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Drugs

, Volume 32, Supplement 5, pp 13–26 | Cite as

The Role of Vasodilator Therapy in the Treatment of Severe Chronic Heart Failure

  • Milton Packer
Article

Summary

The rationale for the use of vasodilating agents in the treatment of congestive heart failure is to reverse the systemic vasoconstriction that characterises patients with this disorder, and which may further limit cardiac performance. Nitrates were the first vasodilators used, followed by arterial vasodilators (hydralazine, minoxidil), α-adrenergic blockers (prazosin, trimazosin) and, more recently, calcium antagonists, ACE inhibitors, β-agonists and phosphodiesterase inhibitors.

The choice of vasodilator should be based on consideration of overall benefit-risk profiles. Consideration of pharmacological action together with classification of patients into haemodynamic subsets has been used as a basis from which to initiate vasodilator therapy. However, such a classification may not lead to a logical choice of drug and there is no evidence to suggest that patients so selected do better when given long term treatment with peripherally specific drugs than with agents that are not tailored to pretreatment haemodynamic variables. Moreover, changes in central haemodynamics after administration of specific vasodilator drugs may differ from those expected on the basis of their presumed actions on the peripheral vasculature.

Dosage requirements are difficult to predict with many vasodilator drugs. Traditionally, such requirements have been established by titrating vasodilating drugs to achieve an arbitrarily defined haemodynamic response. However, there is little correlation between haemodynamic end-points and clinical efficacy in patients with heart failure, and short and long term haemodynamic responses to vasodilator drugs are not necessarily related.

Drug-specific haemodynamic and clinical tolerance occurs during the course of treatment with all vasodilator drugs; the extent and frequency with which it develops differs between agents. Tolerance is thought to arise from a reduction in drug receptor affinity and/or density or activation of counter-regulatory forces (mainly neurohormonal) that limit the magnitude of vasodilatation that can be achieved. Development of tolerance to a single agent does not usually preclude efficacy of other agents. ACE inhibitors have been associated with a relatively low incidence of tolerance. This may relate to their natriuretic effect and ability to decrease the degree of neurohormonal activation, actions not shared by other vasodilators. Tolerance is the principal reason for failure of prazosin and nitrates as therapeutic agents in severe chronic heart failure.

Side effects inherent in all vasodilator drugs include hypoperfusion reactions (symptomatic hypotension, renal insufficiency) and those related to secondary activation of the sympathetic nervous and renin-angiotensin systems (tachycardia, fluid retention, myocardial ischaemia). Compared with other vasodilators, ACE inhibitors are more likely to produce hypoperfusion reactions but less likely to cause side effects related to neurohormonal activation. Because of the poor prognosis for severe chronic heart failure, concerns about the occurrence of adverse drug reactions during long term use of some vasodilators (lupus syndrome and hydralazine) should not preclude use or necessitate discontinuation of effective therapy.

The prognosis for heart failure appears to be primarily determined by neurohormonal factors; circulating levels of noradrenaline and angiotensin II are most elevated in patients with the least favourable long term prognosis. Vasodilators such as the ACE inhibitors and β-blockers which modify the neurohormonal response in chronic heart failure may thus be expected to achieve a favourable impact on survival. Large scale trials are currently in progress to prospectively address this issue.

Keywords

Heart Failure Chronic Heart Failure Captopril Prazosin Plasma Renin Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adam WR, Goland GJ, Wellard RM. Renal potassium adaptation in the rat: role of glucocorticoids and aldosterone. American Journal of Physiology 246: F300–308, 1984PubMedGoogle Scholar
  2. Anderson JL, Lutz JR, Gilbert EM, et al. A randomized trial of low-dose beta-blockade therapy for idiopathic dilated cardiomyopathy. American Journal of Cardiology 55: 471–475, 1985PubMedCrossRefGoogle Scholar
  3. Agostoni PG, de Cesare N, Doria E, Polese A, Tamborini G, Guazzi MD. Afterload reduction: a comparison of captopril and nifedipine in dilated cardiomyopathy. British Heart Journal 55: 391, 1986PubMedCrossRefGoogle Scholar
  4. Awan NA, Evenson MK, Needham KE, et al. Hemodynamic effects of oral pirbuterol in chronic severe congestive heart failure. Circulation 63: 96–101, 1981PubMedCrossRefGoogle Scholar
  5. Bayliss J, Norell MS, Canepa-Anson R, Reid C, Poole-Wilson P, Sutton G. Clinical importance of the renin-angiotensin system in chronic heart failure: double-blind comparison of captopril and prazosin. British Medical Journal 290: 1861–1865, 1985PubMedCrossRefGoogle Scholar
  6. Benotti JR, Grossman W, Braunwald E, Davolos DD, Alousi AA. Hemodynamic assessment of amrinone. New England Journal of Medicine 299: 1373–1377, 1978PubMedCrossRefGoogle Scholar
  7. Brown MJ, Bown DC, Murphy MB. Hypokalaemia from beta-receptor stimulation by circulating epinephrine. New England Journal of Medicine 309: 1414–1418, 1983PubMedCrossRefGoogle Scholar
  8. Captopril Multicenter Research Group. A placebo-controlled trial of captopril in refractory chronic congestive heart failure. Journal of the American College of Cardiology 2: 755–763, 1983CrossRefGoogle Scholar
  9. Chadda K, Goldstein S, Byington R, Curb JD. Effect of propranolol after acute myocardial infarction in patients with congestive heart failure. Circulation 73: 503–510, 1986PubMedCrossRefGoogle Scholar
  10. Chatterjee K, Parmley WW, Swan HJC, Berman G, Forrester J, Marcus HS. Beneficial effects of vasodilator agents in severe mitral regurgitation due to dysfunction of subvalvular apparatus. Circulation 48: 684–690, 1973PubMedCrossRefGoogle Scholar
  11. Chatterjee K, Parmley WW, Massie B, et al. Oral hydralazine therapy for chronic refractory heart failure. Circulation 54: 879–883, 1976PubMedCrossRefGoogle Scholar
  12. Cleland JGF, Dargie HJ, Hodsman GP, et al. Captopril in heart failure: a double-blind controlled trial. British Heart Journal 52: 530–535, 1984PubMedCrossRefGoogle Scholar
  13. Cleland JGF, Dargie HJ, Ball SG, et al. Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state. British Heart Journal 54: 305–312, 1985PubMedCrossRefGoogle Scholar
  14. Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. New England Journal of Medicine 311: 819–823, 1984PubMedCrossRefGoogle Scholar
  15. 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 (VHeFT). New England Journal of Medicine 314: 1547–1552, 1986PubMedCrossRefGoogle Scholar
  16. Colucci WS, Williams GH, Braunwald E. Increased plasma norepinephrine levels during prazosin therapy for severe congestive heart failure. Annals of Internal Medicine 93: 452–453, 1980PubMedGoogle Scholar
  17. Colucci WS, Alexander RW, Williams GH, et al. Decreased lymphocyte beta-receptor density in patients with heart failure and tolerance to the beta-adrenergic agonist pirbuterol. New England Journal of Medicine 305: 185–190, 1981PubMedCrossRefGoogle Scholar
  18. Creager MA, Massie BM, Faxon DP, et al. Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure. Journal of the American College of Cardiology 6: 163, 1985PubMedCrossRefGoogle Scholar
  19. Elkayam U, Weber L, Torkan B, McKay CR, Rahimtoola SH. Comparison of hemodynamic responses to nifedipine and nitroprusside in severe chronic congestive heart failure. American Journal of Cardiology 53: 1321–1325, 1984PubMedCrossRefGoogle Scholar
  20. Franciosa JA, Nordstrom LA, Cohn JN. Nitrate therapy for congestive heart failure. Journal of the American Medical Association 240: 443–446, 1978PubMedCrossRefGoogle Scholar
  21. Franciosa JA, Goldsmith SR, Cohn JN. Contrasting immediate and long-term effects of isosorbide dinitrate on exercise capacity in congestive heart failure. American Journal of Medicine 69: 559–566, 1980PubMedCrossRefGoogle Scholar
  22. Franciosa JA, Park M, Levine TB. Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. American Journal of Cardiology 47: 33–39, 1981PubMedCrossRefGoogle Scholar
  23. Franciosa JA, Weber KT, Levine TB, et al. Hydralazine in the long-term treatment of chronic heart failure: lack of difference from placebo. American Heart Journal 104: 587–594, 1982PubMedCrossRefGoogle Scholar
  24. Franciosa JA, Dunkman B, Leddy CL. Hemodynamic effects of vasodilators and long-term response in heart failure. Journal of the American College of Cardiology 3: 1521–1530, 1984PubMedCrossRefGoogle Scholar
  25. Franciosa JA, Wilen MM, Jordan RA. Effects of enalapril, a new angiotensin-converting enzyme inhibitor, in a controlled trial in heart failure. Journal of the American College of Cardiology 5: 101–107, 1985PubMedCrossRefGoogle Scholar
  26. Francis GS, Goldsmith SR, Olivari MT, Levine TB, Cohn JN. The neurohormonal axis in congestive heart failure. Annals of Internal Medicine 101: 370–377, 1984PubMedGoogle Scholar
  27. Furberg CD. Yusuf S. Effect of vasodilators on survival in chronic congestive heart failure. American Journal of Cardiology 1110–1113, 1985Google Scholar
  28. Greenberg BH, Massie BM, Brundage BH, Botvinick EH, Parmley WW, Chatterjee K. Beneficial effects of hydralazine in severe mitral regurgitation. Circulation 58: 273–279, 1978PubMedCrossRefGoogle Scholar
  29. Gruetter CA, Gruetter DY, Lyon JE, Kadowitz PJ, Ignarro LJ. Relationship between cyclic guanosine 3′:5′-monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite and nitric oxide: effect of methylene blue and methemoglobin. Journal of Pharmacology and Experimental Therapeutics 219: 181–186, 1981PubMedGoogle Scholar
  30. Hall JE, Guyton AC, Jackson TE, Coleman TG, Lohmeier TE, Trippodo NC. Control of glomerular filtration rate by renin-angiotensin system. American Journal of Physiology 233: F366–372, 1977PubMedGoogle Scholar
  31. Ke Y, Manthey J, Dietz R, Leinberger H, Schomig A, Kubler W. Effects of hydralazine on sympathetic nervous activity in heart failure. American Journal of Cardiology 49: 933, 1982CrossRefGoogle Scholar
  32. Klugmann S, Salvi A, Camerini F. Haemodynamic effects of nifedipine in heart failure. British Heart Journal 43: 440–446, 1980PubMedCrossRefGoogle Scholar
  33. Kramer BL, Massie BM, Topic N. Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study. Circulation 67: 807–816, 1983PubMedCrossRefGoogle Scholar
  34. Lambertz H, Meyer J, Erbel R. Long-term hemodynamic effects of prenalterol in patients with severe chronic congestive heart failure. Circulation 69: 298–305, 1984PubMedCrossRefGoogle Scholar
  35. Lee WH, Packer M. Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation 73: 257–267, 1986PubMedCrossRefGoogle Scholar
  36. Leier CV, Huss P, Magorien RD, Unverferth DV. Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure. Circulation 67: 817–822, 1983PubMedCrossRefGoogle Scholar
  37. Lilly L, Dzau VJ, Williams GH, Hollenberg NK. Captopril vs hydralazine in advanced congestive heart failure: comparison of one-year survival (abstract). Circulation 72(Suppl. 3): III–408, 1985Google Scholar
  38. Lown B, Verrier RI. Neural activity and ventricular fibrillation. New England Journal of Medicine 294: 1165–1170, 1976PubMedCrossRefGoogle Scholar
  39. Ludbrook PA, Byrne JD, Kurnik PB, McKnight RC. Influence of reduction of preload and afterload by nitroglycerin on left ventricular diastolic pressure-volume relations and relaxation in man. Circulation 56: 937–943, 1977PubMedCrossRefGoogle Scholar
  40. Markham RV, Corbett JR, Gilmore A, Pettinger WA, Firth BG. Efficacy of prazosin in the management of chronic congestive heart failure: a 6-month randomized, double-blind, placebo-controlled study. American Journal of Cardiology 51: 1346–1352, 1983PubMedCrossRefGoogle Scholar
  41. Massie BM, Kramer BL, Topic N. Lack of relationship between short-term hemodynamic effects of captopril and subsequent clinical responses. Circulation 69: 1135–1141, 1984PubMedCrossRefGoogle Scholar
  42. Massie B, Bourassa M, DiBianco R, Hess M, Konstam M, et al. Long-term oral amrinone for congestive heart failure: lack of efficacy in a multicenter controlled trial. Circulation 71: 963–971, 1985PubMedCrossRefGoogle Scholar
  43. Mettauer B, Rouleau J-L, Bichet D, et al. Differential long-term intrarenal and neurohormonal effects of captopril and prazosin in patients with chronic congestive heart failure: importance of initial plasma renin activity. Circulation 73: 492–502, 1986PubMedCrossRefGoogle Scholar
  44. Miller RR, Awan NA, Maxwell KS, Mason DT. Sustained reduction of cardiac impedance and preload in congestive heart failure with the antihypertensive vasodilator prazosin. New England Journal of Medicine 297: 303–307, 1977PubMedCrossRefGoogle Scholar
  45. Packer M. New perspectives on the therapeutic application of nitrates as vasodilator agents for severe chronic heart failure. American Journal of Medicine 74(6B): 61–72, 1983aPubMedCrossRefGoogle Scholar
  46. Packer M. Vasodilator and inotropic therapy for severe chronic heart failure: Passion and skepticism. Journal of the American College of Cardiology 2: 841–852, 1983bPubMedCrossRefGoogle Scholar
  47. Packer M. Conceptual dilemmas in the classification of vasodilator drugs for severe heart failure. Advocacy of a pragmatic approach to the selection of a therapeutic agent. American Journal of Medicine 76(6A): 3–13, 1984PubMedCrossRefGoogle Scholar
  48. Packer M. Converting-enzyme inhibition for severe chronic heart failure: views from a skeptic. International Journal of Cardiology 7: 111–120, 1985aPubMedCrossRefGoogle Scholar
  49. Packer M. Is the renin-angiotensin system really unnecessary in patients with severe chronic heart failure? The price we pay for interfering with evolution. Journal of the American College of Cardiology 6: 171–173, 1985bCrossRefGoogle Scholar
  50. Packer M, Meller J. Oral vasodilator therapy for chronic heart failure. A plea for caution. American Journal of Cardiology 42: 686–689, 1978PubMedCrossRefGoogle Scholar
  51. Packer M, Meller J, Gorlin R, Herman MV. Clinical and hemodynamic tachyphylaxis to prazosin mediated afterload reduction in severe congestive heart failure. Circulation 59: 531–539, 1979PubMedCrossRefGoogle Scholar
  52. Packer M, Meller J, Medina N, Gorlin R, Herman MV. Dose requirements of hydralazine in patients with severe chronic congestive heart failure. American Journal of Cardiology 45: 655–659, 1980aPubMedCrossRefGoogle Scholar
  53. Packer M, Meller J, Medina N, Gorlin R, Herman MV. Importance of left ventricular chamber size in determining the response to hydralazine in severe chronic heart failure. New England Journal of Medicine 303: 250–255, 1980bPubMedCrossRefGoogle Scholar
  54. Packer M, Meller J, Medina N, Yushak M, Gorlin R. Provocation of myocardial ischemic events during initiation of vasodilator therapy for severe chronic heart failure. Clinical and hemodynamic evaluation of 52 consecutive patients with ischemic cardiomyopathy. American Journal of Cardiology 48: 939–946, 1981PubMedCrossRefGoogle Scholar
  55. Packer M, Meller J, Medina N, Yushak M, Gorlin R. Hemodynamic characterization of tolerance to long-term hydralazine therapy in severe chronic heart failure. New England Journal of Medicine 306: 57–62, 1982PubMedCrossRefGoogle Scholar
  56. Packer M, Medina N, Yushak M, Meller J. Hemodynamic patterns of response during long-term captopril therapy for severe chronic heart failure. Circulation 68: 803–812, 1983PubMedCrossRefGoogle Scholar
  57. Packer M, Lee WH, Bair J, Medina N, Yushak M. Does vasodilatory therapy alter prognosis in patients with severe chronic heart failure? Comparative effects of hydralazine and captopril on clinical outcome and survival in 175 patients treated over a 6-year period. Journal of the American College of Cardiology 3: 561, 1984aCrossRefGoogle Scholar
  58. Packer M, Medina N, Medina M. Adverse hemodynamic and clinical effects of calcium channel blockade in pulmonary hypertension secondary to obliterative pulmonary vascular disease. Journal of the American College of Cardiology 4: 890–901, 1984bPubMedCrossRefGoogle Scholar
  59. Packer M, Medina N, Yushak M. Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure. Circulation 70: 1038–1047, 1984cPubMedCrossRefGoogle Scholar
  60. Packer M, Medina M, Yushak M. Correction of dilutional hyponatremia in patients with severe chronic heart failure by converting-enzyme inhibition. Annals of Internal Medicine 100: 782–789, 1984dPubMedGoogle Scholar
  61. Packer M, Medina N, Yushak M. Relationship between serum sodium concentration and the hemodynamic and clinical responses to converting-enzyme inhibition with captopril in severe heart failure. Journal of the American College of Cardiology 3: 1035–1043, 1984ePubMedCrossRefGoogle Scholar
  62. Packer M, Medina N, Yushak M, Lee WH. Usefulness of plasma renin activity in predicting hemodynamic and clinical responses and survival during long-term converting-enzyme inhibition in severe chronic heart failure. Experience in 100 consecutive patients. British Heart Journal 54: 298–304, 1985PubMedCrossRefGoogle Scholar
  63. Packer M, Lee WH, Kessler P, Medina N, Yushak M. Induction of nitrate tolerance in human heart failure by continuous intravenous infusion of nitroglycerin and reversal of tolerance by N-acetylcysteine, a sulfhydryl donor. Journal of the American College of Cardiology 7: 27A, 1986aCrossRefGoogle Scholar
  64. Packer M, Medina N, Yushak M. Role of the renin-angiotensin system in the development of hemodynamic and clinical tolerance to long-term prazosin therapy in patients with severe chronic heart failure. Journal of the American College of Cardiology 7: 671–680, 1986bPubMedCrossRefGoogle Scholar
  65. Packer M, Medina N, Yushak M, Lee WH. Hemodynamic factors limiting the response to transdermal nitroglycerin in patients with severe chronic congestive heart failure. American Journal of Cardiology 57: 260–267, 1986cPubMedCrossRefGoogle Scholar
  66. Packer M, Medina N, Yushak M. Comparative hemodynamic and clinical effects of long-term treatment with prazosin and captopril for severe chronic congestive heart failure secondary to either coronary artery disease or idiopathic dilated cardiomyopathy. American Journal of Cardiology 57: 1323–1328, 1986dPubMedCrossRefGoogle Scholar
  67. Packer M, Lee WH, Medina N, Yushak M, Kessler P. Identification of patients with severe heart failure most likely to fail long-term therapy with converting-enzyme inhibitors. Journal of the American College of Cardiology 7: 181A, 1986eCrossRefGoogle Scholar
  68. Packer M, Lee WH, Medina N, Yushak M. Influence of renal function on the hemodynamic and clinical responses to long-term captopril therapy in severe chronic heart failure. Annals of Internal Medicine 104: 147–154, 1986fPubMedGoogle Scholar
  69. Packer M, Gottlieb SS, Kessler PD. Hormone-electrolyte interactions in the pathogenesis of lethal cardiac arrhythmias in patients with congestive heart failure. The basis of a new physiologic approach to control of arrhythmia. American Journal of Medicine 80(4A): 23–29, 1986gPubMedCrossRefGoogle Scholar
  70. Packer M, Lee WH, Kessler PD. Hemodynamic factors underlying the occurrence of functional renal insufficiency during long-term converting-enzyme inhibition in severe chronic heart failure. Clinical Research 34: 333A, 1986hGoogle Scholar
  71. Packer M, Lee WH, Kessler PD. Preservation of glomerular filtration rate in human heart failure by activation of the renin-angiotensin system. Circulation, in pressGoogle Scholar
  72. Pfeffer MA, Pfeffer JM, Steinberg C, Finn P. Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation 72: 406–412, 1985PubMedCrossRefGoogle Scholar
  73. Pouleur H, Covell JW, Ross Jr J. Effects of alterations in aortic input impedance on the force-velocity-length relationship in the intact canine heart. Circulation Research 45: 126–135, 1979PubMedCrossRefGoogle Scholar
  74. Pratt JH. Role of angiotensin II in potassium-mediated stimulation of aldosterone secretion in the dog. Journal of Clinical Investigation 70: 667–672, 1982PubMedCrossRefGoogle Scholar
  75. Riegger AJC, Lever AF, Millar JA, Morton JJ, Slack B. Correction of renal hypertension in the rat by prolonged infusion of angiotensin II inhibitors. Lancet 2: 1317–1319, 1977PubMedCrossRefGoogle Scholar
  76. Riegger GAJ, Liebau G, Holzehuh M, Witkowski D, Steilner H, Hochsiek K. Role of the renin-angiotensin system in the development of congestive heart failure in the dog as assessed by chronic converting-enzyme blockade. American Journal of Cardiology 53: 614–618, 1984PubMedCrossRefGoogle Scholar
  77. Rubin S, Chatterjee K, Parmley WW. Metabolic assessment of exercise in chronic heart failure patients treated with short-term vasodilators. Circulation 67: 817–822, 1983CrossRefGoogle Scholar
  78. Serruys PW, Brower RW, den Katen HJ, Born AH, Hugenholtz PG. Regional wall motion from radioopaque after intravenous and intracoronary injection of nifedipine. Circulation 63: 584–591, 1981PubMedCrossRefGoogle Scholar
  79. Sharpe DN, Murphy J, Coxon R, Hannan SF. Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation 70: 271–278, 1984PubMedCrossRefGoogle Scholar
  80. Swedberg K, Hjalmarson A, Waagstein F, Wallentin I. Prolongation of survival in congestive cardiomyopathy by beta-receptor blockade. Lancet 1: 1374–1376, 1979PubMedCrossRefGoogle Scholar
  81. Textor SC, Bravo EL, Fouad FM, Tarazi RC. Hyperkalemia in azotemic patients during angiotensin-converting enzyme inhibition and aldosterone reduction with captopril. American Journal of Medicine 73: 719–725, 1982PubMedCrossRefGoogle Scholar
  82. Yates JC, Beamish RE, Dhalla NS. Ventricular dysfunction and necrosis produced by adrenochrome metabolites of epinephrine: relation to pathogenesis of catecholamine cardiomyopathy. American Heart Journal 102: 210–221, 1981PubMedCrossRefGoogle Scholar

Copyright information

© ADIS Press Limited 1986

Authors and Affiliations

  • Milton Packer
    • 1
  1. 1.Division of Cardiology, Department of MedicineThe Mount Sinai School of Medicine of The City University of New YorkNew YorkUSA

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