Customize your JAMA Network experience by selecting one or more topics from the list below.
Wright, Jr JT, Bakris G, Greene T, et al. Effect of Blood Pressure Lowering and Antihypertensive Drug Class on Progression of Hypertensive Kidney Disease: Results From the AASK Trial. JAMA. 2002;288(19):2421–2431. doi:https://doi.org/10.1001/jama.288.19.2421
Author Affiliations: Departments of Medicine, University Hospitals of Cleveland and the Louis Stokes Cleveland Department of Veterans Affairs Medical Center (Dr Wright), Department of Biostatistics, Cleveland Clinic Foundation (Drs Greene and Gassman), and Department of Medicine, Case Western Reserve University (Dr Douglas-Baltimore), Cleveland, Ohio; Department of Preventive Medicine, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill (Dr Bakris); National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md (Dr Agodoa); Department of Preventive Medicine, Johns Hopkins University, Baltimore, Md (Dr Appel and Ms Charleston); Department of Medicine, Medical University of South Carolina, Charleston (Dr Cheek); Department of Medicine, University of California, Los Angeles (Dr Glassock); Department of Medicine, Ohio State University, Columbus (Dr Hebert); Department of Medicine, University of Michigan, Ann Arbor (Dr Jamerson); Department of Medicine, Vanderbilt University, Nashville, Tenn (Dr Lewis); Mt Sinai School of Medicine, New York, NY (Dr Phillips); University of Texas Southwestern Medical Center, Dallas (Drs Toto and Middleton); and University of Alabama, Birmingham (Dr Rostand).
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
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
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.
Create a personal account or sign in to: