Race and the Response to Adrenergic Blockade with Carvedilol in Patients with Chronic Heart Failure
Clyde W. Yancy, M.D., Michael B. Fowler, M.B., B.S., Wilson S. Colucci, M.D., Edward M. Gilbert, M.D., Michael R. Bristow, M.D., Ph.D., Jay N. Cohn, M.D., Mary Ann Lukas, M.D., Sarah T. Young, Ph.D., Milton Packer, M.D., for the U.S. Carvedilol Heart Failure Study Group
Background The benefits of angiotensin-convertingenzymeinhibitors and beta-blockers may be smaller in black patientsthan in patients of other races, but it is unknown whether raceinfluences the response to carvedilol in patients with chronicheart failure.
Methods In the U.S. Carvedilol Heart Failure Trials Program,217 black and 877 nonblack patients (in New York Heart Associationclass II, III, or IV and with a left ventricular ejection fractionof no more than 0.35) were randomly assigned to receive placeboor carvedilol (at doses of 6.25 to 50 mg twice daily) for upto 15 months. The effects of carvedilol on ejection fraction,clinical status, and major clinical events were retrospectivelycompared between black and nonblack patients.
Results As compared with placebo, carvedilol lowered the riskof death from any cause or hospitalization for any reason by48 percent in black patients and by 30 percent in nonblack patients.Carvedilol reduced the risk of worsening heart failure (heartfailure leading to death, hospitalization, or a sustained increasein medication) by 54 percent in black patients and by 51 percentin nonblack patients. The ratios of the relative risks associatedwith carvedilol for these two outcome variables in black ascompared with nonblack patients were 0.74 (95 percent confidenceinterval, 0.42 to 1.34) and 0.94 (95 percent confidence interval,0.43 to 2.05), respectively. Carvedilol also improved functionalclass, ejection fraction, and the patients' and physicians'global assessments in both the black patients and the nonblackpatients. For all these measures of outcome and clinical status,carvedilol was superior to placebo within each racial cohort(P<0.05 in all analyses), and there was no significant interactionbetween race and treatment (P> 0.05 in all analyses).
Conclusions The benefit of carvedilol was apparent and of similarmagnitude in both black and nonblack patients with heart failure.
Source Information
From the University of Texas Southwestern Medical Center, Dallas (C.W.Y.); Stanford University School of Medicine, Palo Alto, Calif. (M.B.F.); Boston University School of Medicine, Boston (W.S.C.); the University of Utah School of Medicine, Salt Lake City (E.M.G.); the University of Colorado School of Medicine, Denver (M.R.B.); the University of Minnesota Medical School, Minneapolis (J.N.C.); Glaxo SmithKline, King of Prussia, Pa. (M.A.L., S.T.Y.); and Columbia University College of Physicians and Surgeons, New York (M.P.).
Address reprint requests to Dr. Yancy at the Division of Cardiology, CS7 102, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9047, or at clyde.yancy{at}utsouthwestern.edu.
Anderson, W.
(2008). Teaching `Race' at Medical School: Social Scientists on the Margin. Social Studies of Science
38: 785-800
[Abstract]
Johnson, J. A.
(2008). Ethnic Differences in Cardiovascular Drug Response: Potential Contribution of Pharmacogenetics. Circulation
118: 1383-1393
[Full Text]
Linas, S. L.
(2008). Are Two Better Than One? Angiotensin-Converting Enzyme Inhibitors Plus Angiotensin Receptor Blockers for Reducing Blood Pressure and Proteinuria in Kidney Disease. CJASN
3: S17-S23
[Abstract][Full Text]
Davis, A. M., Vinci, L. M., Okwuosa, T. M., Chase, A. R., Huang, E. S.
(2007). Cardiovascular Health Disparities: A Systematic Review of Health Care Interventions. Med Care Res Rev
64: 29S-100S
[Abstract]
Barr, D. A.
(2005). The Practitioner's Dilemma: Can We Use a Patient's Race To Predict Genetics, Ancestry, and the Expected Outcomes of Treatment?. ANN INTERN MED
143: 809-815
[Abstract][Full Text]
Taylor, A. L., Wright, J. T. Jr, Cooper, R. S., Psaty, B. M., Taylor, A. L., Wright, J. T. Jr, Cooper, R. S., Psaty, B. M.
(2005). Importance of Race/Ethnicity in Clinical Trials: Lessons From the African-American Heart Failure Trial (A-HeFT), the African-American Study of Kidney Disease and Hypertension (AASK), and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Circulation
112: 3654-3666
[Full Text]
Smith, G. L., Shlipak, M. G., Havranek, E. P., Masoudi, F. A., McClellan, W. M., Foody, J. M., Rathore, S. S., Krumholz, H. M.
(2005). Race and Renal Impairment in Heart Failure: Mortality in Blacks Versus Whites. Circulation
111: 1270-1277
[Abstract][Full Text]
Yancy, C. W., Benjamin, E. J., Fabunmi, R. P., Bonow, R. O.
(2005). Discovering the Full Spectrum of Cardiovascular Disease: Minority Health Summit 2003: Executive Summary. Circulation
111: 1339-1349
[Full Text]
Benjamin, I. J., Arnett, D. K., Loscalzo, J.
(2005). Discovering the Full Spectrum of Cardiovascular Disease: Minority Health Summit 2003: Report of the Basic Science Writing Group. Circulation
111: e120-e123
[Full Text]
Moran, A. E., Cooper, R. S., Fitzgibbons, T. P., Chow, A. Y., Bellin, E. Y., Eisenberger, A. B., Taylor, A. L., Cohn, J., Worcel, M.
(2005). Isosorbide dinitrate and hydralazine in blacks with heart failure.. NEJM
352: 1041-1043
[Full Text]
Taylor, A. L., Ziesche, S., Yancy, C., Carson, P., D'Agostino, R. Jr., Ferdinand, K., Taylor, M., Adams, K., Sabolinski, M., Worcel, M., Cohn, J. N., the African-American Heart Failure Trial Investiga,
(2004). Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure. NEJM
351: 2049-2057
[Abstract][Full Text]
Moreno-John, G., Gachie, A., Fleming, C. M., NApoles-Springer, A., Mutran, E., Manson, S. M., PErez-Stable, E. J.
(2004). Ethnic Minority Older Adults Participating in Clinical Research: Developing Trust. J Aging Health
16: 93S-123S
[Abstract]
Satwani, S., Dec, G. W., Narula, J.
(2004). {beta}-Adrenergic Blockers in Heart Failure: Review of Mechanisms of Action and Clinical Outcomes. J CARDIOVASC PHARMACOL THER
9: 243-255
[Abstract]
Sankar, P., Cho, M. K., Condit, C. M., Hunt, L. M., Koenig, B., Marshall, P., Lee, S. S.-J., Spicer, P.
(2004). Genetic Research and Health Disparities. JAMA
291: 2985-2989
[Abstract][Full Text]
Julius, S., Alderman, M. H., Beevers, G., Dahlof, B., Devereux, R. B., Douglas, J. G., Edelman, J. M., Harris, K. E., Kjeldsen, S. E., Nesbitt, S., Randall, O. S., Wright, J. T. Jr
(2004). Cardiovascular risk reduction in hypertensive black patients with left ventricular hypertrophy: The life study. J Am Coll Cardiol
43: 1047-1055
[Abstract][Full Text]
Sackner-Bernstein, J. D., Skopicki, H. A.
(2004). Racing away from bias. J Am Coll Cardiol
43: 785-786
[Full Text]
de Denus, S., Pharand, C., Williamson, D. R.
(2004). Brain Natriuretic Peptide in the Management of Heart Failure: The Versatile Neurohormone. Chest
125: 652-668
[Abstract][Full Text]
Feldman, A. M.
(2003). The emerging role of pharmacogenomics in the treatment of patients with heart failure. Ann. Thorac. Surg.
76: S2246-2253
[Full Text]
Yang, S.-P., Ho, L.-J., Lin, Y.-L., Cheng, S.-M., Tsao, T.-P., Chang, D.-M., Hsu, Y.-L., Shih, C.-Y., Juan, T.-Y., Lai, J.-H.
(2003). Carvedilol, a new antioxidative {beta}-blocker, blocks in vitro human peripheral blood T cell activation by downregulating NF-{kappa}B activity. Cardiovasc Res
59: 776-787
[Abstract][Full Text]
Rathore, S. S., Foody, J. M., Wang, Y., Smith, G. L., Herrin, J., Masoudi, F. A., Wolfe, P., Havranek, E. P., Ordin, D. L., Krumholz, H. M.
(2003). Race, Quality of Care, and Outcomes of Elderly Patients Hospitalized With Heart Failure. JAMA
289: 2517-2524
[Abstract][Full Text]
Shekelle, P. G., Rich, M. W., Morton, S. C., Atkinson, Col. S. W., Tu, W., Maglione, M., Rhodes, S., Barrett, M., Fonarow, G. C., Greenberg, B., Heidenreich, P. A., Knabel, T., Konstam, M. A., Steimle, A., Warner Stevenson, L.
(2003). Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: A meta-analysis of major clinical trials. J Am Coll Cardiol
41: 1529-1538
[Abstract][Full Text]
Tangeman, H. J, Patterson, J H.
(2003). Extended-Release Metoprolol Succinate in Chronic Heart Failure. The Annals of Pharmacotherapy
37: 701-710
[Abstract][Full Text]
Ben-Yehuda, O.
(2003). Hypertension, angiotensin II, aldosterone, and race. J Am Coll Cardiol
41: 1156-1158
[Full Text]
Bonds, D. E., Zaccaro, D. J., Karter, A. J., Selby, J. V., Saad, M., Goff, D. C. Jr
(2003). Ethnic and Racial Differences in Diabetes Care: The Insulin Resistance Atherosclerosis Study. Diabetes Care
26: 1040-1046
[Abstract][Full Text]
Gheorghiade, M., Colucci, W. S., Swedberg, K.
(2003). {beta}-Blockers in Chronic Heart Failure. Circulation
107: 1570-1575
[Full Text]
Douglas, J. G., Bakris, G. L., Epstein, M., Ferdinand, K. C., Ferrario, C., Flack, J. M., Jamerson, K. A., Jones, W. E., Haywood, J., Maxey, R., Ofili, E. O., Saunders, E., Schiffrin, E. L., Sica, D. A., Sowers, J. R., Vidt, D. G., the Hypertension in African Americans Working Grou,
(2003). Management of High Blood Pressure in African Americans: Consensus Statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med
163: 525-541
[Full Text]
Chassot, P.-G., Delabays, A., Spahn, D. R.
(2002). Preoperative evaluation of patients with, or at risk of, coronary artery disease undergoing non-cardiac surgery. Br J Anaesth
89: 747-759
[Abstract][Full Text]
Benjamin, E. J., Smith, S. C. Jr, Cooper, R. S., Hill, M. N., Luepker, R. V.
(2002). Task Force #1--magnitude of the prevention problem: opportunities and challenges. J Am Coll Cardiol
40: 588-603
[Full Text]
DeMets, D. L., Califf, R. M.
(2002). Lessons Learned From Recent Cardiovascular Clinical Trials: Part I. Circulation
106: 746-751
[Full Text]
Gheorghiade, M., Goldstein, S.
(2002). {beta}-Blockers in the Post-Myocardial Infarction Patient. Circulation
106: 394-398
[Full Text]
Dries, D. L., Strong, M. H., Cooper, R. S., Drazner, M. H.
(2002). Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients. J Am Coll Cardiol
40: 311-317
[Abstract][Full Text]
Kennedy, H. L., Rosenson, R. S.
(2002). Physicians' interpretation of "class effects": A need for thoughtful re-evaluation. J Am Coll Cardiol
40: 19-26
[Abstract][Full Text]
Andreka, P., Aiyar, N., Olson, L. C., Wei, J. Q., Turner, M. S., Webster, K. A., Ohlstein, E. H., Bishopric, N. H.
(2002). Bucindolol Displays Intrinsic Sympathomimetic Activity in Human Myocardium. Circulation
105: 2429-2434
[Abstract][Full Text]
McMurray, J., Pfeffer, M. A.
(2002). New Therapeutic Options in Congestive Heart Failure: Part II. Circulation
105: 2223-2228
[Full Text]
Bundkirchen, A., Brixius, K., Bolck, B., Schwinger, R. H. G.
(2002). Bucindolol Exerts Agonistic Activity on the Propranolol-Insensitive State of beta 1-Adrenoceptors in Human Myocardium. J. Pharmacol. Exp. Ther.
300: 794-801
[Abstract][Full Text]
Farrell, M. H., Foody, J. M., Krumholz, H. M.
(2002). {beta}-Blockers in Heart Failure: Clinical Applications. JAMA
287: 890-897
[Abstract][Full Text]
McNeil, B. J.
(2001). Hidden Barriers to Improvement in the Quality of Care. NEJM
345: 1612-1620
[Full Text]
Bovet, P., Paccaud, F., McLeod, H. L., Masoudi, F. A., Havranek, E. P., Ofili, E., Flack, J., Gibbons, G., Exner, D. V., Domanski, M. J., Cohn, J. N., Schwartz, R. S.
(2001). Race and Responsiveness to Drugs for Heart Failure. NEJM
345: 766-768
[Full Text]
(2001). Race and Response to Therapies. Journal Watch Cardiology
2001: 2-2
[Full Text]
Braunwald, E.
(2001). Expanding Indications for Beta-Blockers in Heart Failure. NEJM
344: 1711-1712
[Full Text]
(2001). Racial Differences in Response to Heart Failure Therapy?. JWatch General
2001: 1-1
[Full Text]
Schwartz, R. S.
(2001). Racial Profiling in Medical Research. NEJM
344: 1392-1393
[Full Text]
Wood, A. J.J.
(2001). Racial Differences in the Response to Drugs -- Pointers to Genetic Differences. NEJM
344: 1393-1396
[Full Text]