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Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic
A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
Mahboob Rahman, MD, MS;
Sara Pressel, MS;
Barry R. Davis, MD, PhD;
Chuke Nwachuku, MA, MPH, DrPH;
Jackson T. Wright, Jr, MD, PhD;
Paul K. Whelton, MD, MSC;
Joshua Barzilay, MD;
Vecihi Batuman, MD;
John H. Eckfeldt, MD, PhD;
Michael Farber, MD;
Mario Henriquez, MD;
Nelson Kopyt, DO;
Gail T. Louis, RN;
Mohammad Saklayen, MD;
Carol Stanford, MD;
Candace Walworth, MD;
Harry Ward, MD;
Thomas Wiegmann, MD; for the ALLHAT Collaborative Research Group
Arch Intern Med. 2005;165:936-946.
Background This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic.
Methods We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased ( 90 mL /min per 1.73m2, n = 8126), mild reduction (60-89 mL /min per 1.73 m2, n = 18 109), or moderate-severe reduction (<60 mL /min per 1.73 m2, n = 5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes.
Results In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR, 0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR, 0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P = .74] and 0.85 [P = .23], respectively) and lisinopril (odds ratios, 1.13 [P = .31] and 1.00 [P = .98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL /min per 1.73 m2 higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum.
Conclusions In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups.
Author Affiliations: Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals of Cleveland, Cleveland Veterans Affairs Medical Center, Cleveland, Ohio (Dr Rahman); University of Texas Health Science Center, School of Public Health, Houston (Ms Pressel and Dr Davis); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (Dr Nwachuku); General Clinical Research Center, Case Western Reserve University, Cleveland (Dr Wright); Tulane University Health Sciences Center, New Orleans, La (Dr Whelton and Ms Louis); Kaiser Permanente of Georgia, Tucker (Dr Barzilay); Veterans Affairs Medical Center and Tulane Medical School, New Orleans (Dr Batuman); Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (Dr Eckfeldt); Pitman Internal Medicine Associates, Pitman, NJ (Dr Farber); Bronx Nephrology Hypertension PC, Bronx, NY (Dr Henriquez); Division of Nephrology, Lehigh Valley Hospital, Allentown, Pa (Dr Kopyt); Veterans Affairs Medical Center Dayton, Dayton, Ohio (Dr Saklayen); University of Missouri Kansas City School of Medicine (Dr Stanford); Androscoggin Clinical Associates, Lewiston, Me (Dr Walworth); King Drew Medical Center, Los Angeles, Calif (Dr Ward); and Department of Veterans Affairs Medical Center, Kansas City, Mo (Dr Wiegmann).
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