Clinical trial NCT01528709: Aggressive Cholesterol Therapy to Inhibit Vein Graft Events After CABG (ACTIVE Trial)
Official title: Aggressive Cholesterol Therapy to Inhibit Vein Graft Events (ACTIVE Trial): Does High-Dose Postoperative Statin Therapy Improve Graft Patency After Coronary Bypass?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Saphenous Vein Graft Disease
Keywords: Statin,
CABG,
saphenous vein graft,
graft occlusion,
lipids
Lead sponsor: Boca Raton Regional Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2012-02-08
Enrollment: 173
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Saphenous Vein Graft Occlusion (Percentage of Vein Grafts Occluded) Based on CT Coronary Angiography at 1 Year
timeFrame: 1 year after CABG
Secondary outcomes:
measure: Vein Graft Stenosis 1 Year After CABG Based on CT Coronary Angiography
timeFrame: Within 1 year after CABG
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Lynn Heart and Vascular Institute, Boca Raton Regional Hospital
state: Florida
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Lynn Heart and Vascular Institute, Boca Raton Regional Hospital
name: Alexander Kulik, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: Marc Ruel, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.