Racial differences in the renal response to blood pressure lowering during chronic angiotensin-converting enzyme inhibition: A prospective double-blind randomized comparison of fosinopril and lisinopril in older hypertensive patients with chronic renal insufficiency

Abstract

This study was undertaken to compare the effects of chronic angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and renal hemodynamics in older black and nonblack hypertensive patients with chronic renal insufficiency. A multicenter, placebo lead-in double-blind, parallel group study was performed to compare the antihypertensive efficacy and renal hemodynamic response to the once-daily ACE inhibitors fosinopril (n = 14) and lisinopril (n = 13) over a 22-week period. The study goal was to lower diastolic blood pressure (DBP) to 90 mm Hg or less. Furosemide was added after 6 weeks if blood pressure goal was not achieved. At outpatient clinics at university medical centers, 27 older hypertensive patients (≥ 45 years; 12 blacks, 15 nonblacks; 19 male, eight female) with DBP of 95 mm Hg or higher and 4-hour creatinine clearance 20 to 70 mL/min/1.73 m 2 were studied. Changes (Δ) from baseline in BP, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured. Mean systolic blood pressure (SBP) and DBP decreased significantly and to a similar extent in randomized groups: fosinopril (mean ± SEM) ΔDBP at 6 weeks was −13 ± 2 ( P < 0.0001; 95% Cl, −16 to −9) and at 22 weeks was −12 ± 2 ( P < 0.0001; 95% CI, −16 to −9); lisinopril ΔBP at 6 weeks was −14 ± 6 ( P < 0.0001; 95% CI, −10 to −18) and at 22 weeks was −16 ± 2 ( P < 0.0001; 95% CI, −12 to −21). GFR and RPF did not change significantly in either group. BP was significantly reduced and to a similar extent in blacks and nonblacks: for blacks, ΔDBP at 6 weeks was −11 ± 3 ( P < 0.05; 95% CI, −0.01 to −9) and at 22 weeks was −16 ± 2 ( P < 0.0001; 95% CI, −11 to −20); for nonblacks, ΔDBP at 6 weeks was −14 ± 1 ( P < 0.0001; 95% CI, −12 to −17) and at 22 weeks was −12 ± 2 ( P < 0.0001; 95% CI, −16 to −8). Eight patients (five blacks and three nonblacks) required an addition of furosemide after 6 weeks to reach the DBP goal of < 90 mm Hg at 22 weeks. GFR was not significantly altered for either racial group at 6 weeks; however, at 22 weeks, GFR decreased significantly in blacks (Δ GFR, −16 ± 5; P < 0.006; 95% Cl, −26 to −5) and tended to increase in nonblacks (Δ GFR, 7 ± 6; P > 0.25). ΔGFR correlated directly with the ΔRPF (ΔGFR = 0.0811∗ΔRPF −2.35 +; r = 0.66; P < 0.003). There was no correlation between ΔMAP and ΔGFR or ΔRPF in blacks or nonblacks. We conclude that chronic ACE inhibition with fosinopril and lisinopril alone or in combination with furosemide lowers BP in older blacks and nonblacks with hypertension and chronic renal insufficiency. Racial differences in the renal hemodynamic response to chronic ACE inhibition were noted and appear to be independent of diuretic use and the magnitude of BP lowering.