Evaluation of long-term efficacy and tolerability of irbesartan in elderly hypertensive patients with renal impairment in an open-label study

Background: Hypertension, left untreated, can lead to serious complications, including stroke myocardial infarction, and renal failure. Because lowering blood pressure correlates with slowing of renal disease progression, the control of hypertension in the presence of renal disease is essential.Objective: We evaluated the efficacy, tolerability, and safety of irbesartan alone or in combination with other antihypertensive agents in elderly patients with hypertension and chronic renal insufficiency.Methods: Patients > 65 years of age with hypertension (sitting diastolic blood pressure [SiDBP] 90-115 mm Hg) and chronic renal sufficiency that was mild (creatinine clearance [CrCL] 30-60 mL/min per 1.73 m²) or moderate to severe CrCL 10-29 mL/min per 1.73 m²) were enrolled. After a 3-week placebo run-in period, irbesartan was administered for 12 months at 150 mg/d. After 4 weeks of therapy, patients whose blood pressure was not adequately controlled (ie, SiDBP ≥90 mm Hg or <5 mm Hg decrease from baseline) had an additional antihypertensive agent added to their daily irbesartan regimen; dosage adjustment of the second drug was permitted after 2 weeks to optimize blood pressure control. Twenty-four-hour CrCL was determined, and renal clearance studies of inulin and p-aminohippurate were performed in a subset of patients.Results: A total of 32 patients (21 men, 11 women; mean age, 70.4 years) were enrolled. Thirty patients had mild renal insufficiency (mean CrCL, 44.45 mL/min per 1.73 m²) and 2 patients had moderate to severe renal insufficiency (mean CrCL 21.32 mL/min per 1.73 m²). Trough sitting blood pressures were reduced at the end of the first week of treatment in all groups. After 8 weeks, 12 weeks, and 1 year of treatment, the mean reductions in systolic blood pressure (SBP)/DBP were −11.9/−8.7 mm Hg, −10.8/−9.4 mm Hg, and −14.7/−12.1 mm Hg, respectively, in patients with mild renal insufficiency and −7.7/−6.3 mm Hg, −13.1/−11.8 mm Hg, and −14.1/−10.6 mm Hg in patients with moderate to severe renal insufficiency. CrCL, glomerular filtration rate, and effective renal plasma flow, as measured in a subset of 11 patients, were stable. Treatment was discontinued for 3 patients because of a clinical adverse event or laboratory parameter abnormality. Hyperkalemia (>6 mEq/L) requiring discontinuation of irbesartan occurred in 1 patient with moderate to severe renal insufficiency.Conclusion: The results of this study suggest that irbesartan, as monotherapy (150 mg once daily) or in combination with other antihypertensive drugs, is effective in reducing blood pressure in elderly hypertensive patients with chronic renal impairment and that irbesartan regimens are well tolerated in this population.