Ignite Creation Date:
2024-05-05 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000463
Status:
COMPLETED
Last Update Posted:
2016-04-14
First Post:
1999-10-27
Brief Title:
Post Coronary Artery Bypass Graft CABG Study
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2004-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine the relative effectiveness of moderate versus more aggressive lipid lowering and of low dose anticoagulation versus placebo in delaying saphenous vein coronary bypass graft atherosclerosis and preventing occlusion of saphenous grafts of patients with saphenous vein coronary bypass grafts placed 1 to 11 years previously
Detailed Description:
BACKGROUND
A large number of studies have reported that following CABG the vessels proximal to the grafts demonstrate accelerated atherosclerosis and the grafts themselves may show progressive obstruction due to thrombosis fibrosis and graft atheroma Pathological and clinical studies have documented that graft obstruction during the perioperative period and the first year is usually due to technical problems at surgery or thrombosis and occurs in about 15 to 20 percent of saphenous vein grafts Antiplatelet drugs such as aspirin have been shown to reduce these early graft occlusions by about 50 percent In addition to thrombosis during the first year most saphenous vein grafts undergo diffuse fibrosis and some distortion However the significance of these changes is not known
After the first year lipid deposition and changes histologically similar to atherosclerosis have been documented both in experimental studies and in human saphenous vein grafts patent at one year completely occlude and an additional 30 percent narrow over a period of ten years These angiographic changes in the saphenous vein grafts correlate with high LDL-cholesterol low HDL-cholesterol and high apolipoprotein B levels In experimental animals cholesterol deposition in the grafts has been substantially increased or decreased by increasing or decreasing the saturated fats and cholesterol in the animals diets In contrast to changes in the saphenous vein grafts internal mammary artery grafts have shown substantially lower rates of obstruction The native vessels both ungrafted vessels and grafted vessels at distal or proximal sites however show evidence of progressive atherosclerosis The long-term follow-up of grafts also demonstrates thrombotic material and even occlusive thrombus as part of acute events
Progression of atherosclerotic lesions in grafts and native vessels lead to recurrent angina unaltered long-term survival and reduced efficacy of repeat CABG surgery Johnson in an 11 year follow-up of 3105 post-CABG patients reported that about 15 percent of patients with preoperative angina have recurrent angina at 1 year with a further 6 percent developing angina every subsequent year In this study patients with recurrent angina had twice the mortality compared to those who were angina-free Long-term follow-up of the VA Cooperative Trial of CABG shows that the survival of the surgical group appears to be initially superior compared to the medical group but this benefit is diminished by about ten years This may relate to graft obstruction and progression of native coronary atherosclerosis Re-operation in these patients carries a higher operative mortality risk and the results are less impressive It had been estimated that approximately 5 percent of all CABG surgery in 1984 were re-operations and that this percentage would double over the next decade Therefore measures to prevent graft occlusion and progression of atherosclerosis in native vessels if successful could have substantial clinical and economic importance by reducing mortality morbidity and the numbers of patients undergoing re-operations
Apart from trials of aspirin and dipyridamole in post-CABG patients that demonstrated a significant reduction in graft closure within the first year after surgery there were no large systematic studies of interventions in these patients Graft occlusion has been shown to correlate with high LDL-cholesterol and low HDL-cholesterol and the severity of atherosclerosis has been additionally shown to be related to cigarette smoking and increased levels of coagulation factor Therefore lowering the LDL cholesterol by diet and drugs and anti-thrombotic therapy with warfarin were logical choices for intervention
Several studies suggested that CABG surgery relieved angina and improved overall quality of life However in the available studies CABG did not consistently appear to be associated with an improvement in employment status physical recreational activity or life style The reasons for these results were not entirely clear and there was a need to identify the biobehavioral and psychosocial factors that predicted successful adjustment after CABG
The initiative was proposed by Institute staff and approved by the September 1985 National Heart Lung and Blood Advisory Council The Request for Proposals was released in September 1985 and awards made in April 1987
DESIGN NARRATIVE
Multicenter double-blind randomized controlled trial All prospective participants received active warfarin treatment for a month prior to randomization Only participants demonstrating a minimal reaction to warfarin and consuming over 90 percent of the prescribed medication were randomized Dietary modification to lower serum cholesterol an exercise program and a smoking cessation program were implemented Patients were randomly assigned in a 2 X 2 factorial design in four treatment groups aggressive LDL-C lowering with lovastatin 40 to 80 mgd and as necessary cholestyramine 8 mgd to achieve and LDL-C of 60 to 85 mgdl moderate LDL-C lowering with lovastatin 25 to 5 mgd with cholestyramin as needed to achieve a LDL-C of 130 to 140 mgdl warfarin 1 to 4 mgd to achieve an INR of 18 to 20 and warfarin-placebo All participants were followed for five years at the end of which selective coronary and graft angiography was performed The primary angiography endpoint was the proportion of major SVG per patient that showed substantial reduction 006 mm or greater in lumen diameter Biobehavioral studies were conducted in 750 participants
Planning for the study began in April 1987 and a final protocol was developed by August 1988 Patient recruitment has been completed Follow-up ended on September 1 1995 and data analysis continues through December 1998 under contract N01-HC-75076
The Post CABG Biobehavioral Study examined a cohort of 759 coronary artery bypass patients 269 women and 490 men who were enrolled at five clinical centers Sociodemographic and medical data were obtained by interview and from medical charts Health-related quality of life and psychosocial data were ascertained preoperatively by interview and questionnaire for those patients whose condition allowed preoperative assessment and was compared among patients from hospitals enrolling both male and female patients
A large number of studies have reported that following CABG the vessels proximal to the grafts demonstrate accelerated atherosclerosis and the grafts themselves may show progressive obstruction due to thrombosis fibrosis and graft atheroma Pathological and clinical studies have documented that graft obstruction during the perioperative period and the first year is usually due to technical problems at surgery or thrombosis and occurs in about 15 to 20 percent of saphenous vein grafts Antiplatelet drugs such as aspirin have been shown to reduce these early graft occlusions by about 50 percent In addition to thrombosis during the first year most saphenous vein grafts undergo diffuse fibrosis and some distortion However the significance of these changes is not known
After the first year lipid deposition and changes histologically similar to atherosclerosis have been documented both in experimental studies and in human saphenous vein grafts patent at one year completely occlude and an additional 30 percent narrow over a period of ten years These angiographic changes in the saphenous vein grafts correlate with high LDL-cholesterol low HDL-cholesterol and high apolipoprotein B levels In experimental animals cholesterol deposition in the grafts has been substantially increased or decreased by increasing or decreasing the saturated fats and cholesterol in the animals diets In contrast to changes in the saphenous vein grafts internal mammary artery grafts have shown substantially lower rates of obstruction The native vessels both ungrafted vessels and grafted vessels at distal or proximal sites however show evidence of progressive atherosclerosis The long-term follow-up of grafts also demonstrates thrombotic material and even occlusive thrombus as part of acute events
Progression of atherosclerotic lesions in grafts and native vessels lead to recurrent angina unaltered long-term survival and reduced efficacy of repeat CABG surgery Johnson in an 11 year follow-up of 3105 post-CABG patients reported that about 15 percent of patients with preoperative angina have recurrent angina at 1 year with a further 6 percent developing angina every subsequent year In this study patients with recurrent angina had twice the mortality compared to those who were angina-free Long-term follow-up of the VA Cooperative Trial of CABG shows that the survival of the surgical group appears to be initially superior compared to the medical group but this benefit is diminished by about ten years This may relate to graft obstruction and progression of native coronary atherosclerosis Re-operation in these patients carries a higher operative mortality risk and the results are less impressive It had been estimated that approximately 5 percent of all CABG surgery in 1984 were re-operations and that this percentage would double over the next decade Therefore measures to prevent graft occlusion and progression of atherosclerosis in native vessels if successful could have substantial clinical and economic importance by reducing mortality morbidity and the numbers of patients undergoing re-operations
Apart from trials of aspirin and dipyridamole in post-CABG patients that demonstrated a significant reduction in graft closure within the first year after surgery there were no large systematic studies of interventions in these patients Graft occlusion has been shown to correlate with high LDL-cholesterol and low HDL-cholesterol and the severity of atherosclerosis has been additionally shown to be related to cigarette smoking and increased levels of coagulation factor Therefore lowering the LDL cholesterol by diet and drugs and anti-thrombotic therapy with warfarin were logical choices for intervention
Several studies suggested that CABG surgery relieved angina and improved overall quality of life However in the available studies CABG did not consistently appear to be associated with an improvement in employment status physical recreational activity or life style The reasons for these results were not entirely clear and there was a need to identify the biobehavioral and psychosocial factors that predicted successful adjustment after CABG
The initiative was proposed by Institute staff and approved by the September 1985 National Heart Lung and Blood Advisory Council The Request for Proposals was released in September 1985 and awards made in April 1987
DESIGN NARRATIVE
Multicenter double-blind randomized controlled trial All prospective participants received active warfarin treatment for a month prior to randomization Only participants demonstrating a minimal reaction to warfarin and consuming over 90 percent of the prescribed medication were randomized Dietary modification to lower serum cholesterol an exercise program and a smoking cessation program were implemented Patients were randomly assigned in a 2 X 2 factorial design in four treatment groups aggressive LDL-C lowering with lovastatin 40 to 80 mgd and as necessary cholestyramine 8 mgd to achieve and LDL-C of 60 to 85 mgdl moderate LDL-C lowering with lovastatin 25 to 5 mgd with cholestyramin as needed to achieve a LDL-C of 130 to 140 mgdl warfarin 1 to 4 mgd to achieve an INR of 18 to 20 and warfarin-placebo All participants were followed for five years at the end of which selective coronary and graft angiography was performed The primary angiography endpoint was the proportion of major SVG per patient that showed substantial reduction 006 mm or greater in lumen diameter Biobehavioral studies were conducted in 750 participants
Planning for the study began in April 1987 and a final protocol was developed by August 1988 Patient recruitment has been completed Follow-up ended on September 1 1995 and data analysis continues through December 1998 under contract N01-HC-75076
The Post CABG Biobehavioral Study examined a cohort of 759 coronary artery bypass patients 269 women and 490 men who were enrolled at five clinical centers Sociodemographic and medical data were obtained by interview and from medical charts Health-related quality of life and psychosocial data were ascertained preoperatively by interview and questionnaire for those patients whose condition allowed preoperative assessment and was compared among patients from hospitals enrolling both male and female patients
Study Oversight
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Is a FDA Regulated Drug?:
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Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: