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RESEARCH PRODUCT

Effects of Losartan and Delapril on the Fibrinolytic System in Patients with Mild to Moderate Hypertension

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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 (AT1) 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 AT1-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 AT1-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 μg/L, pre- and post-treatment, respectively) or in t-PA antigen levels (26.17 ± 6.18 and 27.32 ± 5.91 μ/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 μg/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 μg/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 AT1-receptor blockers may have clinical relevance.