title: Combination therapy of candesartan with statin inhibits progression of atherosclerosis more than statin alone in patients with coronary artery disease.
abstract: OBJECTIVE
  Both statins and renin-angiotensin system (RAS) inhibitors inhibit atherosclerotic progression and reduce cardiovascular events. However, it remains unclear whether combination therapy of RAS inhibitor with statin could inhibit plaque progression more than statin alone.
  
  
  METHODS
  Using 64 multislice computed tomography, vessel wall areas (VWAs) and total vascular areas of the left main trunk (LMT) and proximal right coronary artery (RCA) and the thoracic descending aorta (TDA) were determined in patients with coronary artery disease before and after 2.0-year treatment with atorvastatin and candesartan (n=20) or with atorvastatin alone (n=16), although these patients had been treated with the combination therapy or statin alone at the study enrollment. Plasma levels of high sensitive C-reactive protein, matrix metalloproteinase-9, and urinary 8-iso-prostaglandin F2α were determined at the baseline.
  
  
  RESULTS
  There were no significant differences in low-density lipoprotein and high-density lipoprotein cholesterol, C-reactive protein, matrix metalloproteinase-9, or urinary 8-iso-prostaglandin F2α levels between the two groups. Two years later, total vascular areas of TDA and RCA increased significantly in the atorvastatin group but not in the combination group. Moreover, increases in VWAs were less in the combination group than in the atorvastatin group in TDA (3.6 ± 23.1 vs. 28.6 ± 25.5 mm, P=0.004), RCA (-1.6 ±1.6 vs. 0.6 ± 2.5 mm, P=0.005), and left main trunk (-0.9 ± 3.5 vs. 1.3 ± 2.4 mm, P=0.095). Biomarker levels at the baseline did not affect the progression of VWA.
  
  
  CONCLUSIONS
  Combination therapy of RAS inhibitor with statin is more effective than statin alone in inhibiting atherosclerotic progression of coronary arteries and the aorta in patients with coronary artery disease.
authors.affiliation: Second Department of Internal Medicine, Graduate School of Medicine, University of Toyama, Toyama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Nozawa
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fujii
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sobajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohori
authors.forename: Takuya
authors.initials: T
authors.lastname: Shida
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuki
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kameyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000069059:Atorvastatin; D001562:Benzimidazoles / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001713:Biphenyl Compounds; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015237:Dinoprost / Q000652:urine; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000187:drug effects; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D013777:Tetrazoles / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000924:Anticholesteremic Agents; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D011758:Pyrroles; D013777:Tetrazoles; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin; D015237:Dinoprost; D020780:Matrix Metalloproteinase 9; C081643:candesartan