Skip to main content

Racial Differences in Responses to Drug Treatment

Implications for Pharmacotherapy of Heart Failure

Abstract

Chronic heart failure (CHF) is a common disease with high associated morbidity and mortality, and the outcome appears to be worse in black compared with white patients. There is currently no clear consensus for basing the pharmacological treatment of CHF on racial differences. Most studies that have investigated the potential effects of racial differences on pharmacological responses in heart failure have been based on African Americans and white participants. Using these data, this review will discuss the current understanding of the effects of racial differences in response to pharmacotherapy in heart failure, possible mechanisms for these observed differences, and how this may impact on patient management.

Diuretics have favorable symptomatic benefits in both black and white patients with heart failure with evidence of fluid retention. ACE inhibitors seem to be less effective in the treatment of black patients with heart failure compared with white patients. This may be due to low pre-existing activity of the renin-angiotensin system in blacks. The role of angiotensin receptor blockers (ARBs) in the management of all patients with heart failure is incompletely defined and there are no clear trial data to show any difference in effect between black and white patients with heart failure. There is good evidence for the use of Spironolactone in all patients with heart failure, but no evidence for a different effect in black patients. Similarly, there is no conclusive data to suggest a difference in effect of digoxin in different racial groups. The evidence available would suggest that certain β-adrenoceptor antagonists (certainly Carvedilol but not bucindolol) are effective in both black and white patients with CHF. The combination of hydralazine and nitrates would appear to be particularly effective in black patients with CHF though the African American Heart Failure Trial (A-HeFT) trial should provide clearer evidence for the potentially greater beneficial effects of these two drugs in the black population.

It is important to accept that racial categorization acts as only a surrogate marker for genetic or other factors responsible for individual responses to drug therapy and that any identified differences will not apply to all members of each stratified group. Nonetheless, in managing a complex, common and often fatal condition such as heart failure, recognizing potential individual differences in drug responses should enable the responsible clinician to provide a tailored and evidence-based approach to patient treatment.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Dries DL, Exner DV, Gersh BJ, et al. Racial differences in the outcome of left ventricular dysfunction. N Engl J Med 1999 Feb 25; 340(8): 609–16

    PubMed  Article  CAS  Google Scholar 

  2. Afzal A, Ananthasubramaniam K, Sharma N, et al. Racial differences in patients with heart failure. Clin Cardiol 1999 Dec; 22(12): 791–4

    PubMed  Article  CAS  Google Scholar 

  3. Bourassa MG, Gurne O, Bangdiwala SI, et al. Natural history and patterns of current practice in heart failure: the Studies of Left Ventricular Dysfunction (SOLVD) Investigators. J Am Coll Cardiol 1993 Oct; 22 (4 Suppl A): 14A–9A

    Article  Google Scholar 

  4. Changes in mortality from heart failure-United States, 1980-1995. MMWR Morb Mortal Wkly Rep 1998; 47(30): 633–7

    Google Scholar 

  5. Alexander M, Grumbach K, Selby J, et al. Hospitalization for congestive heart failure: explaining racial differences. JAMA 1995 Oct 4; 274(13): 1037–42

    PubMed  Article  CAS  Google Scholar 

  6. Yancy CW. Heart failure in blacks: etiologic and epidemiologic differences. Curr Cardiol Rep 2001 May; 3(3): 191–7

    PubMed  Article  CAS  Google Scholar 

  7. Singh GK, Kochanek KD, MacDorman MF. Advance report of final morbidity statistics. Mon Vital Stat Rep 1996; 45 Suppl. 3: 1–76

    Google Scholar 

  8. Bayliss J, Norell M, Canepa-Anson R, et al. Untreated heart failure: clinical and neuroendocrine effects of introducing diuretics. Br Heart J 1987 Jan; 57(1): 17–22

    PubMed  Article  CAS  Google Scholar 

  9. Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men: a comparison of six antihypertensive agents with placebo. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med 1993 Apr 1; 328(13): 914–21

    PubMed  Article  CAS  Google Scholar 

  10. Brier ME, Luft FC. Sodium kinetics in white and black normotensive subjects: possible relevance to salt-sensitive hypertension. Am J Med Sci 1994 Feb; 307 Suppl. 1:S38–42

    PubMed  Google Scholar 

  11. Richardson AD, Piepho RW. Effect of race on hypertension and antihypertensive therapy. Int J Clin Pharmacol Ther 2000 Feb; 38(2): 75–9

    PubMed  CAS  Google Scholar 

  12. Turner ST, Schwartz GL, Chapman AB, et al. C825T polymorphism of the G protein beta(3)-subunit and antihypertensive response to a thiazide diuretic. Hypertension 2001 Feb; 37(2 Pt 2): 739–43

    PubMed  Article  CAS  Google Scholar 

  13. Ader R, Chatterjee K, Ports T, et al. Immediate and sustained hemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-converting enzyme inhibitor. Circulation 1980 May; 61(5): 931–7

    PubMed  Article  CAS  Google Scholar 

  14. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316(23): 1429–35

    Article  Google Scholar 

  15. SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions: N Engl J Med 1992 Sep 3; 327(10): 685–91

    Article  Google Scholar 

  16. Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure: ATLAS Study Group. Circulation 1999 Dec 7; 100(23): 2312–8

    PubMed  Article  CAS  Google Scholar 

  17. Cleland JG, Erhardt L, Murray G, et al. Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure: a report from the AIRE Study Investigators. Eur Heart J 1997 Jan; 18(1): 41–51

    PubMed  CAS  Google Scholar 

  18. Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001 Sep; 22(17): 1527–60

    PubMed  Article  CAS  Google Scholar 

  19. Veterans Administration Co-Operative Study Group on Antihypertensive Agents. Racial differences in response to low-dose Captopril are abolished by the addition of hydrochlorothiazide. Br J Clin Pharmacol 1982; 14 Suppl. 2: 97S–101S

    Article  Google Scholar 

  20. Prisant LM, Neutel JM, Ferdinand K, et al. Low-dose combination therapy as first-line hypertension treatment for blacks and nonblacks. J Natl Med Assoc 1999 Jan; 91(1): 40–8

    PubMed  CAS  Google Scholar 

  21. Cappuccio FP, Markandu ND, Singer DR, et al. Amlodipine and lisinopril in combination for the treatment of essential hypertension: efficacy and predictors of response. J Hypertens 1993 Aug; 11(8): 839–47

    PubMed  Article  CAS  Google Scholar 

  22. Agodoa LY, Appel L, Bakris GL, et al. Effect of ramipril vs amlodipine on renal outcomes in hypernephrosclerosis: a randomized controlled trial. JAMA 2001; 285(21): 2719–28

    PubMed  Article  CAS  Google Scholar 

  23. Exner DV, Dries DL, Domanski MJ, et al. Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med 2001 May 3; 344(18): 1351–7

    PubMed  Article  CAS  Google Scholar 

  24. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazineisosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991 Aug 1; 325(5): 303–10

    PubMed  Article  CAS  Google Scholar 

  25. Carson P, Ziesche S, Johnson G, et al. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group. J Card Fail 1999 Sep; 5(3): 178–87

    PubMed  Article  CAS  Google Scholar 

  26. AIRE Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure: the Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet 1993 Oct 2; 342(8875): 821–8

    Google Scholar 

  27. Hall AS, Murray GD, Ball SG. Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy. Lancet 1997 May 24; 349(9064): 1493–7

    PubMed  Article  CAS  Google Scholar 

  28. He J, Klag MJ, Appel LJ, et al. The renin-angiotensin system and blood pressure: differences between blacks and whites. Am J Hypertens 1999 Jun; 12(6): 555–62

    PubMed  Article  CAS  Google Scholar 

  29. James GD, Sealey JE, Muller F, et al. Renin relationship to sex, race and age in a normotensive population. J Hypertens Suppl 1986 Dec; 4(5): S387–9

    PubMed  CAS  Google Scholar 

  30. He FJ, Markandu ND, Sagnella GA, et al. Importance of the renin system in determining blood pressure fall with salt restriction in black and white hypertensives. Hypertension 1998 Nov; 32(5): 820–4

    PubMed  Article  CAS  Google Scholar 

  31. Barley J, Carter ND, Cruickshank JK, et al. Renin and atrial natriuretic peptide restriction fragment length polymorphisms: association with ethnicity and blood pressure. J Hypertens 1991 Nov; 9(11): 993–6

    PubMed  Article  CAS  Google Scholar 

  32. Wagoner LE, Craft LL, Singh B, et al. Polymorphisms of the beta(2)-adrenergic receptor determine exercise capacity in patients with heart failure. Circ Res 2000 Apr 28; 86(8): 834–40

    PubMed  Article  CAS  Google Scholar 

  33. Cardillo C, Kilcoyne CM, Cannon III RO, et al. Attenuation of cyclic nucleotidemediated smooth muscle relaxation in blacks as a cause of racial differences in vasodilator function. Circulation 1999 Jan 5; 99(1): 90–5

    PubMed  Article  CAS  Google Scholar 

  34. Sagnella GA. Why is plasma renin activity lower in populations of African origin? J Hum Hypertens 2001; 15: 17–25

    PubMed  Article  CAS  Google Scholar 

  35. Sealey JE, Atlas SA, Laragh JH, et al. Human urinary kallikrein converts inactive to active renin and is a possible physiological activator of renin. Nature 1978 Sep 14; 275(5676): 144–5

    PubMed  Article  CAS  Google Scholar 

  36. Zinner SH, Margolius HS, Rosner B, et al. Familial aggregation of urinary kalli-krein concentration in childhood: relation to blood pressure, race and urinary electrolytes. Am J Epidemiol 1976 Aug; 104(2): 124–32

    PubMed  CAS  Google Scholar 

  37. White PC, Slutsker L. Haplotype analysis of CYP11B2. Endocr Res 1995 Feb; 21(1–2): 437–42

    PubMed  Article  CAS  Google Scholar 

  38. White PC, Hautanen A, Kupari M. Aldosterone synthase (CYP11B2) polymorphisms and cardiovascular function. Endocr Res 1998 Aug; 24(3–4): 797–804

    PubMed  Article  CAS  Google Scholar 

  39. Rossi E, Regolisti G, Perazzoli F, et al. -344C/T polymorphism of CYP11B2 gene in Italian patients with idiopathic low renin hypertension. Am J Hypertens 2001 Sep; 14(9 Pt 1): 934–41

    PubMed  Article  CAS  Google Scholar 

  40. Tiago AD, Nkeh B, Candy GP, et al. Association study of eight candidate genes with renin status in mild-to- moderate hypertension in patients of African ancestry. Cardiovasc J S Afr 2001 Apr; 12(2): 75–80

    PubMed  CAS  Google Scholar 

  41. Geller DS, Rodriguez-Soriano J, Vallo BA, et al. Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat Genet 1998 Jul; 19(3): 279–81

    PubMed  Article  CAS  Google Scholar 

  42. Ambrosius WT, Bloem LJ, Zhou L, et al. Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension. Hypertension 1999 Oct; 34(4 Pt 1): 631–7

    PubMed  Article  CAS  Google Scholar 

  43. Dong Y, Zhu H, Sagnella GA, et al. Association between the C825T polymorphism of the G protein beta3- subunit gene and hypertension in blacks. Hypertension 1999 Dec; 34(6): 1193–6

    PubMed  Article  CAS  Google Scholar 

  44. Schunkert H, Hense HW, Doring A, et al. Association between a polymorphism in the G protein beta3 subunit gene and lower renin and elevated diastolic blood pressure levels. Hypertension 1998 Sep; 32(3): 510–3

    PubMed  Article  CAS  Google Scholar 

  45. Siffert W, Rosskopf D, Siffert G, et al. Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet 1998 Jan; 18(1): 45–8

    PubMed  Article  CAS  Google Scholar 

  46. Baruch L, Anand I, Cohen IS, et al. Augmented short- and long-term haemodynamic and hormonal effects of an angiotensin receptor blocker added to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure. Circulation 1999 May 25; 99(20): 2658–64

    PubMed  Article  CAS  Google Scholar 

  47. Bassett Jr DR, Duey WJ, Walker AJ, et al. Racial differences in maximal vasodilatory capacity of forearm resistance vessels in normotensive young adults. Am J Hypertens 1992 Nov; 5(11): 781–6

    PubMed  Google Scholar 

  48. Liao Y, Husain A. The chymase-angiotensin system in humans: biochemistry, molecular biology and potential role in cardiovascular diseases. Can J Cardiol 1995 Aug; 11 Suppl. F: 13F–9F

    PubMed  CAS  Google Scholar 

  49. Rump LC, Oberhauser V, Schwertfeger E, et al. Experimental evidence to support ELITE. Lancet 1998 Feb 28; 351(9103): 644–5

    PubMed  Article  CAS  Google Scholar 

  50. Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus Captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997 Mar 15; 349(9054): 747–52

    PubMed  Article  CAS  Google Scholar 

  51. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with Captopril on mortality in patients with symptomatic heart failure: randomised trial: the Losartan Heart Failure Survival Study ELITE II. Lancet 2000 May 6; 355(9215): 1582–7

    PubMed  Article  CAS  Google Scholar 

  52. McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999 Sep 7; 100(10): 1056–64

    PubMed  Article  CAS  Google Scholar 

  53. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001 Dec 6; 345(23): 1667–75

    PubMed  Article  CAS  Google Scholar 

  54. Swedberg K, Pfeffer M, Granger C, et al. Candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM): rationale and design. Charm-Programme Investigators. J Card Fail 1999 Sep; 5(3): 276–82

    PubMed  Article  CAS  Google Scholar 

  55. Dickstein K, Kjekshus J. Comparison of the effects of losartan and Captopril on mortality in patients after acute myocardial infarction: the OPTIMAAL trial design. Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan. Am J Cardiol 1999 Feb 15; 83(4): 477–81

    PubMed  Article  CAS  Google Scholar 

  56. Pfeffer MA, McMurray J, Leizorovicz A, et al. Valsartan in acute myocardial infarction trial (VALIANT): rationale and design. Am Heart J 2000 Nov; 140(5): 727–50

    PubMed  Article  CAS  Google Scholar 

  57. Pitt B, Zannad F, Remme WJ, et al. The effect of Spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999 Sep 2; 341(10): 709–17

    PubMed  Article  CAS  Google Scholar 

  58. MacFadyen RJ, Barr CS, Struthers AD. Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cardiovasc Res 1997 Jul; 35(1): 30–4

    PubMed  Article  CAS  Google Scholar 

  59. Wang W. Chronic administration of aldosterone depresses baroreceptor reflex function in the dog. Hypertension 1994 Nov; 24(5): 571–5

    PubMed  Article  CAS  Google Scholar 

  60. Flamenbaum W, Weber MA, McMahon FG, et al. Monotherapy with labetalol compared with Propranolol: differential effects by race. J Clin Hypertens 1985 Mar; 1(1): 56–69

    PubMed  CAS  Google Scholar 

  61. Nugent LW, Miola SR, Walker JF. A comparison of enalapril and metoprolol as initial therapy for mild to moderate hypertension. J Clin Pharmacol 1987 Jul; 27(7): 461–7

    PubMed  CAS  Google Scholar 

  62. MERIT-HF Study Investigators. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999 Jun 12; 353(9169): 2001–7

    Article  Google Scholar 

  63. CIBIS II Investigators. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999 Jan 2; 353(9146): 9–13

    Article  Google Scholar 

  64. Eichhorn EJ, Bristow MR. The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Curr Control Trials Cardiovasc Med 2001; 2(1): 20–3

    PubMed  Article  CAS  Google Scholar 

  65. Packer M, Bristow MR, Cohn JN, et al. The effect of Carvedilol on morbidity and mortality in patients with chronic heart failure: US Carvedilol Heart Failure Study Group. N Engl J Med 1996 May 23; 334(21): 1349–55

    PubMed  Article  CAS  Google Scholar 

  66. Lechat P, Packer M, Chalon S, et al. Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation 1998 Sep 22; 98(12): 1184–91

    PubMed  Article  CAS  Google Scholar 

  67. Beta Blockers Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001 May 31; 344(22): 1659–67

    Article  Google Scholar 

  68. Yancy CW, Fowler MB, Colucci WS, et al. Race and the response to adrenergic blockade with Carvedilol in patients with chronic heart failure. N Engl J Med 2001 May 3; 344(18): 1358–65

    PubMed  Article  CAS  Google Scholar 

  69. Freudenberger R, Kaiman J, Mannino M, et al. Effect of race in the response to metoprolol in patients with congestive heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. Am J Cardiol 1997 Nov 15; 80(10): 1372–4

    PubMed  Article  CAS  Google Scholar 

  70. Dayer P, Balant L, Courvoisier F, et al. The genetic control of bufuralol metabolism in man. Eur J Drug Metab Pharmacokinet 1982 Jan; 7(1): 73–7

    PubMed  Article  CAS  Google Scholar 

  71. McGourty JC, Silas JH, Lennard MS, et al. Metoprolol metabolism and debrisoquine oxidation polymorphism: population and family studies. Br J Clin Pharmacol 1985 Dec; 20(6): 555–66

    PubMed  Article  CAS  Google Scholar 

  72. McGourty JC, Silas JH, Fleming JJ, et al. Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin. Clin Pharmacol Ther 1985 Oct; 38(4): 409–13

    PubMed  Article  CAS  Google Scholar 

  73. Zhou HH, Wood AJ. Stereoselective disposition of Carvedilol is determined by CYP2D6. Clin Pharmacol Ther 1995 May; 57(5): 518–24

    PubMed  Article  CAS  Google Scholar 

  74. Evans WE, Relling MV, Rahman A, et al. Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in black Americans. J Clin Invest 1993 May; 91(5): 2150–4

    PubMed  Article  CAS  Google Scholar 

  75. Rudner XL, Berkowitz DE, Booth JV, et al. Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age. Circulation 1999 Dec 7; 100(23): 2336–43

    PubMed  Article  CAS  Google Scholar 

  76. Sherwood A, Hinderliter AL. Responses to alpha- and beta-adrenergic receptor agonists: effects of race in borderline hypertension compared to normotensive man. Am J Hypertens 1993 Jul; 6(7 Pt 1): 630–5

    PubMed  CAS  Google Scholar 

  77. Stein CM, Lang CC, Singh I, et al. Increased vascular alpha-adrenergic sensitivity in African-Americans [abstract]. Clin Pharmacol Ther 1998; 63: 176

    Google Scholar 

  78. Stein CM, Lang CC, Singh I, et al. Increased vasoconstriction and decreased vasodilation not increased sympathetic activity are mechanisms for enhanced vascular reactivity in African-Americans [abstract]. Circulation 1998; 98:1472

    Article  Google Scholar 

  79. Xie HG, Kim RB, Stein CM, et al. AlphalA-adrenergic receptor polymorphism: association with ethnicity but not essential hypertension. Pharmacogenetics 1999 Oct; 9(5): 651–6

    PubMed  Article  CAS  Google Scholar 

  80. Veterans Administration Co-operative Study Group on Antihypertensive Agents. Comparison of Propranolol and hydrochlorothiazide for the initial treatment of hypertension: I. results of short-term titration with emphasis on racial differences in response. Veterans Administration Cooperative Study Group on Antihypertensive agents. JAMA 1982 Oct 22; 248(16): 1996–2003

    Article  Google Scholar 

  81. Veterans Administration Co-operative Study Group on Antihypertensive Agents. Efficacy of nadolol alone and combined with bendroflumethiazide and hydralazine for systemic hypertension. Am J Cardiol 1983 Dec 1; 52(10): 1230–7

    Article  Google Scholar 

  82. Johnson JA, Burlew BS, Stiles RN. Racial differences in beta-adrenoceptor-mediated responsiveness. J Cardiovasc Pharmacol 1995 Jan; 25(1): 90–6

    PubMed  Article  CAS  Google Scholar 

  83. Borjesson M, Magnusson Y, Andersson B. A novel polymorphism in the gene coding for the betal-receptor associated with survival in patients with heart failure [abstract]. J Am Coll Cardiol 1999; 33: 261A

    Article  Google Scholar 

  84. Moore JD, Mason DA, Green SA, et al. Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of cl45A>G and c1165G>C [abstract]. Hum Mutat 1999 Sep 19; 14(3): 271

    PubMed  Article  CAS  Google Scholar 

  85. Lang CC, Stein CM, Brown RM, et al. Attenuation of isoproterenol-mediated vasodilatation in blacks. N Engl J Med 1995 Jul 20; 333(3): 155–60

    PubMed  Article  CAS  Google Scholar 

  86. Siffert W, Forster P, Jockei KH, et al. Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J Am Soc Nephral 1999 Sep; 10(9): 1921–30

    CAS  Google Scholar 

  87. Baumgart D, Naber C, Haude M, et al. G protein beta3 subunit 825T allele and enhanced coronary vasoconstriction on alpha(2)-adrenoceptor activation. Circ Res 1999 Nov 12; 85(10): 965–9

    PubMed  Article  CAS  Google Scholar 

  88. Schafers RF, Nurnberger J, Rutz A, et al. Vasoconstrictor response of the human dorsal hand vein in young normotensive men carrying the 825T-allele of the G-protein beta-3 subunit [abstract]. Br J Clin Pharmacol 1999; 48: 872P

    Google Scholar 

  89. Rodriguez I, Abernethy DR, Woosley RL. P-Glycoprotein in clinical cardiology. Circulation 1999 Feb 2; 99(4): 472–4

    PubMed  Article  CAS  Google Scholar 

  90. Andrews PA, Sen M, Chang RW. Racial variation in dosage requirements of tacrolimus [letter]. Lancet 1996 Nov 23; 348(9039): 1446

    PubMed  Article  CAS  Google Scholar 

  91. Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure: the Digitalis Investigation Group. N Engl J Med 1997 Feb 20; 336(8): 525–33

    Article  Google Scholar 

  92. Ferguson DW, Berg WJ, Sanders JS, et al. Sympathoinhibitory responses to digitalis glycosides in heart failure patients: direct evidence from sympathetic neural recordings. Circulation 1989 Jul; 80(1): 65–77

    PubMed  Article  CAS  Google Scholar 

  93. Covit AB, Schaer GL, Sealey JE, et al. Suppression of the renin-angiotensin system by intravenous digoxin in chronic congestive heart failure. Am J Med 1983 Sep; 75(3): 445–7

    PubMed  Article  CAS  Google Scholar 

  94. Ferguson DW. Digitalis and neurohormonal abnormalities in heart failure and implications for therapy. Am J Cardiol 1992 Jun 4; 69(18): 24G–32G

    PubMed  Article  CAS  Google Scholar 

  95. Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study. N Engl J Med 1986 Jun 12; 314(24): 1547–52

    PubMed  Article  CAS  Google Scholar 

  96. Vallance P. Nitric oxide in the human cardiovascular system: SKB lecture 1997. Br J Clin Pharmacol 1998 May; 45(5): 433–9

    PubMed  Article  CAS  Google Scholar 

  97. Jones DS, Andrawis NS, Abernethy DR. Impaired endothelial-dependent forearm vascular relaxation in black Americans. Clin Pharmacol Ther 1999 Apr; 65(4): 408–12

    PubMed  Article  CAS  Google Scholar 

  98. Gainer JV, Stein M, King D, et al. Racial differences in bradykinin-induced forearm blood flow [abstract]. Circulation 1998; 98:1243

    Google Scholar 

  99. Stein CM, Lang CC, Nelson R, et al. Vasodilation in black Americans: attenuated nitric oxide-mediated responses. Clin Pharmacol Ther 1997 Oct; 62(4): 436–43

    PubMed  Article  CAS  Google Scholar 

  100. Cardillo C, Kilcoyne CM, Cannon III RO, et al. Racial differences in nitric oxidemediated vasodilator response to mental stress in the forearm circulation. Hypertension 1998 Jun; 31(6): 1235–9

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgements

Justin Taylor is a clinical research fellow in cardiology. Gethin Ellis is a consultant in cardiology and general medicine. There are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gethin R. Ellis.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Taylor, J.S.W., Ellis, G.R. Racial Differences in Responses to Drug Treatment. Am J Cordiovosc Drugs 2, 389–399 (2002). https://doi.org/10.2165/00129784-200202060-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00129784-200202060-00004

Keywords

  • Chronic Heart Failure
  • Enalapril
  • Carvedilol
  • Valsartan
  • Black Patient