Cardiovascular Outcomes in High-Risk Hypertensive Patients Stratified by Baseline Glomerular Filtration Rate

7 February 2006 | Volume 144 Issue 3 | Pages 172-180

Background: Chronic kidney disease is common in older patients with hypertension.

Objective: To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR.

Design: Post hoc subgroup analysis.

Setting: Multicenter randomized, double-blind, controlled trial.

Participants: Persons with hypertension who were 55 years of age or older with 1 or more risk factors for CHD and who were stratified into 3 baseline GFR groups: normal or increased ( 90 mL/min per 1.73 m²; n = 8126 patients), mild reduction (60 to 89 mL/min per 1.73 m²; n = 18 109 patients), and moderate or severe reduction (< 60 mL/min per 1.73 m²; n = 5662 patients).

Interventions: Random assignment to chlorthalidone, amlodipine, or lisinopril.

Measurements: Rates of ESRD, CHD, stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease).

Results: In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m² (compared with >104 mL/min per 1.73 m²) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure.

Limitations: Proteinuria data were not available, and combination therapies were not tested.

Conclusions: Older high-risk patients with hypertension and reduced GFR are more likely to develop CHD than to develop ESRD. A low GFR independently predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function.

*For a complete listing of the ALLHAT Collaborative Research Group, please refer to the following: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-97. [PMID: 12479763] [Abstract/Free Full Text]

Editors' Notes Context Long-term outcomes of patients with a reduced glomerular filtration rate (GFR) who are treated for hypertension are not well-known. Contribution This analysis of a large multicenter trial found that coronary heart disease (CHD) was much more common than end-stage renal disease (15% vs. 6%) in hypertensive patients with moderate to severe reductions in GFR who were followed for 6 years. Lower baseline GFR was associated with higher risk for CHD independent of other risk factors. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function. Cautions These are post hoc subgroup findings, and proteinuria was not measured. —The Editors

 

Author and Article Information

From Case Western Reserve University, Cleveland, Ohio; University of Texas School of Public Health, Houston, Texas; National Heart, Lung, and Blood Institute, Bethesda, Maryland; Tulane University Health Sciences Center, New Orleans, Louisiana; Kaiser Permanente of Georgia, Tucker, Georgia; University of Minnesota, Minneapolis, Minnesota; Pitman Internal Medicine Associates, Pitman, New Jersey; University of California, Irvine, Irvine, California; Bronx Nephrology Hypertension PC, Bronx, New York; Lehigh Valley Hospital, Allentown, Pennsylvania; Veterans Administration Medical Center, Dayton, Ohio; University of Missouri Kansas City and Veterans Administration Medical Center, Kansas City, Missouri; Androscoggin Clinical Associates, Lewiston, Maine; and King/Drew Medical Center and Veterans Administration Medical Center, Los Angeles, California.

ClinicalTrials.gov Identifier: NCT00000542.

Note: These data were presented in part at the National Kidney Foundation Annual Spring Clinical Meetings, Dallas, Texas, 5 April 2003.

Grant Support: This study was supported by contract NO1-HC-35130 with the National Heart, Lung, and Blood Institute (NHLBI). The ALLHAT investigators received contributions of study medications supplied by Pfizer (New York, New York) (amlodipine and doxazosin), AstraZeneca (Wilmington, Delaware) (atenolol and lisinopril), and Bristol-Myers Squibb (New York, New York) (pravastatin); the investigators also received financial support from Pfizer Inc.

Potential Financial Conflicts of Interest: Consultancies: M. Rahman (King Pharmaceuticals/Monarch), B.R. Davis (Bristol-Myers Squibb, Merck, Pfizer, SmithKline Beecham/Glaxo Wellcome, Takeda), J.T. Wright Jr. (Abbott Laboratories, AstraZeneca, Aventis, Bayer, Bioavail, Bristol-Myers Squibb, Forest Pharmaceuticals, Horizons Pharmaceuticals, King Pharmaceuticals/Monarch, Merck, NitroMed, Novartis, Pfizer, Pharmacia, Reliant Pharm, Sankyo, SmithKline Beecham/Glaxo Wellcome, Wyeth), P.K. Whelton (Pfizer), M. Henriquez (Abbott Laboratories, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Sanofi-Synthelabo), N. Kopyt (Amgen, Merck, Novartis, Sankyo), H. Ward (Abbott Laboratories, Bristol-Myers Squibb, Covance, Keryx, Merck, Pfizer), T. Wiegmann (Boehringer Ingelheim); Honoraria: M. Rahman (Abbott Laboratories, Boehringer Ingelheim, King Pharmaceuticals/Monarch, Pfizer), B.R. Davis (Bristol-Myers Squibb, Merck, Pfizer, SmithKline Beecham/Glaxo Wellcome, Takeda), J.T. Wright Jr. (Abbott Laboratories, AstraZeneca, Aventis, Bayer, Bioavail, Bristol-Myers Squibb, Forest Pharmaceuticals, Horizons Pharmaceuticals, King Pharmaceuticals, Merck, NitroMed, Novartis, Pfizer, Pharmacia, Reliant Pharm, Sankyo, SmithKline Beecham/Glaxo Wellcome, Wyeth), P.K. Whelton (Pfizer), J. Barzilay (Takeda), M. Henriquez (Abbott Laboratories, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Sanofi-Synthelabo), N. Kopyt (Amgen, Merck, Novartis, Sankyo), H. Ward (Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Pfizer), T. Wiegmann (Boehringer Ingelheim); Grants received: J.T. Wright Jr. (Bioavail, Forest Pharmaceuticals, Novartis, Pharmacia, Sankyo, SmithKline Beecham/Glaxo Wellcome), J. Barzilay (Boehringer Ingelheim), M. Henriquez (Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Sanofi-Synthelabo), M. Saklayen (Novartis, Otsuka Maryland), H. Ward (Abbott Laboratories), T. Wiegmann (Boehringer Ingelheim, Bristol-Myers Squibb, Keryx, Kureha/Japan); Stock ownership or options (other than mutual funds): J.H. Eckfeldt (Johnson & Johnson), M.A. Farber (Pfizer), C. Stanford (Merck, Pfizer).

Requests for Single Reprints: Barry R. Davis, MD, PhD, University of Texas Health Science Center, School of Public Health, Coordinating Center for Clinical Trials, 1200 Herman Pressler Street, Suite E801, Houston, TX 77030; e-mail, barry.r.davis{at}uth.tmc.edu.

Current Author Addresses: Dr. Rahman: Case Western Reserve University, University Hospitals of Cleveland, Louis Stokes Cleveland Veterans Administration Medical Center, Clinical Hypertension Program, WRN6053, 11100 Euclid Avenue, Cleveland, OH 44060-6053.

Ms. Pressel and Dr. Davis: University of Texas Health Science Center, School of Public Health, Coordinating Center for Clinical Trials, 1200 Herman Pressler Street, Suite E-801, Houston, TX 77030.

Dr. Nwachuku: National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Room 8135, Bethesda, MD 20892-7936.

Dr. Wright: University Hospitals of Cleveland, General Clinical Research Center, Horvitz Tower, Suite 7311, 11100 Euclid Avenue, Cleveland, OH 44106-5041.

Dr. Whelton: Tulane University Health Sciences Center, 1440 Canal Street, TW-5, Suite 2400, New Orleans, LA 70112.

Dr. Barzilay: Kaiser Permanente of Georgia, 200 Crescent Centre Parkway, Tucker, GA 30084.

Dr. Batuman: Tulane Medical School, Nephrology Section, Slot 45, 1430 Tulane, New Orleans, LA 70112.

Dr. Eckfeldt: Department of Laboratory Medicine and Pathology, University of Minnesota Hospital and Clinic, FUMC 609, Fairview-University Medical Center, Room B203 Mayo Building, 420 Delaware Street SE, Minneapolis, MN 55455.

Dr. Farber: Pitman Internal Medicine Associates, 410 North Broadway, Suite 1, Pitman, NJ 08071.

Dr. Franklin: 155 Barlock Avenue, Los Angeles, CA 90049.

Dr. Henriquez: Bronx Nephrology Hypertension PC, 2452 Bronx Park East, Bronx, NY 10467.

Dr. Kopyt: Nephrology–Hypertension Associates of Lehigh Valley, 401 North 17th Street, Suite 212, Allentown, PA 18104.

Ms. Louis: Tulane University Health Sciences Center, 1440 Canal Street, TW-5 Suite 2400, New Orleans, LA 70112.

Dr. Saklayen: Veterans Administration Medical Center, Wright State University, 4100 West 3rd Street, Dayton, OH 45428.

Dr. Stanford: University of Missouri Kansas City School of Medicine, 2411 Holmes Street, Kansas City, MO 64108-2792.

Dr. Walworth: Androscoggin Clinical Associates, 710 Main Street, Lewiston, ME 04240.

Dr. Ward: Department of Hypertension and Nephrology, King/Drew Medical Center, 12021 Wilmington Avenue, Los Angeles, CA 90059.

Dr. Wiegmann: Department of Veterans Affairs Medical Center (111A), Veterans Administration Medical Center Kansas City, 4801 East Linwood Boulevard, Kansas City, MO 64128-2295.

Author Contributions: Conception and design: B.R. Davis, J.T. Wright Jr., J.H. Eckfeldt, M. Saklayen, C. Stanford.

Analysis and interpretation of the data: M. Rahman, S. Pressel, B.R. Davis, C. Nwachuku, J.T. Wright Jr., P.K. Whelton, J. Barzilay, V. Batuman, J.H. Eckfeldt, M. Henriquez, N. Kopyt, G.T. Louis, M. Saklayen, C. Stanford, H. Ward, T. Wiegmann.

Drafting of the article: M. Rahman, S. Pressel, B.R. Davis, C. Nwachuku, J.T. Wright Jr., J. Barzilay, V. Batuman, M.A. Farber, S. Franklin, M. Henriquez, N. Kopyt, M. Saklayen, C. Stanford, C. Walworth, T. Wiegmann.

Critical revision of the article for important intellectual content: M. Rahman, B.R. Davis, J.T. Wright Jr., P.K. Whelton, J. Barzilay, J.H. Eckfeldt, S. Franklin, M. Henriquez, N. Kopyt, G.T. Louis, M. Saklayen, C. Stanford, C. Walworth.

Final approval of the article: M. Rahman, S. Pressel, B.R. Davis, J.T. Wright Jr., P.K. Whelton, J. Barzilay, M.A. Farber, S. Franklin, M. Henriquez, N. Kopyt, G.T. Louis, M. Saklayen, C. Stanford, H. Ward, T. Wiegmann.

Provision of study materials or patients: J. Barzilay, M.A. Farber, M. Henriquez, N. Kopyt, M. Saklayen, C. Stanford, C. Walworth, H. Ward, T. Wiegmann.

Statistical expertise: S. Pressel, B.R. Davis, P.K. Whelton.

Obtaining of funding: S. Pressel, B.R. Davis, C. Nwachuku, J.T. Wright Jr.

Administrative, technical, or logistic support: S. Pressel, B.R. Davis, C. Nwachuku, J.T. Wright Jr., P.K. Whelton, J.H. Eckfeldt, G.T. Louis.

Collection and assembly of data: M. Rahman, S. Pressel, B.R. Davis, J.T. Wright Jr., N. Kopyt, C. Stanford.

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