Losartan and perindopril effects on plasma plasminogen activator inhibitor-1 and fibrinogen in hypertensive type 2 diabetic patients.
BACKGROUND
This study compared the effects of losartan and perindopril on plasma plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in hypertensive type 2 diabetic patients.


METHODS
We studied 85 nonsmoking outpatients, aged 46 to 64 years, with mild to moderate essential hypertension (diastolic blood pressure [BP] > 90 and < 110 mm Hg) and well controlled type 2 diabetes mellitus. After a 4-week washout placebo period, patients were randomized to received perindopril 4 mg once daily (n = 42) or losartan 50 mg once daily (n = 43) for 12 weeks according to a double-blind, parallel-group design. At the end of the placebo and active treatment periods, BP was measured and plasma PAI-1 and fibrinogen were evaluated.


RESULTS
Both perindopril and losartan reduced systolic and diastolic BP values (-16/15 mm Hg and -15/14, respectively; P < .001 v placebo), with no difference between the two treatments. Plasma PAI-1 was reduced by perindopril (-10 ng/dL, P = .028 v placebo) but not by losartan (+4 ng/dL, NS), the difference between the two treatments being statistically significant (P < .01). Plasma fibrinogen showed no significant change with both drugs, although a decreasing trend was noted with perindopril.


CONCLUSIONS
These findings indicate that perindopril but not losartan decreases PAI-1 in hypertensive type 2 diabetic patients, which suggests that the PAI-1 lowering effect is unrelated with AT, receptor blockade and could rather be due to the fact that the endothelial receptors that mediate PAI-1 expression in response to angiotensin II are not type 1 receptor subtypes. Different effects of the two drugs on the bradykinin system might also be implicated.
Fogari
Roberto
R
Department of Internal Medicine and Therapeutics, IRCCS Policlinico S Matteo, University of Pavia, Italy.
Mugellini
Amedeo
A
Zoppi
Annalisa
A
Corradi
Luca
L
Preti
Paola
P
Lazzari
Pierangelo
P
Derosa
Giuseppe
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D019808:Losartan; D020913:Perindopril