Effect of benazepril amlodipine combination on fibrinolysis in hypertensive diabetic patients.
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.
Fogari
Roberto
R
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
Preti
Paola
P
Lazzari
Pierangelo
P
Corradi
Luca
L
Zoppi
Annalisa
A
Fogari
Elena
E
Mugellini
Amedeo
A
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D002121:Calcium Channel Blockers; D017395:Plasminogen Activator Inhibitor 1; D017311:Amlodipine; D010959:Tissue Plasminogen Activator; C044946:benazepril