Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: Results from the AASK trial

Context: Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD. Objective: To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension. Design: Randomized 3 × 2 factorial trial with enrollment from February 1995 to September 1998. Setting and Participants: A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m²) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years. Interventions: Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n =554) or 92 mm Hg or less (lower; n =540), and to initial treatment with either a β-blocker (metoprolol 50-200 mg/d; n =441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n =436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n =217). Open-label agents were added to achieve the assigned BP goals. Main Outcome Measures: Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or ≥25 mL/min per 1.73 m²) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol. Results: Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m² per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m² per year; P=.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group=2%; 95% confidence interval [CI], -22% to 21%; P=.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22 % (95% CI, 1%-38%; P=.04) and 38% (95% CI, 14%-56%; P=.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups. Conclusions: No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than β-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.