Low-Dose Combination Therapy With Perindopril
Low-Dose Combination Therapy With Perindopril
Introduction: A study was undertaken in patients with essential hypertension to compare, by ambulatory blood pressure monitoring, the response to a fixed low dose of perindopril/indapamide with that to irbesartan.
Patients and design: After a 4-week placebo run-in period, 47 patients with a mean ambulatory blood pressure measurement (ABPM) ≥140mm Hg systolic and/or ≥90mm Hg diastolic were randomised, double-blind, to perindopril/indapamide (2/0.625mg; 24 patients) or irbesartan (150mg; 23 patients). Blood pressure normalisation rates were compared using Fisher's exact test and blood pressure decreases using the paired t-test.
Methods: The total duration of the study was 12 weeks. If the clinic blood pressure 8 weeks later was ≥140/90mm Hg, the dose was doubled. The primary efficacy variable was a final 24-hour ABPM ≤140/90mm Hg, with a fall in systolic blood pressure ≥10mm Hg.
Results: More patients (15/23) achieved normalisation taking perindopril/indapamide than taking irbesartan (7/21) [p < 0.02]. The mean 24-hour systolic and diastolic blood pressure fell by 17 ± 2.3/8 ± 1.3mm Hg (p < 0.001), respectively, in patients taking perindopril/indapamide and by 14 ± 2.9/7 ± 1.6 (p < 0.001), respectively, in patients taking irbesartan. The falls were not significantly different. Systolic and diastolic blood pressure divided into day, night and early morning time periods fell significantly in both groups, but the falls did not differ between treatments. Both treatments were well tolerated and there were no significant adverse biochemical effects.
Conclusion: A fixed low-dose combination of perindopril/indapamide had greater efficacy than irbesartan with a similarly well tolerated adverse effect profile. This makes it a suitable first-line treatment in patients with essential hypertension.
Achieving good blood pressure control requires effective drug treatment that has few adverse effects and can be administered once daily. In previously untreated patients with hypertension, monotherapy may only achieve target blood pressure in less than 30% of patients when corrected for placebo effect. The relative ineffectiveness of monotherapy, particularly in elderly people with systolic hypertension, means that most patients will require more than one drug to obtain a systolic blood pressure <140mm Hg. This requirement for more than one drug was clearly demonstrated in the Hypertension Optimal Treatment (HOT) study. However, as we increase the number of tablets taken, patient compliance declines, leading to inadequate control. Recognition of this problem has led to the suggestion in the Joint National Committee's Sixth Report (JNC VI) that fixed-dose combinations may be used as first-line therapy for essential hypertension.
ACE inhibitors are effective antihypertensive drugs and their effectiveness is increased by salt restriction and diuretics. Fixed combinations of an ACE inhibitor or an angiotensin I (AT1) receptor blocker and a diuretic have been developed, and there is little doubt that they are more effective than either agent alone. Perindopril and indapamide have been combined in a single tablet in doses that are not effective as monotherapy and have been shown to reduce blood pressure. If standard doses of ACE inhibitors and diuretics are used in a combination tablet it may not be justified to advocate them as first-line treatment. However, a fixed-dose tablet that uses subtherapeutic doses of both compounds may justify such an indication if it can be shown to be more effective than monotherapy with fewer adverse effects. This study compared a fixed low-dose combination of perindopril 2mg and indapamide 0.625mg with irbesartan 150mg. Irbesartan was chosen as representative of the AT1 receptor blocking drugs, which are reported to be effective with an adverse effect profile similar to that of placebo.
Introduction: A study was undertaken in patients with essential hypertension to compare, by ambulatory blood pressure monitoring, the response to a fixed low dose of perindopril/indapamide with that to irbesartan.
Patients and design: After a 4-week placebo run-in period, 47 patients with a mean ambulatory blood pressure measurement (ABPM) ≥140mm Hg systolic and/or ≥90mm Hg diastolic were randomised, double-blind, to perindopril/indapamide (2/0.625mg; 24 patients) or irbesartan (150mg; 23 patients). Blood pressure normalisation rates were compared using Fisher's exact test and blood pressure decreases using the paired t-test.
Methods: The total duration of the study was 12 weeks. If the clinic blood pressure 8 weeks later was ≥140/90mm Hg, the dose was doubled. The primary efficacy variable was a final 24-hour ABPM ≤140/90mm Hg, with a fall in systolic blood pressure ≥10mm Hg.
Results: More patients (15/23) achieved normalisation taking perindopril/indapamide than taking irbesartan (7/21) [p < 0.02]. The mean 24-hour systolic and diastolic blood pressure fell by 17 ± 2.3/8 ± 1.3mm Hg (p < 0.001), respectively, in patients taking perindopril/indapamide and by 14 ± 2.9/7 ± 1.6 (p < 0.001), respectively, in patients taking irbesartan. The falls were not significantly different. Systolic and diastolic blood pressure divided into day, night and early morning time periods fell significantly in both groups, but the falls did not differ between treatments. Both treatments were well tolerated and there were no significant adverse biochemical effects.
Conclusion: A fixed low-dose combination of perindopril/indapamide had greater efficacy than irbesartan with a similarly well tolerated adverse effect profile. This makes it a suitable first-line treatment in patients with essential hypertension.
Achieving good blood pressure control requires effective drug treatment that has few adverse effects and can be administered once daily. In previously untreated patients with hypertension, monotherapy may only achieve target blood pressure in less than 30% of patients when corrected for placebo effect. The relative ineffectiveness of monotherapy, particularly in elderly people with systolic hypertension, means that most patients will require more than one drug to obtain a systolic blood pressure <140mm Hg. This requirement for more than one drug was clearly demonstrated in the Hypertension Optimal Treatment (HOT) study. However, as we increase the number of tablets taken, patient compliance declines, leading to inadequate control. Recognition of this problem has led to the suggestion in the Joint National Committee's Sixth Report (JNC VI) that fixed-dose combinations may be used as first-line therapy for essential hypertension.
ACE inhibitors are effective antihypertensive drugs and their effectiveness is increased by salt restriction and diuretics. Fixed combinations of an ACE inhibitor or an angiotensin I (AT1) receptor blocker and a diuretic have been developed, and there is little doubt that they are more effective than either agent alone. Perindopril and indapamide have been combined in a single tablet in doses that are not effective as monotherapy and have been shown to reduce blood pressure. If standard doses of ACE inhibitors and diuretics are used in a combination tablet it may not be justified to advocate them as first-line treatment. However, a fixed-dose tablet that uses subtherapeutic doses of both compounds may justify such an indication if it can be shown to be more effective than monotherapy with fewer adverse effects. This study compared a fixed low-dose combination of perindopril 2mg and indapamide 0.625mg with irbesartan 150mg. Irbesartan was chosen as representative of the AT1 receptor blocking drugs, which are reported to be effective with an adverse effect profile similar to that of placebo.
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