title: Effect of amlodipine-atorvastatin combination on fibrinolysis in hypertensive hypercholesterolemic patients with insulin resistance.
abstract: BACKGROUND
  The aim of this study was to evaluate the effect of the amlodipine-atorvastatin combination on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) activity in hypercholesterolemic, hypertensive patients with insulin resistance.
  
  
  METHODS
  The study population included 45 patients, aged 41 to 70 years, with mild to moderate essential hypertension (diastolic blood pressure [BP] > or = 95 and < or = 105 mm Hg), hypercholesterolemia (total cholesterol > 200 and < 350 mg/dL), and insulin resistance (HOMA index > 2.5) After a 4-week wash-out period, they were randomized to amlodipine (5 mg) or atorvastatin (20 mg) or their combination at the same oral dosage for 12 weeks in three cross-over periods each separated by a 4-week placebo period (3 by 3 latin square design). At the end of the placebo wash-out and of each treatment period, office BP, total cholesterol, PAI-1, and t-PA activity were evaluated.
  
  
  RESULTS
  The amlodipine-atorvastatin combination, in addition to the expected hypocholesterolemic effect, produced: 1) a greater decrease in PAI-1 activity (-10.2 U/mL, P <.01 v placebo) and an even greater increase in t-PA activity (+0.26 U/mL, P <.01 v placebo) than amlodipine (-0.5 U/mL for PAI-1, P = not significant; +0.17 U/mL for t-PA, P <.01 v placebo) and atorvastatin alone (respectively, -9.9 U/mL, P <.01 v placebo and +0.08 U/mL, P <.05 v placebo); and 2) a greater systolic BP/diastolic BP mean reduction (-22/17 mm Hg, P <.005 v placebo) than amlodipine (-18/14 mm Hg, P <.01 v placebo) and atorvastatin alone (-2.8/3.8 mm Hg, P <.05 v placebo only for diastolic BP).
  
  
  CONCLUSIONS
  The positive effect on fibrinolytic balance and BP control observed suggests that in hypertensive, hypercholesterolemic patients with impaired fibrinolysis, the combination of amlodipine and atorvastatin could be the treatment of choice.
authors.affiliation: Department of Internal Medicine and Therapeutics, Clinica Medica II IRCCS Policlinico S.Matteo, University of Pavia, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fogari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Derosa
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Lazzari
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zoppi
authors.forename: Elena
authors.initials: E
authors.lastname: Fogari
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Amedeo
authors.initials: A
authors.lastname: Mugellini
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage*; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D006538:Heptanoic Acids; D017395:Plasminogen Activator Inhibitor 1; D011758:Pyrroles; D017311:Amlodipine; D000069059:Atorvastatin; D010959:Tissue Plasminogen Activator