Effects of four angiotensin II-receptor antagonists on fibrinolysis in postmenopausal women with hypertension

Roberto Fogari, Annalisa Zoppi, Giandomenico Malamani, Gianluigi Marasi, Rosa Maria Pesce, Alessandra Banderali, Amedeo Mugellini

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Reduced fibrinolysis due to increased concentrations of plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of endogenous fibrinolysis, is associated with an increased risk for cardiovascular events. Objective: This study was undertaken to compare the effects of 4 angiotensin II (AII)-receptor antagonists with different pharmacokinetic properties - losartan, valsartan, irbesartan, and candesartan - on levels of PAI-1 antigen in postmenopausal women with hypertension. Methods: Postmenopausal women aged 51 to 60 years with mild to moderate hypertension (diastolic blood pressure [DBP] >90 mm Hg and ≤105 mm Hg) who were not taking any hormone replacement therapy were studied. Patients with diabetes or obesity and patients who smoked were excluded. After a 2-week placebo washout period, patients were assigned to receive losartan 50 mg, valsartan 80 mg, irbesartan 150 mg, candesartan 8 mg, or placebo for 12 weeks according to a double-blind, randomized, parallel-group design, with a titration for nonresponders after 6 weeks. At the end of the placebo period and 6 and 12 weeks after active treatment, blood pressure, PAI-1 antigen levels, heart rate, and body mass index were measured. Results: A total of 156 patients were randomized to receive losartan (n = 31), valsartan (n = 32), irbesartan (n = 31), candesartan (n = 32), or placebo (n = 30); of these, 140 completed the study. All 4 active treatments significantly reduced DBP and systolic blood pressure, with no significant differences in efficacy between groups. Plasma PAI-1 levels decreased slightly after treatment with losartan (-0.9%) and valsartan (-3.8%) and increased slightly with irbesartan (+10.1%), but these values were not significantly different from placebo. In contrast, candesartan significantly increased PAI-1 values by 33.3% (P <0.05 vs placebo). There were no significant changes in heart rate or body mass index in any group. Conclusions: These findings suggest that, despite a comparable antihypertensive efficacy, candesartan differs from the other AII-receptor antagonists studied in that it significantly increases PAI-1 antigen levels. This might be related to its specific pharmacologic characteristics, particularly its insurmountable antagonism of the All AT1 receptor.

Original languageEnglish
Pages (from-to)68-78
Number of pages11
JournalCurrent Therapeutic Research
Volume62
Issue number1
DOIs
Publication statusPublished - 2001

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irbesartan
Valsartan
Angiotensin Receptor Antagonists
Fibrinolysis
Plasminogen Activator Inhibitor 1
Blood Pressure
Hypertension
Losartan
Placebos
Antigens
Body Mass Index
Heart Rate
Hormone Replacement Therapy
Antihypertensive Agents
Therapeutics
Pharmacokinetics
Obesity
candesartan

Keywords

  • Angiotensin II antagonist
  • Fibrinolysis
  • Hypertension

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effects of four angiotensin II-receptor antagonists on fibrinolysis in postmenopausal women with hypertension. / Fogari, Roberto; Zoppi, Annalisa; Malamani, Giandomenico; Marasi, Gianluigi; Pesce, Rosa Maria; Banderali, Alessandra; Mugellini, Amedeo.

In: Current Therapeutic Research, Vol. 62, No. 1, 2001, p. 68-78.

Research output: Contribution to journalArticle

Fogari, Roberto ; Zoppi, Annalisa ; Malamani, Giandomenico ; Marasi, Gianluigi ; Pesce, Rosa Maria ; Banderali, Alessandra ; Mugellini, Amedeo. / Effects of four angiotensin II-receptor antagonists on fibrinolysis in postmenopausal women with hypertension. In: Current Therapeutic Research. 2001 ; Vol. 62, No. 1. pp. 68-78.
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AU - Pesce, Rosa Maria

AU - Banderali, Alessandra

AU - Mugellini, Amedeo

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N2 - Background: Reduced fibrinolysis due to increased concentrations of plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of endogenous fibrinolysis, is associated with an increased risk for cardiovascular events. Objective: This study was undertaken to compare the effects of 4 angiotensin II (AII)-receptor antagonists with different pharmacokinetic properties - losartan, valsartan, irbesartan, and candesartan - on levels of PAI-1 antigen in postmenopausal women with hypertension. Methods: Postmenopausal women aged 51 to 60 years with mild to moderate hypertension (diastolic blood pressure [DBP] >90 mm Hg and ≤105 mm Hg) who were not taking any hormone replacement therapy were studied. Patients with diabetes or obesity and patients who smoked were excluded. After a 2-week placebo washout period, patients were assigned to receive losartan 50 mg, valsartan 80 mg, irbesartan 150 mg, candesartan 8 mg, or placebo for 12 weeks according to a double-blind, randomized, parallel-group design, with a titration for nonresponders after 6 weeks. At the end of the placebo period and 6 and 12 weeks after active treatment, blood pressure, PAI-1 antigen levels, heart rate, and body mass index were measured. Results: A total of 156 patients were randomized to receive losartan (n = 31), valsartan (n = 32), irbesartan (n = 31), candesartan (n = 32), or placebo (n = 30); of these, 140 completed the study. All 4 active treatments significantly reduced DBP and systolic blood pressure, with no significant differences in efficacy between groups. Plasma PAI-1 levels decreased slightly after treatment with losartan (-0.9%) and valsartan (-3.8%) and increased slightly with irbesartan (+10.1%), but these values were not significantly different from placebo. In contrast, candesartan significantly increased PAI-1 values by 33.3% (P <0.05 vs placebo). There were no significant changes in heart rate or body mass index in any group. Conclusions: These findings suggest that, despite a comparable antihypertensive efficacy, candesartan differs from the other AII-receptor antagonists studied in that it significantly increases PAI-1 antigen levels. This might be related to its specific pharmacologic characteristics, particularly its insurmountable antagonism of the All AT1 receptor.

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