title: Rationale and Design of the PROSPECTIVE Trial: Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease.
abstract: BACKGROUND
  Reduction of serum LDL-cholesterol by statins was shown to improve clinical outcomes in patients with coronary heart disease (CHD). Although intensive statin therapy significantly reduced cardiovascular risks, atherosclerotic cardiovascular events have not been completely prevented. Therefore, effective pharmacologic therapy is necessary to improve "residual risks" in combination with statins. Probucol has a potent antioxidative effect, inhibits the oxidation of LDL, and reduces xanthomas. Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease (PROSPECTIVE) is a multicenter, randomized, prospective study designed to test the hypothesis that the addition of probucol to other lipid-lowering drugs will prevent cerebro- and cardiovascular events in patients with prior coronary events and high LDL cholesterol levels.
  
  
  METHODS
  The study will recruit approximately 860 patients with a prior CHD and dyslipidemia with LDL-C level ≥140 mg/dl without any medication and those treated with any lipid-lowering drugs with LDL-C level ≥100 mg/dl. Lipid-lowering agents are continuously administered during the study period in control group, and probucol (500 mg/day, 250 mg twice daily) is added to lipid-lowering therapy in the test group. The efficacy and safety of probucol with regard to the prevention of cerebro- and cardiovascular events and the intima-media thickness of carotid arteries as a surrogate marker will be evaluated.
  
  
  CONCLUSIONS
  PROSPECTIVE will determine whether the addition of probucol to other lipid-lowering drugs improves cerebro- and cardiovascular outcomes in patients with prior coronary heart disease. Furthermore, the safety of a long-term treatment with probucol will be clarified.
authors.affiliation: Department of Community Medicine, Osaka University Graduate School of Medicine.
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Daisaku
authors.initials: D
authors.lastname: Masuda
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohama
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kagimura
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D059168:Carotid Intima-Media Thickness; D002539:Cerebral Arterial Diseases / Q000209:etiology / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000627:therapeutic use*; D011446:Prospective Studies; D012107:Research Design; D055502:Secondary Prevention
chemical_list: D000924:Anticholesteremic Agents; D011341:Probucol