Irbesartan vs Irbesartan Plus Hydrochlorothiazide
Objective:The primary objective of this phase IV, nonblind, multicentre study was to determine the antihypertensive effectiveness of irbesartan alone or combined with hydrochlorothiazide (HCTZ) in women with mild to moderate essential hypertension. A secondary objective was to examine the effects of irbesartan on blood lipid levels.
Methods: 188 female patients (94 premenopausal and 94 postmenopausal) with mild to moderate hypertension [seated diastolic blood pressure (SDBP) 95 to 110mm Hg] participated in the study. A 2-week placebo lead-in period was followed by a 24-week active treatment period. Patients initially received 150mg of oral irbesartan once a day, which was titrated to 300 mg/day after 4 weeks in nonresponders. HCTZ 12.5 mg/day was added to treatment after 8 weeks in patients not responding to irbesartan 300 mg/day. The dose of HCTZ could be increased to 25 mg/day after 12 weeks in nonresponders.
Results: 174 patients completed the study, of whom 172 (98.9%) responded to treatment (SDBP ≤ 90mm Hg or a reduction of at least 10mm Hg from baseline in SDBP). Mean seated systolic blood pressure and SDBP reductions at 24 weeks were 28.1 and 20.0mm Hg (p = 0.0001), respectively. 88 patients completed the study with irbesartan 150mg, 42 patients with irbesartan 300mg, 18 patients with irbesartan plus HCTZ 300/12.5mg and 26 patients with irbesartan plus HCTZ 300/25mg; response rates were 100, 97.6, 100 and 96.2%, respectively. Total, low density lipoprotein- and high density lipoprotein-cholesterol blood levels were significantly reduced (p < 0.05), but there were no significant changes in blood triglyceride levels or the results of other clinical laboratory tests. Antihypertensive treatment was well tolerated.
Conclusion: Irbesartan, either alone or combined with HCTZ, showed excellent antihypertensive efficacy with a low incidence of adverse events. Hence, irbesartan appears to be a suitable agent for the treatment of hypertension in women.
Irbesartan is a long-acting, nonpeptide, angiotensin II receptor antagonist with high selectivity for the angiotensin II receptor subtype 1 (AT1). Clinical trials have demonstrated dose-dependent blood pressure reductions with irbesartan. In patients with mild to moderate hypertension, irbesartan was shown to be an effective anti-hypertensive agent at doses of 150 to 300mg once daily with tolerability comparable to that of placebo. Moreover, it has been shown that the addition of hydrochlorothiazide (HCTZ) increases the antihypertensive efficacy of irbesartan whilst maintaining good tolerability. The effects of angiotensin II antagonists on blood lipids have not yet been established. Results with losartan, a drug that also reduces blood pressure by AT1 blockade, are contradictory. In one study, losartan, administered either alone or combined with nifedipine or HCTZ, failed to lower cholesterol levels at doses that effectively reduced arterial pressure. In contrast, losartan resulted in a significant reduction in plasma cholesterol levels in another study. At present, no information is available on the effects of irbesartan on blood lipid levels.
Cardiovascular disease was considered to be a predominantly male problem until the mid-1980s when it was reported that postmenopausal women develop cardiovascular disease at the same rate as men, albeit 6 to 10 years later in life. As in men, hypertension is the most prevalent cardiovascular risk factor and is a major determinant of the development of cardiovascular disease in women. In the USA, at least 50% of the 43 million hypertensive population are women. Recent observations have provided evidence that the incidence of hypertension in Mexico is similar to that in developed countries such as the USA(E. Meaney, personal communication). Moreover, there are data to indicate that in Mexican individuals over 60 years of age who are covered by the public health system the incidence of hypertension is higher in women than in men. High blood cholesterol levels have also been associated with an increase in cardiovascular risk. Since the early 1980s, the Food and Drug Administration in the USA and other regulatory agencies have been interested in demographic factors, such as gender, that may influence drug efficacy and tolerability. Clinical trials on the efficacy of antihypertensive medications in women are scarce, thus the purpose of the present study was to specifically address the effectiveness of irbesartan, alone or combined with HCTZ, in female patients with mild to moderate hypertension. A secondary objective was to examine the effects of irbesartan on blood lipid levels in this patient population.
Objective:The primary objective of this phase IV, nonblind, multicentre study was to determine the antihypertensive effectiveness of irbesartan alone or combined with hydrochlorothiazide (HCTZ) in women with mild to moderate essential hypertension. A secondary objective was to examine the effects of irbesartan on blood lipid levels.
Methods: 188 female patients (94 premenopausal and 94 postmenopausal) with mild to moderate hypertension [seated diastolic blood pressure (SDBP) 95 to 110mm Hg] participated in the study. A 2-week placebo lead-in period was followed by a 24-week active treatment period. Patients initially received 150mg of oral irbesartan once a day, which was titrated to 300 mg/day after 4 weeks in nonresponders. HCTZ 12.5 mg/day was added to treatment after 8 weeks in patients not responding to irbesartan 300 mg/day. The dose of HCTZ could be increased to 25 mg/day after 12 weeks in nonresponders.
Results: 174 patients completed the study, of whom 172 (98.9%) responded to treatment (SDBP ≤ 90mm Hg or a reduction of at least 10mm Hg from baseline in SDBP). Mean seated systolic blood pressure and SDBP reductions at 24 weeks were 28.1 and 20.0mm Hg (p = 0.0001), respectively. 88 patients completed the study with irbesartan 150mg, 42 patients with irbesartan 300mg, 18 patients with irbesartan plus HCTZ 300/12.5mg and 26 patients with irbesartan plus HCTZ 300/25mg; response rates were 100, 97.6, 100 and 96.2%, respectively. Total, low density lipoprotein- and high density lipoprotein-cholesterol blood levels were significantly reduced (p < 0.05), but there were no significant changes in blood triglyceride levels or the results of other clinical laboratory tests. Antihypertensive treatment was well tolerated.
Conclusion: Irbesartan, either alone or combined with HCTZ, showed excellent antihypertensive efficacy with a low incidence of adverse events. Hence, irbesartan appears to be a suitable agent for the treatment of hypertension in women.
Irbesartan is a long-acting, nonpeptide, angiotensin II receptor antagonist with high selectivity for the angiotensin II receptor subtype 1 (AT1). Clinical trials have demonstrated dose-dependent blood pressure reductions with irbesartan. In patients with mild to moderate hypertension, irbesartan was shown to be an effective anti-hypertensive agent at doses of 150 to 300mg once daily with tolerability comparable to that of placebo. Moreover, it has been shown that the addition of hydrochlorothiazide (HCTZ) increases the antihypertensive efficacy of irbesartan whilst maintaining good tolerability. The effects of angiotensin II antagonists on blood lipids have not yet been established. Results with losartan, a drug that also reduces blood pressure by AT1 blockade, are contradictory. In one study, losartan, administered either alone or combined with nifedipine or HCTZ, failed to lower cholesterol levels at doses that effectively reduced arterial pressure. In contrast, losartan resulted in a significant reduction in plasma cholesterol levels in another study. At present, no information is available on the effects of irbesartan on blood lipid levels.
Cardiovascular disease was considered to be a predominantly male problem until the mid-1980s when it was reported that postmenopausal women develop cardiovascular disease at the same rate as men, albeit 6 to 10 years later in life. As in men, hypertension is the most prevalent cardiovascular risk factor and is a major determinant of the development of cardiovascular disease in women. In the USA, at least 50% of the 43 million hypertensive population are women. Recent observations have provided evidence that the incidence of hypertension in Mexico is similar to that in developed countries such as the USA(E. Meaney, personal communication). Moreover, there are data to indicate that in Mexican individuals over 60 years of age who are covered by the public health system the incidence of hypertension is higher in women than in men. High blood cholesterol levels have also been associated with an increase in cardiovascular risk. Since the early 1980s, the Food and Drug Administration in the USA and other regulatory agencies have been interested in demographic factors, such as gender, that may influence drug efficacy and tolerability. Clinical trials on the efficacy of antihypertensive medications in women are scarce, thus the purpose of the present study was to specifically address the effectiveness of irbesartan, alone or combined with HCTZ, in female patients with mild to moderate hypertension. A secondary objective was to examine the effects of irbesartan on blood lipid levels in this patient population.
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