Effect of Ramipril vs Amlodipine on Renal Outcomes in Hypertensive Nephrosclerosis

A Randomized Controlled Trial

Agodoa, Lawrence Y. MD
Appel, Lawrence MD, MPH
Bakris, George L. MD
Beck, Gerald PhD
Bourgoignie, Jacques MD
Briggs, Josephine P. MD
Charleston, Jeanne RN
Cheek, DeAnna MD
Cleveland, William MD
Douglas, Janice G. MD
Douglas, Margaret MPH
Dowie, Donna MD
Faulkner, Marquetta MD
Gabriel, Avril RN
Gassman, Jennifer PhD
Greene, Tom PhD
Hall, Yvette RN
Hebert, Lee MD
Hiremath, Leena PhD
Jamerson, Kenneth MD
Johnson, Carolyn J. RN
Kopple, Joel MD
Kusek, John PhD
Lash, James MD
Lea, Janice MD
Lewis, Julia B. MD
Lipkowitz, Michael PhD
Massry, Shaul MD
Middleton, John MD
Miller, Edgar R. III MD
Norris, Keith MD
O'Connor, Daniel MD
Ojo, Akinlou MD
Phillips, Robert A. MD, PhD
Pogue, Velvie MD
Rahman, Mahboob MD, MS
Randall, Otelio S. MD
Rostand, Stephen MD
Schulman, Gerald MD
Smith, Winifred MPH
Thornley-Brown, Denyse MD
Tisher, C. Craig MD
Toto, Robert D. MD
Wright, Jackson T. Jr MD, PhD
Xu, Shichen MD

Author Affiliations: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md (Drs Agodoa, Briggs, and Kusek); Department of Preventive Medicine, Johns Hopkins University, Baltimore, Md (Drs Appel and Miller and Ms Charleston); Department of Preventive Medicine, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill (Dr Bakris); Department of Biostatistics, Cleveland Clinic Foundation, Cleveland, Ohio (Drs Beck, Gassman, and Greene); Department of Medicine, University of Miami, Coral Gables, Fla (Dr Bourgoignie); Department of Medicine, Medical University of South Carolina, Charleston (Dr Cheek); Department of Medicine, Morehouse School of Medicine, Atlanta, Ga (Dr Cleveland and Mr Smith); Department of Medicine, Case Western Reserve University Hospitals, Cleveland, Ohio (Drs Douglas, Rahman, and Wright, and Ms Hall); Department of Medicine, Emory University Medical Center, Atlanta, Ga (Ms Douglas and Dr Lea); Department of Medicine, Harlem Hospital Center, New York, NY (Drs Dowie and Pogue); Department of Medicine, Meharry Medical College, Nashville, Tenn (Dr Faulkner); Department of Medicine, Mount Sinai School of Medicine, New York, NY (Ms Gabriel and Drs Lipkowitz and Phillips); Department of Medicine, Ohio State University, Columbus (Drs Hebert and Hiremath); Department of Medicine, University of Michigan, Ann Arbor (Drs Jamerson and Ojo); Department of Medicine, Harbor Medical Center, University of California, Los Angeles (Dr Kopple); Department of Medicine, University of Illinois, Chicago (Dr Lash); Department of Medicine, Vanderbilt University, Nashville, Tenn (Drs Lewis and Schulman); Department of Medicine, University of Southern California, Los Angeles (Dr Massry); Department of Medicine, University of Texas Southwestern Medical Center, Dallas (Drs Middleton and Toto); Department of Medicine, Martin L. King–Charles R. Drew Medical Center, Los Angeles, Calif (Dr Norris); Department of Medicine, University of California, San Diego (Dr O'Connor); Department of Medicine, Howard University, Washington, DC (Drs Randall and Xu); Department of Medicine, University of Alabama, Birmingham (Drs Rostand and Thornley-Brown and Ms Johnson); Department of Medicine, University of Florida, Gainesville (Dr Tisher); and Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio (Dr Wright).

Corresponding Author and Reprints: Jackson T. Wright, Jr, MD, PhD, Case Western Reserve University, Clinical Hypertension Program, University Hospitals of Cleveland and the Louis Stokes Cleveland Veterans Affairs Medical Center, 10900 Euclid Ave, Wood Bldg Room W-165, Cleveland, OH 44106-4982 (e-mail: [email protected]).

JAMA: The Journal of the American Medical Association 285(21):p 2719-2728, June 6, 2001.

Context

Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans.

Objective

To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a β-blocker (metoprolol) on hypertensive renal disease progression.

Design, Setting, and Participants

Interim analysis of a randomized, double-blind, 3 × 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m²) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000.

Interventions

Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals.

Main Outcome Measures

The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m², end-stage renal disease, or death.

Results

Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m²/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001).

Conclusion

Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

JAMA.2001;285:2719-2728