FIXED LOW-DOSE PERINDOPRIL-INDAPAMIDE COMBINATION IN HYPERTENSIVE PATIENTS WITH CHRONIC-RENAL-FAILURE

The angiotensin converting enzyme inhibitor perindopril and the diuret ic indapamide have been shown to be effective antihypertensive agents in patients with chronic renal failure. A fixed low-dose combination o f these two agents has been proposed in the treatment of hypertension. We evaluated this combination in 26 patients with mild to moderate es sential hypertension and mild to severe chronic renal failure that did not require dialysis. This was a multicenter, open trial consisting o f a 2-week single-blind placebo washout period followed by 12 weeks of active treatment. At week 0, the patients received 2 mg perindopril/0 .625 mg indapamide once a day or every other day, with the possibility of dosage adjustment to perindopril 4 mg/indapamide 1.25 mg at week 2 , week 4, or week 8. A pharmacokinetic analysis using a population pha rmacokinetic approach was performed at week 8. Twenty-three patients c ompleted the 12-week study, at which time 14 patients were receiving 2 mg perindopril/0.625 mg indapamide daily, three were receiving 2 mg p erindopril/0.625 mg indapamide every other day, and six perindopril 4 mg/indapamide 1.25 mg. Blood pressure readings (supine) decreased from 170.4 +/- 19.2/101.5 +/- 6.7 mm Hg before active treatment to 146.5 /- 19.7/86.5 +/- 10.6 mm Hg at the end of treatment (P < .0001). Pharm acokinetic analysis showed that for indapamide and perindoprilat (the active metabolite of perindopril) the area under the curve (AUC(24)) i ncreased with the severity of renal failure. No interaction was noted between the two drugs. Mean serum creatinine and sodium and serum pota ssium levels remained stable during the study. Impairment of renal fun ction occurred in one patient and was considered unrelated to treatmen t. We conclude that a fixed low-dose perindopril-indapamide combinatio n as first-line treatment has a good safety/efficacy ratio in hyperten sive patients with chronic renal failure. Am J Hypertens 1998;11:1087- 1092 (C) 1998 American Journal of Hypertension, Ltd.