BACKGROUND: Deaths in African Americans from hypertensive renal disease have risen in recent years. The effects of various antihypertensives on mortality are unknown, since studies have included few African Americans.
POPULATION STUDIED: This study included 1094 African Americans between the ages of 18 and 70 years with hypertensive renal disease, defined as a glomerular filtration rate (GFR) of 20 to 65 mL per minute. The patients included in this study had no other identified causes of renal disease, and were excluded if they had diabetes mellitus, malignant hypertension, secondary hypertension, or congestive heart failure. The average age of the participants was 54 years, and they had a history of hypertension for a mean of 14 years. Nearly half were women with a mean arterial pressure (MAP) of 115. Patients with more than 2.5 g per day of urinary protein excretion were excluded; however, approximately one third of the study participants had proteinuria greater than 300 mg per day, with the average being 600 mg per day. Half of the subjects had a history of heart disease. At enrollment, 40% were taking an angiotensin-converting enzyme (ACE) inhibitor, 27% a b-blocker, 60% a calcium channel blocker (CCB), and 45% a dihydropyridine calcium channel blocker (DHP-CCB).
STUDY DESIGN AND VALIDITY: The patients were randomized to 1 of 3 antihypertensive medications: the ACE inhibitor ramipril 2.5 to 10 mg per day, the sustained-release b-blocker metoprolol 50 to 200 mg per day, or the DHP-CCB amlodipine 5 to 10 mg per day. Each of these groups was further divided into 2 target blood pressure groups: “usual” (MAP) goal of 102 or a “low” MAP goal of 92. Blood pressures were checked and medications adjusted monthly to achieve target MAPs, and GFR was evaluated at baseline and every 3 months. Data were analyzed using an intention-to-treat approach. This is an interim analysis of the African American Study of Kidney Disease and Hypertension (AASK) trial, a multicentered and double-blinded study. Allocation concealment was maintained for study drug assignments but not for the blood pressure goals. Because interim analysis showed large differences between the ramipril and metoprolol groups compared with the amlodipine group, the amlodipine arm was terminated. Follow-up of patients in the remaining arms is ongoing and will be reported at a later time.
OUTCOMES MEASURED: The primary outcome measured was the effect of the study drugs on the long-term rate of decline of GFR. Secondary outcomes were “GFR events” (a decrease of GFR greater than 50%), progression to ESRD, death, and combinations of these.
RESULTS: Baseline characteristics were similar between the amlodipine and ramipril groups, and the average follow-up was 3 years. Overall, the rate of decline in GFR was 36% slower in the ramipril group compared with the amlodipine group (P=.002). This slowed decline in GFR was more pronounced in the subgroup of participants with proteinuria and in the subgroup that had a baseline GFR of less than 40 mL per minute.
Although African Americans have traditionally been thought to be less responsive to ACE inhibitors, in this study ramipril (2.5-10 mg/day) was useful in the treatment of already established hypertensive nephropathy in this population. Ramipril slowed progression to ESRD, especially in those patients with preexisting proteinuria and in those with more advanced renal failure (GFR less than 40 mg/minute). Interestingly, amlodipine was inferior to both ramipril and metoprolol in the treatment of hypertensive renal disease. The question of which is better, ramipril or metoprolol, is currently under study.