Efficacy and acceptability of the fixed low-dose perindopril-indapamide combination as first-line therapy in hypertension

Aims The present studies were undertaken to establish the efficacy and the safety of a fixed low-dose combination of perindopril (2 mg) and indapamide (0.625 mg). This combination was compared with atenolol (50 mg) in middle-aged subjects with essential hypertension and with placebo in elderly subjects with systolic and diastolic hypertension or with isolated systolic hypertension. Methods and Results Both studies were multinational, randomized and double-blind and were conducted in outpatients with mild-to-moderate hypertension. The primary outcome was agreed to be the change in trough supine diastolic blood pressure assessed using intention-to-treat analysis. The comparison with atenolol was conducted over 12 weeks, while the placebo-controlled study was conducted in two phases, with an initial 12-week period followed by a 48- week extension phase. The primary outcome for patients with isolated systolic hypertension was the supine trough systolic blood pressure. The primary outcome for adverse events was a potassium level below 34 mmol. l(-1) . In the 446 middle-aged adults (mean age 55.8 years) with essential hypertension, the perindopril-indapamide combination reduced diastolic blood pressure by 15.1 mmHg over the 12-week study period compared with atenolol which lowered it by 16 2 mmHg (not significant). In 383 elderly subjects (mean age 72.4 years) with diastolic or systolic hypertension, the combination reduced supine systolic and diastolic blood pressure by 10.2 mmHg and 5.9 mmHg more than placebo, respectively, in the initial 12-week test phase. In the 123 patients with isolated systolic hypertension, the fall in systolic blood pressure in this 12-week period was 9.8 mmHg greater in those receiving the combination than in those on placebo. Over the remaining 48 weeks of the extension study, the blood pressure was normalized to below 150/90 mmHg in over 80% of hypertensive patients taking the combination. Adverse events, including hypokalaemia, were infrequent and their incidence was similar in all groups of subjects, including those over the age of 75 years. Conclusions A fixed, low-dose combination of perindopril (2 mg) and indapamide (0.625 mg) taken once daily is safe and effective in middle-aged patients with essential hypertension and in elderly patients with either systolic or diastolic hypertension. It fulfils the requirements of the JNC VI and of the 1999 WHO-ISH guidelines for first-line therapy in hypertension and has the potential to improve hypertension control in populations.