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Effect of amlodipine-atorvastatin combination on fibrinolysis in hypertensive hypercholesterolemic patients with insulin resistance.

AbstractBACKGROUND:
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.
AuthorsRoberto Fogari, Giuseppe Derosa, Pierangelo Lazzari, Annalisa Zoppi, Elena Fogari, Andrea Rinaldi, Amedeo Mugellini
JournalAmerican journal of hypertension (Am J Hypertens) Vol. 17 Issue 9 Pg. 823-7 (Sep 2004) ISSN: 0895-7061 [Print] United States
PMID15363826 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
CopyrightCopyright 2004 American Journal of Hypertension, Ltd.
Chemical References
  • Anticholesteremic Agents
  • Antihypertensive Agents
  • Heptanoic Acids
  • Plasminogen Activator Inhibitor 1
  • Pyrroles
  • Amlodipine
  • Atorvastatin
  • Tissue Plasminogen Activator
Topics
  • Adult
  • Aged
  • Amlodipine (administration & dosage)
  • Anticholesteremic Agents (administration & dosage)
  • Antihypertensive Agents (administration & dosage)
  • Atorvastatin
  • Drug Therapy, Combination
  • Female
  • Fibrinolysis (drug effects)
  • Heptanoic Acids (administration & dosage)
  • Humans
  • Hypercholesterolemia (complications, drug therapy)
  • Hypertension (complications, drug therapy)
  • Insulin Resistance
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 (metabolism)
  • Pyrroles (administration & dosage)
  • Tissue Plasminogen Activator (metabolism)

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