title: Lack of effect on coronary atherosclerotic disease biomarkers with modest dosing of an angiotensin-converting enzyme inhibitor, angiotensin II type-1 receptor blocker, and the combination.
abstract: BACKGROUND
  Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, used alone or in combination, have been shown to improve outcomes in certain populations, primarily when administered in high doses. For stable coronary atherosclerotic disease, however, the relative physiologic effect of these therapies is unclear. Furthermore, because of the notorious subtarget dosing of such agents in clinical practice, we explored the influence of a modest dosing of an angiotensin-converting enzyme inhibitor, angiotensin II type 1 receptor blockers, and the combination on common biologic markers of coronary atherosclerotic disease.
  
  
  METHODS
  This randomized, cross-over study enrolled stable coronary atherosclerotic disease patients (n=20), each receiving three treatments: candesartan 16 mg daily, ramipril 5 mg daily, and candesartan 8 mg plus ramipril 2.5 mg daily. Treatments were administered for 2 weeks with a 2-week washout. Blood samples were collected before and after each treatment. Markers of endothelial function, fibrinolytic balance, and vascular inflammation were measured.
  
  
  RESULTS
  No significant differences were observed in the pretreatment concentrations of angiotensin-converting enzyme or of any measured biologic marker. Relative to pretreatment levels, candesartan alone was the only therapy to exhibit an action on any measured biomarker--a trend toward increased nitric oxide concentrations (P=0.054). Otherwise, no effects on biologic markers were observed with the treatments.
  
  
  CONCLUSIONS
  This study of various methods of the renin-angiotensin system inhibition in stable coronary atherosclerotic disease patients demonstrates negligible effects of a modest dosing of ramipril and the combination of ramipril plus candesartan on common biologic markers of coronary atherosclerotic disease. Candesartan at modest doses may favorably influence endothelial function. Overall, however, the results indicate that the commonly practiced subtarget dosing of such treatments provides little, if any, benefit pertaining to key physiologic components of coronary atherosclerotic disease.
authors.affiliation: University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Tsikouris
authors.forename: Craig D
authors.initials: CD
authors.lastname: Cox
authors.forename: Jan S
authors.initials: JS
authors.lastname: Simoni
authors.forename: Charles F
authors.initials: CF
authors.lastname: Seifert
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Peek
authors.forename: Gary E
authors.initials: GE
authors.lastname: Meyerrose
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers; D001713:Biphenyl Compounds; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000008:administration & dosage / Q000494:pharmacology*; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017257:Ramipril; C081643:candesartan