title: Effect of benazepril amlodipine combination on fibrinolysis in hypertensive diabetic patients.
abstract: OBJECTIVE
  The aim of this study was to compare the effects of benazepril and amlodipine in monotherapy versus in combination with plasma t-PA and PAI-1 activity in hypertensive type-2 diabetic patients.
  
  
  METHODS
  After an initial 6-week wash-out, single-blind placebo period, 38 patients, 17 men and 21 females, were randomly assigned to receive benazepril 10 mg o.d. or amlodipine 5 mg o.d. or their combination o.d. at the same dosage for 6 weeks in three crossover periods each separated by a 2-week placebo wash-out period (3x3 latin square). At the end of the placebo run-in period and of each treatment period, BP, plasma PAI-1 and tPA activity were evaluated.
  
  
  RESULTS
  Both benazepril and amlodipine were similarly effective in reducing systolic blood pressure (SBP) (-17.6 mmHg with benazepril and -19.8 mmHg with amlodipine; P<0.001 versus placebo), and diastolic blood pressure (DBP) (-11.1 mmHg, -13.2 mmHg, respectively). Combination therapy produced greater reduction in SBP/DBP values (-28.3/-20.5 mmHg; P<0.001 versus placebo, P<0.01 versus benazepril and amlodipine). Benazepril monotherapy significantly decreased plasma PAI-1 activity (-8.4 IU/ml, P<0.05) while it did not influence t-PA activity (+0.02 IU/ml). Amlodipine monotherapy produced a significant increase in t-PA activity (+0.27 IU/ml, P<0.05) while it did not influence PAI-1 activity (+0.8 IU/ml). The amlodipine/benazepril combination produced both a significant decrease in plasma PAI-1 activity (-8.7 IU, P<0.05) and a significant increase in t-PA activity (+0.26 IU/ml, P<0.05).
  
  
  CONCLUSIONS
  These data suggest that in hypertensive type-2 diabetic patients, a population with an impaired fibrinolysis, the benazepril/amlodipine combination, may improve the fibrinolytic balance more than the single drugs.
authors.affiliation: Department of Internal Medicine and Therapeutics, Clinica Medica II, IRCCS Policlinico San Matteo, University of Pavia, Piazza Golgi 2, 27100, Pavia, Italy. r.fogari@smatteo.pv.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Fogari
authors.forename: Paola
authors.initials: P
authors.lastname: Preti
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Lazzari
authors.forename: Luca
authors.initials: L
authors.lastname: Corradi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zoppi
authors.forename: Elena
authors.initials: E
authors.lastname: Fogari
authors.forename: Amedeo
authors.initials: A
authors.lastname: Mugellini
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001552:Benzazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D016037:Single-Blind Method; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D002121:Calcium Channel Blockers; D017395:Plasminogen Activator Inhibitor 1; D017311:Amlodipine; D010959:Tissue Plasminogen Activator; C044946:benazepril