Skip to main content
Log in

Combination Drug Therapy in Chronic Heart Failure: Is Treatment Part of the Problem in Heart Failure?

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Despite advances in medical treatment, the annual mortality associated with severe heart failure remains over 40%, and even in mild heart failure the associated mortality is 40% over 4 years. Once it has been demonstrated that the morbidity and mortality to heart failure can be adequately addressed by combinations of drug therapy, then it is logical to attempt to strip out redundant components of these therapeutic regimes. In the meantime, however, combination therapy is required to counter many of the pathophysiological facets of the heart failure syndrome, including fluid retention, neuroendocrine activation, progressive ventricular dysfunction, and sudden cardiac death. Diuretics and ACE inhibitors are well-established drug treatments. Digoxin appears to lessen the rate of progression of heart failure without altering survival. New evidence suggests that beta-blockers may be useful additions to the heart failure therapeutic armamentarium, although whether all beta-blockers are equally effective remains to be established.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cleland JGF, on behalf of the Task Force on Heart Failure of the European Society of Cardiology: Guidelines for the diagnosis of heart failure. Eur Heart J 1995;16:741–751.

    Google Scholar 

  2. Narang R, Cleland JGF, Ball SG, et al. Mode of death in chronic heart failure: A request for more accurate classification. Eur Heart J 1996;17:1390–1403.

    Google Scholar 

  3. Jiang BY, Habib F, Oakley CM, Cleland JGF: Shortened duration of post-ischaemic hyperaemic blood flow in heart failure. Am J Cardiol 1995;77:300–302.

    Google Scholar 

  4. Puri S, Baker BL, Dutka DP, Oakley CM, Hughes JMB, Cleland JGF. Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure: Its pathophysiological relevance and relationship to exercise performance. Circulation 1995;91:2769–2774.

    Google Scholar 

  5. Puri S, Baker BL, Oakley CM, Hughes JMB, Cleland JGF. Increased alveolar/capillary membrane resistance to gas transfer in patients with chronic heart failure. Br Heart J 1994;72:140–144.

    Google Scholar 

  6. Cleland JGF. ACE inhibitors for the prevention and treatment of heart failure: Why are they “under-used”? J Hum Hyperten 1995;9:435–442.

    Google Scholar 

  7. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996;334:1349–1355.

    Google Scholar 

  8. Lechat P, Jaillon P, Fontaine ML, et al. A randomized trial of beta-blockade in heart failure: The Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation 1994;90:1765–1773.

    Google Scholar 

  9. O'Connor CM, Belkin RN, Carson PE, et al. Effect of amlodipine on mode of death in severe chronic heart failure: The PRAISE trial. Circulation, in press.

  10. Waagstein F, Bristow MR, Swedberg K, et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet 1993;342:1441–1446.

    Google Scholar 

  11. Anand IS, Chandrashekhar Y, Ferrari R, et al. Pathogenesis of congestive state in chronic obstructive pulmonary disease: Studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery. Circulation 1992;86:12–21.

    Google Scholar 

  12. Anand IS, Veall N, Kalra GS, et al. Treatment of heart failure with diuretics: Body compartments, renal function and plasma hormones. Eur Heart J 1989;10:445–450.

    Google Scholar 

  13. Anand IS, Ferrari R, Kalra GS, Wahi PL, Poole Wilson PA, Harris PC. Edema of cardiac origin. Studies of body water and sodium, renal function, hemodynamic indexes, and plasma hormones in untreated congestive cardiac failure. Circulation 1989;80:299–305.

    Google Scholar 

  14. Cleland JGF, Dargie HJ, Robertson I, et al. Total body electrolyte composition in patients with heart failure: A comparison with normal subjects and patients with untreated hypertension. Br Heart J 1987;58:230–238.

    Google Scholar 

  15. Cleland JGF, Oakley CM. Vascular tone in heart failure: The neuroendocrine-therapeutic interface. Br Heart J 1991;66:264–267.

    Google Scholar 

  16. Cleland JGF, Dargie HJ. Heart failure, renal function, and angiotensin converting enzyme inhibitors. Kidney Int 1987;31:S220-S228.

    Google Scholar 

  17. Cleland JGF. The clinical course of heart failure and its modification by ACE inhibitors: Insights from recent clinical trials. Eur Heart J 1994;15:125–130.

    Google Scholar 

  18. Good JM, Peters M, Wilkins M, Jackson N, Oakley CM, Cleland JGF. Renal response to candoxatrilat in patients with heart failure. J Am Coll Cardiol 1995;25:1273–1281.

    Google Scholar 

  19. Dossegger L, Aldor E, Baird MG, et al. Influence of angiotensin converting enzyme inhibition on exercise performance and clinical symptoms in chronic heart failure: A multicentre, double-blind, placebo-controlled trial. Eur Heart J 1993;14:18–23.

    Google Scholar 

  20. Good JM, Brady AJB, Noormohamed FH, Oakley CM, Cleland JGF. Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition. Circulation 1994;90:220–224.

    Google Scholar 

  21. Good J, Frost G, Oakley CM, Cleland JGF. The renal effects of dopamine and dobutamine in stable chronic heart failure. Postgrad Med J 1992;68:S7-S11.

    Google Scholar 

  22. Good J, Sbarouni E, Frost G, Meek J, Oakley CM, Cleland JGF. Does digoxin facilitate the renal response to furosemide in heart failure? J Am Coll Cardi 1993;21(Suppl):467. (abstr)

    Google Scholar 

  23. Good J, Frost G, Oakley CM, Cleland JGF. Sodium restriction impairs a frusemide-induced diuresis in patients with heart failure. Euro Heart J 1992;13(Suppl):217. (abstr)

    Google Scholar 

  24. Ram CVS, Garret BN, Kaplan NM. Moderate sodium restriction and various diuretics in the treatment of hypertension. Arch Intern Med 1981;141:1015–1019.

    Google Scholar 

  25. Dzau VJ, Colucci WS, Hollenberg NK, Williams GH. Relation of the renin-angiotensin-aldosterone system to clinical state in congestive heart failure. Circulation 1981;63:645–651.

    Google Scholar 

  26. Loeb HS, Johnson G, Henrick A, Smith R, Wilson J, Cremo R, Cohn JN. Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. Circulation 1993;87:VI78-VI87.

    Google Scholar 

  27. Cleland JGF, Cowburn PJ, McMurray JJV. Heart Failure: a systematic guide to clinical practice, in Cleland JGF (ed): London, Science Press, 1997.

    Google Scholar 

  28. Cohn JN, Ziesche SM, Loss LE, Anderson GF. Effect of felodipine on short-term exercise and neurohormones and long-term mortality in heart failure: Results of V-HeFT-III. Circulation 1995;92:I143. (abstr)

    Google Scholar 

  29. Dargie HJ, McMurray JJV. Diagnosis and management of heart failure. Br Med J 1994;308:321–328.

    Google Scholar 

  30. Cleland JGF, Gillen G, Dargie HJ. The effects of frusemide and angiotensin-converting enzyme inhibitors and their combination on cardiac and renal haemodynamics in heart failure. Eur Heart J 1988;9:132–141.

    Google Scholar 

  31. 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. Br Heart J 1985;54:305–312.

    Google Scholar 

  32. Cleland JGF, Shah D, Krikler S, Dritsas A, Nihoyannopoulos P, Frost G, Oakley CM. Effects of lisinopril on cardiorespiratory, neuroendocrine, and renal function in patients with asymptomatic left ventricular dysfunction. Br Heart J 1993;69:512–515.

    Google Scholar 

  33. Berglund H, Nyquist O, Beermann B, Jensen Urstad M, Theodorsson E. Influence of angiotensin converting enzyme inhibition on relation of atrial natriuretic peptide concentration to atrial pressure in heart failure. Br Heart J 1994;72:521–527.

    Google Scholar 

  34. Rouleau JL, Bichet D, Kortas C. Atrial natriuretic peptide in congestive heart failure: Postural changes and reset with chronic captopril therapy. Am Heart J 1988;115:1060–1067.

    Google Scholar 

  35. Cleland JGF, Cowburn PJ, Morgan K. Neuroendocrine activation after myocardial infarction: Causes and consequences. Br Heart J 1996, in press.

  36. Riegger GAJ, Haeske W, Kraus C, et al. Contribution of the renin-angiotensin-aldosterone system to development of tolerance and fluid retention in chronic congestive heart failure during prazosin treatment. Am J Cardiol 1987;59:906–910.

    Google Scholar 

  37. Wieshammer S, Hetzel M, Hetzel J, Kochs M, Hombach V. Lack of effect of nitrates on exercise tolerance in patients with mild to moderate heart failure caused by coronary disease already treated with captopril. Br Heart J 1993;70:17–21.

    Google Scholar 

  38. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the studies of left ventricular dysfunction (SOLVD). Circulation 1990;82:1724–1729.

    Google Scholar 

  39. Cleland JGF, Bristow M, Erdmann E, Remme WJ, Swedberg K, Waagstein F. Beta-blockers in heart failure: Should they be used and how? Eur Heart J 1996, in press.

  40. Anderson JL, Platia EV, hallstrom A, Henthorn RW, Buckingham TA, Carlson MD, Carson PE. Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction: A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST). Circulation 1994;90:2843–2852.

    Google Scholar 

  41. Peters RW, Mitchell LB, Brooks MM, et al. Circadian pattern of arrhythmic death in patients receiving encainide, flecainide or moricizine in the cardiac arrhythmia suppression trial (CAST). J Am Coll Cardiol 1994;23:283–289.

    Google Scholar 

  42. Doval HC, Nul DR, Grancelli HI, Perrone SV, Bortman GR, Curiel R. Randomised trial of low-dose amiodarone in severe congestive heart failure. Lancet 1994;344:493–498.

    Google Scholar 

  43. Singh SN, Fletcher RD, Fisher SG, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmias. N Eng J Med 1995;333:77–82.

    Google Scholar 

  44. Cleland JGF, Dutka DP. Optimising heart failure pharmacotherapy: The ideal combination. Br Heart J 1994;72:S73-S79.

    Google Scholar 

  45. Cleland JGF, Puri S. How do ACE inhibitors reduce mortality in patients with left ventricular dysfunction with and without heart failure: Remodelling, resetting, or sudden death? Br Heart J 1994;72:S81-S86.

    Google Scholar 

  46. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure Lancet 1993;342:812–828.

    Google Scholar 

  47. Cleland JGF, Bulpitt CJ, Falk RH, et al. Is aspirin safe for patients with heart failure? Bri Heart J 1995;74:215–219.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cleland, J.G. Combination Drug Therapy in Chronic Heart Failure: Is Treatment Part of the Problem in Heart Failure?. Cardiovasc Drugs Ther 11 (Suppl 1), 297–303 (1997). https://doi.org/10.1023/A:1007700215917

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007700215917

Navigation