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CLINICAL STUDY: ATHEROSCLEROSIS

Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia

Fukuoka atherosclerosis trial (FAST)

Yasunori Sawayama, MD, PhD^*, Chie Shimizu, MD^*, Naoyasu Maeda, MD^*, Masafumi Tatsukawa, MD^*, Naoko Kinukawa, MS, Samon Koyanagi, MD, PhD, Seizaburo Kashiwagi, MD, PhD and Jun Hayashi, MD, PhD^*,*

^* General Medicinel, Fukuoka, Japan
Medical Informatics, Kyushu University Hospital, Fukuoka, Japan,
National Kyushu Medical Center, Fukuoka, Japan

Manuscript received April 3, 2001; revised manuscript received November 5, 2001, accepted November 16, 2001.

^* Reprint requests and correspondence: Dr. Jun Hayashi, Department of General Medicine, Kyushu University Hospital, Higashi-ku, Fukuoka 812-8582, Japan.
hayashij{at}genmedpr.med.kyushu-u.ac.jp

OBJECTIVES: This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness (IMT) in asymptomatic patients with hypercholesterolemia from Fukuoka, Japan.

BACKGROUND: Carotid atherosclerosis is a strong, independent predictor of morbidity and mortality in patients with coronary heart disease (CHD).

METHODS: A total of 246 asymptomatic hypercholesterolemic patients (mean age 66 years) were randomized to receive either probucol (500 mg/day, n = 82) or pravastatin (10 mg/day, n = 83) or to enter a control group (diet alone, n = 81); they were followed for two years. The change in IMT in the common carotid artery was the primary end point measure, and the incidence of major cardiovascular events was the secondary measure.

RESULTS: Over the two-year period, serum low-density lipoprotein (LDL) cholesterol was significantly reduced in the pravastatin group (36%), the probucol group (29%) and the control group (12%) (p < 0.0001, p < 0.0001 and p < 0.05, respectively). After two years, the probucol and pravastatin groups showed a significant reduction in IMT (–13.9% and –13.9% and p < 0.01 and p < 0.01, respectively), but there was significant IMT thickening (23.2%; p < 0.05) in the control group. Probucol reduced the rate of IMT increase, independently of its reduction of LDL or high-density lipoprotein cholesterol. Moreover, there was a significantly lower incidence of cardiac events in the probucol group (2.4%) than in the control group (13.6%) (p = 0.0136).

CONCLUSIONS: Probucol reduced cholesterol levels and stabilized plaque, leading to a lower incidence of cardiac events in these hypercholesterolemic patients.

Abbreviations and Acronyms   CETP   CETP   cholesterol ester transfer protein   CHD   coronary heart disease   HDL   high-density lipoprotein   IMT   intima-media thickness   LDL   low-density lipoprotein   MI   myocardial infarction

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