Effects of losartan and delapril on the fibrinolytic system in patients with mild to moderate hypertension.

BACKGROUND AND OBJECTIVES: Angiotensin-converting enzyme (ACE) probably influences the fibrinolytic system at a central point by converting angiotensin I to angiotensin II, which increases plasminogen activator inhibitor-1 (PAI-1) activity. This effect appears to be mediated in humans via the angiotensin II type 1 (AT(1)) receptor. The objective of this study was to evaluate, in patients with mild to moderate hypertension, the change in tissue plasminogen activator (t-PA) and PAI-1 plasma levels after treatment with an AT(1)-receptor blocker (losartan 50 mg/day) or an ACE inhibitor (delapril 60 mg/day).

PATIENTS AND METHODS: 30 hypertensive patients and 15 controls were enrolled. Essential hypertension was established by a medical history, physical examination and the absence of clinical findings suggestive of a secondary form of hypertension. Preliminary investigations, routine biochemical tests (including clearance of creatinine and oral glucose tolerance test), chest x-ray, standard and 24-hour ECG monitoring, M- and B-mode echocardiography and fundus oculi examinations were performed. No patients had previously received ACE inhibitors or AT(1)-receptor blockers. After a 14-day run-in period with placebo, patients were randomised in a double-blind fashion into two groups: 15 patients were randomised to losartan 50 mg/day (group 1), 15 patients were randomised to delapril 60 mg/day (group 2), and 15 healthy subjects were used as controls (group 3). Plasma PAI-1 and t-PA antigen were determined by enzyme-linked immunosorbent assay and a photometric method at the end of the run-in period and after 6 months of treatment.

RESULTS: There were no significant differences among the three groups regarding age, sex, body mass index and smoking. After 6 months, both groups of patients showed a reduction in blood pressure values. The losartan group did not demonstrate significant changes in PAI-1 levels (96.52 +/- 23.73 and 99.89 +/- 22.18 mug/L, pre- and post-treatment, respectively) or in t-PA antigen levels (26.17 +/- 6.18 and 27.32 +/- 5.91 mug/L, pre- and post-treatment, respectively). The delapril group showed no significant changes in PAI-1 levels (97.73 +/- 25.75 and 86.12 +/- 13.12 mug/L, pre- and post-treatment, respectively), but did show a statistically significant difference (p < 0.005) in t-PA antigen levels (25.71 +/- 6.40 and 32.24 +/- 5.31 mug/L, pre- and post-treatment, respectively). The losartan group demonstrated significantly higher post-treatment PAI-1 values than the delapril group (p = 0.048).

CONCLUSION: The study showed that losartan does not affect fibrinolytic parameters, while delapril resulted in an insignificant reduction in PAI-1 and a significant increase in t-PA levels. Further studies are clearly required in order to establish whether these different effects on the fibrinolytic system between ACE inhibitors and AT(1)-receptor blockers may have clinical relevance.