Prevention of the Angiographic Progression of Coronary and Vein-Graft Atherosclerosis by Gemfibrozil After Coronary Bypass Surgery in Men With Low Levels of HDL Cholesterol - LOCAT

Description:

This is a double-blind, randomized study of the effect of gemfibrozil on angiographic progression of atherosclerosis following coronary artery bypass surgery (CABG).

Hypothesis:

Gemfibrozil will be associated with a reduction in the progression of coronary atherosclerosis in a population of men following CABG.

Study Design

Study Design:

Patients Enrolled: 395
Mean Follow Up: On average 32 months
Female: 0
Mean Ejection Fraction: ≥35%

Patient Populations:

  • HDL cholesterol ≤1.1 mmol/l (42.5 mg/dl)
  • LDL ≤4.5 mmol/l (174 mg/dl)
  • Serum triglycerides ≤4.0 mmol/l (354 mg/dl)
  • Blood pressure ≤160/95 mm Hg
  • Body mass index ≤30 kg/m2
  • Left ventricular ejection fraction ≥35%

Exclusions:

  • History of diabetes
  • Fasting serum glucose concentration <7.8 mmol/l (140 mg/dl)
  • Any condition requiring calcium channel blockers, angiotensin-converting enzyme inhibitors, or diuretics
  • Smoking greater than 20 cigarettes/week

Primary Endpoints:

  1. Change from baseline to follow-up angiogram in the average diameter and minimum luminal diameter of stenoses in native coronary arteries and bypass vessels
  2. New coronary lesions (causing at least 20% diameter reduction)
  3. Changes in baseline and on-trial lipid levels

Drug/Procedures Used:

Patients were randomized to slow-release gemfibrozil therapy 1200 mg/day (n=197) or placebo (n=198). Treatment continued for an average of 32 months.

Principal Findings:

  • Changes in lipid levels in the gemfibrozil group: Triglyceride and low-density lipoprotein (LDL) levels were reduced by 36% and 4.5%, respectively, while high-density lipoprotein (HDL) levels were increased by 21% from baseline to mean on-trial levels. In the placebo group, triglyceride, LDL, and HDL levels increased by 4.6%, 5.3%, and 7.0%, respectively. All between-group on-trial differences in lipid levels were highly significant (p<0.001).
  • Changes in angiographic endpoints: The change in per-patient means an average diameter of native coronary arteries was -0.04 ± 0.11 mm and -0.01 ± 0.10 mm in the placebo and gemfibrozil group, respectively (p=0.009). The corresponding change in minimum luminal diameter of native coronary segments was -0.09 ± 0.18 and -0.04 ± 0.15 mm (p=0.02). Two percent of those in the treatment group compared with 14% of those in the placebo group had new lesions in the aortocoronary bypass grafts (p<0.001).

Interpretation:

Among nondiabetic men post-CABG, treatment with gemfibrozil was associated with slower progression of coronary atherosclerosis compared with placebo. The applicability of this study is limited by the population—nondiabetic men with low HDL levels and mild hypertension at three university hospitals in Finland.

References:

Frick MH, Syvanne M, Nieminen MS, et al. Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group. Circulation 1997; 96:2137-43.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Hypertension

Keywords: Hospitals, University, Atherosclerosis, Body Mass Index, Gemfibrozil, Saphenous Vein, Hypolipidemic Agents, Stroke Volume, Blood Pressure, Hypercholesterolemia, Coronary Artery Bypass, Triglycerides, Hypertension


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