vein graft disease will be examined with computed tomography (CT) coronary angiography one year after CABG. This study will address the subject of postoperative high-dose statin therapy and help determine the optimal lipid-lowering strategy following CABG.

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
• United States
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Heart and Vascular Institute, Boca Raton Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing first-time CABG with at least 1 saphenous vein graft

Exclusion Criteria:

• Redo-CABG
• Statin allergy
• Severe renal dysfunction
• Severe liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dose statin therapy; Atorvastatin 80 mg daily	Drug: Atorvastatin 80 mg daily; Atorvastatin 80 mg daily for 1 year
Active Comparator: Moderate-dose statin therapy; Atorvastatin 10 mg daily	Drug: Atorvastatin 10 mg daily; Atorvastatin 10 mg daily for 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Saphenous Vein Graft Occlusion (Percentage of Vein Grafts Occluded) Based on CT Coronary Angiography at 1 Year	Vein graft patency will be assessed in a blinded fashion by CT coronary angiography 1 year after CABG	1 year after CABG

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vein Graft Stenosis 1 Year After CABG Based on CT Coronary Angiography	Vein graft stenosis 1 year after CABG based on CT coronary angiography	Within 1 year after CABG

Collaborators and Investigators

• Sponsor: Boca Raton Regional Hospital
• Collaborators: Pfizer
• Investigators: Principal Investigator: Alexander Kulik, MD MPH, Lynn Heart and Vascular Institute, Boca Raton Regional Hospital; Principal Investigator: Marc Ruel, MD MPH, Ottawa Heart Institute Research Corporation

Publications and helpful links

General Publications

• Kulik A, Voisine P, Mathieu P, Masters RG, Mesana TG, Le May MR, Ruel M. Statin therapy and saphenous vein graft disease after coronary bypass surgery: analysis from the CASCADE randomized trial. Ann Thorac Surg. 2011 Oct;92(4):1284-90; discussion 1290-1. doi: 10.1016/j.athoracsur.2011.04.107.
• Kulik A, Ruel M. Lipid-lowering therapy and coronary artery bypass graft surgery: what are the benefits? Curr Opin Cardiol. 2011 Nov;26(6):508-17. doi: 10.1097/HCO.0b013e32834b9fb1.
• Kulik A, Ruel M. Statins and coronary artery bypass graft surgery: preoperative and postoperative efficacy and safety. Expert Opin Drug Saf. 2009 Sep;8(5):559-71. doi: 10.1517/14740330903188413.
• Kulik A, Abreu AM, Boronat V, Ruel M. Intensive versus moderate atorvastatin therapy and one-year graft patency after CABG: Rationale and design of the ACTIVE (Aggressive Cholesterol Therapy to Inhibit Vein Graft Events) randomized controlled trial (NCT01528709). Contemp Clin Trials. 2017 Aug;59:98-104. doi: 10.1016/j.cct.2017.06.006. Epub 2017 Jun 10.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: February 6, 2012
• First Submitted That Met QC Criteria: February 7, 2012
• First Posted (Estimate): February 8, 2012

Study Record Updates

• Last Update Posted (Actual): September 7, 2018
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: lipids; Statin,; CABG,; saphenous vein graft,; graft occlusion,
• Additional Relevant MeSH Terms: Behavioral Symptoms; Aggression; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 2011.02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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