American Journal of Cardiovascular Drugs

, Volume 4, Issue 6, pp 345–353 | Cite as

Angiotensin Antagonism in Patients with Heart Failure

ACE Inhibitors, Angiotensin Receptor Antagonists or Both?
Current Opinion

Abstract

Chronic heart failure (CHF) is a major cause of morbidity and mortality in western society. It is now widely accepted that the renin-angiotensin-aldosterone system (RAAS) and, in particular, angiotensin II (A-II) play a key role in the pathophysiology of CHF. Large-scale clinical trials have demonstrated that inhibitors of angiotensin-converting enzyme (ACE), the principal enzyme responsible for A-II production, improve symptoms and survival in patients with CHF. This enzyme is also responsible for the breakdown of the vasodilator hormone bradykinin. Administration of ACE inhibitors is associated with increased plasma bradykinin levels and this is thought to contribute to the vascular changes associated with ACE inhibitor therapy. However, RAAS inhibition with ACE inhibitors remains incomplete because ACE inhibitors do not block the non-ACE-mediated conversion of angiotensin I to A-II. Angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) antagonize the action of A-II at the A-II type 1 (AT1) receptor, whilst allowing the potentially beneficial actions of A-II mediated via the A-II type 2 (AT2) receptor. Evidence that the clinical benefit demonstrated with ACE inhibitors in patients with CHF may extend to ARBs has only emerged recently. Combination therapy with both an ACE inhibitor and an ARB has a number of potential advantages and has been investigated in several large-scale clinical trials recently. In patients with CHF, first-line therapy should include an ACE inhibitor and a β-adrenoceptor antagonist. The addition of an ARB provides symptomatic relief but has not been shown to improve survival. Where an ACE inhibitor is not tolerated, treatment with an ARB would seem an appropriate alternative. There is insufficient data to support the routine use of ARBs as first-line therapy in the management of CHF.

Notes

Acknowledgments

Drs Cruden and Newby have received funding from Pfizer (UK) Ltd in the form of an unrestricted educational award. There are no other potential conflicts of interest directly relevant to this manuscript.

References

  1. 1.
    Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–9PubMedCrossRefGoogle Scholar
  2. 2.
    HOPE Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000; 355: 253–9CrossRefGoogle Scholar
  3. 3.
    Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-convertingenzyme inhibition on diabetic nephropathy: the Collaborative Study Group. N Engl J Med 1993; 329: 1456–62PubMedCrossRefGoogle Scholar
  4. 4.
    Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–60PubMedCrossRefGoogle Scholar
  5. 5.
    Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–8PubMedCrossRefGoogle Scholar
  6. 6.
    The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857–63CrossRefGoogle Scholar
  7. 7.
    Ruggenenti P, Perna A, Gherardi G, et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999; 354: 359–64PubMedCrossRefGoogle Scholar
  8. 8.
    Yu HT. Progression of chronic renal failure. Arch Intern Med 2003; 163: 1417–29PubMedCrossRefGoogle Scholar
  9. 9.
    Erdös EG, Yang HYT. An enzyme in microsomal fraction of kidney that inactivates bradykinin. Life Sci 1967; 6: 569–74PubMedCrossRefGoogle Scholar
  10. 10.
    Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002; 89: 3A–9APubMedCrossRefGoogle Scholar
  11. 11.
    Hein L, Barsh GS, Pratt RE, et al. Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature 1995; 377: 744–7PubMedCrossRefGoogle Scholar
  12. 12.
    Tanaka M, Tsuchida S, Imai T, et al. Vascular response to angiotensin II is exaggerated through an upregulation of AT1 receptor in AT2 knockout mice. Biochem Biophys Res Commun 1999; 258: 194–8PubMedCrossRefGoogle Scholar
  13. 13.
    Adachi Y, Saito Y, Kishimoto I, et al. Angiotensin II type 2 receptor deficiency exacerbates heart failure and reduces survival after acute myocardial infarction in mice. Circulation 2003; 107: 2406–8PubMedCrossRefGoogle Scholar
  14. 14.
    Oishi Y, Ozono R, Yano Y, et al. Cardioprotective role of AT2 receptor in postinfarction left ventricular remodeling. Hypertension 2003; 41: 814–8PubMedCrossRefGoogle Scholar
  15. 15.
    Wu L, Iwai M, Nakagami H, et al. Effect of angiotensin II type 1 receptor blockade on cardiac remodeling in angiotensin II type 2 receptor null mice. Arterioscler Thromb Vasc Biol 2002; 22: 49–54PubMedCrossRefGoogle Scholar
  16. 16.
    Xu J, Carretero OA, Liu YH, et al. Role of AT2 receptors in the cardioprotective effect of AT1 antagonists in mice. Hypertension 2002; 40: 244–50PubMedCrossRefGoogle Scholar
  17. 17.
    Ichihara S, Senbonmatsu T, Price Jr E, et al. Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and cardiac fibrosis in chronic angiotensin II-induced hypertension. Circulation 2001; 104: 346–51PubMedCrossRefGoogle Scholar
  18. 18.
    Senbonmatsu T, Ichihara S, Price Jr E, et al. Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J Clin Invest 2000; 106: R1–5PubMedCrossRefGoogle Scholar
  19. 19.
    Levy BI, Benessiano J, Henrion D, et al. Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat vascular structure. J Clin Invest 1996; 98: 418–25PubMedCrossRefGoogle Scholar
  20. 20.
    Schneider MD, Lorell BH. AT(2), judgment day: which angiotensin receptor is the culprit in cardiac hypertrophy? Circulation 2001; 104: 247–8PubMedCrossRefGoogle Scholar
  21. 21.
    Gavras H, Brunner HR, Turini GA, et al. Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. N Engl J Med 1978; 298: 991–5PubMedCrossRefGoogle Scholar
  22. 22.
    MacFadyen RJ, Lee AF, Morton JJ, et al. How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure? Heart 1999; 82: 57–61PubMedGoogle Scholar
  23. 23.
    Petrie MC, Padmanabhan N, McDonald JE, et al. Angiotensin converting enzyme (ACE) and non-ACE dependent angiotensin II generation in resistance arteries from patients with heart failure and coronary heart disease. J Am Coll Cardiol 2001; 37: 1056–61PubMedCrossRefGoogle Scholar
  24. 24.
    Roig E, Perez-Villa F, Morales M, et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J 2000; 21: 53–7PubMedCrossRefGoogle Scholar
  25. 25.
    Beermann B, Nyquist O, Hoglund C, et al. Acute haemodynamic effects and pharmacokinetics of ramipril in patients with heart failure: a placebo controlled three-dose study. Eur J Clin Pharmacol 1993; 45: 241–6PubMedCrossRefGoogle Scholar
  26. 26.
    Mitrovic V, Mudra H, Bonzel T, et al. Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart failure. Clin Pharmacol Ther 1996; 59: 686–98PubMedCrossRefGoogle Scholar
  27. 27.
    Flammang D, Waynberger M, Chassing A. Acute and long-term efficacy of perindopril in severe chronic congestive heart failure. Am J Cardiol 1993; 71: 48E–56EPubMedCrossRefGoogle Scholar
  28. 28.
    Powers ER, Bannerman KS, Stone J, et al. The effect of captopril on renal, coronary, and systemic hemodynamics in patients with severe congestive heart failure. Am Heart J 1982; 104: 1203–10PubMedCrossRefGoogle Scholar
  29. 29.
    Hollenberg NK. Angiotensin converting enzyme inhibition and the kidney. Curr Opin Cardiol 1988; 3: S19–29PubMedCrossRefGoogle Scholar
  30. 30.
    Antony I, Lerebours G, Nitenberg A. Angiotensin-converting enzyme inhibition restores flow-dependent and cold pressor test-induced dilations in coronary arteries of hypertensive patients. Circulation 1996; 94: 3115–22PubMedCrossRefGoogle Scholar
  31. 31.
    Anderson TJ, Elstein E, Haber H, et al. Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease: BANFF study. J Am Coll Cardiol 2000; 35: 60–6PubMedCrossRefGoogle Scholar
  32. 32.
    O’Driscoll G, Green D, Maiorana A, et al. Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 1999; 33: 1506–11PubMedCrossRefGoogle Scholar
  33. 33.
    Hornig B, Landmesser U, Kohler C, et al. Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of Superoxide dismutase. Circulation 2001; 103: 799–805PubMedCrossRefGoogle Scholar
  34. 34.
    Hornig B, Arakawa N, Haussmann D, et al. Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure. Circulation 1998; 98: 2842–8PubMedCrossRefGoogle Scholar
  35. 35.
    Goodfield NE, Newby DE, Ludlam CA, et al. Effects of acute angiotensin II type 1 receptor antagonism and angiotensin converting enzyme inhibition on plasma fibrinolytic parameters in patients with heart failure. Circulation 1999; 99: 2983–5PubMedCrossRefGoogle Scholar
  36. 36.
    Ridker PM, Gaboury CL, Conlin PR, et al. Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II: evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function. Circulation 1993; 87: 1969–73PubMedCrossRefGoogle Scholar
  37. 37.
    Witherow FN, Dawson P, Ludlam CA, et al. Marked bradykinin-induced tissue plasminogen activator release in patients with heart failure maintained on long-term angiotensin-converting enzyme inhibitor therapy. J Am Coll Cardiol 2002; 40: 961–6PubMedCrossRefGoogle Scholar
  38. 38.
    Jaspard E, Wei L, Alhenc-Gelas F. Differences in the properties and enzymatic specificities of the two active sites of angiotensin I-converting enzyme (kininase II): studies with bradykinin and other natural peptides. J Biol Chem 1993; 268: 9496–503PubMedGoogle Scholar
  39. 39.
    Gainer JV, Morrow JD, Loveland A, et al. Effect of bradykinin-receptor blockade on the response to angiotensin-converting-enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med 1998; 339: 1285–92PubMedCrossRefGoogle Scholar
  40. 40.
    Squire IB, O’Kane KP, Anderson N, et al. Bradykinin B(2) receptor antagonism attenuates blood pressure response to acute angiotensin-converting enzyme inhibition in normal men. Hypertension 2000; 36: 132–6PubMedCrossRefGoogle Scholar
  41. 41.
    Witherow FN, Helmy A, Webb DJ, et al. Bradykinin contributes to the vasodilator effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure. Circulation 2001; 104: 2177–81PubMedCrossRefGoogle Scholar
  42. 42.
    Cruden NL, Witherow FN, Webb DJ, et al. Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure. Arterioscler Thromb Vasc Biol 2004; 24: 1043–8PubMedCrossRefGoogle Scholar
  43. 43.
    Vaughan DE, Pfeffer MA. Angiotensin converting enzyme inhibitors and cardio vascular remodelling. Cardiovasc Res 1994; 28: 159–65PubMedCrossRefGoogle Scholar
  44. 44.
    Pfeffer JM, Pfeffer MA, Mirsky I, et al. Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. Proc Natl Acad Sci USA 1982; 79: 3310–4PubMedCrossRefGoogle Scholar
  45. 45.
    Nakashima Y, Fouad FM, Tarazi RC. Regression of left ventricular hypertrophy from systemic hypertension by enalapril. Am J Cardiol 1984; 53: 1044–9PubMedCrossRefGoogle Scholar
  46. 46.
    Pfeffer MA, Lamas GA, Vaughan DE, et al. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 1988; 319: 80–6PubMedCrossRefGoogle Scholar
  47. 47.
    The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293–302CrossRefGoogle Scholar
  48. 48.
    Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS): effects of enalapril on mortality in severe congestive heart failure. The CONSENSUS Trial Study Group. N Engl J Med 1987; 316: 1429–35CrossRefGoogle Scholar
  49. 49.
    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; 100: 2312–8PubMedCrossRefGoogle Scholar
  50. 50.
    The 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; 327: 685–91CrossRefGoogle Scholar
  51. 51.
    Flather MD, Yusuf S, Kober L, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000; 355: 1575–81PubMedCrossRefGoogle Scholar
  52. 52.
    Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327: 669–77PubMedCrossRefGoogle Scholar
  53. 53.
    Yusuf S, Pepine CJ, Garces C, et al. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions. Lancet 1992; 340: 1173–8PubMedCrossRefGoogle Scholar
  54. 54.
    Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145–53PubMedCrossRefGoogle Scholar
  55. 55.
    Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebocontrolled, multicentre trial (the EUROPA study). Lancet 2003; 362: 782–8PubMedCrossRefGoogle Scholar
  56. 56.
    Brown NJ, Vaughan DE. Angiotensin-converting enzyme inhibitors. Circulation 1998; 97: 1411–20PubMedCrossRefGoogle Scholar
  57. 57.
    Havranek EP, Thomas I, Smith WB, et al. Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure. J Am Coll Cardiol 1999; 33: 1174–81PubMedCrossRefGoogle Scholar
  58. 58.
    Riegger GA, Bouzo H, Petr P, et al. Improvement in exercise tolerance and symptoms of congestive heart failure during treatment with candesartan cilexe-til: Symptom, Tolerability, Response to Exercise Trial of Candesartan Cilexetil in Heart Failure (STRETCH) Investigators. Circulation 1999; 100: 2224–30PubMedCrossRefGoogle Scholar
  59. 59.
    Baruch L, Anand I, Cohen IS, et al. Augmented short- and long-term hemodynamic and hormonal effects of an angiotensin receptor blocker added to angiotensin converting enzyme inhibitor therapy in patients with heart failure: Vasodilator Heart Failure Trial (V-HeFT) Study Group. Circulation 1999; 99: 2658–64PubMedCrossRefGoogle Scholar
  60. 60.
    Crozier I, Ikram H, Awan N, et al. Losartan in heart failure: hemodynamic effects and tolerability. Losartan Hemodynamic Study Group. Circulation 1995; 91: 691–7PubMedCrossRefGoogle Scholar
  61. 61.
    Prasad A, Tupas-Habib T, Schenke WH, et al. Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis. Circulation 2000; 101: 2349–54PubMedCrossRefGoogle Scholar
  62. 62.
    Brown NJ, Kumar S, Painter CA, et al. ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time. Hypertension 2002; 40: 859–65PubMedCrossRefGoogle Scholar
  63. 63.
    Lottermoser K, Hertfelder HJ, Vetter H, et al. Fibrinolytic function in diureticinduced volume depletion. Am J Hypertens 2000; 13: 359–63PubMedCrossRefGoogle Scholar
  64. 64.
    Soejima H, Ogawa H, Suefuji H, et al. Comparison of effects of losartan versus enalapril on fibrinolysis and coagulation in patients with acute myocardial infarction. Am J Cardiol 2001; 87: 1408–11PubMedCrossRefGoogle Scholar
  65. 65.
    Erdem Y, Usalan C, Haznedaroglu IC, et al. Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension. Am J Hypertens 1999; 12: 1071–6PubMedCrossRefGoogle Scholar
  66. 66.
    Seljeflot I, Moan A, Kjeldsen S, et al. Effect of angiotensin II receptor blockade on fibrinolysis during acute hyperinsulinemia in patients with essential hypertension. Hypertension 1996; 27: 1299–304PubMedCrossRefGoogle Scholar
  67. 67.
    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; 341: 709–17PubMedCrossRefGoogle Scholar
  68. 68.
    Segev A, Mekori YA. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353: 9–13CrossRefGoogle Scholar
  69. 69.
    Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309–21PubMedCrossRefGoogle Scholar
  70. 70.
    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; 349: 747–52PubMedCrossRefGoogle Scholar
  71. 71.
    Sharma D, Buyse M, Pitt B, et al. Meta-analysis of observed mortality data from all-controlled, double-blind, multiple-dose studies of losartan in heart failure: Losartan Heart Failure Mortality Meta-analysis Study Group. Am J Cardiol 2000; 85: 187–92PubMedCrossRefGoogle Scholar
  72. 72.
    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: Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582–7PubMedCrossRefGoogle Scholar
  73. 73.
    Hall A. Comparison of losartan and captopril in ELITE II. Lancet 2000; 356: 851–3PubMedCrossRefGoogle Scholar
  74. 74.
    Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002; 360: 752–60PubMedCrossRefGoogle Scholar
  75. 75.
    Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893–906PubMedCrossRefGoogle Scholar
  76. 76.
    Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003; 362: 759–66PubMedCrossRefGoogle Scholar
  77. 77.
    Granger CB, McMurray JJV, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362: 772–6PubMedCrossRefGoogle Scholar
  78. 78.
    McMurray JJV, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003; 362: 767–71PubMedCrossRefGoogle Scholar
  79. 79.
    Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial. Lancet 2003; 362: 777–81PubMedCrossRefGoogle Scholar
  80. 80.
    Hamroff G, Katz SD, Mancini D, et al. Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure. Circulation 1999; 99: 990–2PubMedCrossRefGoogle Scholar
  81. 81.
    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; 100: 1056–64PubMedCrossRefGoogle Scholar
  82. 82.
    Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 1667–75PubMedCrossRefGoogle Scholar
  83. 83.
    Maggioni AP, Anand I, Gottlieb SO, et al. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 2002; 40: 1414–21PubMedCrossRefGoogle Scholar
  84. 84.
    Jong P, Demers C, McKelvie RS, et al. Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Cardiol 2002; 39: 463–70PubMedCrossRefGoogle Scholar
  85. 85.
    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; 314: 1547–52PubMedCrossRefGoogle Scholar
  86. 86.
    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; 325: 303–10PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of Cardiology, Cardiovascular ResearchUniversity of Edinburgh, Royal Infirmary of EdinburghEdinburghScotland

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